Effect of Human Burn Wound Exudate on Pseudomonas aeruginosa Virulence.

Burn wound sepsis is currently the main cause of morbidity and mortality after burn trauma. Infections by notorious pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii impair patient recovery and can even lead to fatality. In this study, we investigated the effect of burn wound exudates (BWEs) on the virulence of those pathogens. BWEs were collected within 7 days after burn trauma from 5 burn patients. We first monitored their effect on pathogen growth. In contrast to A. baumannii and S. aureus, P. aeruginosa was the only pathogen able to grow within these human fluids. Expression of typical virulence factors such as pyocyanin and pyoverdine was even enhanced compared the levels seen with standard laboratory medium. A detailed chemical composition analysis of BWE was performed, which enabled us to determine the major components of BWE and underline the metabolic modifications induced by burn trauma. These data are essential for the development of an artificial medium mimicking the burn wound environment and the establishment of an in vitro system to analyze the initial steps of burn wound infections. IMPORTANCE Microbial infection of severe burn wounds is currently a major medical challenge. Of the infections by bacteria able to colonize such injuries, those by Pseudomonas aeruginosa are among the most severe, causing major delays in burn patient recovery or leading to fatal issues. In this study, we investigated the growth properties of several burn wound pathogens in biological fluids secreted from human burn wounds. We found that P. aeruginosa strains were able to proliferate but not those of the other pathogens tested. In addition, burn wound exudates (BWEs) stimulate the expression of virulence factors in P. aeruginosa. The chemical composition analysis of BWEs enabled us to determine the major components of these fluids. These data are essential for the development of an artificial medium mimicking the burn wound environment and for in vitro analysis of the initial step in the development of burn wound infections

Developing a career and education framework for advanced clinical practice in midwifery

Introduction: This study outlines the nature of Advanced Clinical Practice in Midwifery (ACPiM), reporting on a stakeholder analysis as part of a national project to develop a career framework for advanced practice in midwifery on behalf of the National Health Service (NHS) in England. Methods: Between June and July 2022, 31 advanced practice midwives were recruited across England within the NHS settings. Convenience sampling was used to identify midwives working as advanced practitioners, and those pursuing this career route. Focus group and one-to-one interviews were conducted, recorded, and transcribed. These stakeholder data were then analyzed using a reflexive thematic approach. Results: ACP midwives were active across many professional settings. The findings resulted in three themes: Midwifery autonomy, Desire for progression, and Avenues of support. Midwifery autonomy highlighted a midwifery desire to utilize specialist skills and expert decision-making to provide holistic care directly to women and families. Desire for progression highlighted that, regardless of career stage, midwives aspired to advance their practice requiring a range of pathways to fulfil career satisfaction and meet local population health needs. Avenues of support discussed the barriers and facilitators to progression, highlighting the need for service vision, a multi-disciplinary approach to facilitate support for individuals, and strong midwifery leadership. Conclusions: Although the ACPiM role is desired by maternity institutions and organizations, midwives remain unclear about how to achieve this position, and employers remain unsure of how an ACPiM could transform services. If midwives are to successfully achieve ACPiM status, organizational support is needed to facilitate individuals drive for career progression, resulting in a strengthened workforce and improved patient experience

International Society of Sports Nutrition Position Stand: Nutritional recommendations for single-stage ultra-marathon; training and racing

Background. In this Position Statement, the International Society of Sports Nutrition (ISSN) provides an objective and critical review of the literature pertinent to nutritional considerations for training and racing in single-stage ultra-marathon. Recommendations for Training. i) Ultra-marathon runners should aim to meet the caloric demands of training by following an individualized and periodized strategy, comprising a varied, food-first approach; ii) Athletes should plan and implement their nutrition strategy with sufficient time to permit adaptations that enhance fat oxidative capacity; iii) The evidence overwhelmingly supports the inclusion of a moderate-to-high carbohydrate diet (i.e., ~60% of energy intake, 5 – 8 g⸱kg−1·d−1) to mitigate the negative effects of chronic, training-induced glycogen depletion; iv) Limiting carbohydrate intake before selected low-intensity sessions, and/or moderating daily carbohydrate intake, may enhance mitochondrial function and fat oxidative capacity. Nevertheless, this approach may compromise performance during high-intensity efforts; v) Protein intakes of ~1.6 g·kg−1·d−1 are necessary to maintain lean mass and support recovery from training, but amounts up to 2.5 g⸱kg−1·d−1 may be warranted during demanding training when calorie requirements are greater; Recommendations for Racing. vi) To attenuate caloric deficits, runners should aim to consume 150 - 400 kcal⸱h−1 (carbohydrate, 30 – 50 g⸱h−1; protein, 5 – 10 g⸱h−1) from a variety of calorie-dense foods. Consideration must be given to food palatability, individual tolerance, and the increased preference for savory foods in longer races; vii) Fluid volumes of 450 – 750 mL⸱h−1 (~150 – 250 mL every 20 min) are recommended during racing. To minimize the likelihood of hyponatraemia, electrolytes (mainly sodium) may be needed in concentrations greater than that provided by most commercial products (i.e., >575 mg·L−1 sodium). Fluid and electrolyte requirements will be elevated when running in hot and/or humid conditions; viii) Evidence supports progressive gut-training and/or low-FODMAP diets (fermentable oligosaccharide, disaccharide, monosaccharide and polyol) to alleviate symptoms of gastrointestinal distress during racing; ix) The evidence in support of ketogenic diets and/or ketone esters to improve ultra-marathon performance is lacking, with further research warranted; x) Evidence supports the strategic use of caffeine to sustain performance in the latter stages of racing, particularly when sleep deprivation may compromise athlete safety

Potential return on investment of a family-centered early childhood intervention: a cost-effectiveness analysis

Abstract Background ParentCorps is a family-centered enhancement to pre-kindergarten programming in elementary schools and early education centers. When implemented in high-poverty, urban elementary schools serving primarily Black and Latino children, it has been found to yield benefits in childhood across domains of academic achievement, behavior problems, and obesity. However, its long-term cost-effectiveness is unknown. Methods We determined the cost-effectiveness of ParentCorps in high-poverty, urban schools using a Markov Model projecting the long-term impact of ParentCorps compared to standard pre-kindergarten programming. We measured costs and quality adjusted life years (QALYs) resulting from the development of three disease states (i.e., drug abuse, obesity, and diabetes); from the health sequelae of these disease states; from graduation from high school; from interaction with the judiciary system; and opportunity costs of unemployment with a lifetime time horizon. The model was built, and analyses were performed in 2015–2016. Results ParentCorps was estimated to save $4387 per individual and increase each individual’s quality adjusted life expectancy by 0.27 QALYs. These benefits were primarily due to the impact of ParentCorps on childhood obesity and the subsequent predicted prevention of diabetes, and ParentCorps’ impact on childhood behavior problems and the subsequent predicted prevention of interaction with the judiciary system and unemployment. Results were robust on sensitivity analyses, with ParentCorps remaining cost saving and health generating under nearly all assumptions, except when schools had very small pre-kindergarten programs. Conclusions Effective family-centered interventions early in life such as ParentCorps that impact academic, behavioral and health outcomes among children attending high-poverty, urban schools have the potential to result in longer-term health benefits and substantial cost savings

The amputee mobility predictor: an instrument to assess determinants of the lower-limb amputee's ability to ambulate

To describe the development of the Amputee Mobility Predictor (AMP) instrument designed to measure ambulatory potential of lower-limb amputees with (AMPPRO) and without (AMPnoPRO) the use of a prosthesis, and to test its reliability and validity. Measurement study using known groups method and concurrence with existing measures. Academic medical center. A convenience sample of 191 lower-limb amputee subjects who had completed prosthetic training, 24 in the reliability study (mean age +/- standard deviation, 68.3+/-17.9y, range, 28-99y) and 167 in the validity study (mean age, 54.8+/-18.6y; range, 18-100y). Not applicable. Intra- and interrater reliability; construct validity by known groups method; concurrent validity by comparisons with 6-minute walk test, Comorbidity Index, age, and time since amputation; predictive validity by comparison with 6-minute walk test after controlling for other factors. Interrater reliability was.99 for subjects tested with and without their prosthesis; intrarater reliability was.96 and.97. Both the AMPnoPRO (P<.0001) and the AMPPRO scores (P<.0001) distinguished among the 4 Medicare functional classification levels. The AMP correlated strongly with 6-minute walk scores (AMPnoPRO r=.69, P<.0001; AMPPRO r=.82, P<.0001) and the amputee activity survey (AMPnoPRO r=.67, P<.0001; AMPPRO r=.77, P<.0001), and negatively correlated with age (AMPnoPRO r=-.69, P<.0001; AMPPRO r=.56, P<.0001) and comorbidity (AMPnoPRO r=-.43, P<.0001; AMPPRO r=.38, P<.0001). The AMP with and without a prosthesis are reliable and valid measures for the assessment of functional ambulation in lower-limb amputee subjects

Limited naturally occurring escape in broadly neutralizing antibody epitopes in hepatitis C glycoprotein E2 and constrained sequence usage in acute infection

Broadly neutralizing antibodies have been associated with spontaneous clearance of the hepatitis C infection as well as viral persistence by immune escape. Further study of neutralizing antibody epitopes is needed to unravel pathways of resistance to virus neutralization, and to identify conserved regions for vaccine design. All reported broadly neutralizing antibody (BNAb) epitopes in the HCV Envelope (E2) glycoprotein were identified. The critical contact residues of these epitopes were mapped onto the linear E2 sequence. All publicly available E2 sequences were then downloaded and the contact residues within the BNAb epitopes were assessed for the level of conservation, as well as the frequency of occurrence of experimentally-proven resistance mutations. Epitopes were also compared between two sequence datasets obtained from samples collected at well-defined time points from acute ( 180days) infections, to identify any significant differences in residue usage. The contact residues for all BNAbs were contained within 3 linear regions of the E2 protein sequence. An analysis of 1749 full length E2 sequences from public databases showed that only 10 out of 29 experimentally-proven resistance mutations were present at a frequency >5%. Comparison of subtype 1a viral sequences obtained from samples collected during acute or chronic infection revealed significant differences at positions 610 and 655 with changes in residue (p <0.05), and at position 422 (p <0.001) with a significant difference in variability (entropy). The majority of experimentally-described escape variants do not occur frequently in nature. The observed differences between acute and chronically isolated sequences suggest constraints on residue usage early in infectio