Detection of β-alanyl aminopeptidase as a biomarker for Pseudomonas aeruginosa in the sputum of patients with cystic fibrosis using exogenous volatile organic compound evolution

A novel, rapid and sensitive analytical method has been developed and applied to 105 sputum samples from patients with cystic fibrosis, including 5 samples from post-lung transplant patients. This new method is specifically targeted to measure β-alanyl aminopeptidase activity which is characteristic of some important Gram-negative pathogens. Of relevance to this study are Pseudomonas aeruginosa and pathogens of the Burkholderia cepacia complex both of which are commonly associated with respiratory infections as well as increased morbidity and mortality in adult cystic fibrosis patients. The analytical method involves the addition of a novel enzyme substrate (i.e. 3-amino-N-(3-fluorophenyl)propanamide) that interacts with β-alanyl aminopeptidase to generate an exogenous volatile organic compound 3-fluoroaniline (LOD 0.02 μg mL−1; LOQ 0.06 μg mL−1). 3-Fluoroaniline was determined at 20 times above its calculated limit of quantification in the sputum samples by HS-SPME-GC-MS and then the results compared with standard culture methods and bacterial identification using MALDI-TOF-MS. Detection of 3-fluoroaniline was possible after only 8 h incubation of the sputum samples with a 95% success rate; this increased to 100% at 24 h which was well within the typical routine timeframe of 48 h. To our knowledge, this is the first demonstration of detection of P. aeruginosa by use of a custom-designed substrate to liberate a detectable and unique VOC. The very high negative predictive value (100% in this study) means such an assay could be appropriate as a screening technique for patients who are not yet colonized by this pathogen

American eel state of buoyancy and barotrauma susceptibility associated with hydroturbine passage

American eel are likely to encounter and pass through hydropower turbines, particularly during the downstream spawning migration, where exposure to stressors can potentially lead to injuries and mortality. Previous research has recovered dead eels downstream of hydropower facilities and, for some fish, injuries were easily attributed to blade strike; however, others showed no external signs of injury suggesting that other stressors, such as rapid decompression may be a potential source of mortality. For this research, yellow– and silver-phase American eel were held and allowed to acclimate to 172 kPa (absolute pressure) in hyper/hypobaric hydro-chambers for about 1 d. After acclimation, the state of buoyancy was determined prior to exposure to a rapid decompression simulating pressures encountered during hydroturbine passage. Fish were then examined for signs of barotrauma. Eel did not attain a state of neutral buoyancy but rather maintained negative buoyancy suggesting that eels, and possibly other benthic species, likely maintain a state of negative buoyancy to facilitate occupancy on or near the substrate. Additionally, eel were found to be resilient to rapid decompression, displaying no instantaneous mortality and minimal injuries, suggesting that barotrauma is not likely a major concern for American eel passing downstream through hydroturbines

The domestication of SARS-CoV-2 into a seasonal infection by viral variants

IntroductionThe COVID-19 pandemic was caused by the zoonotic betacoronavirus SARS-CoV-2. SARS-CoV-2 variants have emerged due to adaptation in humans, shifting SARS-CoV-2 towards an endemic seasonal virus. We have termed this process ‘virus domestication’.MethodsWe analyzed aggregate COVID-19 data from a publicly funded healthcare system in Canada from March 7, 2020 to November 21, 2022. We graphed surrogate calculations of COVID-19 disease severity and SARS-CoV-2 variant plaque sizes in tissue culture.Results and DiscussionMutations in SARS-CoV-2 adapt the virus to better infect humans and evade the host immune response, resulting in the emergence of variants with altered pathogenicity. We observed a decrease in COVID-19 disease severity surrogates after the arrival of the Delta variant, coinciding with significantly smaller plaque sizes. Overall, we suggest that SARS-CoV-2 has become more infectious and less virulent through viral domestication. Our findings highlight the importance of SARS-CoV-2 vaccination and help inform public policy on the highest probability outcomes during viral pandemics

Androgen receptor agonists increase lean mass, improve cardiopulmonary functions and extend survival in preclinical models of Duchenne muscular dystrophy

© The Author 2017. Duchenne muscular dystrophy (DMD) is a neuromuscular disease that predominantly affects boys as a result of mutation(s) in the dystrophin gene. DMD is characterized by musculoskeletal and cardiopulmonary complications, resulting in shorter life-span. Boys afflicted by DMD typically exhibit symptoms within 3-5 years of age and declining physical functions before attaining puberty. We hypothesized that rapidly deteriorating health of pre-pubertal boys with DMD could be due to diminished anabolic actions of androgens in muscle, and that intervention with an androgen receptor (AR) agonist will reverse musculoskeletal complications and extend survival. While castration of dystrophin and utrophin double mutant (mdx-dm) mice to mimic pre-pubertal nadir androgen condition resulted in premature death, maintenance of androgen levels extended the survival. Non-steroidal selective-AR modulator, GTx-026, which selectively builds muscle and bone was tested in X-linked muscular dystrophy mice (mdx). GTx-026 significantly increased body weight, lean mass and grip strength by 60-80% over vehicle-treated mdx mice. While vehicle-treated castrated mdx mice exhibited cardiopulmonary impairment and fibrosis of heart and lungs, GTx-026 returned cardiopulmonary function and intensity of fibrosis to healthy control levels. GTx-026 elicits its musculoskeletal effects through pathways that are distinct from dystrophin-regulated pathways, making AR agonists ideal candidates for combination approaches. While castration of mdx-dm mice resulted in weaker muscle and shorter survival, GTx-026 treatment increased the muscle mass, function and survival, indicating that androgens are important for extended survival. These preclinical results support the importance of androgens and the need for intervention with AR agonists to treat DMD-affected boys

Anthropometric indices of Gambian children after one or three annual rounds of mass drug administration with azithromycin for trachoma control.

BACKGROUND: Mass drug administration (MDA) with azithromycin, carried out for the control of blinding trachoma, has been linked to reduced mortality in children. While the mechanism behind this reduction is unclear, it may be due, in part, to improved nutritional status via a potential reduction in the community burden of infectious disease. To determine whether MDA with azithromycin improves anthropometric indices at the community level, we measured the heights and weights of children aged 1 to 4 years in communities where one (single MDA arm) or three annual rounds (annual MDA arm) of azithromycin had been distributed. METHODS: Data collection took place three years after treatment in the single MDA arm and one year after the final round of treatment in the annual MDA arm. Mean height-for-age, weight-for-age and weight-for-height z scores were compared between treatment arms. RESULTS: No significant differences in mean height-for-age, weight-for-age or weight-for-height z scores were found between the annual MDA and single MDA arms, nor was there a significant reduction in prevalence of stunting, wasting or underweight between arms. CONCLUSIONS: Our data do not provide evidence that community MDA with azithromycin improved anthropometric outcomes of children in The Gambia. This may suggest reductions in mortality associated with azithromycin MDA are due to a mechanism other than improved nutritional status

Multiple populations in globular clusters. Lessons learned from the Milky Way globular clusters

Recent progress in studies of globular clusters has shown that they are not simple stellar populations, being rather made of multiple generations. Evidence stems both from photometry and spectroscopy. A new paradigm is then arising for the formation of massive star clusters, which includes several episodes of star formation. While this provides an explanation for several features of globular clusters, including the second parameter problem, it also opens new perspectives about the relation between globular clusters and the halo of our Galaxy, and by extension of all populations with a high specific frequency of globular clusters, such as, e.g., giant elliptical galaxies. We review progress in this area, focusing on the most recent studies. Several points remain to be properly understood, in particular those concerning the nature of the polluters producing the abundance pattern in the clusters and the typical timescale, the range of cluster masses where this phenomenon is active, and the relation between globular clusters and other satellites of our Galaxy.Comment: In press (The Astronomy and Astrophysics Review

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Psychosocial Needs of Children in Foster Care and the Impact of Sexual Abuse

Children in family foster care, especially those who have experienced sexual abuse, require a safe and nurturing environment in which their psychosocial needs are met. However, there is limited knowledge on how youth prioritize various needs and what impact previous experiences have on these needs. In this study, we asked youth (formerly) in family foster care to indicate their psychosocial needs, and analyzed if youth with a history of sexual abuse have different needs. A Q methodological study was conducted with 44 youth (age 16–28). Fifteen of them reported sexual abuse during their childhood. Using by-person factor analyses, respondents who share similar subjective views were grouped together. Qualitative interpretations of the factors show differences and similarities between and within the two groups, related to help from others, being independent, processing the past, and working toward the future. Although the needs of youth with and without experiences of sexual abuse seem mostly similar, one group of sexually abused youth specifically indicated not wanting an emotional connection to foster parents, but instead a strictly instrumental, professional relationship. This study captured the diverse perspectives of youth themselves, revealing that children in foster care differ with regard to what they consider as (most) important safety, belonging, self-esteem and self-actualization needs