Baseline Psychological Traits Contribute to Lake Louise Acute Mountain Sickness Score at High Altitude

Talks, Benjamin James, Catherine Campbell, Stephanie J. Larcombe, Lucy Marlow, Sarah L. Finnegan, Christopher T. Lewis, Samuel J.E. Lucas, Olivia K. Harrison, and Kyle T.S. Pattinson. Baseline psychological traits contribute to Lake Louise Acute Mountain Sickness score at high altitude. High Alt Med Biol. 23:69-77, 2022. Background: Interoception refers to an individual's ability to sense their internal bodily sensations. Acute mountain sickness (AMS) is a common feature of ascent to high altitude that is only partially explained by measures of peripheral physiology. We hypothesized that interoceptive ability may explain the disconnect between measures of physiology and symptom experience in AMS. Methods: Two groups of 18 participants were recruited to complete a respiratory interoceptive task three times at 2-week intervals. The control group remained in Birmingham (140 m altitude) for all three tests. The altitude group completed test 1 in Birmingham, test 2 the day after arrival at 2,624 m, and test 3 at 2,728 m after an 11-day trek at high altitude (up to 4,800 m). Results: By measuring changes to metacognitive performance, we showed that acute ascent to altitude neither presented an interoceptive challenge, nor acted as interoceptive training. However, AMS symptom burden throughout the trek was found to relate to sea level measures of anxiety, agoraphobia, and neuroticism. Conclusions: This suggests that the Lake Louise AMS score is not solely a reflection of physiological changes on ascent to high altitude, despite often being used as such by researchers and commercial trekking companies alike. Keywords: acute mountain sickness; altitude; breathlessness; exercise; filter detection task; interoceptio

A framework to assess the quality and impact of bioinformatics training across ELIXIR.

ELIXIR is a pan-European intergovernmental organisation for life science that aims to coordinate bioinformatics resources in a single infrastructure across Europe; bioinformatics training is central to its strategy, which aims to develop a training community that spans all ELIXIR member states. In an evidence-based approach for strengthening bioinformatics training programmes across Europe, the ELIXIR Training Platform, led by the ELIXIR EXCELERATE Quality and Impact Assessment Subtask in collaboration with the ELIXIR Training Coordinators Group, has implemented an assessment strategy to measure quality and impact of its entire training portfolio. Here, we present ELIXIR's framework for assessing training quality and impact, which includes the following: specifying assessment aims, determining what data to collect in order to address these aims, and our strategy for centralised data collection to allow for ELIXIR-wide analyses. In addition, we present an overview of the ELIXIR training data collected over the past 4 years. We highlight the importance of a coordinated and consistent data collection approach and the relevance of defining specific metrics and answer scales for consortium-wide analyses as well as for comparison of data across iterations of the same course

Antibiotic-associated pathogens: the use of animal models to explore disease and alternative therapeutics

This thesis focused on the study of antibiotic-resistant disease-causing bacteria in the gut, exploring how they cause gut damage, and how they can be displaced without antibiotics. The prevalence of these bacteria in the gut is often impacted by antibiotic use, which creates imbalance by disrupting normal flora, and promoting antibiotic resistance. Using animal models of infection and gut colonisation, this thesis showed how a range of disease-causing bacteria can take advantage of this imbalance to cause disease, and how antibiotic resistant bacteria that cause urinary tract infections can be removed from the gut using a colostrum-based therapy

Hyperimmune bovine colostrum reduces gastrointestinal carriage of uropathogenic Escherichia coli

Debilitating recurrent urinary tract infections (UTIs) are often associated with gastrointestinal colonisation by uropathogens, such as uropathogenic Escherichia coli (UPEC), suggesting that these populations might be a suitable target for the treatment and prevention of recurrent UTI. However, antimicrobial treatment is generally unable to prevent recurrent UTI, and often selects for multidrug resistant uropathogens in the gut, and causes dysbiosis of the gut, vaginal, and urinary microbiota. Of note, the globally-disseminated multi drug resistant UPEC lineage, ST131, is known to both persistently colonise the gut and the urinary tract, and is associated with antibiotic treatment failure, indicating the need for novel non-antibiotic therapeutics for the treatment of UTI. This study therefore presents hyperimmune bovine colostrum (HBC) as a suitable therapy for the treatment of UPEC gastrointestinal colonisation. This work demonstrates that the vaccination of pregnant cows with inactivated cells from a ST131 UPEC isolate results in a highly specific anti-UPEC HBC, and that this product is able to disrupt the gastrointestinal colonisation of ST131 UPEC in mice

Disruption of the Gut Microbiome: Clostridium difficile Infection and the Threat of Antibiotic Resistance

Clostridium difficile is well recognized as the leading cause of antibiotic-associated diarrhea, having a significant impact in both health-care and community settings. Central to predisposition to C. difficile infection is disruption of the gut microbiome by antibiotics. Being a Gram-positive anaerobe, C. difficile is intrinsically resistant to a number of antibiotics. Mobile elements encoding antibiotic resistance determinants have also been characterized in this pathogen. While resistance to antibiotics currently used to treat C. difficile infection has not yet been detected, it may be only a matter of time before this occurs, as has been seen with other bacterial pathogens. This review will discuss C. difficile disease pathogenesis, the impact of antibiotic use on inducing disease susceptibility, and the role of antibiotic resistance and mobile elements in C. difficile epidemiology

<i>Clostridium sordellii</i> outer spore proteins maintain spore structural integrity and promote bacterial clearance from the gastrointestinal tract

<div><p>Bacterial spores play an important role in disease initiation, transmission and persistence. In some species, the exosporium forms the outermost structure of the spore and provides the first point of contact between the spore and the environment. The exosporium may also be involved in spore adherence, protection and germination. <i>Clostridium sordellii</i> is a highly lethal, spore forming pathogen that causes soft-tissue infections, enteritis and toxic-shock syndrome. Despite the importance of <i>C</i>. <i>sordellii</i> spores in disease, spore proteins from this bacterium have not been defined or interrogated functionally. In this study, we identified the <i>C</i>. <i>sordellii</i> outer spore proteome and two of the identified proteins, CsA and CsB, were characterised using a genetic and phenotypic approach. Both proteins were essential for the correct formation and positioning of the <i>C</i>. <i>sordellii</i> spore coat and exosporium. The absence of CsA reduced sporulation levels and increased spore sensitivity to heat, sodium hydroxide and hydrochloric acid. By comparison, CsB was required for normal levels of spore adherence to cervical, but not vaginal, cells, with <i>csB</i> mutant spores having increased adherence properties. The establishment of a mouse infection model of the gastrointestinal tract for <i>C</i>. <i>sordellii</i> allowed the role of CsA and CsB to be interrogated in an infected host. Following the oral administration of spores to mice, the wild-type strain efficiently colonized the gastrointestinal tract, with the peak of bacterial numbers occurring at one day post-infection. Colonization was reduced by two logs at four days post-infection. By comparison, mice infected with the <i>csB</i> mutant did not show a reduction in bacterial numbers. We conclude that <i>C</i>. <i>sordellii</i> outer spore proteins are important for the structural and functional integrity of spores. Furthermore, outer spore proteins are required for wild-type levels of colonization during infection, possibly as a result of the role that the proteins play in spore structure and morphology.</p></div