e-Delphi in the outdoors: Stakeholder contributions to the development of a wellbeing-focused outdoor adventure education intervention program.

ISSUE ADDRESSED: Outdoor adventure education (OAE) (programs involving outdoor activities such as rock climbing or white-water canoeing) that participants perceive as risky, conducted in a social support setting, can be utilised by practitioners to elicit changes in educational and psychosocial outcomes to support participant adolescent wellbeing. METHODS: This study garnered the opinions of an expert OAE panel on the content of future programs aiming to impact adolescent wellbeing. The panel consisted of local (Western Australia, n = 7), national (Australia, n = 4), and international (Canada, Germany, New Zealand, United Kingdom, United States, n = 7) experts. A two-round, mixed-methods Delphi approach was employed. Extensive formative work led to the development of a series of open-ended questions requiring qualitative responses for round one. Panellists were also asked to respond to 17 statements using Likert scales in the second round. RESULTS: After analysis, a consensus was reached for all statements, with five statements having high consensus and being considered important by panellists. CONCLUSIONS: The statement 'Equity for all participants requires flexible delivery and facilitation' had the highest level of agreement amongst panellists. Connections, authentic experiences, and equitable experiences developed as key themes. SO WHAT?: Future OAE interventions focused on wellbeing impact could use the findings of this research as a basis for program design.

Emerging role of immune cells as drivers of pulmonary fibrosis.

The pathogenesis of pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and other forms of interstitial lung disease, involves a complex interplay of various factors including host genetics, environmental pollutants, infection, aberrant repair and dysregulated immune responses. Highly variable clinical outcomes of some ILDs, in particular IPF, have made it difficult to identify the precise mechanisms involved in disease pathogenesis and thus the development of a specific cure or treatment to halt and reverse the decline in patient health. With the advent of in-depth molecular diagnostics, it is becoming evident that the pathogenesis of IPF is unlikely to be the same for all patients and therefore will likely require different treatment approaches. Chronic inflammation is a cardinal feature of IPF and is driven by both innate and adaptive immune responses. Inflammatory cells and activated fibroblasts secrete various pro-inflammatory cytokines and chemokines that perpetuate the inflammatory response and contribute to the recruitment and activation of more immune cells and fibroblasts. The balance between pro-inflammatory and regulatory immune cell subsets, as well as the interactions between immune cell types and resident cells within the lung microenvironment, ultimately determines the extent of fibrosis and the potential for resolution. This review examines the role of the innate and adaptive immune responses in pulmonary fibrosis, with an emphasis on IPF. The role of different immune cell types is discussed as well as novel anti-inflammatory and immunotherapy approaches currently in clinical trial or in preclinical development.

Immunological Phenotyping of Mice with a Point Mutation in Cdk4.

Cyclin-dependent kinases (CDKs) play a crucial role in regulation of the mammalian cell cycle. CDK4 and CDK6 control the G1/S restriction checkpoint through their ability to associate with cyclin D proteins in response to growth factor signals. CDK4 deficiency in mice gives rise to a range of endocrine-specific phenotypes including diabetes, infertility, dwarfism, and atrophy of the anterior pituitary. Although CDK6 deficiency can cause thymic atrophy due to a block in the double-negative (DN) to double-positive (DP) stage of T cell development, there are no overt defects in immune cell development reported for CDK4-deficient mice. Here, we examined the impact of a novel N-ethyl-N-nitrosourea-induced point mutation in the gene encoding CDK4 on immune cell development. Mutant mice (Cdk4wnch/wnch) showed normal development and differentiation of major immune cell subsets in the thymus and spleen. Moreover, T cells from Cdk4wnch/wnch mice exhibited normal cytokine production in response to in vitro stimulation. However, analysis of the mixed bone marrow chimeras revealed that Cdk4wnch/wnch-derived T cell subsets and NK cells are at a competitive disadvantage compared to Cdk4+/+-derived cells in the thymus and periphery of recipients. These results suggest a possible role for the CDK4wnch mutation in the development of some immune cells, which only becomes apparent when the Cdk4wnch/wnch mutant cells are in direct competition with wild-type immune cells in the mixed bone marrow chimera.

"I love being in the outdoors": A qualitative descriptive study of outdoor adventure education program components for adolescent wellbeing.

BACKGROUND: This qualitative descriptive study gauged the perceptions of adolescent focus group participants and outdoor adventure education teachers on their preferred program components to improve adolescent wellbeing during a secondary school outdoor adventure education program. METHODS: Five student focus groups (N = 29) and four key informant interviews were conducted. Manual clustering of transcripts and template thematic analysis involving the development of a priori codes from interview questions resulted in an initial deductive code frame, followed by an inductive coding process. FINDINGS: Six themes were developed, namely perceptions of the outdoors, motivators for participation, barriers to participation, staff traits, and ideal program components. The main findings were that self-efficacy, resilience, and individual empowerment opportunities were highly valued. Students also valued autonomy and independence, which presented a challenge for teachers managing the risks of their programs. Social connections and relationships were also held in high regard. CONTRIBUTION: Whilst adrenalin-fuelled adventurous activities such as white water canoeing or rock climbing were popular with students and staff, the most valued aspects of outdoor adventure education were the opportunities to develop relationships, build social connections, self-efficacy, resilience, and a sense of individual empowerment. Greater access to this style of education for adolescent students from lower socio-economic areas would be beneficial due to the extant "opportunity gap" for this population.

Exercise-induced responses in matrix metalloproteinases and osteopontin are not moderated by exercise format in males with overweight or obesity.

PURPOSE: Matrix metalloproteinase-2 (MMP-2) and -3 (MMP-3), and osteopontin (OPN) are associated with adipose-tissue expansion and development of metabolic disease. The purpose of the current study was to assess the circulating concentration of these markers, along with adiponectin and glucose concentrations, in response to acute exercise in individuals with overweight or obesity. METHODS: Fourteen sedentary males with overweight or obesity (29.0 ± 3.1 kg/m2) completed two separate, 3-day trials in randomised and counterbalanced order. An oral glucose tolerance test (OGTT) was performed on each day of the trial. Day two of each trial consisted of a single 30 min workload-matched bout of either high-intensity interval exercise (HIIE; alternating 100% and 50% of peak pulmonary oxygen uptake, [Formula: see text]O2peak) or continuous moderate intensity (CME; 60% [Formula: see text]O2peak) cycling completed 1 h prior to the OGTT. Glucose and physical activity were continuously monitored, while MMP-2, MMP-3, OPN and adiponectin were measured pre-, 0 h post-, 1 h post- and 25 h post-exercise. RESULTS: Exercise transiently increased MMP-3 and decreased OPN (both p < 0.01), but not MMP-2 or adiponectin. There were no differences in the response of inflammatory markers to the different exercise formats. Exercise increased mean daily glucose concentration and area under the glucose curve during the OGTT on Day 2 and Day 3 (main effect of time; p < 0.05). CONCLUSION: Acute cycling exercise decreased OPN, which is consistent with longer term improvements in cardiometabolic health and increased MMP-3, which is consistent with its role in tissue remodelling. Interestingly, exercise performed prior to the morning OGTT augmented the glucose concentrations in males. TRIAL REGISTRATION: ACTRN12613001086752.

Attributes of Expert Anticipation Should Inform the Design of Virtual Reality Simulators to Accelerate Learning and Transfer of Skill.

Expert sport performers cope with a multitude of visual information to achieve precise skill goals under time stress and pressure. For example, a major league baseball or cricket batter must read opponent variations in actions and ball flight paths to strike the ball in less than a second. Crowded playing schedules and training load restrictions to minimise injury have limited opportunity for field-based practice in sports. As a result, many sports organisations are exploring the use of virtual reality (VR) simulators. Whilst VR synthetic experiences can allow greater control of visual stimuli, immersion to create presence in an environment, and interaction with stimuli, compared to traditional video simulation, the underpinning mechanisms of how experts use visual information for anticipation have not been properly incorporated into its content design. In themes, this opinion article briefly explains the mechanisms underpinning expert visual anticipation, as well as its learning and transfer, with a view that this knowledge can better inform VR simulator content design. In each theme, examples are discussed for improved content design of VR simulators taking into consideration its advantages and limitations relative to video simulation techniques. Whilst sport is used as the exemplar, the points discussed have implications for skill learning in other domains, such as military and law enforcement. It is hoped that our paper will stimulate improved content design of VR simulators for future research and skill enhancement across several domains.

Plasma cell but not CD20-mediated B-cell depletion protects from bleomycin-induced lung fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease associated with chronic inflammation and tissue remodelling leading to fibrosis, reduced pulmonary function, respiratory failure and death. Bleomycin (Blm)-induced lung fibrosis in mice replicates several clinical features of human IPF, including prominent lymphoid aggregates of predominantly B-cells that accumulate in the lung adjacent to areas of active fibrosis. We have shown previously a requirement for B-cells in the development of Blm-induced lung fibrosis in mice. To determine the therapeutic potential of inhibiting B-cell function in pulmonary fibrosis, we examined the effects of anti-CD20 B-cell ablation therapy to selectively remove mature B-cells from the immune system and inhibit Blm-induced lung fibrosis. Anti-CD20 B-cell ablation did not reduce fibrosis in this model; however, immune phenotyping of peripheral blood and lung resident cells revealed that anti-CD20-treated mice retained a high frequency of CD19+ CD138+ plasma cells. Interestingly, high levels of CD138+ cells were also identified in the lung tissue of patients with IPF, consistent with the mouse model. Treatment of mice with bortezomib, which depletes plasma cells, reduced the level of Blm-induced lung fibrosis, implicating plasma cells as important effector cells in the development and progression of pulmonary fibrosis.

Acute T-Cell-Driven Inflammation Requires the Endoglycosidase Heparanase-1 from Multiple Cell Types.

It has been accepted for decades that T lymphocytes and metastasising tumour cells traverse basement membranes (BM) by deploying a battery of degradative enzymes, particularly proteases. However, since many redundant proteases can solubilise BM it has been difficult to prove that proteases aid cell migration, particularly in vivo. Recent studies also suggest that other mechanisms allow BM passage of cells. To resolve this issue we exploited heparanase-1 (HPSE-1), the only endoglycosidase in mammals that digests heparan sulfate (HS), a major constituent of BM. Initially we examined the effect of HPSE-1 deficiency on a well-characterised adoptive transfer model of T-cell-mediated inflammation. We found that total elimination of HPSE-1 from this system resulted in a drastic reduction in tissue injury and loss of target HS. Subsequent studies showed that the source of HPSE-1 in the transferred T cells was predominantly activated CD4+ T cells. Based on bone marrow chimeras, two cellular sources of HPSE-1 were identified in T cell recipients, one being haematopoiesis dependent and the other radiation resistant. Collectively our findings unequivocally demonstrate that an acute T-cell-initiated inflammatory response is HPSE-1 dependent and is reliant on HPSE-1 from at least three different cell types.

An Outbreak of Highly Pathogenic Avian Influenza (H7N7) in Australia and the Potential for Novel Influenza A Viruses to Emerge.

In 2020, several geographically isolated farms in Victoria, Australia, experienced an outbreak of highly pathogenic avian influenza (HPAI) virus H7N7 and low pathogenic avian influenza (LPAI) viruses H5N2 and H7N6. Effective containment and control measures ensured the eradication of these viruses but the event culminated in substantial loss of livestock and significant economic impact. The avian HPAI H7N7 virus generally does not infect humans; however, evidence shows the ocular pathway presents a favourable tissue tropism for human infection. Through antigenic drift, mutations in the H7N7 viral genome may increase virulence and pathogenicity in humans. The Victorian outbreak also detected LPAI H7N6 in emus at a commercial farm. Novel influenza A viruses can emerge by mixing different viral strains in a host susceptible to avian and human influenza strains. Studies show that emus are susceptible to infections from a wide range of influenza viral subtypes, including H5N1 and the pandemic H1N1. The emu's internal organs and tissues express abundant cell surface sialic acid receptors that favour the attachment of avian and human influenza viruses, increasing the potential for internal genetic reassortment and the emergence of novel influenza A viruses. This review summarises the historical context of H7N7 in Australia, considers the potential for increased virulence and pathogenesis through mutations and draws attention to the emu as potentially an unrecognised viral mixing vessel.

Strength Training Improves Exercise Economy in Triathletes During a Simulated Triathlon.

PURPOSE: The completion of concurrent strength and endurance training can improve exercise economy in cyclists and runners; however, the efficacy of strength training (ST) implementation to improve economy in long-distance (LD) triathletes has not yet been investigated. The purpose of this study was to investigate physiological outcomes in LD triathletes when ST was completed concurrently to endurance training. METHODS: A total of 25 LD triathletes were randomly assigned to either 26 weeks of concurrent endurance and ST (n = 14) or endurance training only (n = 11). The ST program progressed from moderate (8-12 repetitions, ≤75% of 1-repetition maximum, weeks 0-12) to heavy loads (1-6 repetitions, ≥85% of 1-repetition maximum, weeks 14-26). Physiological and performance indicators (cycling and running economy, swim time, blood lactate, and heart rate) were measured during a simulated triathlon (1500-m swim, 60-min cycle, and 20-min run) at weeks 0, 14, and 26. Maximal strength and anthropometric measures (skinfolds and body mass) were also collected at these points. RESULTS: The endurance strength group significantly improved maximal strength measures at weeks 14 and 26 (P < .05), cycling economy from weeks 0 to 14 (P < .05), and running economy from weeks 14 to 26 (P < .05) with no change in body mass (P > .05). The endurance-only group did not significantly improve any economy measures. CONCLUSIONS: The addition of progressive load ST to LD triathletes' training programs can significantly improve running and cycling economy without an increase in body mass.

Strength Training in Long-Distance Triathletes: Barriers and Characteristics.

ABSTRACT: Luckin, KM, Badenhorst, CE, Cripps, AJ, Landers, GJ, Merrells, RJ, Bulsara, MK, and Hoyne, GF. Strength training in long-distance triathletes: Barriers and characteristics. J Strength Cond Res 35(2): 495-502, 2021-The purpose of this investigation was to identify perceived and physical barriers toward the completion of concurrent strength training and endurance training in long-distance triathletes. Three hundred ninety long-distance triathletes (224 women, 166 men; age [y]: 39 ± 10) completed a 68-question self-administered, semiquantitative survey that assessed endurance and strength training characteristics, experience in triathlon, and perceived barriers regarding the completion of strength training. Mean training hours per week was 14.92 ± 5.25, with 54.6% reporting participation in strength training. Heavy strength training was the most commonly reported (39.4%), with significantly more men completing this form of strength training (p < 0.001). Results from subjects who did not complete strength training indicated that perceived time constraints (53.1%) in addition to lack of knowledge on exercise progression and form (52.5%) are prominent perceived barriers to strength training completion. Identification of the barriers perceived by long-distance triathletes that prevent them from completing concurrent strength training and endurance training may be useful for coaches, athletes, and sports scientists who seek to incorporate strength training for injury prevention and performance improvement.

Loss of hnRNPLL-dependent splicing of Ptprc has no impact on B-cell development, activation and terminal differentiation into antibody-secreting cells.

The RNA-binding protein heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) controls alternative splicing of protein tyrosine phosphatase receptor type C (Ptprc) which encodes CD45. hnRNPLL deficiency leads to a failure in silencing Ptprc exons 4-6 causing aberrant expression of the corresponding CD45 isoforms, namely, CD45RA, RB and RC. While an N-ethyl-N-nitrosourea-induced point mutation in murine Hnrnpll results in loss of peripheral naïve T cells, its role in B-cell biology remains unclear. Here, we demonstrate that B-cell development in the bone marrow of Hnrnpllthu/thu mice is normal and the number of mature B-cell subsets in the spleen and peritoneal cavity is comparable to control littermates. In response to in vivo immunization, Hnrnpllthu/thu mice were deficient in generating germinal center (GC) B cells, and analysis of mixed bone marrow chimeras revealed that the GC B-cell deficiency was a B-cell extrinsic effect of the hnRNPLL mutation. Mature Hnrnpllthu/thu B cells proliferated normally in response to various B-cell receptor- and Toll-like receptor-mediated stimuli. Similarly, in vitro stimulation of mutant B cells led to normal generation of plasmablasts, but mutant plasmablasts failed to downregulate B220 expression because of the inability of cells to undergo proper CD45 pre-messenger RNA alternative splicing. These findings collectively suggest that, like in T and natural killer T cells, the mutation disrupts hnRNPLL-mediated alternative splicing of the Ptprc gene in plasmablasts, but this dysregulation of Ptprc alternative splicing does not affect the development and function of B cells.

Behavioural phenotyping of thunder mice with a hypomorphic mutation of heterogeneous nuclear ribonuclear protein L-like (hnRNPLL) and reduced T cell function.

Heterogeneous nuclear ribonuclear protein l-like (hnRNPLL) is an RNA binding protein that regulates alternative splicing of mRNA and is abundantly expressed in memory T lymphocytes of the immune system and in the brain. A hypomorphic allele of the gene encoding hnRNPLL (Hnrpllthunder) selectively reduces T cell accumulation in lymphoid tissues, but little is known about its effects in the brain. Therefore, we exposed Hnrpllthunder mice to a test battery with relevance for a range of psychiatric illnesses. Thunder mice showed enhanced immobility in the tail-suspension test for depression-related behaviours, impaired short-term spatial memory in the Y-maze and reduced avoidance learning in the active avoidance test. Thus, in addition to its reported effects on immune function, the hnRNPLL mutation in thunder mice selectively affected aspects of behaviour.

Interdisciplinary Sport Research Can Better Predict Competition Performance, Identify Individual Differences, and Quantify Task Representation.

Sport performance consists of interacting individual, task and environmental constraints, but research has used a monodisciplinary, rather than an interdisciplinary approach to understand performance. This study used Australian football (AF) as the exemplar sport to investigate the value of an interdisciplinary approach to understand sport performance. Through this, it was also possible to quantify individual differences and representative task design. Fifty-nine semi-professional Australian footballers participated. Based upon accessibility, combinations of these players completed physiological (3 × 1 km trial) and perceptual-cognitive-motor (small-sided game, SSG) tests, with coach rating of psychological skill (mental toughness coach, MTC). Univariate monodisciplinary models indicated that all tests predicted disposal efficiency; 3 × 1 km trial (p = 0.047), SSG (p = 0.001), and MTC (p = 0.035), but only the SSG predicted coaches' vote (p = 0.003). A multivariate interdisciplinary model indicated that SSG and MTC tests predicted disposal efficiency with a better model fit than the corresponding univariate model. The interdisciplinary model formulated an equation that could identify individual differences in disposal efficiency. In addition, the interdisciplinary model showed that the higher representative SSG test contributed a greater magnitude to the prediction of competition performance, than the lower representative MTC rating. Overall, this study demonstrates that a more comprehensive understanding of sport performance, individual differences, and representative tasks, can be obtained through an interdisciplinary approach.

The contribution of animal models to understanding the role of the immune system in human idiopathic pulmonary fibrosis.

Pulmonary fibrosis occurs in a heterogeneous group of lung disorders and is characterised by an excessive deposition of extracellular matrix proteins within the pulmonary interstitium, leading to impaired gas transfer and a loss of lung function. In the past 10 years, there has been a dramatic increase in our understanding of the immune system and how it contributes to fibrogenic processes within the lung. This review will compare some of the models used to investigate the pathogenesis and treatment of pulmonary fibrosis, in particular those used to study immune cell pathogenicity in idiopathic pulmonary fibrosis, highlighting their advantages and disadvantages in dissecting human disease.

Mesothelial cells regulate immune responses in health and disease: role for immunotherapy in malignant mesothelioma.

The mesothelium when first described was thought to function purely as a non-adhesive surface to facilitate intracoelomic movement of organs. However, the mesothelium is now recognized as a dynamic cellular membrane with many important functions that maintain serosal integrity and homeostasis. For example, mesothelial cells interact with and help regulate the body's inflammatory and immune system following infection, injury, or malignancy. With recent advances in our understanding of checkpoint molecules and the advent of novel immunotherapy approaches, there has been an increase in the number of studies examining mesothelial and immune cell interaction, in particular the role of these interactions in malignant mesothelioma. This review will highlight some of the recent advances in our understanding of how mesothelial cells help regulate serosal immunity and how in a malignant environment, the immune system is hijacked to stimulate tumor growth. Ways to treat mesothelioma using immunotherapy approaches will also be discussed.

Evolution and Adaptation of the Avian H7N9 Virus into the Human Host.

Influenza viruses arise from animal reservoirs, and have the potential to cause pandemics. In 2013, low pathogenic novel avian influenza A(H7N9) viruses emerged in China, resulting from the reassortment of avian-origin viruses. Following evolutionary changes, highly pathogenic strains of avian influenza A(H7N9) viruses emerged in late 2016. Changes in pathogenicity and virulence of H7N9 viruses have been linked to potential mutations in the viral glycoproteins hemagglutinin (HA) and neuraminidase (NA), as well as the viral polymerase basic protein 2 (PB2). Recognizing that effective viral transmission of the influenza A virus (IAV) between humans requires efficient attachment to the upper respiratory tract and replication through the viral polymerase complex, experimental evidence demonstrates the potential H7N9 has for increased binding affinity and replication, following specific amino acid substitutions in HA and PB2. Additionally, the deletion of extended amino acid sequences in the NA stalk length was shown to produce a significant increase in pathogenicity in mice. Research shows that significant changes in transmissibility, pathogenicity and virulence are possible after one or a few amino acid substitutions. This review aims to summarise key findings from that research. To date, all strains of H7N9 viruses remain restricted to avian reservoirs, with no evidence of sustained human-to-human transmission, although mutations in specific viral proteins reveal the efficacy with which these viruses could evolve into a highly virulent and infectious, human-to-human transmitted virus.

Coach Rating Combined With Small-Sided Games Provides Further Insight Into Mental Toughness in Sport.

Literature indicates that mental toughness contributes to successful performance when faced with challenge. This study used an exemplar sport of Australian Rules football to investigate whether skilled performance thrived across increased challenge in small-sided games. Higher (n = 14) and lower (n = 17) skilled Australian footballers were recruited. First, coaches rated participants' mental toughness (MTC) using the Mental Toughness Index. Second, participants competed in small-sided games where challenge was manipulated by varying the attacker to defender ratio to create lower and higher pressure scenarios. Decision-making, motor skill execution, and a combined total were measured. MTC rating was higher for higher skilled players. Total score of higher skilled players was significantly superior to lower skilled players in higher and lower pressure scenarios (p = 0.003). A "pressure differential score," calculated to determine whether participants maintained performance across increased challenge, indicated a significant decrease in performance (total score) from lower to higher pressure scenarios for lower skilled (p = 0.011), but not for higher skilled (p = 0.060) players. Furthermore, MTC scores were predictive of high pressure scenario total scores (p = 0.011). Findings suggest higher levels of mental toughness may contribute to maintain performance across the increased challenge of pressure within small-sided games. Practitioners can subjectively rate athlete mental toughness and then structure small-sided games to objectively measure performance under pressure scenarios. This provides an interdisciplinary approach to assess and train psychomotor skill.