The chronic leukocyte and inflammatory cytokine responses of older adults to resistance training in normobaric hypoxia; a randomized controlled trial.

TRIAL DESIGN: Older adults experience chronic dysregulation of leukocytes and inflammatory cytokines, both at rest and in response to resistance training. Systemic hypoxia modulates leukocytes and cytokines, therefore this study characterized the effects of normobaric hypoxia on the leukocyte and cytokine responses of older adults to resistance training. METHODS: 20 adults aged 60-70 years performed eight weeks of moderate-intensity resistance training in either normoxia or normobaric hypoxia (14.4% O2), consisting of two lower body and two upper body exercises. Venous blood was drawn before and after the training intervention and flow cytometry was used to quantify resting neutrophils, lymphocytes, monocytes, eosinophils and basophils, in addition to the subsets of lymphocytes (T, B and natural killer (NK) cells). Inflammatory cytokines were also quantified; interleukin 1 beta (IL-1ß), IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor alpha (TNF-α). Acute changes in leukocytes and cytokines were also measured in the 24 h following the last training session. RESULTS: After the intervention there was a greater concentration of resting white blood cells (p = 0.03; 20.3% higher) T cells (p = 0.008; 25.4% higher), B cells (p = 0.004; 32.6% higher), NK cells (p = 0.012; 43.9% higher) and eosinophils (p = 0.025; 30.8% higher) in hypoxia compared to normoxia, though the cytokines were unchanged. No acute effect of hypoxia was detected in the 24 h following the last training session for any leukocyte population or inflammatory cytokine (p < 0.05). CONCLUSIONS: Hypoxic training caused higher concentrations of resting lymphocytes and eosinophils, when compared to normoxic training. Hypoxia may have an additional beneficial effect on the immunological status of older adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). TRIAL NUMBER: ACTRN12623001046695. Registered 27/9/2023. Retrospectively registered. All protocols adhere to the COSORT guidelines.

The acute leukocyte and cytokine response of older adults to resistance exercise in normobaric hypoxia.

Ageing causes a decline in leukocyte function and blunted leukocyte responses to resistance exercise. Systemic hypoxia exposure augments the leukocyte response to resistance exercise in young adults, yet this response remains uncharacterised in older adults. This study characterised the effects of normobaric hypoxia on the acute leukocyte and inflammatory cytokine responses to resistance exercise in older adults. We recruited 20 adults aged 60-70 years to perform an acute bout of resistance exercise in normobaric hypoxia (FiO2 14.4%; n = 10) or normoxia (FiO2 20.93%; n = 10). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% of their predicted 1-repetition maximum. Venous blood was sampled before and up to 24 hours post-exercise to quantify neutrophils, lymphocytes, monocytes, eosinophils, basophils and cytokines (IL-1ß, IL-4, IL-6, IL-8, IL-10, TNFα). Flow cytometry was used to classify lymphocytes as T (CD4+ helper and CD8+ cytotoxic), B and NK cells, in addition to the expression of the senescence marker CD45RA on T cells. The hypoxic group showed a larger lymphocyte response over the 24 hours post-exercise compared to the normoxic group (p = 0.035). Specifically, there were greater concentrations of CD4+ T helper cells following hypoxic exercise compared to normoxia (p = 0.046). There was also a greater proportion of CD45RA+ CD4+ T helper cells, suggesting that the cells were more senescent (p = 0.044). Hypoxia did not impact any other leukocyte population or cytokine following exercise. Normobaric hypoxia increases the lymphocyte response to an acute bout of resistance exercise in older adults.

The effects of normobaric hypoxia on the leukocyte responses to resistance exercise.

There is growing interest in the use of systemic hypoxia to improve the training adaptations to resistance exercise. Hypoxia is a well-known stimulator of the immune system, yet the leukocyte responses to this training modality remain uncharacterised. The current study characterised the acute leukocyte responses to resistance exercise in normobaric hypoxia. The single-blinded, randomised trial recruited 13 healthy males aged 18-35 years to perform a bout of resistance exercise in normobaric hypoxia (14.4% O2; n = 7) or normoxia (20.9% O2; n = 6). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% 1-repetition maximum. Oxygen saturation, rating of perceived exertion and heart rate were measured during the session. Venous blood was sampled before and up to 24 hours post-exercise to quantify blood lactate, glucose and leukocytes including neutrophils, lymphocytes, monocytes, eosinophils and basophils. Neutrophils were higher at 120 and 180 minutes post-exercise in hypoxia compared to normoxia (p<0.01), however lymphocytes, monocytes, eosinophils and basophils were unaffected by hypoxia. Oxygen saturation was significantly lower during the four exercises in hypoxia compared to normoxia (p < 0.001). However, there were no differences in blood lactate, heart rate, perceived exertion or blood glucose between groups. Hypoxia amplified neutrophils following resistance exercise, though all other leukocyte subsets were unaffected. Therefore, hypoxia does not appear to detrimentally affect the lymphocyte, monocyte, eosinophil or basophil responses to exercise.

Augmented reality in medical education: students' experiences and learning outcomes.

Augmented reality (AR) is a relatively new technology that allows for digitally generated three-dimensional representations to be integrated with real environmental stimuli. AR can make use of smart phones, tablets, or other devices to achieve a highly stimulating learning environment and hands-on immersive experience. The use of AR in industry is becoming widespread with applications being developed for use not just for entertainment and gaming but also healthcare, retail and marketing, education, military, travel and tourism, automotive industry, manufacturing, architecture, and engineering. Due to the distinct learning advantages that AR offers, such as remote learning and interactive simulations, AR-based teaching programs are also increasingly being adopted within medical schools across the world. These advantages are further highlighted by the current COVID-19 pandemic, which has caused an even greater shift towards online learning. In this review, we investigate the use of AR in medical training/education and its effect on students' experiences and learning outcomes. This includes the main goals of AR-based learning, such as to simplify the delivery and enhance the comprehension of complex information. We also describe how AR can enhance the experiences of medical students, by improving knowledge and understanding, practical skills and social skills. These concepts are discussed within the context of specific AR medical training programs, such as HoloHuman, OculAR SIM, and HoloPatient. Finally, we discuss the challenges of AR in learning and teaching and propose future directions for the use of this technology in medical education.

Development of an anti-porcine CD34 monoclonal antibody that identifies hematopoietic stem cells.

OBJECTIVES: The isolation of porcine hematopoietic stem cells (HSC) would be an important step toward development of porcine-to-human chimerism for induction of tolerance in clinical xenotransplantation. CD34 is a common marker of HSC and has not been developed as a marker in pigs. In this study we have generated and characterized a monoclonal antibody (mAb) that identifies porcine CD34 on a subset of porcine bone marrow (BM) stem/progenitor cells. METHODS: The porcine CD34 gene was cloned and a recombinant protein produced. An anti-porcine CD34 mAb was produced that could detect both the recombinant protein and a subset of porcine BM cells. The CD34(+) cells were phenotyped by lineage and HSC associated markers. Furthermore, the CD34(+) cells were analyzed by colony-forming unit (CFU) assay. RESULTS: Two splice variants of the porcine CD34 gene were cloned and a recombinant protein produced for mAb production. The mAb developed can detect both the recombinant protein and the native CD34 protein on a range of pig tissues, including BM. This subset of BM cells was negative for hematopoietic lineage makers, including CD3, CD14, and CD21 and positive for other known porcine HSC markers, including CD90, CD172a, histocompatibility complex (MHC) class I, and MHC class II. Moreover, the CD34(+) BM cells were enriched for multilineage progenitor cells as determined by CFU assay. CONCLUSIONS: Similar to human and mouse CD34, pig CD34 detects a subset of BM progenitor cells. This mAb will now provide a means for isolating porcine CD34(+) cells to be further analyzed for HSC activity and to assess their potential to develop pig-to-human chimeras to induce xenograft tolerance.

Steroid 21-hydroxylase expression in cultured rat astrocytes.

Over the past decade or so it has become widely recognised that the brain is a significant steroidogenic organ. Many publications have highlighted the ability of the brain to synthesise and interconvert a large number of steroid products including cholesterol, progesterone and testosterone. In this study, in vitro experiments were performed to determine if 21-hydroxylation of steroids is undertaken by rat brain astrocytes in culture. This is a common reaction that occurs in the adrenal gland and other organs in mammals, catalysing the conversion of pregn-4-ene-3,20-dione (progesterone) to 21-hydroxypregn-4-ene-3,20-dione (deoxycorticosterone). Previous reports have indicated that 21-hydroxylation occurs within the rat brain, however, the precise identity of the cells expressing 21-hydroxylase has not yet been determined. Several metabolites, such as 5alpha-pregnan-3alpha-ol-20-one (tetrahydroprogesterone) and 3alpha,21-dihydroxy-5-pregnan-20-one (tetrahydrodeoxycorticosterone) were of particular interest because of their modulatory role in neuronal function, such as their agonist activity at gamma-aminobutyric acid (GABA(A)) receptors. Evidence was obtained for the expression of peripheral 21-hydroxylase enzyme (P450c21) in cultured rat brain astrocytes by a combination of mass spectroscopy and molecular biology techniques. This is a significant finding as expression of 21-hydroxylase within astrocytes may be indicative of a wider role for these cells in modulating neuronal behaviour.