Relationships between lower-body muscle structure and, lower-body strength, explosiveness and eccentric leg stiffness in adolescent athletes

The purpose of the present study was to determine whether any relationships were present between lower-body muscle structure and, lower-body strength, variables measured during a counter-movement jump (CMJ) and squat jump (SJ), and eccentric leg stiffness, in adolescent athletes. Thirty junior male (n = 23) and female (n = 7) surfing athletes (14.8 ± 1.7 y; 1.63 ± 0.09 m; 54.8 ± 12.1 kg) undertook lower-body muscle structure assessment with ultrasonography and performed a; CMJ, SJ and an isomet-ric mid-thigh pull (IMTP). In addition, eccentric leg stiffness was calculated from variables of the CMJ and IMTP. Moderate to very large relationships (r = 0.46-0.73) were identified be-tween the thickness of the vastus lateralis (VL) and lateral gas-trocnemius (LG) muscles, and VL pennation angle and; peak force (PF) in the CMJ, SJ and IMTP. Additionally, moderate to large relationships (r = 0.37-0.59) were found between eccentric leg stiffness and; VL and LG thickness, VL pennation angle, and LG fascicle length, with a large relationship (r = 0.59) also present with IMTP PF. These results suggest that greater thick-ness of the VL and LG were related to improved maximal dy-namic and isometric strength, likely due to increased hypertro-phy of the extensor muscles. Furthermore, this increased thickness was related to greater eccentric leg stiffness, as the associated enhanced lower-body strength likely allowed for greater neuromuscular activation, and hence less compliance, during a stretch-shortening cycle

Using Wireless Sensor Networks for Aged Care: The Patient's Perspective

This paper presents the findings of a qualitative study on the perceptions and thoughts of elderly people on the use of current sensor network technology for assisted aged care. Focus groups of elderly people were presented with examples of current sensor nodes and example scenarios of their use, and then invited to provide input on a range of issues surrounding the design and use of the technology. The focus group findings were verified with a health care professional as a control measure. This study examines sensing based interaction, implementation methodologies and user acceptance issues specifically for the elderly, and from the elderly's perspective. A significant finding of the study is that the two most important factors for elderly acceptance of sensor technology are cost and contro

Bar shoes and ambient temperature are risk factors for exercise-induced pulmonary haemorrhage in Thoroughbred racehorses

Reasons for performing study Ambient temperature has been identified as a risk factor for exercise-induced pulmonary haemorrhage (EIPH) in racing Thoroughbreds. This warranted a more expansive investigation of climatic conditions on the incidence and severity of EIPH. The impact of other variables such as the type of bit used, tongue ties and nonstandard shoes has not been reported and also warrant investigation. Objectives To examine the effect of various climatic variables as contributing risk factors for EIPH. Other previously uninvestigated variables as well as standard track and population factors will also be examined. Study design Cross-sectional study. Methods Thoroughbred racehorses competing at metropolitan racetracks in Perth, Western Australia were examined 30–200 min post race with tracheobronchoscopy. Examination took place at 48 race meetings over a 12 month period. Examinations were graded (0–4), independently by two experienced veterinarians. Univariable analyses were performed and variables with a P<0.25 were entered into a multivariable logistic regression analysis. The analysis was performed twice using the presence of blood (EIPH grade 0 vs. grades ≥1) and EIPH grades ≤1 vs. EIPH grades ≥2 as dependent variables. Results Exercise-induced pulmonary haemorrhage was diagnosed in 56.6% of observations. Lower ambient temperature was significantly associated with EIPH grades ≥1 (OR 0.95; 95% CI 0.93–0.98) and EIPH grades ≥2 (OR 0.97; 95% CI 0.94–1.0). Bar shoes were significantly associated with EIPH grades ≥1 (OR 6.35; 95% CI 2.17–18.54) and EIPH grades ≥2 (OR 2.72; 95% CI 1.3–5.68). Increasing race distance was significantly associated with EIPH grade ≥1 and increasing lifetime starts was significantly associated with EIPH grade ≥2. Conclusions Ambient temperature is a risk factor for EIPH in Thoroughbred racehorses, with lower temperatures associated with increased risk. Bar shoes are a novel risk factor for EIPH in this population

Exploration of the gut microbiome as a predictive factor for cancer treatment-induced gastrointestinal toxicity

Gastrointestinal toxicity is a significant side effect of many cancer treatments. Characterised by diarrhoea, abdominal pain and bleeding, this toxicity can affect up to 80% of patients, depending on treatment regimen. Currently, there are no highly effective intervention strategies for the vast majority of people affected, thus more evidence is required to improve future management. This thesis focussed primarily on gastrointestinal toxicity stemming from two major types of cancer treatment. These are chemotherapy, the most common form of cancer treatment, and small molecule tyrosine kinase inhibitors (SM-TKIs), a class of targeted therapies, often used in combination with chemotherapy. There is a clear gap in knowledge in understanding how these different cancer treatments cause gastrointestinal toxicity, and how the population of microorganisms in the intestine, the gut microbiome, links to these responses. This thesis therefore aimed to investigate the role of the gut microbiome in influencing the development and exacerbation of gastrointestinal toxicity stemming from cancer treatment. This was investigated in three main sections. Firstly, I aimed to examine the interaction between the gut microbiome and the innate immune system (chiefly the innate immune receptor Toll-like receptor 4 (TLR4)), and determine how this interaction could be involved in the development of gastrointestinal toxicity following chemotherapy. In order to achieve this aim, I characterised the microbial composition of a TLR4 conditional knockout mouse model and assessed changes due to chemotherapy treatment. There were no clear differences in the microbiome of wild type and TLR4 conditional knockout mice. Secondly, I aimed to characterise the role of the gut microbiome in diarrhoea stemming from the SM-TKI treatment neratinib, which causes high levels of diarrhoea. I found that, in a pre-clinical model, neratinib treatment does cause changes to microbial composition, however it was unclear if these changes were a key driver of diarrhoea development or simply a side effect of this diarrhoea. Therefore I analysed diarrhoea development following an initial, antibiotic-induced perturbation, showing that addition of narrow-spectrum antibiotics caused a significant decrease in diarrhoea severity and timespan. Finally, I clinically appraised the use of the gut microbiome in predicting risk of cancer treatment-induced gastrointestinal toxicity in two defined patient cohorts. A retrospective cohort showed that participants who went on to develop diarrhoea had significantly lower amounts of the bacterial genera Blautia and significantly higher amounts of the genera Collinsella. A longitudinal study was then developed. Pilot results did not show clear microbial clustering based on diarrhoea status. The results of my thesis demonstrate the emerging role gut microbiome composition has on the development of diarrhoea following cancer treatment. However I was unable to definitively identify any particular bacterial type that is a key mediator of this effect. The results presented here however provide strong rationale for further research in this area using specific machine learning and metabolomic techniques to identify compositional features that may be important in accurately predicting diarrhoea development following cancer treatment.Thesis (Ph.D.) -- University of Adelaide, School of Biomedicine, 202

Feeding the Critically Ill Obese Patient

Obesity is increasing in prevalence. Supporting the critically ill obese patient will become an increasingly important skill in the intensivist’s armamentarium, and enteral nutritional therapy forms a cornerstone of this support. Despite this, neither an optimal total caloric goal nor the macronutrient components of a nutritional strategy for the critically ill obese patient has been established. The objective of the research described in this thesis was to systematically review the best available evidence describing nutritional strategies that target energy and protein delivery to reduce morbidity and mortality in the obese patient who is critically ill. A search for published and grey literature was conducted across a range of electronic databases including PubMed, Embase, CINAHL, ProQuest Dissertations and Theses and Conference Papers Index, Cochrane Central Trials Register, and the WHO Clinical Trials Register, and was supplemented by a hand search of the reference lists of study publications retrieved. Studies were selected for inclusion and subsequent assessment of methodological quality if they evaluated the clinical effect of targeting calorie and protein delivery in critically ill obese adult patients. In order to identify studies representative of critically ill patients, only studies conducted in intensive care units and in which ≥ 50% of recruited patients were receiving mechanical ventilation for ≥ 24 hours were eligible, while the World Health Organization definition (body mass Index ≥ 30 kg/m2) was used to classify obese patients. The search yielded 1000 unique records that were screened for eligibility. After removal of duplicates and screening of titles and abstracts, 18 studies were retrieved in full and underwent full text screening, of which six were excluded. Of the remaining 12 studies, only one recruited an obese population (albeit with an alternative definition of obesity). The remaining 11 studies identified recruited ICU patients without stratifying for, or targeting a particular weight, and therefore a proportion of whom would be expected to be obese. Contact was attempted with all corresponding authors to request access to the obese subgroup data for each study identified. Replies were received from eight authors representing 10 studies. Only two were able to provide raw data regarding the obese patients recruited to their studies; however, heterogeneity in research design of these two studies precluded meaningful data synthesis. The augmented versus routine approach to giving energy (TARGET) study compared two different enteral formulae with different caloric density, but with an identical protein component, the difference in caloric density being made up of fat and carbohydrate. The control arm targeted 19.9 kcal/kg/day, while the intervention arm targeted 29.3 kcal/kg/day. In the second study for which raw data were available, patients were randomised to either a eucaloric arm in which 100% of their estimated daily energy requirements were targeted (13 kcal/kg/day), or to a hypo- caloric arm in which 50% of their estimated daily energy requirements were targeted (8.8 kcal/kg/day). There was neither a signal for benefit nor for harm in the primary outcome of interest (mortality), nor in any of the secondary outcomes for which data were available (length of stay, nosocomial infection, duration of mechanical ventilation, gastro-intestinal intolerance or insulin requirement). In conclusion, there is a paucity of data supporting any approach to nutritional therapy for the critically ill obese patient. The optimal calorie and protein target remains elusive and further robust primary research is urgently required.Thesis (MClinSc) -- University of Adelaide, Joanna Briggs Institute, 201

Can bronchoconstriction and bronchodilatation in horses be detected using electrical impedance tomography?

Background Electrical impedance tomography (EIT) generates images of the lungs based on impedance change and was able to detect changes in airflow after histamine challenge in horses. Objectives To confirm that EIT can detect histamine‐provoked changes in airflow and subsequent drug‐induced bronchodilatation. Novel EIT flow variables were developed and examined for changes in airflow. Methods Bronchoconstriction was induced using stepwise histamine bronchoprovocation in 17 healthy sedated horses. The EIT variables were recorded at baseline, after saline nebulization (control), at the histamine concentration causing bronchoconstriction (Cmax) and 2 and 10 minutes after albuterol (salbutamol) administration. Peak global inspiratory (PIFEIT) and peak expiratory EIT (PEFEIT) flow, slope of the global expiratory flow‐volume curve (FVslope), steepest FVslope over all pixels in the lung field, total impedance change (surrogate for tidal volume; VTEIT) and intercept on the expiratory FV curve normalized to VTEIT (FVintercept/VTEIT) were indexed to baseline and analyzed for a difference from the control, at Cmax, 2 and 10 minutes after albuterol. Multiple linear regression explored the explanation of the variance of Δflow, a validated variable to evaluate bronchoconstriction using all EIT variables. Results At Cmax, PIFEIT, PEFEIT, and FVslope significantly increased whereas FVintercept/VT decreased. All variables returned to baseline 10 minutes after albuterol. The VTEIT did not change. Multivariable investigation suggested 51% of Δflow variance was explained by a combination of PIFEIT and PEFEIT. Conclusions and Clinical Importance Changes in airflow during histamine challenge and subsequent albuterol administration could be detected by various EIT flow volume variables

The effect of geographic location on circannual adrenocorticotropic hormone plasma concentrations in horses in Australia

Background: Longitudinal evaluation of plasma endogenous ACTH concentration in clinically normal horses has not been investigated in the Southern Hemisphere. Objectives: To longitudinally determine monthly upper reference limits for plasma ACTH in 2 disparate Australian geographic locations and to examine whether location affected the circannual rhythm of endogenous ACTH in the 2 groups of horses over a 12-month period. Animals: Clinically normal horses <20 years of age from 4 properties (institutional herd and client owned animals) in Perth (n = 40) and Townsville (n = 41) were included in the study. Methods: A prospective longitudinal descriptive study to determine the upper reference limit and confidence intervals for plasma ACTH in each geographic location using the ASVCP reference interval (RI) guidelines, for individual months and monthly groupings for 12 consecutive months. Results: Plasma endogenous ACTH concentrations demonstrated a circannual rhythm. The increase in endogenous ACTH was not confined to the autumnal months but was associated with changes in photoperiod. During the quiescent period, plasma ACTH concentrations were lower, ≤43 pg/mL (upper limit of the 90% confidence interval (CI)) in horses from Perth and ≤67 pg/mL (upper limit of the 90% CI) in horses from Townsville, than at the acrophase, ≤94 pg/mL (upper limit of the 90% CI) in horses from Perth, ≤101 pg/mL (upper limit of the 90% CI) in horses from Townsville. Conclusions and Clinical Importance: Circannual rhythms of endogenous ACTH concentrations vary between geographic locations, this could be due to changes in photoperiod or other unknown factors, and upper reference limits should be determined for specific locations

Decapentaplegic is required for arrest in G1 phase during Drosophila eye development

During eye development in Drosophila, cell cycle progression is coordinated with differentiation. Prior to differentiation, cells arrest in G1 phase anterior to and within the morphogenetic furrow. We show that Decapentaplegic (Dpp), a TGF-&bgr; family member, is required to establish this G1 arrest, since Dpp-unresponsive cells located in the anterior half of the morphogenetic furrow show ectopic S phases and ectopic expression of the cell cycle regulators Cyclins A, E and B. Conversely, ubiquitous over-expression of Dpp in the eye imaginal disc transiently inhibits S phase without affecting Cyclin E or Cyclin A abundance. This Dpp-mediated inhibition of S phase occurs independently of the Cyclin A inhibitor Roughex and of the expression of Dacapo, a Cyclin E-Cdk2 inhibitor. Furthermore, Dpp-signaling genes interact genetically with a hypomorphic cyclin E allele. Taken together our results suggest that Dpp acts to induce G1 arrest in the anterior part of the morphogenetic furrow by a novel inhibitory mechanism. In addition, our results provide evidence for a Dpp-independent mechanism that acts in the posterior part of the morphogenetic furrow to maintain G1 arrest

A novel in vitro platform for the study of SN38-induced mucosal damage and the development of Toll-like receptor 4-targeted therapeutic options

Tight junction and epithelial barrier disruption is a common trait of many gastrointestinal pathologies, including chemotherapy-induced gut toxicity. Currently, there are no validated in vitro models suitable for the study of chemotherapy-induced mucosal damage that allow paralleled functional and structural analyses of tight junction integrity. We therefore aimed to determine if a transparent, polyester membrane insert supports a polarized T84 monolayer with the phenotypically normal tight junctions. T84 cells (passage 5-15) were seeded into either 0.6 cm(2), 0.4 µm pore mixed-cellulose transwell hanging inserts or 1.12 cm(2), 0.4 µm pore polyester transwell inserts at varying densities. Transepithelial electrical resistance was measured daily to assess barrier formation. Immunofluoresence for key tight junction proteins (occludin, zonular occludens-1, claudin-1) and transmission electron microscopy were performed to assess tight junction integrity, organelle distribution, and polarity. Reverse transcription-polymerase chain reaction was performed to determine expression of toll-like receptor 4 (TLR4). Liquid chromatography was also conducted to assess SN38 degradation in this model. Polyester membrane inserts support a polarized T84 phenotype with functional tight junctions in vitro. Transmission electron microscopy indicated polarity, with apico-laterally located tight junctions. Immunofluorescence showed membranous staining for all tight junction proteins. No internalization was evident. T84 cells expressed TLR4, although this was significantly lower than levels seen in HT29 cells (P = .0377). SN38 underwent more rapid degradation in the presence of cells (-76.04 ± 1.86%) compared to blank membrane (-48.39 ± 4.01%), indicating metabolic processes. Polyester membrane inserts provide a novel platform for paralleled functional and structural analysis of tight junction integrity in T84 monolayers. T84 cells exhibit the unique ability to metabolize SN38 as well as expressing TLR4, making this an excellent platform to study clinically relevant therapeutic interventions for SN38-induced mucosal damage by targeting TLR4.Hannah R Wardill, Rachel J Gibson, Ysabella ZA Van Sebille, Kate R Secombe, Richard M Logan, and Joanne M Bowe