Biomechanical comparison of the pullout properties of external skeletal fixation pins in the tibiae of intact and ovariectomised ewes.

The pin-bone interface is the least stable component of the external skeletal fixator. Concerns exist regarding the ability to obtain adequate implant purchase in poor quality bone. Consequently, reduced bone quality has been viewed as a contra-indication for the use of external skeletal fixators. The aim of this study was to investigate the holding power of two different fixator pin designs in bone from entire and ovariectomised sheep. Thirty-two aged ewes were divided into two groups. Group 1 were controls, and Group 2 were ovariectomised (OVX). The ewes were sacrificed 12 months post-ovariectomy and five pairs of tibiae were harvested from each group. The holding power of cortical and cancellous fixator pins was assessed at five standardised locations on each tibia. An increase in mean cortical thickness was noted in the OVX group. The holding power of cancellous fixator pins was superior to that of cortical pins, irrespective of whether or not ovariectomy had been performed. Cancellous pins had an increased holding power in post ovariectomy bone compared to control bone. Cortical pin performance was not affected by ovariectomy. There was a lack of correlation between the incidence of insertional fractures of the far cortex and implant holding power. The results raise questions over the effectiveness of ovariectomy in establishing osteopaenic bone suitable for assessing implant performance, hence further investigations are warranted

Prediction of Rowing Functional Threshold Power using Body Mass, Blood Lactate and GxT Peak Power Data.

International Journal of Exercise Science 16(4): 31-41, 2023. Functional Threshold Power (FTP) is a validated index of a maximal quasi steady-state cycling intensity. The central component of the FTP test is a maximal 20-min time-trial effort. A model to predict FTP from a cycling graded exercise test (m-FTP) was published that estimated FTP without the requirement of the exhaustive 20-min time-trial. The predictive model (m-FTP) was trained (developed to find the best combination of weights and bias) on a homogenous group of highly-trained cyclists and triathletes. This investigation appraised the external validity of the m-FTP model vis-à-vis the alternate modality of rowing. The reported m-FTP equation purports to be sensitive to both changing levels of fitness, and exercise capacity. To assess this claim, eighteen (7 female, 11 male) heterogeneously-conditioned rowers were recruited from regional rowing clubs. The first rowing test was a 3-min graded incremental test with a 1-min break between increments. The second test was a rowing adapted FTP test. There were no significant differences between rowing FTP (r-FTP) and m-FTP (230 ± 64 versus 233 ± 60 W, respectively, F = 1.13, P = 0.80). Computed Bland-Altman 95% LoA between r-FTP and m-FTP were (-18 W to + 15 W), sy.x was 7 W, and 95 %CI of regression were 0.97 to 0.99. The r-FTP equation was demonstrated to be effective in predicting a rowers 20-min maximum power; further appraisal of the physiological response to rowing for 60-min at the corresponding calculated FTP requires investigation

Is the FTP Test a Reliable, Reproducible and Functional Assessment Tool in Highly-Trained Athletes?

International Journal of Exercise Science 12(4): 1334-1345, 2019. The aim of the current study was to assess reliability of the Functional Threshold Power test (FTP) and the corresponding intensity sustainable for 1-hour in a “quasi-steady state”. Highly-trained athletes (n = 19) completed four non-randomized tests over successive weeks on a Wattbike; a 3-min incremental test (GxT) to exhaustion, two 20-min FTP tests and a 60-min test at computed FTP (cFTP). Power at cFTP was calculated by reducing 20-min FTP data by 5% and was compared with power at Dmax and lactate threshold (TLac). Ventilatory and blood lactate (BLa) responses to cFTP were measured to determine whether cFTP was quasi-steady state. Agreement between consecutive FTP tests was quantified using a Bland-Altman plot with 95% limits of agreement (95% LoA) set at ± 20 W. Satisfactory agreement between FTP tests was detected (95% LoA = +13 and -17 W, bias +2 W). The 60-min effort at cFTP was successfully completed by 17 participants, and BLa and ventilatory data at cFTP were classified as quasi-steady state. A 5% increase in power above cFTP destabilized BLa data (p \u3c 0.05) and prompted VO2 to increase to peak GxT rates. The FTP test is therefore deemed representative of the uppermost power a highly-trained athlete can maintain in a quasi-steady state for 60-min. Agreement between repeated 20-min FTP tests was judged acceptable

Do Critical and Functional Threshold Powers Equate in Highly- Trained Athletes?

International Journal of Exercise Science 14(4): 45-59, 2021. The purpose of this investigation was to determine whether Critical Power (CP) and Functional Threshold Power (FTP) can be used interchangeably for a highly-trained group of cyclists and triathletes. CP was ascertained using multiple fixed load trials and FTP determined from a single cycling trial. Three different models for the determination of CP were initially addressed, one hyperbolic (Hmodel) and two linear (Jmodel and Imodel). The Jmodel was identified as most appropriate for a comparison with FTP. The Jmodel and FTP were not found to be interchangeable as ANOVA detected significant differences (282 ± 53 vs. 266 ± 55 W, p \u3c 0.001) between these indices and the associated Bland-Altman 95% limits of agreement exceeded those set a priori. As the Jmodel was found to be consistently higher than FTP, a correction factor was posited to anticipate CP from FTP in this homogenous group of athletes using the mean bias (16 W). An alternate method for assessing CP trial intensities using Dmax as a proxy for ventilatory threshold is also proposed. The concept of both CP and FTP representing a maximal metabolic steady-state requires further investigation as the mechanical power at CP was significantly greater than at FTP

Towards defining the nuclear proteome

Direct evidence is reported for 2,568 mammalian proteins within the nuclear proteome, consisting of at least 14% of the entire proteome

Characterization of the Biodistribution of a Silica Vesicle Nanovaccine Carrying a Rhipicephalus (Boophilus) microplus Protective Antigen With in vivo Live Animal Imaging

Development of veterinary subunit vaccines comes with a spectrum of challenges, such as the choice of adjuvant, antigen delivery vehicle, and optimization of dosing strategy. Over the years, our laboratory has largely focused on investigating silica vesicles (SVs) for developing effective veterinary vaccines for multiple targets. Rhipicephalus microplus (cattle tick) are known to have a high impact on cattle health and the livestock industry in the tropical and subtropical regions. Development of vaccine using Bm86 antigen against R. microplus has emerged as an attractive alternative to control ticks. In this study, we have investigated the biodistribution of SV in a live animal model, as well as further explored the SV ability for vaccine development. Rhodamine-labeled SV-140-C18 (Rho-SV-140-C18) vesicles were used to adsorb the Cy5-labeled R. microplus Bm86 antigen (Cy5-Bm86) to enable detection and characterization of the biodistribution of SV as well as antigen in vivo in a small animal model for up to 28 days using optical fluorescence imaging. We tracked the in vivo biodistribution of SVs and Bm86 antigen at different timepoints (days 3, 8, 13, and 28) in BALB/c mice. The biodistribution analysis by live imaging as well as by measuring the fluorescent intensity of harvested organs over the duration of the experiment (28 days) showed greater accumulation of SVs at the site of injection. The Bm86 antigen biodistribution was traced in lymph nodes, kidney, and liver, contributing to our understanding how this delivery platform successfully elicits antibody responses in the groups administered antigen in combination with SV. Selected tissues (skin, lymph nodes, spleen, kidney, liver, and lungs) were examined for any cellular abnormalities by histological analysis. No adverse effect or any other abnormalities were observed in the tissues

Synergistic Effect of Two Nanotechnologies Enhances the Protective Capacity of the Theileria parva Sporozoite p67C Antigen in Cattle

Multimerization of p67C Ag as nanoparticle increases its immunogenicity.Vaccine efficacy of p67C Ag increases delivered as nanoparticles.East Coast fever (ECF), caused by Theileria parva, is the most important tick-borne disease of cattle in sub-Saharan Africa. Practical disadvantages associated with the currently used live-parasite vaccine could be overcome by subunit vaccines. An 80-aa polypeptide derived from the C-terminal portion of p67, a sporozoite surface Ag and target of neutralizing Abs, was the focus of the efforts on subunit vaccines against ECF and subjected to several vaccine trials with very promising results. However, the vaccination regimen was far from optimized, involving three inoculations of 450 μg of soluble p67C (s-p67C) Ag formulated in the Seppic adjuvant Montanide ISA 206 VG. Hence, an improved formulation of this polypeptide Ag is needed. In this study, we report on two nanotechnologies that enhance the bovine immune responses to p67C. Individually, HBcAg-p67C (chimeric hepatitis B core Ag virus-like particles displaying p67C) and silica vesicle (SV)–p67C (s-p67C adsorbed to SV-140-C18, octadecyl-modified SVs) adjuvanted with ISA 206 VG primed strong Ab and T cell responses to p67C in cattle, respectively. Coimmunization of cattle (Bos taurus) with HBcAg-p67C and SV-p67C resulted in stimulation of both high Ab titers and CD4 T cell response to p67C, leading to the highest subunit vaccine efficacy we have achieved to date with the p67C immunogen. These results offer the much-needed research depth on the innovative platforms for developing effective novel protein-based bovine vaccines to further the advancement

An extended set of PRDM1/BLIMP1 target genes links binding motif type to dynamic repression

The transcriptional repressor B lymphocyte-induced maturation protein-1 (BLIMP1) regulates gene expression and cell fate. The DNA motif bound by BLIMP1 in vitro overlaps with that of interferon regulatory factors (IRFs), which respond to inflammatory/immune signals. At such sites, BLIMP1 and IRFs can antagonistically regulate promoter activity. In vitro motif selection predicts that only a subset of BLIMP1 or IRF sites is subject to antagonistic regulation, but the extent to which antagonism occurs is unknown, since an unbiased assessment of BLIMP1 occupancy in vivo is lacking. To address this, we identified an extended set of promoters occupied by BLIMP1. Motif discovery and enrichment analysis demonstrate that multiple motif variants are required to capture BLIMP1 binding specificity. These are differentially associated with CpG content, leading to the observation that BLIMP1 DNA-binding is methylation sensitive. In occupied promoters, only a subset of BLIMP1 motifs overlap with IRF motifs. Conversely, a distinct subset of IRF motifs is not enriched amongst occupied promoters. Genes linked to occupied promoters containing overlapping BLIMP1/IRF motifs (e.g. AIM2, SP110, BTN3A3) are shown to constitute a dynamic target set which is preferentially activated by BLIMP1 knock-down. These data confirm and extend the competitive model of BLIMP1 and IRF interaction