Validity of oxygen uptake cut-off criteria in plateau identification during horizontal treadmill running

BACKGROUND: When determining achievement of maximal oxygen uptake (VO2max) during treadmill running using speed increments, the VO2 cut-off criteria applied during plateau identification is often not justified, not protocol specific, or not related to actual change in VO2 (ΔVO2) with speed increment, which can influence plateau achievement rates between studies. The purpose of this study was to compare plateau incidence using an individualised plateau criteria approach based on a ‘percentage’ ΔVO2 compared to using previously established criteria of ΔVO2≤2.1 ml-kg-1⋅min-1 not developed on running speed. METHODS: Fifty-four males completed a ramp horizontal treadmill test with 0.5 or 1.0 km⋅h-1 per minute (km⋅h-1⋅min-1) speed increments to measure VO2max. Average ΔVO2 for the each 1-minute speed increment was determined and used to develop individualised cut-off criteria deemed to be a plateau: a final ΔVO2 of less than 50% of the average change elicited between consecutive speed increments during the test ( VO2≤50%); plateau incidence using this was compared to ΔVO2 ≤2.1 ml⋅kg-1⋅min-1 ( VO2≤2.1). RESULTS: Mean ΔVO2 was 1.74±0.59 and 3.09±0.59 ml⋅kg-1⋅ min-1 for 0.5 and 1.0 km⋅ h-1⋅ min-1 increments respectively. VO2 cut-off criteria were met by 48%/65% (1.0 km⋅h-1⋅min-1) (P=0.234) and 53%/100% (0.5 km⋅h-1⋅ min-1) (P=0.003) for VO2≤50% and VO2≤2.1 respectively. CONCLUSIONS: Use of VO2≤2.1 resulted in distortedly high plateau achievement, particularly for smaller speed increments where the VO2-speed relationship was actually less than VO2≤2.1 making its use inappropriate. Use of VO2≤50% may be a suitable alternative, but as a plateau was not consistently demonstrated, application of cut-off criteria should not be a requirement in deciding whether one’s achieved VO2max. KEYWORDS: VO2-speed relationship - VO2 plateau - VO2 cut-off criteria - Horizontal treadmill runnin

Impact of the January 2012 solar proton event on polar mesospheric clouds

We use data from the Aeronomy of Ice in the Mesosphere mission and simulations using the Whole Atmosphere Community Climate Model to determine the impact of the 23–30 January 2012 solar proton event (SPE) on polar mesospheric clouds (PMCs) and mesospheric water vapor. We see a small heating and loss of ice mass on 26 January that is consistent with prior results but is not statistically significant. We also find a previously unreported but statistically significant ~10% increase in ice mass and in water vapor in the sublimation area in the model that occurs in the 7 to 14 days following the start of the event. The magnitude of the response to the January 2012 SPE is small compared to other sources of variability like gravity waves and planetary waves; however, sensitivity tests suggest that with larger SPEs this delayed increase in ice mass will increase, while there is little change in the loss of ice mass early in the event. The PMC response to SPEs in models is dependent on the gravity wave parameterization, and temperature anomalies from SPEs may be useful in evaluating and tuning gravity wave parameterizations

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426

Somatostatin receptor 5 and cannabinoid receptor 1 activation inhibit secretion of glucose-dependent insulinotropic polypeptide from intestinal K cells in rodents.

AIMS/HYPOTHESIS: Glucose-dependent insulinotropic polypeptide (GIP) is an enteroendocrine hormone that promotes storage of glucose and fat. Its secretion from intestinal K cells is triggered by nutrient ingestion and is modulated by intracellular cAMP. In view of the proadipogenic actions of GIP, this study aimed to identify pathways in K cells that lower cAMP levels and GIP secretion. METHODS: Murine K cells purified by flow cytometry were analysed for expression of G(αi)-coupled receptors by transcriptomic microarrays. Somatostatin and cannabinoid receptor expression was confirmed by quantitative RT-PCR. Hormone secretion in vitro was measured in GLUTag and primary murine intestinal cultures. cAMP was monitored in GLUTag cells using the genetically encoded sensor Epac2-camps. In vivo tolerance tests were performed in cannulated rats. RESULTS: Purified murine K cells expressed high mRNA levels for somatostatin receptors (Sstrs) Sstr2, Sstr3 and Sstr5, and cannabinoid receptor type 1 (Cnr1, CB1). Somatostatin inhibited GIP and glucagon-like peptide-1 (GLP-1) secretion from primary small intestinal cultures, in part through SSTR5, and reduced cAMP generation in GLUTag cells. Although the CB1 agonist methanandamide (mAEA) inhibited GIP secretion, no significant effect was observed on GLP-1 secretion from primary cultures. In cannulated rats, treatment with mAEA prior to an oral glucose tolerance test suppressed plasma GIP but not GLP-1 levels, whereas the CB1 antagonist AM251 elevated basal GIP concentrations. CONCLUSIONS/INTERPRETATION: GIP release is inhibited by somatostatin and CB1 agonists. The differential effects of CB1 ligands on GIP and GLP-1 release may provide a new tool to dissociate secretion of these incretin hormones and lower GIP but not GLP-1 levels in vivo

Consumption of dark chocolate attenuates subsequent food intake compared with milk and white chocolate in postmenopausal women.

BACKGROUND: Chocolate has a reputation for contributing to weight gain due to its high fat, sugar and calorie content. However, the effect of varying concentrations of cocoa in chocolate on energy intake and appetite is not clear. OBJECTIVE: To compare the acute effect of consuming an isocaloric dose of dark, milk and white chocolate on subsequent energy intake, appetite and mood in postmenopausal women. METHODS: Fourteen healthy postmenopausal women (57.6 ± 4.8yr) attended an introductory session followed by three experimental trials performed in a counterbalanced order at a standardised time of day, each separated by one week. Ad libitum energy intake, perceived appetite, mood and appetite-related peptides were assessed in response to consumption of 80% cocoa [dark chocolate], 35% cocoa [milk chocolate] and cocoa butter [white chocolate] (2099 kJ), prepared from a single-origin cacao bean. RESULTS: Ad libitum energy intake was significantly lower following dark (1355 ± 750 kJ) compared with both milk (1693 ± 969 kJ; P = 0.008) and white (1842 ± 756 kJ; P = 0.001) chocolate consumption. Blood glucose and insulin concentrations were transiently elevated in response to white and milk chocolate consumption compared with the dark chocolate (P  0.05). CONCLUSIONS: Dark chocolate attenuates subsequent food intake in postmenopausal women, compared to the impact of milk and white chocolate consumption

The Anti-ROR1 Monoclonal Antibody Zilovertamab Inhibits the Proliferation of Ovarian and Endometrial Cancer Cells

The non-canonical Wnt signalling receptor ROR1 is aberrantly expressed in numerous cancers, including ovarian and endometrial cancer. We previously reported that silencing ROR1 could inhibit the proliferation and metastatic potential of ovarian and endometrial cancer cells in vitro. Zilovertamab is an ROR1-targeting humanised monoclonal antibody, with demonstrated safety and efficacy in clinical trials of several ROR1-related malignancies. The aim of this study was to investigate the potential of zilovertamab alone, or in combination with commonly utilised gynaecological cancer therapies (cisplatin, paclitaxel and the PARP inhibitor—Olaparib) on high-grade serous ovarian cancer (HGSOC), including models of platinum resistance and homologous recombination deficiency (CaOV3, CaOV3CisR, PEO1 and PEO4) and endometrial cancer (EC) cell lines (Ishikawa and KLE). The effect of zilovertamab (at 25 µg/mL or 50 µg/mL) +/− agents was investigated using the IncuCyte S3 Live Cell imaging system. Zilovertamab alone inhibited the proliferation of HGSOC and EC cells in vitro, including in models of platinum resistance and homologous recombination deficiency. In general, the addition of commonly used chemotherapies to a fixed dose of zilovertamab did not enhance the observed anti-proliferative activity. This study supports the potential of zilovertamab, or other ROR1-targeting therapies, for treating women with HGSOC and EC.</jats:p

Targeting Homologous Recombination Deficiency in Ovarian Cancer with PARP Inhibitors: Synthetic Lethal Strategies That Impact Overall Survival

The advent of molecular targeted therapies has made a significant impact on survival of women with ovarian cancer who have defects in homologous recombination repair (HRR). High-grade serous ovarian cancer (HGSOC) is the most common histological subtype of ovarian cancer, with over 50% displaying defective HRR. Poly ADP ribose polymerases (PARPs) are a family of enzymes that catalyse the transfer of ADP-ribose to target proteins, functioning in fundamental cellular processes including transcription, chromatin remodelling and DNA repair. In cells with deficient HRR, PARP inhibitors (PARPis) cause synthetic lethality leading to cell death. Despite the major advances that PARPis have heralded for women with ovarian cancer, questions and challenges remain, including: can the benefits of PARPis be brought to a wider range of women with ovarian cancer; can other drugs in clinical use function in a similar way or with greater efficacy than currently clinically approved PARPis; what can we learn from long-term responders to PARPis; can PARPis sensitise ovarian cancer cells to immunotherapy; and can synthetic lethal strategies be employed more broadly to develop new therapies for women with ovarian cancer. We examine these, and other, questions with focus on improving outcomes for women with ovarian cancer.</jats:p

Impact of shortened crop rotation of oilseed rape on soil and rhizosphere microbial diversity in relation to yield decline

Oilseed rape (OSR) grown in monoculture shows a decline in yield relative to virgin OSR of up to 25%, but the mechanisms responsible are unknown. A long term field experiment of OSR grown in a range of rotations with wheat was used to determine whether shifts in fungal and bacterial populations of the rhizosphere and bulk soil were associated with the development of OSR yield decline. The communities of fungi and bacteria in the rhizosphere and bulk soil from the field experiment were profiled using terminal restriction fragment length polymorphism (TRFLP) and sequencing of cloned internal transcribed spacer regions and 16S rRNA genes, respectively. OSR cropping frequency had no effect on rhizosphere bacterial communities. However, the rhizosphere fungal communities from continuously grown OSR were significantly different to those from other rotations. This was due primarily to an increase in abundance of two fungi which showed 100% and 95% DNA identity to the plant pathogens Olpidium brassicae and Pyrenochaeta lycopersici, respectively. Real-time PCR confirmed that there was significantly more of these fungi in the continuously grown OSR than the other rotations. These two fungi were isolated from the field and used to inoculate OSR and Brassica oleracea grown under controlled conditions in a glasshouse to determine their effect on yield. At high doses, Olpidium brassicae reduced top growth and root biomass in seedlings and reduced branching and subsequent pod and seed production. Pyrenochaeta sp. formed lesions on the roots of seedlings, and at high doses delayed flowering and had a negative impact on seed quantity and quality

Stress related epigenetic changes may explain opportunistic success in biological invasions in Antipode mussels

Different environmental factors could induce epigenetic changes, which are likely involved in the biological invasion process. Some of these factors are driven by humans as, for example, the pollution and deliberate or accidental introductions and others are due to natural conditions such as salinity. In this study, we have analysed the relationship between different stress factors: time in the new location, pollution and salinity with the methylation changes that could be involved in the invasive species tolerance to new environments. For this purpose, we have analysed two different mussels’ species, reciprocally introduced in antipode areas: the Mediterranean blue mussel Mytilus galloprovincialis and the New Zealand pygmy mussel Xenostrobus securis, widely recognized invaders outside their native distribution ranges. The demetylathion was higher in more stressed population, supporting the idea of epigenetic is involved in plasticity process. These results can open a new management protocols, using the epigenetic signals as potential pollution monitoring tool. We could use these epigenetic marks to recognise the invasive status in a population and determine potential biopollutants

Improving the psychological evaluation of exercise referral: psychometric properties of the Exercise Referral Quality of Life Scale

There is a growing need to assess the psychological outcomes of exercise referral and the National Institute of Health and Care Excellence has called for the routine assessment of life-quality. However, a quality of life scale specific to the requirements of exercise referral is currently unavailable. Therefore, the aim of this study was to produce a quality of life measure for this purpose. The Exercise Referral Quality of Life Scale is a 22-item measure comprising three domains: mental and physical health, injury pain and illness and physical activity facilitators. Exploratory factor analysis determined the initial factor structure and was subsequently confirmed by confirmatory factor analysis. Additional scale properties were also assessed. The scale contributes to the global need for improved consistent psychological outcome assessment of exercise referral