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Introduction Ageing skeletal muscles become both insulin resistant and atrophic. The hormone glucagon-like peptide 1 (GLP-1) facilitates postprandial glucose uptake as well as augmenting muscle perfusion, independent of insulin action. We thus hypothesized exogenous GLP-1 infusions would enhance muscle perfusion and positively affect glucose metabolism during fed-state clamps in older people. Methods Eight men (71 ± 1 years) were studied in a randomized crossover trial. Basal blood samples were taken before postprandial (fed-state) insulin and glucose clamps, accompanied by amino acid infusions, for 3 hours. Reflecting this, following insertions of peripheral and femoral vessels cannulae and baseline measurements, peripheral IV infusions of octreotide, insulin (Actrapid), 20% glucose, and mixed amino acids; Vamin 14-EF with or without a femoral arterial GLP-1 infusion were started. GLP-1, insulin, and C-peptide were measured by ELISA. Muscle microvascular blood flow was assessed via contrast enhanced ultrasound. Whole-body glucose handling was assayed by assessing glucose infusion rate parameters. Results Skeletal muscle microvascular blood flow significantly increased in response to GLP-1 vs feeding alone (5.0 ± 2.1 vs 1.9 ± 0.7 fold-change from basal, respectively; P = 0.008), while also increasing whole-body glucose uptake (area under the curve 16.9 ± 1.7 vs 11.4 ± 1.8 mg/kg−1/180 minutes−1, P = 0.02 ± GLP, respectively). Conclusions The beneficial effects of GLP-1 on whole-body glycemic control are evident with insulin clamped at fed-state levels. GLP-1 further enhances the effects of insulin on whole-body glucose uptake in older men, underlining its role as a therapeutic target. The effects of GLP-1 in enhancing microvascular flow likely also affects other glucose-regulatory organs, reflected by greater whole-body glucose uptake.

Therapeutic interventions aimed at enhancing blood flow may combat the postprandial vascular and metabolic dysfunction that manifests with chronological ageing. We compared the effects of acute curcumin (1000 mg) coupled with an oral nutritional supplement (ONS, 7.5 g protein, 24 g carbohydrate and 6 g fat) versus a placebo and ONS (control) on cerebral and leg macrovascular blood flow, leg muscle microvascular blood flow, brachial artery endothelial function, and leg insulin and glucose responses in healthy older adults (n = 12, 50% male, 73 ± 1 year). Curcumin enhanced m. tibialis anterior microvascular blood volume (MBV) at 180 and 240 min following the ONS (baseline: 1.0 vs. 180 min: 1.08 ± 0.02, p = 0.01 vs. 240 min: 1.08 ± 0.03, p = 0.01), and MBV was significantly higher compared with the control at both time points (p < 0.05). MBV increased from baseline in the m. vastus lateralis at 240 min after the ONS in both groups (p < 0.05), and there were no significant differences between groups. Following the ONS, leg blood flow and leg vascular conductance increased, and leg vascular resistance decreased similarly in both conditions (p < 0.05). Brachial artery flow-mediated dilation and middle cerebral artery blood flow were unchanged in both conditions (p > 0.05). Similarly, the curcumin and control groups demonstrated comparable increases in glucose uptake and insulin in response to the ONS. Thus, acute curcumin supplementation enhanced ONS-induced increases in m. tibialis anterior MBV without potentiating m. vastus lateralis MBV, muscle glucose uptake, or systemic endothelial or macrovascular function in healthy older adults.

Validated diagnostics of skeletal muscle vitality could benefit clinical and basic science in terms of mechanistic insights and in determining the efficacy of interventions, e.g. exercise/pharmaceuticals/nutrients. We recently developed a Combined Oral Assessment of Muscle (COSIAM) that can be used to simultaneously quantify whole-body muscle mass (WBMM), muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Here, we aimed to establish, in a cross-sectional fashion, links between COSIAM parameters and established aspects of muscle function. We recruited 37 healthy older adults (male (M):female (F) (21/16); 72 ± 5 y)) into a 3-day trial. Subjects consumed D3-creatine (D3-Cr dilution to assess WBMM), D2O (MPS by incorporation of alanine) and D3-3-methylhistidine (D3-MH dilution to assess MPB). A biopsy at day 3 was used to determine MPS, and blood/urine samples were collected to determine D3-Cr/D3-MH dilution for WBMM and MPB. Physiological measures of muscle mass (e.g. DXA/ultrasound) and function (e.g. handgrip strength, maximum voluntary contraction (MVC), one-repetition maximum (1-RM)) were ascertained. A stepwise linear regression approach was used to address links between facets of COSIAM (MPS, MPB, WBMM) and muscle physiology. Despite expected differences in muscle mass, there were no significant differences in MPS or MPB between sexes. WBMM as measured using D3-Cr positively correlated with DXA-derived lean body mass (LBM) and appendicular LBM (ABLM). Stepwise linear regression was used to assess which combination of MPS, MPB, D3-Cr and absolute synthesis rate (ASR) best predicted physiological measures of muscle health in these older adults. D3-Cr WBMM alone was the best predictor of handgrip, 1RM and MVC, and outperformed more traditional measures of muscle mass by DXA. The COSIAM approach substantiates D3-Cr as a robust biomarker of multiple muscle physiology health biomarkers. Future work using COSIAM should focus upon how and which parameters it can inform upon in relation to disease progression and the efficacy of interventions.

Postprandial macro- and microvascular blood flow and metabolic dysfunction manifest with advancing age, so vascular transmuting interventions are desirable. In this randomised, single-blind, placebo-controlled, crossover trial, we investigated the impact of the acute administration of green tea extract (GTE, containing ~500 mg epigallocatechin-3-gallate) versus placebo (CON), alongside an oral nutritional supplement (ONS), on muscle macro- and microvascular, cerebral macrovascular (via ultrasound) and leg glucose/insulin metabolic responses (via arterialised/venous blood samples) in twelve healthy older adults (42% male, 74 ± 1 y). GTE increased m. vastus lateralis microvascular blood volume (MBV) at 180 and 240 min after ONS (baseline: 1.0 vs. 180 min: 1.11 ± 0.02 vs. 240 min: 1.08 ± 0.04, both p &lt, 0.005), with MBV significantly higher than CON at 180 min (p &lt, 0.05). Neither the ONS nor the GTE impacted m. tibialis anterior perfusion (p &gt, 0.05). Leg blood flow and vascular conductance increased, and vascular resistance decreased similarly in both conditions (p &lt, 0.05). Small non-significant increases in brachial artery flow-mediated dilation were observed in the GTE only and middle cerebral artery blood flow did not change in response to GTE or CON (p &gt, 0.05). Glucose uptake increased with the GTE only (0 min: 0.03 ± 0.01 vs. 35 min: 0.11 ± 0.02 mmol/min/leg, p = 0.007), however, glucose area under the curve and insulin kinetics were similar between conditions (p &gt, 0.05). Acute GTE supplementation enhances MBV beyond the effects of an oral mixed meal, but this improved perfusion does not translate to increased leg muscle glucose uptake in healthy older adults.

We explored the views of older (≥65 years) past and potential volunteers in regard to participating in physiology research during the COVID-19 pandemic. Using an online questionnaire and focus groups, we found that past volunteers (n = 55) were more likely to take part in both acute (p < 0.05) and chronic (p < 0.05) physiology studies, compared with potential future volunteers (n = 57). Both cohorts demonstrated a positive attitude towards volunteering during the COVID-19 pandemic, although concern was evident. Novelty: Volunteers demonstrated a positive attitude and also concern towards participating in physiology research during COVID-19.

While the literature on doctoral writing groups suggests that these groups can have a substantial positive effect on doctoral dissertation completion, little is known about how group practices cont...

Introduction: Serious health implications from having low levels of cardiorespiratory fitness (CRF) and being overweight in young adulthood are carried forward into later life. High-intensity interval training (HIIT) is a time-effective, potent stimulus for improving CRF and indices of cardiometabolic health. To date, few studies have investigated the use of equipment-free HIIT or the impact of supervision for improving CRF via HIIT.Methods: Thirty healthy young adults (18–30 y) were randomised to 4 weeks (12 sessions) equipment-free, bodyweight based supervised laboratory HIIT (L-HIIT), unsupervised home HIIT (H-HIIT) or no-intervention (CON). Utilised exercises were star jumps, squats and standing sprints. Measurements of CRF (anaerobic threshold (AT) and VO2peak), blood pressure (BP), body mass index (BMI), blood glucose and plasma insulin by oral glucose tolerance test (OGTT), and muscle architecture were performed at baseline and after the intervention.Results: When compared to the control group, both HIIT protocols improved CRF (AT: L-HIIT mean difference compared to the control group (MD) +2.1 (95% CI: 0.34–4.03) ml/kg/min; p = 0.02; H-HIIT MD +3.01 (1.17–4.85) ml/kg/min; p = 0.002), VO2peak: L-HIIT (MD +2.94 (0.64–5.25) ml/kg/min; p = 0.01; H-HIIT MD +2.55 (0.34–4.76) ml/kg/min; p = 0.03), BMI (L-HIIT MD −0.43 (−0.86 to 0.00) kg/m2; p = 0.05; H-HIIT: MD −0.51 (−0.95 to −0.07) kg/m2; p = 0.03) and m. vastus lateralis pennation angle (L-HIIT MD 0.2 (0.13–0.27)°; p < 0.001; H-HIIT MD 0.17 (0.09 to 0.24)°; p < 0.001). There was no significant change in BP, blood glucose or plasma insulin in any of the groups.Conclusions: Four weeks time-efficient, equipment-free, bodyweight-based HIIT is able to elicit improvements in CRF irrespective of supervision status. Unsupervised HIIT may be a useful tool for counteracting the rise of sedentary behaviours and consequent cardiometabolic disorders in young adults.

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05, 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p &lt, 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p &lt, 0.05), but these responses were not different between conditions (p &gt, 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p &lt, 0.05) comparably between conditions (p &gt, 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.

Close Homolog of L1 (CHL1), an L1 cell adhesion molecule expressed on thalamocortical and corticofugal axons, is identified as a regulator of thalamocortical axon guidance via extracellular interactions with Neuropilin1 (Npn1) and integrins and intracellular interactions with the actin cytoskeleton. CHL1 deletion in mice disrupted the topographic projection of somatosensory thalamic axons, causing them to inappropriately target the visual cortex. This shift was first observed in the ventral telencephalon (VTe), an intermediate target with graded Sema3A expression, where axons from the ventral basal complex (VB) of the dorsal thalamus were shifted caudally. Caudal thalamic axons were also dependent upon CHL1 for preferential guidance through high Sema3A territories. A similar pattern of aberrant guidance was observed in Npn1Sema-/- mutant embryos, in which axons are nonresponsive to Sema3A. CHL1 associated with Npn1 through a sequence in the extracellular domain of CHL1, which was required for Sema3A-induced growth cone collapse. Deletion of both L1 and CHL1 further disrupted thalamocortical topography, resulting in aberrant targeting of somatosensory and motor thalamic axons to the visual cortex. For the first time, these results demonstrate a role for Sema3A, Npn1, and CHL1 in regulating the topography of thalamocortical axons in the VTe. CHL1 linkage to the cytoskeleton through ezrin, radixin, and moesin (ERM) proteins and ankyrin is critical for axon growth and guidance and cell migration. CHL1 associated with ERM proteins through a conserved sequence in the intracellular domain of CHL1, important for cell migration, neurite outgrowth and branching, and for Sema3A-mediated growth cone collapse. The cytoskeletal adaptor protein, ankyrin, was also recruited to the plasma membrane though a sequence in the CHL1 cytoplasmic domain containing a conserved tyrosine residue (Phe-Ile-Gly-Ala-Try), which was required for promoting integrin-dependent migration. CHL1 potentiated cell migration to extracellular matrix proteins by functionally interacting with [beta]1 integrins, mediated by c-Src, phosphatidylinositol 3- kinase, and ERK MAP (mitogen-activated protein) kinase. In summary, a novel role for CHL1 has been demonstrated in mediating the cellular responses of Sema3A and Npn1, important for thalamic axon guidance. In addition, the mechanism by which CHL1 associates with Npn1 and couples to the actin cytoskeleton has been defined.

This paper describes initial work to develop an optical system to detect small concentrations, less than 1 ppm, of chemical or biological agents by monitoring the fluorescence emission from a hollow optical fiber. This class of sensors would enable highly sensitive detection of chemical or biological agents by a small and lightweight sensor. The sensors would also be readily adaptable to different types of analyte by changing the fluorescent coating. Hollow core optical fibers can be filled with a sol-gel matrix that incorporates a fluorophor. Current work has established the sensitivity of an amine dye to weak concentrations of formaldehyde. Formaldehyde can be introduced into a spacecraft crew environment by out-gassing, crew activities, experimental payloads, and human and bacterial metabolism. Formaldehyde is an important trace contaminant to monitor because it is detrimental in small doses and long term exposure to low concentrations causes hypersensitivity. These issues become increasingly important in a closed-loop environment such as the crew habitat for astronauts on a long term mission.

Many clinical trials have proven that oral supplementation of vitamin B12 provides adequate replacement for deficiencies. Despite the consideration of poor absorption of the oral form due to lack of intrinsic factor or gastric acidity, oral supplementation may be preferred in most patients.1 Pharmacists should feel confident recommending oral supplementation of vitamin B12 to elderly patients for mild to moderate deficiencies and prevention or treatment of pernicious anemia.