Sleep behaviours and associated habits and the progression of pre-diabetes to type 2 diabetes mellitus in adults: A systematic review and meta-analysis.

INTRODUCTION: Certain sleep behaviours increase risk of type 2 diabetes mellitus (T2DM) in the general population, but whether they contribute to the progression from pre-diabetes to T2DM is uncertain. We conducted a systematic review to assess this. METHODS: Structured searches were performed on bibliographic databases (MEDLINE, EMBASE and CINAHL) from inception to 26/04/2021 for longitudinal studies/trials consisting of adults⩾18 years with pre-diabetes and sleep behaviours (short or long sleep duration (SD), late chronotype, insomnia, obstructive sleep apnoea, daytime napping and/or night-shift employment) that reported on incident T2DM or glycaemic changes. The Newcastle-Ottawa Scale was used for quality assessment. RESULTS: Six studies were included. Meta-analysis of three studies (n = 20,139) demonstrated that short SD was associated with greater risk of progression to T2DM, hazard ratio (HR) 1.59 (95% CI 1.29-1.97), I2 heterogeneity score 0%, p < 0.0001, but not for long SD, HR 1.50 (0.86-2.62), I2 heterogeneity 77%, p = 0.15. The systematic review showed insomnia and night-shift duty were associated with higher progression to T2DM. Studies were rated as moderate-to-high quality. CONCLUSIONS: Progression from pre-diabetes to T2DM increases with short SD, but only limited data exists for insomnia and night-shift duty. Whether manipulating sleep could reduce progression from pre-diabetes to T2DM needs to be examined.

Sleep spindles track cortical learning patterns for memory consolidation.

Memory consolidation-the transformation of labile memory traces into stable long-term representations-is facilitated by post-learning sleep. Computational and biophysical models suggest that sleep spindles may play a key mechanistic role for consolidation, igniting structural changes at cortical sites involved in prior learning. Here, we tested the resulting prediction that spindles are most pronounced over learning-related cortical areas and that the extent of this learning-spindle overlap predicts behavioral measures of memory consolidation. Using high-density scalp electroencephalography (EEG) and polysomnography (PSG) in healthy volunteers, we first identified cortical areas engaged during a temporospatial associative memory task (power decreases in the alpha/beta frequency range, 6-20 Hz). Critically, we found that participant-specific topographies (i.e., spatial distributions) of post-learning sleep spindle amplitude correlated with participant-specific learning topographies. Importantly, the extent to which spindles tracked learning patterns further predicted memory consolidation across participants. Our results provide empirical evidence for a role of post-learning sleep spindles in tracking learning networks, thereby facilitating memory consolidation.

Postexercise urinary alpha-1 acid glycoprotein is not dependent on hypoxia.

Proteinuria is a transient physiological phenomenon that occurs with a range of physical activities and during ascent to altitude. Exercise intensity appears to dictate the magnitude of postexercise proteinuria; however, evidence also indicates the possible contributions from exercise-induced hypoxemia or reoxygenation. Using an environmental hypoxic chamber, this crossover-designed study aimed to evaluate urinary alpha-1 acid glycoprotein (α1-AGP) excretion pre/postexercise performed in hypoxia (HYP) and normoxia (NOR). Sixteen individuals underwent experimental sessions in normoxia (NOR, 20.9% O2) and hypoxia (HYP, 12.0% O2). Sessions began with a 2-h priming period before completing a graded maximal exercise test (GXT) on a cycle ergometer, which was followed by continuation of exposure for an additional 2 h. Physiological responses (i.e., blood pressure, heart rate, and peripheral oxygenation), Lake Louise Scores (LLSs), and urine specimens (analyzed for albumin and α1-AGP) were collected pre- and postexercise (after 30, 60, and 120 min). Peak power output was significantly reduced in HYP (193 ± 45 W) compared with NOR (249 ± 59 W, P < 0.01). Postexercise urinary α1-AGP was greater in NOR (20.04 ± 14.84 µg·min-1) than in HYP (15.08 ± 13.46 µg·min-1), albeit the difference was not significant (P > 0.05). Changes in urinary α1-AGP from pre- to post-30 min were not related to physiological responses or performance outcomes observed during GXT in NOR or HYP. Despite profound systemic hypoxemia with maximal exercise in hypoxia, postexercise α1-AGP excretion was not elevated above the levels observed following normoxic exercise.NEW & NOTEWORTHY By superimposing hypoxic exposure and maximal exercise, we were able to investigate the impact of hypoxia on postexercise proteinuria. Urinalysis for α1-AGP (via particle-enhanced immunoturbidimetry) in specimens collected pre-/postexercise enabled the sensitive detection of altered glomerular permeability. Data indicated that exercise intensity, rather than the degree of exercise-induced hypoxemia, determines postexercise proteinuria.

The middle cerebral artery blood velocity response to acute normobaric hypoxia occurs independently of changes in ventilation in humans.

NEW FINDINGS: What is the central question of this study? Does the ventilatory response to moderate acute hypoxia increase cerebral perfusion independently of changes in arterial oxygen tension in humans? What is the main finding and its importance? The ventilatory response does not increase middle cerebral artery mean blood velocity during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation. ABSTRACT: Hypoxia induces ventilatory, cardiovascular and cerebrovascular adjustments to defend against reductions in systemic oxygen delivery. We aimed to determine whether the ventilatory response to moderate acute hypoxia increases cerebral perfusion independently of changes in arterial oxygenation. Eleven young healthy individuals were exposed to four 15 min experimental conditions: (1) normoxia (partial pressure of end-tidal oxygen, PETO2  = 100 mmHg), (2) hypoxia ( PETO2  = 50 mmHg), (3) normoxia with breathing volitionally matched to levels observed during hypoxia (hyperpnoea; PETO2  = 100 mmHg) and (4) hypoxia ( PETO2  = 50 mmHg) with respiratory frequency and tidal volume volitionally matched to levels observed during normoxia (i.e., restricted breathing (RB)). Isocapnia was maintained in all conditions. Middle cerebral artery mean blood velocity (MCA Vmean ), assessed by transcranial Doppler ultrasound, was increased during hypoxia (58 ± 12 cm/s, P = 0.04) and hypoxia + RB (61 ± 14 cm/s, P < 0.001) compared to normoxia (55 ± 11 cm/s), while it was unchanged during hyperpnoea (52 ± 13 cm/s, P = 0.08). MCA Vmean was not different between hypoxia and hypoxia + RB (P > 0.05). These findings suggest that the hypoxic ventilatory response does not increase cerebral perfusion, indexed using MCA Vmean , during moderate isocapnic acute hypoxia beyond that elicited by reduced oxygen saturation.

Feasibility and acceptability of a multi-domain intervention to increase Mediterranean diet adherence and physical activity in older UK adults at risk of dementia: protocol for the MedEx-UK randomised controlled trial.

INTRODUCTION: Dementia prevalence continues to increase, and effective interventions are needed to prevent, delay or slow its progression. Higher adherence to the Mediterranean diet (MedDiet) and increased physical activity (PA) have been proposed as strategies to facilitate healthy brain ageing and reduce dementia risk. However, to date, there have been no dementia prevention trials in the UK focussed on combined dietary and PA interventions. This study aims to: (1) assess feasibility and acceptability of a theory-underpinned digital and group-based intervention for dementia risk reduction in an 'at risk' UK cohort; (2) evaluate behaviour change responses to the intervention; and, (3) provide information on cognitive, neurological, vascular and physiological outcomes to inform the design of a follow-on, full-scale efficacy trial. METHODS: One hundred and eight participants aged 55 to 74 years with a QRISK2 score of ≥10% will be recruited to take part in this 24-week multi-site study. Participants will be randomised into three parallel arms: (1) Control; (2) MedDiet; and, (3) MedDiet+PA. The study will evaluate a personalised website, group session and food delivery intervention to increase MedDiet adherence and PA in older adults at risk of dementia. Diet and PA will be monitored prior to, during and following the intervention. Feasibility, acceptability and hypothesised mediators will be assessed in addition to measures of cognitive function, brain structure/perfusion (MRI), vascular function and metabolic markers (blood, urine and faecal) prior to, and following, the intervention. DISCUSSION: This trial will provide insights into the feasibility, acceptability and mechanism of effect of a multi-domain intervention focussed on the MedDiet alone and PA for dementia risk reduction in an 'at risk' UK cohort. ETHICS AND DISSEMINATION: The study has received NHS REC and HRA approval (18/NI/0191). Findings will be disseminated via conference presentations, public lectures, and peer-reviewed publications. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov NCT03673722.

Does sleep-dependent consolidation favour weak memories?

Sleep stabilizes newly acquired memories, a process referred to as memory consolidation. According to recent studies, sleep-dependent consolidation processes might be deployed to different extents for different types of memories. In particular, weaker memories might benefit greater from post-learning sleep than stronger memories. However, under standard testing conditions, sleep-dependent consolidation effects for stronger memories might be obscured by ceiling effects. To test this possibility, we devised a new memory paradigm (Memory Arena) in which participants learned temporospatial arrangements of objects. Prior to a delay period spent either awake or asleep, training thresholds were controlled to yield relatively weak or relatively strong memories. After the delay period, retrieval difficulty was controlled via the presence or absence of a retroactive interference task. Under standard testing conditions (no interference), a sleep-dependent consolidation effect was indeed observed for weaker memories only. Critically though, with increased retrieval demands, sleep-dependent consolidation effects were seen for both weaker and stronger memories. These results suggest that all memories are consolidated during sleep, but that memories of different strengths require different testing conditions to unveil their benefit from post-learning sleep.

The implementation of a physical activity intervention in adults with Obstructive Sleep Apnoea over the age of 50 years: a feasibility uncontrolled clinical trial.

BACKGROUND: Obstructive Sleep Apnoea (OSA) is a risk factor for cardiovascular disease (CVD) and Type 2 diabetes (T2D). Observational studies suggested that OSA treatment might reduce CVD and T2D but RCTs failed to support these observations in part due to poor adherence to continuous positive airway pressure (CPAP). Physical activity (PA) has been shown to have favourable impact on CVD and the risk of T2D independent of its impact on weight and therefore might provide additional health gains to patients with OSA, whether or not adherent to CPAP. METHODS: The main aim of this study was to explore the feasibility of providing a 12-week PA intervention to adults aged over 50 with OSA. The secondary aim was to assess the impact of the PA intervention on OSA severity. Patients with moderate-severe OSA (apnoea hypopnea index (AHI) ≥ 15 events/hour (based on overnight ApneaLink™) were recruited in response to posters displayed in workplaces. A 12-week daily PA intervention was delivered in participant's home setting and PA was monitored via text and validated by objective PA measures (GT3X accelerometers). RESULTS: The intervention was feasible as all 10 patients (8 males, mean (SD) age 57.3 (6.01)) completed the intervention and PA increased across the 12-weeks. The duration of PA increased from baseline (113.1 min (64.69) per week to study-end following the intervention (248.4 min (148.31) (p = 0.02). Perceived Exertion (RPE) (physical effort) increased significantly between baseline (M = 10.7 (1.94)) to end of intervention (M = 13.8, (1.56) (p < 0.001). The intervention had no significant impact on weight or composition. Following the intervention, there was a statistically non-significant a reduction in AHI from baseline to study end (22.3 (7.35) vs. 15.8 (7.48); p = 0.09). CONCLUSION: It is feasible to deliver a PA intervention to adults aged over 50 with OSA. The intervention resulted in improved PA and AHI levels somewhat and seemingly independent of weight changes. Future trials need to examine whether PA can reduce the burden of OSA associated comorbidities. TRIAL REGISTRATION: CTN: ISRCTN11016312 Retrospectively Registered 21/07/20.

A novel mixed living high training low intervention and the hematological module of the athlete biological passport.

Exposure to either natural or simulated hypoxia induces hematological adaptations that may affect the parameters of the Athlete Biological Passport (ABP). The aim of the present study was to examine the effect of a novel, mixed hypoxic dose protocol on the likelihood of producing an atypical ABP finding. Ten well-trained middle-distance runners participated in a "live high, train low and high" (LHTLH) altitude training camp for 14 days. The participants spent ˜6 hr.d-1 at 3000-5400 m during waking hours and ˜10 h.d-1 overnight at 2400-3000 m simulated altitude. Venous blood samples were collected before (B0), and after 1 (D1), 4 (D4), 7 (D7), and 14 (D14) days of hypoxic exposure, and again 14 days post exposure (P14). Samples were analyzed for key parameters of the ABP including reticulocyte percentage (Ret%), hemoglobin concentration ([Hb]), and the OFF-score. The ABP adaptive model was administered at a specificity of 99% to test for atypical findings. We found significant changes in [Hb] and Ret% during the hypoxic intervention. Consequently, this led to ABP threshold deviations at 99% specificity in three participants. Only one of these was flagged as an "atypical passport finding" (ATPF) due to deviation of the OFF-score. When this sample was evaluated by ABP experts it was considered "normal". In conclusion, it is highly unlikely that the present hypoxic exposure protocol would have led to a citation for a doping violation according to WADA guidelines.

Diurnal Variations in Vascular Endothelial Vasodilation Are Influenced by Chronotype in Healthy Humans.

Introduction: The time of day when cardiovascular events are most likely to occur is thought to be aligned with the circadian rhythm of physiological variables. Chronotype has been shown to influence the time of day when cardiovascular events happen, with early chronotypes reported to be more susceptible in the morning and late chronotypes in the evening. However, no studies have investigated the influence of chronotype on physiological variables responsible for cardiovascular regulation in healthy individuals. Methods: 312 individuals completed the Munich ChronoType Questionnaire to assess chronotype. Twenty participants were randomly selected to continue into the main study. In a repeated-measures experiment, participants were tested between 08:00 and 10:00 h and again between 18:00 and 20:00 h. Measurements of mean arterial pressure, heart rate and vascular endothelial vasodilation via flow-mediated dilatation (FMD) were obtained at each session. Results: Individual diurnal differences in mean arterial pressure and heart rate show no significant relationship with chronotype. Diurnal differences in FMD showed a significant correlation (p = 0.010), driven by a clear significant relationship in the evening and not the morning (p < 0.001). Conclusion: These preliminary data indicate that chronotype influences the diurnal variation of endothelial vasodilation measured using flow-mediated dilatation. Furthermore, we show that the influence of chronotype is much stronger in the evening, highlighting an increased susceptibility for later types. These findings are consistent with the diurnal rhythm in cardiovascular events and uncover potential mechanisms of local mediators that may underpin the influence of chronotype in the onset of these events.

Isolating the independent effects of hypoxia and hyperventilation-induced hypocapnia on cerebral haemodynamics and cognitive function.

NEW FINDINGS: What is the central question of this study? What are the independent effects of hypoxia and hypocapnia on cerebral haemodynamics and cognitive function? What is the main finding and its importance? Exposure to hyperventilation-induced hypocapnia causes cognitive impairment in both normoxia and hypoxia. In addition, supplementation of carbon dioxide during hypoxia alleviates the cognitive impairment and reverses hypocapnia-induced vasoconstriction of the cerebrovasculature. These data provide new evidence for the independent effect of hypocapnia on the cognitive impairment associated with hypoxia. ABSTRACT: Hypoxia, which is accompanied by hypocapnia at altitude, is associated with cognitive impairment. This study examined the independent effects of hypoxia and hypocapnia on cognitive function and assessed how changes in cerebral haemodynamics may underpin cognitive performance outcomes. Single reaction time (SRT), five-choice reaction time (CRT) and spatial working memory (SWM) tasks were completed in 20 participants at rest and after 1 h of isocapnic hypoxia (IH, end-tidal oxygen partial pressure ( PETO2 ) = 45 mmHg, end-tidal carbon dioxide partial pressure ( PETCO2 ) clamped at normal) and poikilocapnic hypoxia (PH, PETO2  = 45 mmHg, PETCO2 not clamped). A subgroup of 10 participants were also exposed to euoxic hypocapnia (EH, PETO2  = 100 mmHg, PETCO2 clamped 8 mmHg below normal). Middle cerebral artery velocity (MCAv) and prefrontal cerebral haemodynamics were measured with transcranial Doppler and near infrared spectroscopy, respectively. IH did not affect SRT and CRT performance from rest (566 ± 50 and 594 ± 70 ms), whereas PH (721 ± 51 and 765 ± 48 ms) and EH (718 ± 55 and 755 ± 34 ms) slowed response times (P < 0.001 vs. IH). Performance on the SWM task was not altered by condition. MCAv increased during IH compared to PH (P < 0.05), which was unchanged from rest. EH caused a significant fall in MCAv and prefrontal cerebral oxygenation (P < 0.05 vs. baseline). MCAv was moderately correlated to cognitive performance (R2  = 0.266-0.289), whereas prefrontal cerebral tissue perfusion and saturation were not (P > 0.05). These findings reveal a role of hyperventilation-induced hypocapnia per se on the development of cognitive impairment during normoxic and hypoxic exposures.

Intravenous iron delivers a sustained (8-week) lowering of pulmonary artery pressure during exercise in healthy older humans.

In older individuals, pulmonary artery pressure rises markedly during exercise, probably due in part to increased pulmonary vascular resistance and in part to an increase in left-heart filling pressure. Older individuals also show more marked pulmonary vascular response to hypoxia at rest. Treatment with intravenous iron reduces the rise in pulmonary artery pressure observed during hypoxia. Here, we test the hypothesis that intravenous iron administration may also attenuate the rise in pulmonary artery pressure with exercise in older individuals. In a randomized double-blind placebo-controlled physiology study in 32 healthy participants aged 50-80 years, we explored the hypothesis that iron administration would deliver a fall in systolic pulmonary artery pressure (SPAP) during moderate cycling exercise (20 min duration; increase in heart rate of 30 min-1 ) and a change in maximal cycling exercise capacity ( V˙O2max ). Participants were studied before, and at 3 h to 8 weeks after, infusion. SPAP was measured using Doppler echocardiography. Iron administration resulted in marked changes in indices of iron homeostasis over 8 weeks, but no significant change in hemoglobin concentration or inflammatory markers. Resting SPAP was also unchanged, but SPAP during exercise was lower by ~3 mmHg in those receiving iron (P < 0.0001). This effect persisted for 8 weeks. Although V˙O2max remained unaffected in the iron-replete healthy participants studied here, this study demonstrates for the first time the ability of intravenous iron supplementation to reduce systolic pulmonary artery pressure during exercise.

An acute exposure to intermittent negative airway pressure elicits respiratory long-term facilitation in awake humans.

BACKGROUND: A sustained elevation in respiratory drive following removal of the inducing stimulus is known as respiratory long-term facilitation (rLTF). We investigated whether an acute exposure to intermittent negative airway pressure (INAP) elicits rLTF in humans. METHOD: 13 healthy males (20.9 ±â€¯2.8 years) undertook two trials (INAP and Control). In the INAP trial participants were exposed to one hour of 30-second episodes of breathing against negative pressure (-10 cmH2O) interspersed by 60-second intervals of breathing at atmospheric pressure. In the Control trial participants breathed at atmospheric pressure for one hour. Ventilation following INAP (recovery phase) was compared to that during baseline. RESULTS: Ventilation increased from baseline to recovery in the INAP trial (14.9 ±â€¯0.9 vs 19.1 ±â€¯0.7 L/min, P = 0.002). This increase was significantly greater than the equivalent during the Control trial (P = 0.019). Data shown as mean ± SEM. CONCLUSION: In this study INAP elicited rLTF in awake, healthy humans. Further research is required to investigate the responsible mechanisms.

Sensitivity of the human ventilatory response to muscle metaboreflex activation during concurrent mild hypercapnia.

NEW FINDINGS: What is the central question of this study? What is the relationship between the level of systemic hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation? What is the main finding and its importance? When a standardized activation of the muscle metaboreflex was combined with exposure to increasing levels of hypercapnia, the hyperpnoea this caused increased linearly. The concept of a synergistic interaction between the muscle metaboreflex and the central chemoreflex in humans is supported by this finding. ABSTRACT: Ventilation increases during muscle metaboreflex activation when postexercise circulatory occlusion (PECO) traps metabolites in resting human muscle, but only in conditions of concurrent systemic hypercapnia. We hypothesize that a linear relationship exists between the level of hypercapnia and the magnitude of the additional hyperpnoea produced in response to a standardized level of muscle metaboreflex activation. Fifteen male subjects performed four trials, in which the end-tidal partial pressure of carbon dioxide ( P ET , C O 2 ) was elevated by 1, 3, 7 or 10 mmHg above resting values using a dynamic end-tidal forcing system. In each trial, subjects were seated in an isometric dynamometer designed to measure ankle plantar flexor force. Rest for 2 min in room air was followed by 15 min of exposure to one of the four levels of hypercapnia, at which 5 min further rest was followed by 2 min of sustained isometric calf muscle contraction at 50% of predetermined maximal voluntary strength. Immediately before cessation of exercise, a cuff around the upper leg was inflated to a suprasystolic pressure to cause PECO for 3 min, before its deflation and a further 5 min of rest, concluding exposure to hypercapnia. The PECO consistently elevated mean arterial blood pressure by ∼10 mmHg in all trials, indicating similar levels of metaboreflex activation. Increased ventilation during PECO was related to P ET , C O 2 as described by the following linear regression equation: Change in minute ventilation (l min-1 ) = 0.85 ×  P ET , C O 2 (mmHg) + 0.80 (l min-1 ). This finding supports our hypothesis and furthers the idea of a synergistic interaction between muscle metaboreflex activation and central chemoreflex stimulation.

Undiagnosed Obstructive Sleep Apnea and Physical Activity in Older Manual Workers.

Cardiovascular disease is a negative health outcome of obstructive sleep apnea (OSA). Risk factors associated with OSA development include low physical activity (PA), high body mass index (BMI), and increasing age (>50 years), and weight loss is usually recommended as treatment. This cross-sectional study examined the association between PA, BMI, and OSA severity in manual workers. Fifty-five participants (23 females and 32 males; mean age 55.2 years), were examined for OSA and completed a PA and anthropometric assessment. On average, OSA severity was mild, PA levels were moderate, and 32% of the sample was classified as obese. PA was negatively associated with OSA severity, but BMI strongly independently predicted OSA severity, with no evidence of mediation. As both PA and BMI were significantly associated with OSA in older manual workers, increasing PA should also be a focus of treatment for OSA.

The effects of time of day and chronotype on cognitive and physical performance in healthy volunteers.

BACKGROUND: Whether you are a morning lark or a night owl has proven to be a key contributor in the timing of peak athletic performance. Recent evidence suggests that accounting for these differences, known as one's chronotype, results in significantly different diurnal performance profiles. However, there is limited research investigating multiple measures of performance simultaneously over the course of a socially constrained day. OBJECTIVES: This study aimed to investigate the impact of chronotype on indices of cognitive and physical performance at different times of day in healthy volunteers. METHODS: We recruited 56 healthy individuals categorised as early (ECT, n = 25) or late (LCT, n = 31) chronotypes using the Munich ChronoType Questionnaire, circadian phase markers and objective actigraphy. Measures of cognitive and physical performance, along with self-reported daytime sleepiness, were taken at multiple times of day (14:00 h, 20:00 h and 08:00 h the following morning). RESULTS: Here, we find significantly different diurnal variation profiles between ECTs and LCTs, for daytime sleepiness, psychomotor vigilance, executive function and isometric grip strength. LCTs were significantly impaired in all measures in the morning compared to ECTs. CONCLUSION: Our results provide evidence to support the notion that 'night owls' are compromised earlier in the day. We offer new insight into how differences in habitual sleep patterns and circadian rhythms impact cognitive and physical measures of performance. These findings may have implications for the sports world, e.g. athletes, coaches and teams, who are constantly looking for ways to minimise performance deficits and maximise performance gains.

Presenteeism, stress resilience, and physical activity in older manual workers: a person-centred analysis.

This study used a person-centred approach to explore typologies of older manual workers based on presenteeism, stress resilience, and physical activity. Older manual workers (n = 217; 69.1% male; age range 50-77; M age = 57.11 years; SD = 5.62) from a range of UK-based organisations, representing different manual job roles, took part in the study. A cross-sectional survey design was used. Based on the three input variables: presenteeism, stress resilience and physical activity, four distinct profiles were identified on using Latent Profile Analysis. One group ('High sport/exercise and well-functioning'; 5.50%) engaged in high levels of sport/exercise and exhibited low levels of stress resilience and all types of presenteeism. Another profile ('Physically burdened'; 9.70%) reported high levels of work and leisure-time physical activity, low stress resilience, as well as high levels of presenteeism due to physical and time demands. A 'Moderately active and functioning' group (46.50%) exhibited moderate levels on all variables. Finally, the fourth profile ('Moderately active with high presenteeism'; 38.20%) reported engaging in moderate levels of physical activity and had relatively high levels of stress resilience, yet also high levels of presenteeism. The profiles differed on work affect and health perceptions largely in the expected directions. There were no differences between the profiles in socio-demographics. These results highlight complex within-person interactions between presenteeism, stress resilience, and physical activity in older manual workers. The identification of profiles of older manual workers who are at risk of poor health and functioning may inform targeted interventions to help retain them in the workforce for longer.

Cardiopulmonary phenotype associated with human PHD2 mutation.

Oxygen-dependent regulation of the erythropoietin gene is mediated by the hypoxia-inducible factor (HIF) family of transcription factors. When oxygen is plentiful, HIF undergoes hydroxylation by a family of oxygen-dependent prolyl hydroxylase domain (PHD) proteins, promoting its association with the von Hippel-Lindau (VHL) ubiquitin E3 ligase and subsequent proteosomal degradation. When oxygen is scarce, the PHD enzymes are inactivated, leading to HIF accumulation and upregulation not only of erythropoietin expression, but also the expression of hundreds of other genes, including those coordinating cardiovascular and ventilatory adaptation to hypoxia. Nevertheless, despite the identification of over 50 mutations in the PHD-HIF-VHL pathway in patients with previously unexplained congenital erythrocytosis, there are very few reports of associated cardiopulmonary abnormalities. We now report exaggerated pulmonary vascular and ventilatory responses to acute hypoxia in a 35-year-old man with erythrocytosis secondary to heterozygous mutation in PHD2, the most abundant of the PHD isoforms. We compare this phenotype with that reported in patients with the archetypal disorder of cellular oxygen sensing, Chuvash polycythemia, and discuss the possible clinical implications of our findings, particularly in the light of the emerging role for small molecule PHD inhibitors in clinical practice.

Resilience, work engagement and stress reactivity in a middle-aged manual worker population.

Work stress is a growing problem in Europe. Together, the negative physiological effect of stress on health, and increasing age increases the risk of developing cardiovascular disease in those aged over 50years. Therefore, identifying older workers who may be at risk of work-related stress, and its physiological effects, is key to promoting their health and wellbeing in the workforce. The present study examined the relationship between perceived psychological resilience and work-related factors (work engagement and presenteeism) and the physiological response to acute psychological stress in older manual workers in the UK. Thirty-one participants, mean (SD) age 54.9 (3.78)years reported perceived levels of resilience, work engagement, and presenteeism using standardized questionnaires. Cardiovascular measurements (heart rate (HR) and blood pressure (BP) and salivary cortisol were used to assess their physiological response to an acute psychological stress task. Resilience was not associated with work-related factors or reactivity. However, workers with higher work engagement showed lower SBP (p=0.02) and HR (p=0.001) reactivity than those with lower work engagement. Further, those with higher sickness presenteeism also had higher HR reactivity (p=0.03). This suggests a potential pathway by which higher work stress might contribute to the risk of future cardiovascular disease.

Frequency-domain vs continuous-wave near-infrared spectroscopy devices: a comparison of clinically viable monitors in controlled hypoxia.

The Near-infrared spectroscopy (NIRS) has not been adopted as a mainstream monitoring modality in acute neurosurgical care due to concerns about its reliability and consistency. However, improvements in NIRS parameter recovery techniques are now available that may improve the quantitative accuracy of NIRS for this clinical context. Therefore, the aim of this study was to compare the abilities of a continuous-wave (CW) NIRS device with a similarly clinically viable NIRS device utilising a frequency-domain (FD) parameter recovery technique in detecting changes in cerebral tissue saturation during stepwise increases of experimentally induced hypoxia. Nine healthy individuals (6M/3F) underwent a dynamic end-tidal forced manipulation of their expiratory gases to induce a stepwise induced hypoxia. The minimum end-tidal oxygen partial pressure (EtO2) achieved was 40 mm Hg. Simultaneous neurological and extra-cranial tissue NIRS reading were obtained during this protocol by both tested devices. Both devices detected significant changes in cerebral tissue saturation during the induction of hypoxia (CW 9.8 ± 2.3 %; FD 7.0 ± 3.4 %; Wilcoxon signed rank test P < 0.01 for both devices). No significant difference was observed between the saturation changes observed by either device (P = 0.625). An observably greater degree of noise was noticed in parameters recovered by the FD device, and both demonstrated equally variable baseline readings (Coefficient of variance 8.4 and 9.7 % for the CW and FD devices, respectively) between individuals tested. No advantageous difference was observed in parameters recovered from the FD device compared with those detected by CW.

Muscle metaboreflex and cerebral blood flow regulation in humans: implications for exercise with blood flow restriction.

We investigated the effect of activating metabolically sensitive skeletal muscle afferents (muscle metaboreflex) on cerebral blood flow and the potentially confounding influence of concomitant changes in the partial pressure of arterial carbon dioxide. Eleven healthy males (25 ± 4 yr) performed submaximal leg cycling exercise on a semirecumbent cycle ergometer (heart rate: ∼120 beats/min), and assessments were made of the partial pressure of end-tidal carbon dioxide (PetCO2 ), internal carotid artery blood flow (ICAQ) and conductance (ICACVC), and middle cerebral artery mean blood velocity (MCAvm) and conductance index (MCACVCi).The muscle metaboreflex was activated during cycling with leg blood flow restriction (BFR) or isolated with postexercise ischemia (PEI). In separate trials, PetCO2 was either permitted to fluctuate spontaneously (control trial) or was clamped at 1 mmHg above resting levels (PetCO2 clamp trial). In the control trial, leg cycling with BFR decreased PetCO2 (Δ-4.8 ± 0.9 mmHg vs. leg cycling exercise) secondary to hyperventilation, while ICAQ, ICACVC, and MCAvm were unchanged and MCACVCi decreased. However, in the PetCO2 clamp trial, leg cycling with BFR increased both MCAvm (Δ5.9 ± 1.4 cm/s) and ICAQ (Δ20.0 ± 7.8 ml/min) and attenuated the decrease in MCACVCi, while ICACVC was unchanged. In the control trial, PEI decreased PetCO2 (Δ-7.0 ± 1.3 mmHg vs. rest), MCAvm and MCACVCi, whereas ICAQ and ICACVC were unchanged. In contrast, in the PetCO2 clamp trial both ICAQ (Δ18.5 ± 11.9 ml/min) and MCAvm (Δ8.8 ± 2.0 cm/s) were elevated, while ICACVC and MCACVCi were unchanged. In conclusion, when hyperventilation-related decreases in PetCO2 are prevented the activation of metabolically sensitive skeletal muscle afferent fibers increases cerebral blood flow.