The sensation of breathlessness is often attributed to perturbations in cardio-pulmonary physiology, leading to changes in afferent signals. New evidence suggests that these signals are interpreted ...in the light of prior "expectations". A misalignment between afferent signals and expectations may underly unexplained breathlessness. Using a novel immersive virtual reality (VR) exercise paradigm, we investigated whether manipulating an individual's expectation of effort (determined by a virtual hill gradient) may alter their perception of breathlessness, independent from actual effort (the physical effort of cycling).
Nineteen healthy volunteers completed a single experimental session where they exercised on a cycle ergometer while wearing a VR headset. We created an immersive virtual cycle ride where participants climbed up 100 m hills with virtual gradients of 4%, 6%, 8%, 10% and 12%. Each virtual hill gradient was completed twice: once with a 4% cycling ergometer resistance and once with a 6% resistance, allowing us to dissociate expected effort (virtual hill gradient) from actual effort (power). At the end of each hill, participants reported their perceived breathlessness. Linear mixed effects models were used to examine the independent contribution of actual effort and expected effort to ratings of breathlessness (0-10 scale).
Expectation of effort (effect estimate ± std. error, 0.63 ± 0.11, P < 0.001) and actual effort (0.81 ± 0.21, P < 0.001) independently explained subjective ratings of breathlessness, with comparable contributions of 19% and 18%, respectively. Additionally, we found that effort expectation accounted for 6% of participants' power and was a significant, independent predictor (0.09 ± 0.03; P = 0.001).
An individuals' expectation of effort is equally important for forming perceptions of breathlessness as the actual effort required to cycle. A new VR paradigm enables this to be experimentally studied and could be used to re-align breathlessness and enhance training programmes.
Although it has long been hypothesized that attachment figures provide individuals with a sense of safety and security, the neural mechanisms underlying attachment-induced safety have not been ...explored. Here, we investigated whether an attachment figure acts as a safety signal by exploring whether viewing an attachment figure during a threatening experience (physical pain) led to increased activity in a neural region associated with safety signaling, the ventromedial prefrontal cortex (VMPFC), and corresponding reductions in pain. Female participants in long-term romantic relationships were scanned as they received painful stimuli while viewing pictures of their partner and control images (stranger, object). Consistent with the idea that the attachment figure may signal safety, results revealed that viewing partner pictures while receiving painful stimulation led to reductions in self-reported pain ratings, reductions in pain-related neural activity (dorsal anterior cingulate cortex, anterior insula), and increased activity in the VMPFC. Moreover, greater VMPFC activity in response to partner pictures was associated with longer relationship lengths and greater perceived partner support, further highlighting a role for the VMPFC in responding to the safety value of the partner. Last, greater VMPFC activity while viewing partner pictures was associated with reduced pain ratings and reduced pain-related neural activity. An implication of these findings is that, in the same way that stimuli that historically have threatened survival (e.g., snakes, spiders) are considered to be prepared fear stimuli, attachment figures, who have historically benefited survival, may serve as prepared safety stimuli, reducing threat- or distress-related responding in their presence.
OBJECTIVE
To determine the correlates of the “metabolically healthy obese” (MHO) phenotype and the longitudinal risks of diabetes and cardiovascular disease (CVD)/stroke associated with this ...phenotype.
RESEARCH DESIGN AND METHODS
The North West Adelaide Health Study is a prospective cohort study of 4,056 randomly selected adults aged ≥18 years. Participants free of CVD/stroke and not underweight (n = 3,743) were stratified by BMI categories and metabolic risk, defined as having two or more International Diabetes Federation metabolic syndrome criteria, excluding waist circumference.
RESULTS
Correlates of the MHO (n = 454 12.1%) included smoking, socioeconomic disadvantage, and physical inactivity. Compared with metabolically healthy normal-weight subjects (n = 1,172 31.3%), the MHO were more likely to develop metabolic risk (15.5 vs. 33.1%, P < 0.001) and incident diabetes (odds ratio 2.09 95% CI 0.87–5.03) but not CVD/stroke (1.16 0.58–2.29) during 5.5–10.3 years of follow-up. These risks were not seen in MHO subjects maintaining metabolic health (n = 188 67%). Sustained metabolic health in obese participants was associated with age ≤40 years and lower waist circumference. Compared with the metabolically at-risk obese, MHO women demonstrated a significantly higher (mean SE) percentage of leg fat (49.9 0.5 vs. 53.2 0.7) and lower waist circumference (104 0.6 vs. 101 cm 0.8), despite no significant differences in overall adiposity.
CONCLUSIONS
“Healthy” obesity was a transient state for one-third of subjects. Persistence of a MHO phenotype, which was associated with favorable outcomes, was related to younger age and a more peripheral fat distribution. The MHO phenotype may be sustained by promoting lower waist circumferences.
Abstract Objective To measure the prevalence and social impacts of sleep problems in Australia. Design Cross-sectional national adult online survey. Setting Community-based sample. Participants ...Australian adults ≥18 years, n = 1011. Results Self-reported inadequate sleep, of either duration or quality, and its daytime consequences affect 33%-45% of adults. Diagnosed sleep apnea is reported by 8%, significant insomnia by 20%, and restless legs by18% of adults. Besides specific clinical sleep disorders, poor sleep habits were common. Average reported sleep time is 7 hours, although 12% sleep less than 5½ hours and 8% over 9 hours. Three-quarters (76%) of those who sleep less than 5½ hours report frequent daytime impairment or sleep-related symptoms. Frequent, loud snoring is reported by 24% of men and 17% of women. Among these, 70% report daytime impairment or other sleep-related symptoms. Twenty-six percent report Internet use most or every night just before bed and frequent sleep difficulties or daytime impairments. Similarly, 16% of working adults do work just before bed and also have frequent sleep difficulties or daytime sleep-related symptoms. Younger adults (18-34 years) sleep around 1 hour longer before non-work days than working days compared with 18 minutes in older age groups. In the past 3 months, 29% of adults report making errors at work due to sleepiness or sleep problems. Driving while drowsy at least every month is reported by 29% of people, 20% have nodded off while driving, and 5% have had an accident in the past year because they dozed off. Conclusion Sleep problems and daytime consequences are endemic among Australian adults. A focus on healthy sleep at a policy level as well as increased clinician and public awareness may be warranted.
To determine the correlates of the "metabolically healthy obese" (MHO) phenotype and the longitudinal risks of diabetes and cardiovascular disease (CVD)/stroke associated with this phenotype. The ...North West Adelaide Health Study is a prospective cohort study of 4,056 randomly selected adults aged ≥18 years. Participants free of CVD/stroke and not underweight (n = 3,743) were stratified by BMI categories and metabolic risk, defined as having two or more International Diabetes Federation metabolic syndrome criteria, excluding waist circumference. Correlates of the MHO (n = 454 12.1%) included smoking, socioeconomic disadvantage, and physical inactivity. Compared with metabolically healthy normal-weight subjects (n = 1,172 31.3%), the MHO were more likely to develop metabolic risk (15.5 vs. 33.1%, P < 0.001) and incident diabetes (odds ratio 2.09 95% CI 0.87-5.03) but not CVD/stroke (1.16 0.58-2.29) during 5.5-10.3 years of follow-up. These risks were not seen in MHO subjects maintaining metabolic health (n = 188 67%). Sustained metabolic health in obese participants was associated with age ≤40 years and lower waist circumference. Compared with the metabolically at-risk obese, MHO women demonstrated a significantly higher (mean SE) percentage of leg fat (49.9 0.5 vs. 53.2 0.7) and lower waist circumference (104 0.6 vs. 101 cm 0.8), despite no significant differences in overall adiposity. "Healthy" obesity was a transient state for one-third of subjects. Persistence of a MHO phenotype, which was associated with favorable outcomes, was related to younger age and a more peripheral fat distribution. The MHO phenotype may be sustained by promoting lower waist circumferences.
ObjectiveOmega-3 polyunsaturated fatty acids (PUFAs) have anticolorectal cancer (CRC) activity. The intestinal microbiota has been implicated in colorectal carcinogenesis. Dietary omega-3 PUFAs alter ...the mouse intestinal microbiome compatible with antineoplastic activity. Therefore, we investigated the effect of omega-3 PUFA supplements on the faecal microbiome in middle-aged, healthy volunteers (n=22).DesignA randomised, open-label, cross-over trial of 8 weeks’ treatment with 4 g mixed eicosapentaenoic acid/docosahexaenoic acid in two formulations (soft-gel capsules and Smartfish drinks), separated by a 12-week ‘washout’ period. Faecal samples were collected at five time-points for microbiome analysis by 16S ribosomal RNA PCR and Illumina MiSeq sequencing. Red blood cell (RBC) fatty acid analysis was performed by liquid chromatography tandem mass spectrometry.ResultsBoth omega-3 PUFA formulations induced similar changes in RBC fatty acid content, except that drinks were associated with a larger, and more prolonged, decrease in omega-6 PUFA arachidonic acid than the capsule intervention (p=0.02). There were no significant changes in α or β diversity, or phyla composition, associated with omega-3 PUFA supplementation. However, a reversible increased abundance of several genera, including Bifidobacterium, Roseburia and Lactobacillus was observed with one or both omega-3 PUFA interventions. Microbiome changes did not correlate with RBC omega-3 PUFA incorporation or development of omega-3 PUFA-induced diarrhoea. There were no treatment order effects.ConclusionOmega-3 PUFA supplementation induces a reversible increase in several short-chain fatty acid-producing bacteria, independently of the method of administration. There is no simple relationship between the intestinal microbiome and systemic omega-3 PUFA exposure.Trial registration numberISRCTN18662143.
Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed ...condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor. Disruption of C17orf89 markedly reduced CI activity, and its depletion is found in an unresolved case of CI deficiency. We likewise discovered that LYRM5 interacts with and deflavinates the electron-transferring flavoprotein that shuttles electrons to coenzyme Q (CoQ). Finally, we identified a dynamic human CoQ biosynthetic complex involving multiple MXPs whose topology we map using purified components. Collectively, our data lend mechanistic insight into respiratory chain-related activities and prioritize hundreds of additional interactions for further exploration of mitochondrial protein function.
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•PPI mapping of 50 MXPs reveals mitochondrial protein functions•C17orf89 is a CI assembly factor depleted in a case of CI deficiency•LYRM5 interacts with and deflavinates the electron transferring flavoprotein•Proteins involved in coenzyme Q biosynthesis form a dynamic “complex Q”
Mitochondria are essential organelles, yet hundreds of their proteins lack robust functional characterization. Floyd et al. (2016) define interaction partners for 50 such proteins, providing hypotheses about their roles in mitochondria. In particular, their work lends mechanistic insight into respiratory chain activities related to complex I, the electron transferring flavoprotein, and coenzyme Q.
Frailty is prevalent in older adults and has adverse effects on multiple health outcomes. Pain, insomnia, and depressive symptoms are commonly seen and treatable symptoms in older adults and are ...associated with frailty. However, it is unknown whether these symptoms are independently associated with frailty and how they interact with each other creating a greater impact on frailty than individual symptoms. It is important to understand these associations for nurses to provide high-quality patient-centered care for older adults with frailty.
To determine independent associations of pain, insomnia, and depressive symptoms with frailty and examine their synergistic impact on frailty among older adults.
A cross-sectional analysis of a cohort study.
Communities in the United States.
Community-dwelling older adults from the National Health and Aging Trend Study (N = 7,609), a nationally representative survey of Medicare Beneficiaries in the United States.
Frailty status was determined by five criteria of the Physical Frailty Phenotype: exhaustion, low physical activity, weakness, slowness, and shrinking. Pain was determined by self-reports of bothersome pain in the last month. Insomnia included self-reports of difficulty initiating sleep and difficulty maintaining sleep. Depressive symptom was assessed by the Patient Health Questionnaire-2. Logistic regression models were used adjusting for sociodemographic, health-related and behavioral covariates.
The sample was mainly under 80 years old (72%), female (57%), and non-Hispanic White (81%). Approximately 53% experienced bothersome pain, 11% had difficulty initiating sleep, 6% had difficulty maintaining sleep, and 15% had depressive symptom; 46% were pre-frail and 14% were frail. Independent associations with pre-frailty and frailty were found in pain (odds ratio OR: 1.81, 95% CI: 1.60, 2.04), difficulty initiating sleep (OR: 1.23, 95% CI: 1.04, 1.46) and depressive symptom (OR: 2.29, 95% CI: 1.85, 2.84). Interaction terms between pain and depressive symptom (OR: 1.87, 95% CI: 1.14, 3.07), and between difficulty initiating sleep and depressive symptom (OR: 2.66, 95% CI: 1.15, 6.13) were significant, suggesting a synergistic impact on pre-frailty and frailty.
Pain, difficulty initiating sleep, and depressive symptoms are independent risk factors of frailty and may have a synergistic impact on frailty. Interventions should be developed to address these symptoms to reduce the adverse effects of frailty.
Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and ...protein mediators of inflammation. Because delayed inflammation is essential for Y. pestis to cause lethal infection, defining the Y. pestis mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen's virulence. While previous studies have established that Y. pestis actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB4 prior to infection limited bacterial proliferation, suggesting that the absence of LTB4 synthesis during plague contributes to Y. pestis immune evasion. Using primary leukocytes from mice and humans further revealed that Y. pestis actively inhibits the synthesis of LTB4. Finally, using Y. pestis mutants in the Ysc type 3 secretion system (T3SS) and Yersinia outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB4. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that Y. pestis actively inhibits the synthesis of the inflammatory lipid LTB4 contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.
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