The influence of gender and anthropometry on haemodynamic status at rest and in response to graded incremental head-up tilt in young, healthy adults

The body's ability to rapidly and appropriately regulate blood pressure in response to changing physiological demand is a key feature of a healthy cardiovascular system. Passively tilting the body, thereby changing central blood volume, is a well-recognized and controlled method of evaluating this ability. However, such studies usually involve single tilt angles, or intermittent tilting separated by supine, resting periods; valuable information concerning the adaptive capacity of the regulatory systems involved is therefore currently lacking. Furthermore, despite increasing recognition that men and women differ in the magnitude of their haemodynamic response to such stimuli, little is known about the degree to which gender differences in body composition and anthropometry influence these regulatory pathways, or indeed if these differences are apparent in response to graded, incremental tilting. In the present study we measured, in 23 young, healthy adults (13 men, 10 women), the continuous beat-to-beat haemodynamic response to graded, incremental tilting (0°, 20°, 40°, 60°, and back to 40°) with each tilt angle lasting 16 min. On average, we observed increases in heart rate (+41%), blood pressure (+10%), and total peripheral resistance (+16%) in response to tilting. However, whilst men showed an immediate decrease in cardiac output upon tilting (−8.9%) cardiac output in women did not change significantly from supine values. Interestingly, the decrease in stroke volume observed in women was significantly less than that observed in men (−22 vs. −36%, p per se or due to differences in body size (in particular height) between the two gender groups. Such disparities in the magnitude of autonomic response may indicate (in the case of our gradual incremental tilt procedure) a better buffering capacity to progressive changes in central blood volume in women; which warrants further investigation, particularly in light of the well-recognized differences in cardiovascular disease risk between men and women

Posture allocation revisited: breaking the sedentary threshold of energy expenditure for obesity management

There is increasing recognition that low-intensity physical activities of daily life play an important role in achieving energy balance and that their societal erosion through substitution with sedentary (mostly sitting) behaviours, whether occupational or for leisure, impact importantly on the obesity epidemic. This has generated considerable interest for better monitoring, characterizing and promoting countermeasures to sedentariness through a plethora of low-level physical activities (e.g. active workstations, standing desks, sitting breaks), amid the contention that altering posture allocation (lying, sitting, standing) can modify energy expenditure to impact upon body weight regulation and health. In addressing this contention, this paper first revisits the past and more recent literature on postural energetics, with particular emphasis on potential determinants of the large inter-individual variability in the energy cost of standing and the impact of posture on fat oxidation. It subsequently analyses the available data pertaining to various strategies by which posture allocations, coupled with light physical activity, may increase energy expenditure beyond the sedentary threshold, and their relevance as potential targets for obesity management

Energy cost of standing in a multi-ethnic cohort: are energy-savers a minority or the majority?

The disease risks associated with sedentary behavior are now firmly established, and consequently there is much interest in methods of increasing low-intensity physical activity. In this context, it is a widely held belief that altering posture allocation can modify energy expenditure (EE) to impact upon body weight regulation and health. However, we recently showed the existence of two distinct phenotypes pertaining to the energy cost of standing–with the majority of a Caucasian cohort showing no sustained increase in EE during standing relative to sitting. Here we investigated whether this phenomenon is also observed across a multi-ethnic male cohort.Objective: To determine the magnitude and time-course of changes in EE and respiratory quotient (RQ) during steady-state standing versus sitting, and to explore inter-individual variability in these responses across 4 ethnic groups (European, Indian, Chinese, African)Design: Min-by-min monitoring using posture-adapted ventilated-hood indirect calorimetry was conducted in 35 healthy, men (20–43 years) during 10 min of steady-state standing versus sitting comfortably.Results: 69% of subjects showed little or no increase (<5%) in EE during standing compared to sitting (energy savers). Furthermore, the proportion of energy savers did not significantly differ between ethnic groups, despite ethnic differences in anthropometry; with body weight as the primary predictor of the energy cost of standing maintenance (r2 = 0.30, p = 0.001).Conclusion: Our results indicate that the majority of individuals in a multi-ethnic cohort display a postural energy-saver phenotype. The mechanisms by which the large majority of individuals appear to maintain sitting and standing postures at the same energetic cost remains to be elucidated but is of considerable importance to our understanding of the spontaneous physical activity compartment of EE and its potential as a target for weight regulation

Evaluation of person-level heterogeneity of treatment effects in published multiperson N-of-1 studies: systematic review and reanalysis.

OBJECTIVE:Individual patients with the same condition may respond differently to similar treatments. Our aim is to summarise the reporting of person-level heterogeneity of treatment effects (HTE) in multiperson N-of-1 studies and to examine the evidence for person-level HTE through reanalysis. STUDY DESIGN:Systematic review and reanalysis of multiperson N-of-1 studies. DATA SOURCES:Medline, Cochrane Controlled Trials, EMBASE, Web of Science and review of references through August 2017 for N-of-1 studies published in English. STUDY SELECTION:N-of-1 studies of pharmacological interventions with at least two subjects. DATA SYNTHESIS:Citation screening and data extractions were performed in duplicate. We performed statistical reanalysis testing for person-level HTE on all studies presenting person-level data. RESULTS:We identified 62 multiperson N-of-1 studies with at least two subjects. Statistical tests examining HTE were described in only 13 (21%), of which only two (3%) tested person-level HTE. Only 25 studies (40%) provided person-level data sufficient to reanalyse person-level HTE. Reanalysis using a fixed effect linear model identified statistically significant person-level HTE in 8 of the 13 studies (62%) reporting person-level treatment effects and in 8 of the 14 studies (57%) reporting person-level outcomes. CONCLUSIONS:Our analysis suggests that person-level HTE is common and often substantial. Reviewed studies had incomplete information on person-level treatment effects and their variation. Improved assessment and reporting of person-level treatment effects in multiperson N-of-1 studies are needed

Fasting substrate oxidation at rest assessed by indirect calorimetry: is prior dietary macronutrient level and composition a confounder?

Indirect calorimetry, the measurement of O₂ consumption and CO₂ production, constitutes an invaluable tool as the most common method for analyzing whole-body energy expenditure, and also provides an index of the nature of macronutrient substrate oxidation—namely, carbohydrate (CHO) versus fat oxidation. The latter constitutes a key etiological factor in obesity as this condition can only develop when total fat oxidation is chronically lower than total exogenous fat intake. The standardization of indirect calorimetry measurements is essential for accurately tracking the relative proportion of energy expenditure derived from CHO and fat oxidation. Here we analyze literature data to show that the average fasting respiratory quotient typically shifts from approximately 0.80 to 0.90 (indicating a doubling of resting CHO oxidation) in response to a switch in dietary CHO intake (as % energy) from 30 to 60%. This underscores the importance of taking into account dietary macronutrient composition prior to indirect calorimetry studies in the interpretation of data on substrate utilization and oxidation

Competing risks of cancer mortality and cardiovascular events in individuals with multimorbidity

Background: Cancer patients with cardiovascular and other comorbidities are at concurrent risk of multiple adverse outcomes. However, most treatment decisions are guided by evidence from single-outcome models, which may be misleading for multimorbid patients. Objective: We assessed the interacting effects of cancer, cardiovascular, and other morbidity burdens on the competing outcomes of cancer mortality, serious cardiovascular events, and other-cause mortality. Design: We analyzed a cohort of 6,500 adults with initial cancer diagnosis between 2001 and 2008, SEER 5-year survival ≥26%, and a range of cardiovascular risk factors. We estimated the cumulative incidence of cancer mortality, a serious cardiovascular event (myocardial infarction, coronary revascularization, or cardiovascular mortality), and other-cause mortality over 5 years, and identified factors associated with the competing risks of each outcome using cause-specific Cox proportional hazard models. Results: Following cancer diagnosis, there were 996 (15.3%) cancer deaths, 328 (5.1%) serious cardiovascular events, and 542 (8.3%) deaths from other causes. In all, 4,634 (71.3%) cohort members had none of these outcomes. Although cancer prognosis had the greatest effect, cardiovascular and other morbidity also independently increased the hazard of each outcome. The effect of cancer prognosis on outcome was greatest in year 1, and the effect of other morbidity was greater in individuals with better cancer prognoses. Conclusion: In multimorbid oncology populations, comorbidities interact to affect the competing risk of different outcomes. Quantifying these risks may provide persons with cancer plus cardiovascular and other comorbidities more accurate information for shared decision-making than risks calculated from single-outcome models. Journal of Comorbidity 2014:4(1):29–3

Passive and active roles of fat-free mass in the control of energy intake and body composition regulation

While putative feedback signals arising from adipose tissue are commonly assumed to provide the molecular links between the body’s long-term energy requirements and energy intake, the available evidence suggests that the lean body or fat-free mass (FFM) also plays a role in the drive to eat. A distinction must, however, be made between a ‘passive’ role of FFM in driving energy intake, which is likely to be mediated by ‘energy-sensing’ mechanisms that translate FFM-induced energy requirements to energy intake, and a more ‘active’ role of FFM in the drive to eat through feedback signaling between FFM deficit and energy intake. Consequently, a loss of FFM that results from dieting or sedentarity should be viewed as a risk factor for weight regain and increased fatness not only because of the impact of the FFM deficit in lowering the maintenance energy requirement but also because of the body’s attempt to restore FFM by overeating—a phenomenon referred to as ‘collateral fattening’. A better understanding of these passive and active roles of FFM in the control of energy intake will necessitate the elucidation of peripheral signals and energy-sensing mechanisms that drive hunger and appetite, with implications for both obesity prevention and its management

Implementing a Hearing Screening Readiness Assessment Tool for Preterm and Term Neonates in the Newborn Intensive Care Unit: A Pilot Project

Newborn intensive care unit (NICU) patients are at risk for hearing loss. Early detection mitigates consequences of speech and language delay. The Joint Committee on Infant Hearing (JCIH) recommends hearing screening (HS) on all infants by 1 month of age. Often hearing screening is performed around the time of NICU discharge, often beyond JCIH recommendations. Automated auditory brainstem response (AABR) screening can be performed once an infant reaches 32 to 34 weeks corrected gestational age (GA). Our project aimed to reduce HS delay among NICU infants. We created and implemented a HS assessment tool defining gestational age and medical stability parameters for initial HS. Data were compared between 100 infants pre-implementation and 325 infants post-implementation. After implementation, infants had HS performed 4 days earlier in days of life (p=0.28) and 4 days earlier, prior to discharge (p14 days earlier prior to discharge (p \u3c 0.0001). More preterm infants completed HS at \u3c 1 month of age (34% vs 61%, p=0.06). Earlier HS is associated with a 6.3% increase in false positive screens among premature neonates, requiring repeat screening. While evidence suggest the tool may promote earlier HS for preterm infants, additional work on optimizing the HS technique is needed to lower false positive results

Bioenergetic Profiling of Zebrafish Embryonic Development

Many debilitating conditions are linked to bioenergetic defects. Developing screens to probe the genetic and/or chemical basis for such links has proved intractable. Furthermore, there is a need for a physiologically relevant assay of bioenergetics in whole organisms, especially for early stages in life where perturbations could increase disease susceptibility with aging. Thus, we asked whether we could screen bioenergetics and mitochondrial function in the developing zebrafish embryo. We present a multiplexed method to assay bioenergetics in zebrafish embryos from the blastula period (3 hours post-fertilization, hpf) through to hatching (48 hpf). In proof of principle experiments, we measured respiration and acid extrusion of developing zebrafish embryos. We quantified respiratory coupling to various bioenergetic functions by using specific pharmacological inhibitors of bioenergetic pathways. We demonstrate that changes in the coupling to ATP turnover and proton leak are correlated with developmental stage. The multiwell format of this assay enables the user to screen for the effects of drugs and environmental agents on bioenergetics in the zebrafish embryo with high sensitivity and reproducibility

Heterogeneity in the energy cost of posture maintenance during standing relative to sitting: phenotyping according to magnitude and time-Course

Background: Reducing sitting-time may decrease risk of disease and increase life-span. In the search for approaches to reduce sitting-time, research often compares sitting to standing and ambulation, but the energetic cost of standing alone versus sitting is equivocal, with large variation in reported mean values (0% to > 20% increase in energy expenditure (EE) during standing).Objective: To determine the magnitude and time-course of changes in EE and respiratory quotient (RQ) during steady-state standing versus sitting.Design: Min-by-min monitoring using a posture-adapted ventilated-hood indirect calorimetry system was conducted in 22 young adults with normal BMI during 10 min of steady-state standing versus sitting comfortably.Results: This study reveals three distinct phenotypes based on the magnitude and time-course of the EE response to steady-state standing. One-third of participants (8/22) showed little or no change in EE during standing relative to sitting (ΔEE < 5%; below first quartile). Of the 14 responders (ΔEE 7–21%), 4 showed sustained, elevated EE during standing, while 10 decreased their EE to baseline sitting values during the second half of the standing period. These EE phenotypes were systematically mirrored by alterations in RQ (a proxy of substrate oxidation), with ΔEE inversely correlated with ΔRQ (r = 0.6–0.8, p < 0.01).Conclusion: This study reveals different phenotypes pertaining to both energy cost and fuel utilization during standing, raising questions regarding standing as a strategy to increase EE and thermogenesis for weight control, and opening new avenues of research towards understanding the metabolic and psychomotor basis of variability in the energetics of standing and posture maintenance