In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular ...function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106;
431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98;
251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: -31 ± 18 ml) than the young (LBF: -129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.
•Higher socioeconomic position is associated with mostly beneficial home environments.•However, certain sources of pollution may be higher in these homes.•Affective disorders, may be especially ...strongly related to the home environment.•Housing age, type and household composition cluster with a number of indoor factors.•Mould and moisture correlate, while candle burning is largely unrelated to other factors.
Housing and indoor home environments are associated with the risk of infections and asthma in children. To better understand the determinants and characteristics of these environments, we aimed to describe the associations between parental health and socioeconomic position and housing and indoor home environments of children in Denmark, and the clustering of the factors within these environments.
Offspring in the Danish National Birth Cohort (DNBC) whose parents responded to the 11-year follow-up were eligible for inclusion. We included complete cases only. Data on the indoor and housing environments (i.e. variables on housing, sources of gaseous and particle pollution, mould and moisture, and pets) were collected through an online questionnaire responded to by a parent. Data on socioeconomic position were obtained through linkage with registry data on maternal education at offspring birth and household equivalized income at offspring birth. Data on parental health were obtained by linking self-reported data from the 11-year follow-up for mother and father with administrative registry data for the mother. We present descriptive statistics and exploratory factor analyses.
A total of 42 723 offspring were included for analyses. The distributions of nearly all indoor and housing environments differed according to educational and income strata, with patterns similar for both education and income. Generally, higher parental educational and income strata had more favorable indoor and housing environments (less secondhand smoking, gas stove use, mould and condensation and higher house ownership, detached house dwellings and newer building age). However, candle use was approximately similar between strata, fireplace use among lower educational and income strata tended towards the extremes (none or daily), and water damage was more common among higher educational and income strata. Parental health was strongly associated with housing and indoor home environment factors - especially parental affective disorders was strongly associated with mould. Four factors were extracted from the exploratory factor analyses, relating primarily in order of extraction to: housing ownership, mould and moisture, candle use and household density.
Parental health and socioeconomic position are strongly related to housing and indoor home environments. Additionally, several factors in these environments correlate strongly and cluster together. Observational studies on associations and causal effects of factors in the indoor and housing environments of children on their morbidity, must consider both of these conclusions to arrive at valid estimates and effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objective To better understand the hemodynamic and autonomic reflex abnormalities in heart-failure patients (HF), we investigated the influence of group III/IV muscle afferents on their ...cardiovascular response to rhythmic exercise. Methods Nine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27 ± 3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents. Results Cardiac-output ( Q ) and femoral blood-flow ( QL ) were determined, and arterial/venous blood samples collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8–13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p < 0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10–14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p < 0.05). Conclusion/practice/implications Although group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
BACKGROUNDSensitization of mechanosensitive afferents, which contribute to the exercise pressor reflex, has been recognized as a characteristic of patients with heart failure (HF); however, the ...hemodynamic implications of this hypersensitivity are unclear.
OBJECTIVESThe present study used passive leg movement (PLM) and intrathecal injection of fentanyl to blunt the afferent portion of this reflex arc to better understand the role of the mechanoreflex on central and peripheral hemodynamics in HF.
METHODSFemoral blood flow (FBF), mean arterial pressure, femoral vascular conductance, HR, stroke volume, cardiac output, ventilation, and muscle oxygenation of the vastus lateralis were assessed in 10 patients with New York Heart Association class II HF at baseline and during 3 min of PLM both with fentanyl and without (control).
RESULTSFentanyl had no effect on baseline measures but increased (control vs fentanyl, P < 0.05) the peak PLM-induced change in FBF (493 ± 155 vs 804 ± 198 ΔmL·min) and femoral vascular conductance (4.7 ± 2 vs 8.5 ± 3 ΔmL·min·mm Hg) while norepinephrine spillover (103% ± 19% vs 58% ± 17%Δ) and retrograde FBF (371 ± 115 vs 260 ± 68 ΔmL·min) tended to be reduced (P < 0.10). In addition, fentanyl administration resulted in greater PLM-induced increases in muscle oxygenation, suggestive of increased microvascular perfusion. Fentanyl had no effect on the ventilation, mean arterial pressure, HR, stroke volume, or cardiac output response to PLM.
CONCLUSIONSAlthough movement-induced central hemodynamics were unchanged by afferent blockade, peripheral hemodynamic responses were significantly enhanced. Thus, in patients with HF, a heightened mechanoreflex seems to augment peripheral sympathetic vasoconstriction in response to movement, a phenomenon that may contribute to exercise intolerance in this population.
We aimed to investigate if declines in youth's mental health during lockdown were dependent on housing condition among 7445 youth (median age ~ 20 years) from the Danish National Birth Cohort (DNBC), ...with data collected at 18 years of age and again three weeks into the first national lockdown (April 2020). We examined associations between housing conditions (access to outdoor spaces, urbanicity, household density, and household composition) and changes in mental health (mental well-being, Quality of Life (QoL) and loneliness). We report results from multivariate linear and logistic regression models. Youth without access to outdoor spaces experienced greater declines in mental well-being (vs. garden; mean difference: - 0·75 (95% CI - 1·14, - 0·36)), and correspondingly greater odds of onset of low mental well-being (vs. garden; OR: 1·72 (95% CI 1·20, 2·48)). Youth in higher density households vs. below median or living alone vs. with parents only also had greater odds of onset of low mental well-being (OR: 1·26 (95% CI 1·08, 1·46) and OR: 1·62 (95% CI 1·17, 2·23), respectively). Living in denser households (vs. below median; OR: 1·18 (95% CI 1·06, 1·33), as well as living alone (vs. with parents; OR: 1·38 (95% CI 1·04, 1·82) was associated with onset of low QoL. Living alone more than doubled odds of onset of loneliness compared to living with parents, OR: 2·12 (95% CI 1·59, 2·82). Youth living alone, in denser households, and without direct access to outdoor spaces may be especially vulnerable to mental health declines.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The vasodilatory response to passive leg movement (PLM) appears to provide a novel, noninvasive assessment of vascular function. However, PLM has yet to be compared with the established noninvasive ...assessment of vascular health, flow-mediated dilation (FMD). Therefore, as an initial evaluation of the construct validity of PLM and upright seated and supine PLM as well as brachial (BA) and superficial femoral (SFA) artery FMDs were performed in 10 young (22 ± 1) and 30 old (73 ± 2) subjects. During upright seated PLM, the peak change in leg blood flow (ΔLBF) and leg vascular conductance (ΔLVC) was significantly correlated with BA (r = 0.57 and r = 0.66) and SFA (r = 0.44 and r = 0.41, ΔLBF and ΔLVC, respectively) FMD. Furthermore, although the relationships were not as strong, the supine PLM response was also significantly correlated with BA (r = 0.38 and r = 0.35) and SFA (r = 0.39 and r = 0.35, ΔLBF and ΔLVC, respectively) FMD. Examination of the young and old separately, however, revealed that significant relationships persisted in both groups only for the upright seated PLM response and BA FMD (young: r = 0.73 and r = 0.77; old: r = 0.35 and r = 0.45, ΔLBF and ΔLVC, respectively). Normalizing FMD for shear rate during PLM abrogated all significant relationships between the PLM and FMD response, suggesting a role for nitric oxide (NO) in these associations. Collectively, these data indicate that PLM, particularly upright seated PLM, likely provides an index of vascular health analogous to the traditional FMD test. Given the relative ease of PLM implementation, these data have important positive implications for PLM as a clinical vascular health assessment.
Many studies have investigated the impact of the COVID-19 pandemic on mental health. Throughout the pandemic, time spent at home increased to a great extent due to restrictive measures. Here we set ...out to investigate the relationship between housing conditions and the mental health of populations across European countries. We analyzed survey data collected during spring 2020 from 69,136 individuals from four cohorts from Denmark, France, and the UK. The investigated housing conditions included household density, composition, and crowding, access to outdoor facilities, dwelling type, and urbanicity. The outcomes were loneliness, anxiety, and life satisfaction. Logistic regression models were used, and results were pooled using random-effects meta-analysis. In the meta-analysis, living alone was associated with higher levels of loneliness (OR = 3.08, 95% CI 1.87-5.07), and lower life satisfaction (OR = 1.27, 95% CI 1.05-0.55), compared to living with others. Not having access to an outdoor space and household crowding were suggestively associated with worse outcomes. Living in crowded households, living alone, or lacking access to outdoor facilities may be particularly important in contributing to poor mental health during a lockdown. Addressing the observed fundamental issues related to housing conditions within society will likely have positive effects in reducing social inequalities, as well as improving preparedness for future pandemics.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Post-cuff occlusion flow-mediated dilation (FMD) is a proposed indicator of nitric oxide (NO) bioavailability and vascular function. FMD is reduced in patients with sepsis and may be a marker of end ...organ damage and mortality. However, FMD likely does not solely reflect NO-mediated vasodilation, is technically challenging, and often demonstrates poor reproducibility. In contrast, passive leg movement (PLM), a novel methodology to assess vascular function, yields a hyperemic response that is predominately NO-dependent, reproducible, and easily measured. This study evaluated PLM as an approach to assess NO-mediated vascular function in patients with sepsis. We hypothesized that PLM-induced hyperemia, quantified by the increase in leg blood flow (LBF), would be attenuated in sepsis. In a cross-sectional study, 17 subjects in severe sepsis or septic shock were compared with 16 matched healthy controls. Doppler ultrasound was used to assess brachial artery FMD and the hyperemic response to PLM in the femoral artery. FMD was attenuated in septic compared with control subjects (1.1 ± 1.7% vs. 6.8 ± 1.3%; values are means ± SD). In terms of PLM, baseline LBF (196 ± 33 ml/min vs. 328 ± 20 ml/min), peak change in LBF from baseline (133 ± 28 ml/min vs. 483 ± 86 ml/min), and the LBF area under the curve (16 ± 8.3 vs. 143 ± 33) were all significantly attenuated in septic subjects. Vascular function, as assessed by both FMD and PLM, is attenuated in septic subjects compared with controls. These data support the concept that NO bioavailability is attenuated in septic subjects, and PLM appears to be a novel and feasible approach to assess NO-mediated vascular function in sepsis.
To better understand the mechanisms contributing to reduced blood flow with age, this study sought to elucidate the impact of altered femoral perfusion pressure (FPP) on movement-induced hyperemia. ...Passive leg movement was performed in 10 young (22 ± 1 yr) and 12 old (72 ± 2 yr) healthy men for 2 min, with and without a posture-induced change in FPP (~7 ± 1 ΔmmHg). Second-by-second measurements of central and peripheral hemodynamic responses were acquired noninvasively (finger photoplethysmography and Doppler ultrasound, respectively), with FPP confirmed in a subset of four young and four old subjects with arterial and venous catheters. Central hemodynamic responses (heart rate, stroke volume, cardiac output, mean arterial pressure) were not affected by age or position. The young exhibited a ~70% greater movement-induced peak change in leg blood flow (ΔLBF(peak)) in the upright-seated posture (supine: 596±68 ml/min; upright: 1,026 ± 85 ml/min). However, in the old the posture change did not alter ΔLBF(peak) (supine: 417±42 ml/min; upright: 412±56 ml/min), despite the similar increases in FPP. Similarly, movement-induced peak change in leg vascular conductance was ~80% greater for the young in the upright-seated posture (supine: 7.1 ± 0.8 ml·min(-1)·mmHg(-1); upright: 12.8 ± 1.3 ml·min(-1)·mmHg(-1)), while the old again exhibited no difference between postures (supine: 4.7 ± 0.4 ml·min(-1)·mmHg(-1); upright: 4.8 ± 0.5 ml·min(-1)·mmHg(-1)). Thus this study reveals that, unlike the young, increased FPP does not elicit an increase in movement-induced hyperemia or vasodilation in the old. In light of recent evidence that the majority of the first minute of passive movement-induced hyperemia is predominantly nitric oxide (NO) dependent in the young, these findings in the elderly may be largely due to decreased NO bioavailability, but this remains to be definitively determined.