Zoonotic diseases, caused by pathogens transmitted between other vertebrate animals and humans, pose a major risk to human health. Rodents are important reservoir hosts for many zoonotic pathogens, ...and rodent population dynamics affect the infection dynamics of rodent-borne diseases, such as diseases caused by hantaviruses. However, the role of rodent population dynamics in determining the infection dynamics of rodent-associated tick-borne diseases, such as Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato bacteria, have gained limited attention in Northern Europe, despite the multiannual abundance fluctuations, the so-called vole cycles, that characterise rodent population dynamics in the region. Here, we quantify the associations between rodent abundance and LB human cases and Puumala Orthohantavirus (PUUV) infections by using two time series (25-year and 9-year) in Finland. Both bank vole (Myodes glareolus) abundance as well as LB and PUUV infection incidence in humans showed approximately 3-year cycles. Without vector transmitted PUUV infections followed the bank vole host abundance fluctuations with two-month time lag, whereas tick-transmitted LB was associated with bank vole abundance ca. 12 and 24 months earlier. However, the strength of association between LB incidence and bank vole abundance ca. 12 months before varied over the study years. This study highlights that the human risk to acquire rodent-borne pathogens, as well as rodent-associated tick-borne pathogens is associated with the vole cycles in Northern Fennoscandia, yet with complex time lags.
Anthropogenic changes to land use drive concomitant changes in biodiversity, including that of the soil microbiota. However, it is not clear how increasing intensity of human disturbance is reflected ...in the soil microbial communities. To address this issue, we used amplicon sequencing to quantify the microbiota (bacteria and fungi) in the soil of forests (n = 312) experiencing four different land uses, national parks (set aside for nature conservation), managed (for forestry purposes), suburban (on the border of an urban area) and urban (fully within a town or city), which broadly represent a gradient of anthropogenic disturbance. Alpha diversity of bacteria and fungi increased with increasing levels of anthropogenic disturbance, and was thus highest in urban forest soils and lowest in the national parks. The forest soil microbial communities were structured according to the level of anthropogenic disturbance, with a clear urban signature evident in both bacteria and fungi. Despite notable differences in community composition, there was little change in the predicted functional traits of urban bacteria. By contrast, urban soils exhibited a marked loss of ectomycorrhizal fungi. Soil pH was positively correlated with the level of disturbance, and thus was the strongest predictor of variation in alpha and beta diversity of forest soil communities, indicating a role of soil alkalinity in structuring urban soil microbial communities. Hence, our study shows how the properties of urban forest soils promote an increase in microbial diversity and a change in forest soil microbiota composition.
High resting heart rate is a cardiovascular risk factor, but limited data exist on the underlying hemodynamics and reproducibility of supine-to-upright increase in heart rate. We recorded noninvasive ...hemodynamics in 574 volunteers age, 44.9 yr; body mass index (BMI), 26.4 kg/m
; 49% male during passive head-up tilt (HUT) using whole body impedance cardiography and radial artery tonometry. Heart rate regulation was evaluated using heart rate variability (HRV) analyses. Comparisons were made between quartiles of supine-to-upright heart rate changes, in which heart rate at rest ranged 62.6-64.8 beats/min (
= 0.285). The average upright increases in heart rate in the
were 4.7, 9.9, 13.5, and 21.0 beats/min, respectively (
< 0.0001). No differences were observed in the low-frequency power of HRV, whether in the supine or upright position, or in the high-frequency power of HRV in the supine position. Upright high-frequency power of HRV was highest in
with lowest upright heart rate and lowest in
with highest upright heart rate. Mean systolic blood pressure before and during HUT (126 vs. 108 mmHg) and the increase in systemic vascular resistance during HUT (650 vs. 173 dyn·s/cm
/m
) were highest in
and lowest in
. The increases in heart rate during HUT on three separate occasions several weeks apart were highly reproducible (
= 0.682) among 215 participants. To conclude, supine-to-upright increase in heart rate is a reproducible phenotype with underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. As heart rate at rest influences prognosis, future research should elucidate the prognostic significance of these phenotypic differences.
Subjects with similar supine heart rates are characterized by variable increases in heart rate during upright posture. Individual heart rate increases in response to upright posture are highly reproducible as hemodynamic phenotypes and present underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. These results indicate that resting heart rate obtained in the supine position alone is not an optimal means of classifying people into groups with differences in cardiovascular function.
Most studies about upright regulation of blood pressure have focused on orthostatic hypotension despite the diverse hemodynamic changes induced by orthostatic challenge. We investigated the effect of ...passive head-up tilt on aortic blood pressure.
Noninvasive peripheral and central hemodynamics in 613 volunteers without cardiovascular morbidities or medications were examined using pulse wave analysis, whole-body impedance cardiography and heart rate variability analysis.
In all participants, mean aortic SBP decreased by -4 (-5 to -3) mmHg mean (95% confidence intervals) and DBP increased by 6 (5--6) mmHg in response to upright posture. When divided into tertiles according to the supine-to-upright change in aortic SBP, two tertiles presented with a decrease -15 (-14 to -16) and -4 (-3 to -4) mmHg, respectively whereas one tertile presented with an increase +7 (7-- 8) mmHg in aortic SBP. There were no major differences in demographic characteristics between the tertiles. In regression analysis, the strongest explanatory factors for upright changes in aortic SBP were the supine values of, and upright changes in systemic vascular resistance and cardiac output, and supine aortic SBP.
In participants without cardiovascular disease, the changes in central SBP during orthostatic challenge are not uniform. One-third presented with higher upright than supine aortic SBP with underlying differences in the regulation of systemic vascular resistance and cardiac output. These findings emphasize that resting blood pressure measurements give only limited information about the blood pressure status.
Some people have characteristics of both asthma and COPD (asthma-COPD overlap), and evidence suggests they experience worse outcomes than those with either condition alone.
What is the genetic ...architecture of asthma-COPD overlap, and do the determinants of risk for asthma-COPD overlap differ from those for COPD or asthma?
We conducted a genome-wide association study in 8,068 asthma-COPD overlap case subjects and 40,360 control subjects without asthma or COPD of European ancestry in UK Biobank (stage 1). We followed up promising signals (P < 5 × 10–6) that remained associated in analyses comparing (1) asthma-COPD overlap vs asthma-only control subjects, and (2) asthma-COPD overlap vs COPD-only control subjects. These variants were analyzed in 12 independent cohorts (stage 2).
We selected 31 independent variants for further investigation in stage 2, and discovered eight novel signals (P < 5 × 10–8) for asthma-COPD overlap (meta-analysis of stage 1 and 2 studies). These signals suggest a spectrum of shared genetic influences, some predominantly influencing asthma (FAM105A, GLB1, PHB, TSLP), others predominantly influencing fixed airflow obstruction (IL17RD, C5orf56, HLA-DQB1). One intergenic signal on chromosome 5 had not been previously associated with asthma, COPD, or lung function. Subgroup analyses suggested that associations at these eight signals were not driven by smoking or age at asthma diagnosis, and in phenome-wide scans, eosinophil counts, atopy, and asthma traits were prominent.
We identified eight signals for asthma-COPD overlap, which may represent loci that predispose to type 2 inflammation, and serious long-term consequences of asthma.
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Elevated level of plasma uric acid (PUA) has been associated with cardiovascular disease, but whether uric acid is an independent risk factor or merely a marker remains controversial.
We investigated ...in a cross-sectional setting the association of PUA with hemodynamics in 606 normotensive and never-medicated hypertensive subjects (295 men, 311 women, age range 19-73 years) without cardiovascular disease or gout. In all except 15 individuals, PUA was within the normal range. Supine hemodynamics were recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis.
The mean concentrations of PUA in age, sex and body mass index adjusted quartiles were 234, 278, 314, and 373 µmol/l, respectively. The highest PUA quartile presented with higher aortic to popliteal pulse wave velocity (PWV) than the lowest quartile (8.7 vs. 8.2 m/s, p = 0.026) in analyses additionally adjusted for plasma concentrations of C-reactive protein, low density lipoprotein cholesterol, triglycerides, and mean aortic blood pressure. No differences in radial and aortic blood pressure, wave reflections, heart rate, cardiac output, and systemic vascular resistance were observed between the quartiles. In linear regression analysis, PUA was an independent explanatory factor for PWV (β = 0.168, p < 0.001, R
of the model 0.591), but not for systolic or diastolic blood pressure. When the regression analysis was performed separately for men and women, PUA was an independent predictor of PWV in both sexes.
PUA concentration was independently and directly associated with large arterial stiffness in individuals without cardiovascular disease and PUA levels predominantly within the normal range. Trial registration ClinicalTrials.gov NCT01742702.
The research of rare and devastating orphan diseases, such as idiopathic pulmonary fibrosis (IPF) has been limited by the rarity of the disease itself. The prognosis is poor—the prevalence of IPF is ...only approximately four times the incidence, limiting the recruitment of patients to trials and studies of the underlying biology. Global biobanking efforts can dramatically alter the future of IPF research. We describe a large-scale meta-analysis of IPF, with 8,492 patients and 1,355,819 population controls from 13 biobanks around the globe. Finally, we combine this meta-analysis with the largest available meta-analysis of IPF, reaching 11,160 patients and 1,364,410 population controls. We identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to European ancestry individuals. We observe notable pleiotropy across IPF susceptibility and severe COVID-19 infection and note an unexplained sex-heterogeneity effect at the strongest IPF locus MUC5B.
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•IPF meta-analysis across 6 ancestries with 11,160 cases and 1.4 M controls•Seven novel IPF loci—only one found if restricted to individuals of European ancestry•Genetic overlap with severe COVID-19: Rg ∼ 0.35, p = 0.001•Two-fold higher effect size estimates in clinical cohorts compared with biobanks
Partanen et al. present a multi-ancestry IPF meta-analysis with 11,160 cases and 1.4 M controls. They identify seven novel genome-wide significant loci, only one of which would have been identified if the analysis had been limited to Europeans. They also report notable pleiotropy across IPF susceptibility and severe COVID-19 infection.
High resting heart rate (HR) is associated with increased cardiovascular risk in general populations, possibly due to elevated blood pressure (BP) or sympathetic over-activity. We studied the ...association of resting HR with cardiovascular function, and examined whether the hemodynamics remained similar during passive head-up tilt.
Hemodynamics were recorded using whole-body impedance cardiography and continuous radial pulse wave analysis in 522 subjects (age 20-72 years, 261 males) without medication influencing HR or BP, or diagnosed diabetes, coronary artery, renal, peripheral arterial, or cerebrovascular disease. Correlations were calculated, and results analysed according to resting HR tertiles.
Higher resting HR was associated with elevated systolic and diastolic BP, lower stroke volume but higher cardiac output and work, and lower systemic vascular resistance, both supine and upright (p < 0.05 for all). Subjects with higher HR also showed lower supine and upright aortic pulse pressure and augmentation index, and increased resting pulse wave velocity (p < 0.001). Upright stroke volume decreased less in subjects with highest resting HR (p < 0.05), and cardiac output decreased less in subjects with lowest resting HR (p < 0.009), but clear hemodynamic differences between the tertiles persisted both supine and upright.
Supine and upright hemodynamic profile associated with higher resting HR is characterized by higher cardiac output and lower systemic vascular resistance. Higher resting HR was associated with reduced central wave reflection, in spite of elevated BP and arterial stiffness. The increased cardiac workload, higher BP and arterial stiffness, may explain why higher HR is associated with less favourable prognosis in populations.
Augmentation index, a marker of central wave reflection, is influenced by age, sex, height, blood pressure, heart rate, and arterial stiffness. However, the detailed haemodynamic determinants of ...augmentation index, and their relations, remain uncertain. We examined the association of augmentation index with vascular resistance and other haemodynamic and non-haemodynamic factors.
Background information, laboratory values, and haemodynamics of 488 subjects (239 men, 249 women) without antihypertensive medication were obtained. Indices of central wave reflection, systemic vascular resistance, cardiac function, and pulse wave velocity were measured using continuous radial pulse wave analysis and whole-body impedance cardiography.
In a regression model including only haemodynamic variables, augmentation index in males and female subjects, respectively, was associated with systemic vascular resistance (β = 0.425, β = 0.336), pulse wave velocity (β = 0.409, β = 0.400) (P < 0.001 for all), stroke volume (β = 0.256, β = 0.278) (P = 0.001 for both) and heart rate (β = -0.150, β = -0.156) (P = 0.049 and P = 0.036). When age, height, weight, smoking habits, and laboratory values were included in the regression model, the most significant explanatory variables for augmentation index in males and females, respectively, were age (β = 0.577, β = 0.557) and systemic vascular resistance (β = 0.437, β = 0.295) (P < 0.001 for all). In the final regression model, pulse wave velocity was not a significant explanatory variable for augmentation index, probably due to the high correlation of this variable with age (Spearman's correlation ≥0.617).
Augmentation index is strongly associated with systemic vascular resistance in addition to arterial stiffness.
ClinicalTrials.gov, NCT01742702 .
Hypertension is characterized by increased vascular resistance and arterial stiffness, but information about upright hemodynamics is scarce. We compared hemodynamics in hypertensive versus ...normotensive patients at rest and during passive head-up tilt.
Volunteers (n = 387, 19-72 years) without antihypertensive medication were recorded using continuous tonometric pulse wave analysis and whole-body impedance cardiography. Seated office blood pressure was 4/10 mmHg (systolic/diastolic) higher than average supine values during hemodynamic measurements. As there is no accepted cut-off for hypertension during tilt-table tests, supine level at least 135/85 mmHg defined hypertension (n = 155) versus normotension (n = 232). Age, BMI, and proportion of men were higher among hypertensives (49 vs. 42 years, 28 vs. 25, 55 vs. 38%, respectively), and analyses were adjusted for these differences.
Both at rest and during head-up tilt radial and aortic blood pressure and pulse pressure, cardiac index (CI) and work, systemic vascular resistance (SVR), and augmentation pressure were higher in hypertensive patients (P < 0.05 for all). Adjusted linear regression analyses showed that during passive head-up tilt aortic SBP and pulse pressure, stroke index, and left cardiac work index decreased less; heart rate increased less; and aortic DBP and SVR increased more in hypertensive patients (P < 0.05 for all); whereas reduction in CI and augmentation index did not differ between the groups.
Not only supine hemodynamics, but also responses to head-up tilt differed between normotensive and hypertensive patients, indicating functional alterations beyond increased vascular resistance and higher arterial stiffness in hypertension.
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