Circulating biomarkers predicting longitudinal changes in left ventricular structure and function in a general population

Background Serial imaging studies in the general population remain important to evaluate the usefulness of pathophysiologically relevant biomarkers in predicting progression of left ventricular (LV) remodeling and dysfunction. Here, we assessed in a general population whether these circulating biomarkers at baseline predict longitudinal changes in LV structure and function. Methods and Results In 592 participants (mean age, 50.8 years; 51.4% women; 40.5% hypertensive), we derived echocardiographic indexes reflecting LV structure and function at baseline and after 4.7 years. At baseline, we measured alkaline phosphatase, markers of collagen turnover (procollagen type I, C‐terminal telopeptide, matrix metalloproteinase‐1) and high‐sensitivity cardiac troponin T. We regressed longitudinal changes in LV indexes on baseline biomarker levels and reported standardized effect sizes as a fraction of the standard deviation of LV change. After full adjustment, a decline in LV longitudinal strain (−14.2%) and increase in E/e′ ratio over time (+18.9%; P≤0.019) was associated with higher alkaline phosphatase activity at baseline. Furthermore, longitudinal strain decreased with higher levels of collagen I production and degradation at baseline (procollagen type I, −14.2%; C‐terminal telopeptide, −16.4%; P≤0.029). An increase in E/e′ ratio over time was borderline associated with lower matrix metalloproteinase‐1 (+9.8%) and lower matrix metalloproteinase‐1/tissue inhibitor of metalloproteinase‐1 ratio (+11.9%; P≤0.041). Higher high‐sensitivity cardiac troponin T levels at baseline correlated significantly with an increase in relative wall thickness (+23.1%) and LV mass index (+18.3%) during follow‐up (P≤0.035). Conclusions We identified a set of biomarkers predicting adverse changes in LV structure and function over time. Circulating biomarkers reflecting LV stiffness, injury, and collagen composition might improve the identification of subjects at risk for subclinical cardiac maladaptation

Association between cognition and the retinal microvasculature in 11-year old children born preterm or at term

Background: Retinal microvessels can be visualized non-invasively and mirror the status of the cerebral microvasculature. Aims: To investigate whether in young children born prematurely or at term cognitive performance is related to retinal microvascular traits. Study design, subjects: In 93 prematurely born infants (birth weight < 1000 g) and 87 controls born at term, we measured head circumference (HC) and determined intelligence quotient (IQ) by combining matrix reasoning and spatial span (Wechsler Non-Verbal test, Dutch version) and post-processed retinal photographs using Singapore I Vessel Assessment software (version 3.6). Outcome measures, results: Compared with controls, cases had smaller HC (51.7 vs 53.4 cm; p < 0.001), lower IQ (93.9 vs 109.2; p < 0.001), smaller retinal arteriolar (CRAE; 162.7 vs 174.0 μm; p < 0.001) and venular (CRVE; 234.9 vs 242.8 μm; p = 0.003) diameters and CRAE/CRVE ratio (0.69 vs 0.72; p = 0.001). A 1-SD decrease in CRAE was associated with smaller HC (−0.53 cm; p < 0.001) and lower total IQ (−3.74; p < 0.001), matrix reasoning (−1.77; p = 0.004) and spatial span (−2.03; p = 0.002). These associations persisted after adjustment for sex and age and risk factors for cognitive impairment, including blood pressure, body mass index and parental educational attainment. Conclusions: HC, total IQ, matrix reasoning and spatial span decrease with smaller retinal arteriolar diameter. Our findings suggest that maldevelopment of the cerebral microcirculation, as mirrored by the retinal microvasculature, has lasting effects on the growth of the brain and cognitive performance of prematurely born children

Conventional and ambulatory blood pressure as predictors of diastolic left ventricular function in a Flemish population

Background--No longitudinal study compared associations of echocardiographic indexes of diastolic left ventricular function studies with conventional (CBP) and daytime ambulatory (ABP) blood pressure in the general population. Methods and Results--In 780 Flemish (mean age, 50.2 years; 51.7% women), we measured left atrial volume index (LAVI), peak velocities of the transmitral blood flow (E) and mitral annular movement (e0) in early diastole and E/e0 9.6 years (median) after CBP and ABP. In adjusted models including CBP and ABP, we expressed associations per 10/5-mm Hg systolic/diastolic blood pressure increments. LAVI and E/e0 were 0.65/0.40 mL/m2 and 0.17/0.09 greater with higher systolic/diastolic ABP (P≤0.028), but not with higher baseline CBP (P≤0.086). e0 was lower (P≤0.032) with higher diastolic CBP (-0.09 cm/s) and ABP (-0.19 cm/s). When we substituted baseline CBP by CBP recorded concurrently with echocardiography, LAVI and E/e0 remained 0.45/0.38 mL/m2 and 0.15/0.08 greater with baseline ABP (P≤0.036), while LAVI (+0.53 mL/m2) and E/e0 (+0.19) were also greater (P < 0.001) in relation to concurrent systolic CBP. In categorized analyses of baseline data, sustained hypertension or masked hypertension compared with normotension or white-

Plasmon-phonon coupling in large-area graphene dot and antidot arrays

Nanostructured graphene on SiO2 substrates pave the way for enhanced light-matter interactions and explorations of strong plasmon-phonon hybridization in the mid-infrared regime. Unprecedented large-area graphene nanodot and antidot optical arrays are fabricated by nanosphere lithography, with structural control down to the sub-100 nanometer regime. The interaction between graphene plasmon modes and the substrate phonons is experimentally demonstrated and structural control is used to map out the hybridization of plasmons and phonons, showing coupling energies of the order 20 meV. Our findings are further supported by theoretical calculations and numerical simulations.Comment: 7 pages including 6 figures. Supporting information is available upon request to author

Reproducibility of Retinal Microvascular Traits Decoded by the Singapore i Vessel Assessment Software Across the Human Age Range

Retinal microvascular traits predict adverse health outcomes. The Singapore I Vessel Assessment (SIVA) software improved automated postprocessing of retinal photographs. In addition to microvessel caliber, it generates measure

Aspirin use is associated with increased risk for incident heart failure: a patient-level pooled analysis

Aims: Recent trials evaluating the effect of aspirin in the primary prevention of cardiovascular disease showed little or no benefit. However, the role of aspirin on the risk of incident heart failure (HF) remains elusive. This study aimed to evaluate the role of aspirin use on HF incidence in primary and secondary prevention and whether aspirin use increases the risk of incident HF in patients at risk. Methods and results: Data from 30 827 patients at risk for HF enrolled in six observational studies were analysed [women 33.9%, mean age (±standard deviation) 66.8 ± 9.2 years]. Cardiovascular risk factors and aspirin use were recorded at baseline, and patients were followed up for the first incident of fatal or non-fatal HF. The association of incident HF with aspirin use was assessed using multivariable-adjusted proportional hazard regression, which accounted for study and cardiovascular risk factors. Over 5.3 years (median; 5th–95th percentile interval, 2.1–11.7 years), 1330 patients experienced HF. The fully adjusted hazard ratio (HR) associated with aspirin use was 1.26 [95% confidence interval (CI) 1.12–1.41; P ≤ 0.001]. Further, in a propensity-score-matched analysis, the HR was 1.26 (95% CI 1.10–1.44; P ≤ 0.001). In 22 690 patients (73.6%) without history of cardiovascular disease, the HR was 1.27 (95% CI 1.10–1.46; P = 0.001). Conclusions: In patients, at risk, aspirin use was associated with incident HF, independent of other risk factors. In the absence of conclusive trial evidence, our observations suggest that aspirins should be prescribed with caution in patients at risk of HF or having HF

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk

Bilateral downregulation of Nav1.8 in dorsal root ganglia of rats with bone cancer pain induced by inoculation with Walker 256 breast tumor cells

<p>Abstract</p> <p>Background</p> <p>Rapid and effective treatment of cancer-induced bone pain remains a clinical challenge and patients with bone metastasis are more likely to experience severe pain. The voltage-gated sodium channel Nav1.8 plays a critical role in many aspects of nociceptor function. Therefore, we characterized a rat model of cancer pain and investigated the potential role of Nav1.8.</p> <p>Methods</p> <p>Adult female Wistar rats were used for the study. Cancer pain was induced by inoculation of Walker 256 breast carcinosarcoma cells into the tibia. After surgery, mechanical and thermal hyperalgesia and ambulation scores were evaluated to identify pain-related behavior. We used real-time RT-PCR to determine Nav1.8 mRNA expression in bilateral L4/L5 dorsal root ganglia (DRG) at 16-19 days after surgery. Western blotting and immunofluorescence were used to compare the expression and distribution of Nav1.8 in L4/L5 DRG between tumor-bearing and sham rats. Antisense oligodeoxynucleotides (ODNs) against Nav1.8 were administered intrathecally at 14-16 days after surgery to knock down Nav1.8 protein expression and changes in pain-related behavior were observed.</p> <p>Results</p> <p>Tumor-bearing rats exhibited mechanical hyperalgesia and ambulatory-evoked pain from day 7 after inoculation of Walker 256 cells. In the advanced stage of cancer pain (days 16-19 after surgery), normalized Nav1.8 mRNA levels assessed by real-time RT-PCR were significantly lower in ipsilateral L4/L5 DRG of tumor-bearing rats compared with the sham group. Western-blot showed that the total expression of Nav1.8 protein significantly decreased bilaterally in DRG of tumor-bearing rats. Furthermore, as revealed by immunofluorescence, only the expression of Nav1.8 protein in small neurons down regulated significantly in bilateral DRG of cancer pain rats. After administration of antisense ODNs against Nav1.8, Nav1.8 protein expression decreased significantly and tumor-bearing rats showed alleviated mechanical hyperalgesia and ambulatory-evoked pain.</p> <p>Conclusions</p> <p>These findings suggest that Nav1.8 plays a role in the development and maintenance of bone cancer pain.</p

ALMA Survey of Orion Planck Galactic Cold Clumps (ALMASOP) : How Do Dense Core Properties Affect the Multiplicity of Protostars?

During the transition phase from a prestellar to a protostellar cloud core, one or several protostars can form within a single gas core. The detailed physical processes of this transition, however, remain unclear. We present 1.3 mm dust continuum and molecular line observations with the Atacama Large Millimeter/submillimeter Array toward 43 protostellar cores in the Orion molecular cloud complex (lambda Orionis, Orion B, and Orion A) with an angular resolution of similar to 0.'' 35 (similar to 140 au). In total, we detect 13 binary/multiple systems. We derive an overall multiplicity frequency (MF) of 28% +/- 4% and a companion star fraction (CSF) of 51% +/- 6%, over a separation range of 300-8900 au. The median separation of companions is about 2100 au. The occurrence of stellar multiplicity may depend on the physical characteristics of the dense cores. Notably, those containing binary/multiple systems tend to show a higher gas density and Mach number than cores forming single stars. The integral-shaped filament of the Orion A giant molecular cloud (GMC), which has the highest gas density and hosts high-mass star formation in its central region (the Orion Nebula cluster), shows the highest MF and CSF among the Orion GMCs. In contrast, the lambda Orionis GMC has a lower MF and CSF than the Orion B and Orion A GMCs, indicating that feedback from H ii regions may suppress the formation of multiple systems. We also find that the protostars comprising a binary/multiple system are usually at different evolutionary stages.Peer reviewe