Relative Area Change Research Articles

Dynamic Ranges of Retinal Nerve Fiber and Optic Nerve Head Parameters Measured Using Optical Coherence Tomography in Glaucoma: A Longitudinal Study.

To evaluate the dynamic range of retinal nerve fiber layer (RNFL) and optic nerve head (ONH) parameters measured using optical coherence tomography (OCT) in conditions ranging from nonglaucomatous status to advanced glaucoma by longitudinal observation. A total of 15 eyes from 12 participants with glaucoma progression from a nonglaucomatous status to advanced glaucoma were included. The RNFL and ONH parameters were compared between the nonglaucomatous and advanced stages within the same eye. The absolute and relative changes in OCT parameters were analyzed. The median highest intraocular pressure was 42.5 mmHg (interquartile range, 37.5 to 54.5 mmHg), and the final mean deviation of the visual field test was -24.68 dB (interquartile range, -23.93 to -31.13 dB). The median relative changes in RNFL thickness were -40.6% in the overall area, and -51.9%, -21.4%, -51.1%, and -41.8% in the superior, nasal, inferior, and temporal quadrants, respectively (all p < 0.05). Relative changes in the rim area, disc area, average cup to disc ratio, vertical cup to disc ratio, and cup volume were -56.64%, 0.59%, 62.10%, 66.0%, and 337.90%, respectively (all p < 0.05, except for disc area with a p-value of 0.753). The dynamic range of the RNFL thickness ranged from 40.6% to 51.9%, and the dynamic range of the ONH parameters ranged from 56.64% to 337.90%. During the course of glaucoma progression, the cup volume showed the widest dynamic range. However, the disc area did not show significant changes.

PREDICTING LESION SHRINKAGE IN EYES WITH MYOPIC CHOROIDAL NEOVASCULARIZATION FROM FEATURES ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

To identify baseline morphological predictors of lesion shrinkage in eyes with myopic choroidal neovascularization (mCNV) treated with anti-vascular endothelial growth factor. This retrospective study included 46 eyes (41 consecutive patients) with active mCNV receiving anti-vascular endothelial growth factor treatment. Optical coherence tomography angiography was performed at baseline and 1 year after treatment. Quantitative features were obtained from optical coherence tomography angiography images using AngioTool software. Eyes were classified as "high shrinkage" or "low shrinkage" according to the median relative change in lesion area. Baseline quantitative morphological features associated with mCNV shrinkage were identified in univariate and multivariate analyses. The mCNV area was significantly smaller after 1 year ( P = 0.013), with a median relative change of -16.5%. The relative change in mCNV area was -48.3% in high-shrinkage eyes (n = 23) and -5.2% in low-shrinkage eyes (n = 23). High-shrinkage eyes had a smaller mCNV area ( P = 0.013), shorter total vessel length ( P = 0.023), and higher end point density ( P < 0.001). Multivariate analysis showed significant associations of high shrinkage with end point density (β = -0.037, P = 0.043) and previous anti-vascular endothelial growth factor treatment (β = 0.216, P = 0.029). Morphological features of neovascularization detected by optical coherence tomography angiography can predict lesion shrinkage in eyes with mCNV receiving anti-vascular endothelial growth factor therapy. Higher end point density contributed to shrinkage, particularly of treatment-naive lesions.

Epigenetic regulation at LRP1 risk locus for cardiovascular diseases and assessment of cellular function in hiPSC derived smooth muscle cells

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Research Council (ERC) Background/Introduction Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction in young and middle-aged women. A common genetic variant, rs11172113, located in LRP1 (low density lipoprotein receptor-related protein 1) first intron, was associated with several vascular diseases, including SCAD, coronary artery disease and migraine. However, the biological mechanisms through which rs11172113 influence LRP1 function in the context of non-atherosclerotic arterial lesions is not fully understood. Purpose We aim at defining the specific mechanisms of rs11172113 genotype affecting LRP1 expression in contractile smooth muscle cells (SMCs), leading to alterations of their physiological function. Methods We applied in silico functional annotation to select variants and measured their enhancer activity using luciferase reporter assay in rat primary SMCs (A7r5). We performed siRNA knockdown of LRP1 and 4 transcription factors (TFs) predicted to interact with rs11172113 in human induced pluripotent stem cells (iPSCs) derived SMCs, harboring either synthetic or contractile phenotype. We edited iPSCs prior to differentiation using CRISPR-Cas9 to generate 100 bp deletion of the enhancer region containing rs11172113. We also created frame-shift indels in exons 2 or 5 of LRP1 in iPSCs to create SMCs knockouts and differentiated into SMCs. We then performed a proteomic and transcriptomic characterization of LRP1 knockout effect in these iPSC derived SMCs. We used a computational method of cell tracking and relative cell surface area change to characterize the contractility of LRP1 knockout effect in these iPSC derived SMCs. We performed the assessment of fluo-4 labeled Ca2+ mobilization to characterize the ability of calcium release in iPSC derived SMCs after LPR1 knockout. Results Seven variants in LRP1 locus co-located with enhancer (histone marks) and open chromatin regions (ATAC-Seq peaks) in SMCs and arterial tissues. Reporter assay in rat SMCs confirmed that rs11172113 belongs to a genomic region showing enhancer activity in vitro. iPSCs with homozygous deletion of rs11172113 enhancer region presented the same pluripotency compared with wild type, and iPSC derived SMCs showed positive expression of specific markers for each phenotype (ACTA2, TAGLN for both, MYH11 for contractile SMCs and CALM2 for synthetic SMCs). We found that the deletion of rs11172113 enhancer region decreased the expression of LRP1 while LRP1 knockdown increased cell migration capacity in SMCs. Preliminary results in LRP1-knockout iPSC-derived SMCs suggest LRP1 to enhance the expression of cell contraction markers and decrease capacity of cell proliferation. Conclusions We confirmed rs11172113 to regulate LRP1 expression in iPSCs derived synthetic and contractile SMCs. Our results support LRP1 effect on SMCs cellular function alteration as a potential mechanism in genetic susceptibility for vascular disease.

36-OR: Bromocriptine Quick Release (BCQR) Improves Vascular Health in Youth with Type 1 Diabetes Even if Normal Weight

Background: Global vascular dysfunction is well-recognized in youth with type 1 diabetes (T1D) , accentuating lifetime cardiovascular event risk and making therapeutic strategies to mitigate vascular dysfunction a high priority. In the BCQR-T1D study, we tested the hypothesis that BCQR, a medication used in obese adults with type 2 diabetes, would improve vascular health in T1D youth. Methods: BCQR-T1D was a placebo-controlled, random-order, double-blinded, cross-over study investigating cardiovascular and metabolic impacts of BCQR in T1D. Youth were randomized 1:1 to phase-1: 4-weeks of BCQR or placebo after which blood pressure (BP) , peripheral vascular stiffness by brachial artery distensibility (BrachD) , and central aortic stiffness by pulse wave velocity (PWV) , relative area change (RAC) and distensibility from phase-contrast MRI, were performed. Following a 4-week washout period, phase 2 was performed in identical fashion with the alternate treatment. Results: Forty-two adolescents (mean age 15.9 years, HbA1c 8.6%, BMI %ile 71.4, T1D duration 5.8 years) with T1D were enrolled. Compared to placebo, BCQR therapy decreased systolic (∆ = -5 mmHg, p&amp;lt;0.001) and diastolic BP (∆ = -2 mmHg, p=0.039) . BCQR reduced ascending aortic (AA) PWV (∆ = -0.4 m/s, p=0.005) , and increased RAC (∆ = -2.6%, p=0.022) and distensibility (∆ = 0.%/mmHg, p=0.010) . In the thoraco-abdominal aorta, BCQR decreased PWV (∆ = -0.2 m/s, p=0.013) and increased distensibility (∆ = 0.%/mmHg, p=0.032) . Of interest, in the normal-weight participants, BCQR improved systolic BP (∆ = -5 [95.0%CI: -7, -1] mmHg, p= 0.009) , AA PWV (∆ = -0.4 [95.0%CI: -0.7, 0] m/s, p= 0.030) and BrachD (∆ = 0.56 %/mmHg, p=0.023) , and tended to improve AA distensibility (∆ = 0.[95.0%CI: -0.01, 0.19] %/mmHg, p= 0.084) . Conclusions: BCQR improved BP, central and peripheral aortic stiffness and pressure hemodynamics in T1D adolescents over 4 weeks vs. placebo, even if normal weight, supporting future longer-term studies. Disclosure M.Schäfer: None. I.E.Schauer: None. K.J.Nadeau: None. L.Browne: None. U.Truong: None. P.Bjornstad: Advisory Panel; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Horizon Therapeutics plc, LG Chem, Lilly, Novo Nordisk, Consultant; AstraZeneca, Bristol-Myers Squibb Company. J.K.Snell-bergeon: Stock/Shareholder; GlaxoSmithKline plc. A.Baumgartner: None. K.S.Hunter: None. J.Reusch: Advisory Panel; Medtronic. A.J.Barker: None. Funding JDRF BROM QR THERP3-SRA-2015-125-M-R

Port construction alters dune topography and coastal forest growth: A study on forest decline due to coastal erosion

Coastal forests are critical for protecting those living near the sea from wind, blown sand, salt spray, and tsunami. However, the sustainability of the coastal forest ecosystem is threatened by coastal erosion. To reveal the impact of erosion on coastal forest growth, we focused on the changes in coastal topography caused by port construction. The coastline has been advancing at the near side of a constructed port from the estuary (east) and retreating at the opposite (west) side since the 1980s in Ishikari, Japan. We conducted a transect survey, stem analysis, salt adhesion observation, and remote sensing analysis using airborne laser imaging detection and ranging data as well as an unmanned aerial vehicle. Results showed that the basal-area–weighted mean tree height in the east side was higher than that in the west side in 2019 and has increased by 2.82 m over the last 17 years. The tree height growth rate after the 2000s decreased in the west side, whereas the vigorous growth rate in the east side was maintained. The recent deposition of blown sand on the embryo dune was also detected on the east side. In contrast, the foredune was eroded, and the canopy height growth was inhibited toward several hundreds of meters inland from the seaward forest edge on the west side. The foredune erosion expanded from the point where the vegetation was destroyed, indicating the relevance of foredune vegetation in mitigating it. During winter, salt adhesion was higher in the eroded area, inhibiting canopy height growth. The most useful topographic variable to explain the spatial variability of the canopy height growth was the relative change in the cross-sectional area of the beach and dune upwind of the forest. These findings highlight the importance of monitoring vertical topographic changes in beach and foredune to evaluate the impact of coastal erosion on forest growth through airborne salt stress.

Short TE downfield magnetic resonance spectroscopy in a mouse model of brain glioma.

Enhanced cell proliferation in tumors can be associated with altered metabolic profiles and dramatic microenvironmental changes. Downfield magnetic resonance spectroscopy (MRS) has received increasing attention due to its ability to report on labile resonances of molecules not easily detected in upfield 1 H MRS. Image-selected-in-vivo-spectroscopy-relaxation enhanced MRS (iRE-MRS) was recently introduced for acquiring short echo-time (TE) spectra. Here, iRE-MRS was used to investigate in-vivo downfield spectra in glioma-bearing mice. Experiments were performed in vivo in an immunocompetent glioma mouse model at 9.4T using a cryogenic coil. iRE-MRS spectra were acquired in N=6 glioma-bearing mice (voxel size=2.23 mm3 ) and N=6 control mice. Spectra were modeled by a sum of Lorentzian peaks simulating known downfield resonances, and differences between controls and tumors were quantified using relative peak areas. Short TE tumor spectra exhibited large qualitative differences compared to control spectra. Most peaks appeared modulated, with strong attenuation of NAA (∼7.82, 7.86ppm) and changes in relative peak areas between 6.75 and 8.49ppm. Peak areas tended to be smaller for DF6.83 , DF7.60 , DF8.18 and NAA; and larger for DF7.95 and DF8.24 . Differences were also detected in signals resonating above 8.5ppm, assumed to arise from NAD+. In-vivo downfield 1 H iRE-MRS of mouse glioma revealed differences between controls and tumor bearing mice, including in metabolites which are not easily detectable in the more commonly investigated upfield spectrum. These findings motivate future downfield MRS investigations exploring pH and exchange contributions to these differences.

Impact of climatic abnormities and mitigating technologies on pigeonpea (Cajanus cajan) in central India

A study was carried out on changes in climate; area and productivity of pigeonpea (Cajanus cajan L.) over aperiod of three decades (1982–2016), and impact of climatic abnormalities and mitigation technologies on yield andeconomic benefits was seen. Long-term data on climate change showed that there is a trend of minimum and maximum temperature rise and a decrease in monthly total rainfall in summer and rainy season, while it increases in winter. Study also revealed the prominent disparity in area and productivity of pigeonpea of all agro-climatic zones of Madhya Pradesh (MP) and Chhattisgarh (CG). The absolute change (AC) and relative change (RC) in area of pigeonpea in MP and CG states increased by 34.66 thousand ha and 16.2% and increased productivity by 243.3 kg/ha and 65.4% compared with base years, respectively. Like-wise maximum AC in productivity was at Central Narmada Valley (CNV) and minimum at CG plains, while RC in productivity was maximum increased in Gird region and minimum in CG plains compared to base years. The crop sowing on bed with broad bed furrow (BBF) increased seed yield by 18.2% compared to flat land sowing method. The Fusarium wilt infestation was reduced with resistant cultivar along with seed treatment with Trichoderma harzianum and BBF sowing impacting on yield by 26.2%, whereas increased by 20.7% with control of phytophthora blight resistant cultivar sowing on BBF after seed treatment with Trichoderma viride, compared with existing practices (EP). Similarly control of pod borer with the use of IPM technology enhanced seed yield by 42.2% compared with EP. Results showed that adoption of improved techniques for mitigation of climatic abnormalities gave higher productivity, net returns and B:C ratio compared to EP.

Dynamics of Food Grains Production in Vidisha District of Madhya Pradesh

The examined the relative change in area, production and productivity of major foodgrain crops (paddy, sorghum, maize, pigeonpea, black gram, green gram, wheat, chickpea, peas and lentil) in Vidisha district of Madhya Pradesh. The relative change in area of green gram was noticed highest and wheat was observed lowest, although sorghum, maize, lentil and chickpea were observed negative. The relative change in production of paddy was highest as compared to other food grains, although sorghum and maize were found negative. The variability in area, production and productivity of paddy was highest as compared to other food grains. The growth rates in area of paddy, green gram, black gram, pigeonpea, wheat were observed positive and highly significant. The growth rates in area of sorghum, maize, lentil were noticed negative and highly significant. The growth rate in production of wheat, pigeonpea, black gram, and green gram were positive and highly significant while growth rate in production of sorghum was found negative and highly significant. The growth rate in productivity of paddy, wheat, black gram and lentil were found positive and highly significant

Abstract 14324: Low Pulmonary Venous Flow Drives Cpc-PH Development in a Pulmonary Venous Banding Swine Model of Cpc-PH

Introduction: Combined pre- and post-capillary pulmonary hypertension (Cpc-PH) is the most severe form of PH-LHF. While the impact of elevated left atrial and consequently elevated pulmonary venous (PV) pressure on Cpc-PH progression is well studied, little is known about how compromised PV flow secondary to LHF affects disease progression. To assess the hypothesis that decreased PV flow induces Cpc-PH, we developed a large animal model of Cpc-PH by decreasing PV flow independent of LHF. Methods: Survival pulmonary venous banding (PVB) surgery was performed on a large white male pig (9kg), which was then followed for 16 weeks. A pig of the same sex and weight underwent a sham operation as control. Both animals underwent cardiac 4D flow MRI and right heart catheterization (RHC) in a terminal study. Results: At 16 weeks post-surgery, MR imaging demonstrated that PVB decreased mean flow and peak velocity in the right (RIPV) and left inferior pulmonary veins (LIPV) and MPA (figure and table). PVB also decreased MPA relative area change (RAC) (table). RHC demonstrated elevated PCWP, mPAP, PVR, and decreased RV EF (table). Also, Fulton index was increased demonstrating RV hypertrophy (table). Discussion: In conclusion, this study utilized PVB to demonstrate the ability of decreased PV flow to drive Cpc-PH development in the absence of LHF. Our preliminary data suggest a low flow state in the lung can increase RV afterload and induce RV dysfunction. Further studies with a larger sample size are needed to confirm this pathomechanical mechanism. Figure. MRI image of PV confluence narrowing from the PVB. Insert shows flow rates from RIPV and LIPV (blue), across PVB (red), and into LA (green).

Metformin Prevents Low-dose Isoproterenol-induced Cardiac Dilatation and Systolic Dysfunction in Male Sprague Dawley Rats.

Myocardial metabolic abnormalities are well-recognized alterations in chronic heart failure, effects that may contribute to progressive cardiac dysfunction. However, whether metabolic alterations in-part mediate their deleterious effects by modifying the chronic impact of excess low-dose sympathetic stimulation on cardiac chamber dilatation is uncertain. We therefore aimed to determine the effect of metformin administration on cardiac function and mitochondrial architectural changes in a rat model of chronic sympathetic-induced left ventricular (LV) remodeling and systolic dysfunction [daily subcutaneous isoproterenol (ISO) injection at a low dose of 0.02 mg/kg for 7 months]. Echocardiography was used to assess in vivo LV dimensions and function, and mitochondrial and myofibril arrangement was assessed using transmission electron microscopy. Seven months of low-dose ISO administration increased LV diastolic diameter (in mm) [control (CONT): 7.29 ± 0.19 vs. ISO: 8.76 ± 0.21; P = 0.001], an effect that was attenuated by metformin (ISO + MET: 7.63 ± 0.29 vs. ISO: P = 0.001) administration. Similarly, ISO increased LV end-systolic diameter (CONT: 4.43 ± 0.16 vs. ISO: 5.49 ± 0.16: P < 0.0001), an effect prevented by metformin (ISO + MET: 4.04 ± 0.25 vs. ISO: P < 0.0001). Moreover, chronic ISO administration reduced LV endocardial fractional shortening (P = 0.0001), midwall fractional shortening (P = 0.0001), and ejection fraction (P = 0.0001), effects similarly prevented by metformin administration. Furthermore, changes in mitochondrial arrangement and relative mitochondrial area (CONT: 37.7 ± 2.2 vs. ISO: 28.1 ± 2.9; P = 0.05) were produced by ISO administration, effects prevented by metformin. In conclusion, metformin offers cardiac protection against chronic sympathetic-induced LV dilatation and systolic dysfunction. These data support a role for myocardial metabolic changes in mediating LV dilatation and LV dysfunction produced by chronic neurohumoral activation in cardiac disease.

The New Swiss Glacier Inventory SGI2016: From a Topographical to a Glaciological Dataset

Glaciers in Switzerland are shrinking rapidly in response to ongoing climate change. Repeated glacier inventories are key to monitor such changes at the regional scale. Here we present the new Swiss Glacier Inventory 2016 (SGI2016) that has been acquired based on sub-meter resolution aerial imagery and digital elevation models, bringing together topographical and glaciological approaches and knowledge. We define the process, workflow and required glaciological adaptations to compile a highly detailed inventory based on the digital Swiss Topographic Landscape model. The SGI2016 provides glacier outlines (areas), supraglacial debris cover and ice divides for all Swiss glaciers referring to the years 2013–2018. The SGI2016 maps 1,400 individual glacier entities with a total surface area of 961 ± 22 km2, whereof 11% (104 km2) are debris-covered. It constitutes the so far most detailed cartographic representation of glacier extent in Switzerland. Interpretation in the context of topographic parameters indicates that glaciers with moderate inclination and low median elevation tend to have highest fractions of supraglacial debris. Glacier-specific area changes since 1973 show the largest relative changes for small and low-elevation glaciers. The analysis further indicates a tendency for glaciers with a high share of supraglacial debris to show larger relative area changes. Between 1973 and 2016, an area change rate of –0.6% a−1 is found. Based on operational data sets and the presented methodology, the Swiss Glacier Inventory will be updated in 6-yr time intervals, leading to a high consistency in future glacier change assessments.

Reduction of Visceral Adiposity as a Predictor for Resolution of Nonalcoholic Fatty Liver in Potential Living Liver Donors.

This study aimed to determine the factors associated with resolution of nonalcoholic fatty liver (NAFL) after lifestyle intervention in potential living liver donors as assessed by the gold standards in a longitudinal setting. This retrospective study included 115 potential living liver donors (mean age, 30.5±7.5years; 101 men) with NAFL who underwent paired liver biopsies and abdominal computed tomography (CT) examinations before and after lifestyle intervention between January 2011 and December 2018. Anthropometry, laboratory parameters, body composition, and hepatic steatosis (HS) were evaluated before and after lifestyle intervention. Anthropometry, laboratory parameters, body composition, and HS were significantly decreased after lifestyle intervention (all, P<0.001). Relative changes in HS were weakly correlated with relative changes in the visceral fat area (VFA; r=0.278; P=0.003) and subcutaneous fat area (r=0.382; P<0.001), but not with body weight, body mass index, or skeletal muscle area. Patients with resolved NAFL after lifestyle intervention had significantly lower VFA at follow-up than those with persistent NAFL (mean ± standard deviation, 69.8±39.1 versus 91.5±41.4cm2 ; P=0.01). Multivariable logistic regression analysis demonstrated that the relative reduction of VFA (odds ratio per percent, 1.031; 95% confidence interval, 1.010-1.053; P=0.004) was a significant independent factor associated with resolved NAFL after lifestyle intervention. In potential living liver donors with NAFL, the reduction of VFA is a significant factor associated with the resolution of NAFL after lifestyle intervention.

Reassessing the role of cattle and pasture in Brazil's deforestation: A response to “Fire, deforestation, and livestock: When the smoke clears”

Silva et al. (Land Use Policy, 21 July 2020) offer an assessment of the links between deforestation, livestock production and exports in Brazil. Their analysis, based on relative changes in beef production and pasture area across the whole of Brazil, showed an “apparent decoupling of the link between beef production and deforestation in Brazil”. In reanalysing these links, we find that Silva et al. underestimate the strong, positive and significant associations between Brazilian livestock production and deforestation. Moreover, despite focusing the title, abstract and the beginning of their manuscript on the Amazon, their analyses are conducted at the national level, and fail to recognise marked differences in the development trajectories of Brazilian biomes, and that most of the recent pasture expansion in Brazil has replaced Amazonian forests. To progress any debate and aid decision-making regarding land-use changes in the Amazon, a region often in the spotlight and subjected to many debates that lack evidence, scientists must be open and scrupulous with their data sources and analyses.

Abnormal pulmonary flow is associated with impaired right ventricular coupling in patients with COPD.

Cor Pulmonale or right ventricular (RV) dysfunction due to pulmonary disease is an expected complication of COPD resulting primarily from increased afterload mediated by chronic alveolar hypoxemia and resulting hypoxic pulmonary vasoconstriction. Early detection of elevated RV afterload has been previously demonstrated by visualization of abnormal flow patterns in the proximal pulmonary arteries. Prior analysis of helicity in the pulmonary arteries in pulmonary hypertension patients has demonstrated a strong association between helicity and increased RV afterload. However, these flow hemodynamics have yet to be fully explored in patients with COPD. We hypothesized that patients with COPD will have abnormal pulmonary flow as evaluated by 4D-Flow MRI and associated with RV function and pulmonary arterial stiffness. Patients with COPD (n = 15) (65 years ± 6) and controls (n = 10) (58 years ± 9) underwent 4D-Flow MRI to calculate helicity. The helicity was calculated in the main pulmonary artery (MPA) and along the RV outflow tract (RVOT)-MPA axis. Main pulmonary arterial stiffness was measured using the relative area change (RAC). We found COPD patients had decreased helicity relative to healthy controls in the MPA (19.4 ± 7.8vs 32.8 ± 15.9, P = 0.007) and reduced helicity along the RVOT-MPA axis (33.2 ± 9.0 vs 43.5 ± 8.3, P = 0.010). Our investigation indicates a strong association between helicity along the MPA-RV outflow tract axis and RV function and suggests that 4D-Flow MRI might be a sensitive tool in evaluating RV-pulmonary arterial coupling in COPD.

Statin use, development of sarcopenia, and long-term survival after endovascular aortic repair

ObjectiveStatin therapy, associated with improved short-term survival after treatment of abdominal aortic aneurysms, may also predispose to muscle side effects. Evidence on statin-related sarcopenia is limited mainly to muscle function, and it is subject to several sources of bias. In the long term, postoperative development of sarcopenia is linked to mortality after endovascular repair (EVAR). We investigated statin use and long-term postoperative mortality after EVAR in relation to objective measurable markers of sarcopenia (psoas muscle surface area and density). MethodsAltogether 216 abdominal aortic aneurysm patients treated with EVAR between 2006 and 2014 at Tampere University Hospital (Finland) were retrospectively studied. Psoas muscle parameters at the L3 level were evaluated from baseline and mainly 1- to 3-year follow-up computed tomography studies. Cox regression was used to study the association between statin medication, psoas muscle changes, and all-cause mortality. ResultsThe majority of patients were male (87%), and the mean age was 77.7 years (standard deviation, 7.4). The median duration of follow-up was 6.3 years (interquartile range, 3.5) with a total mortality of 54.2% (n = 117). Regardless of a higher burden of comorbidities, statin users (n = 119) had lower mortality when compared with nonusers (multivariable hazard ratio [HR]: 0.69, 95% confidence interval: 0.48-0.99, P = .048). Furthermore, statin use was not associated with inferior muscle parameter values, and the relative change in psoas muscle area was actually lower in statin users compared with nonusers (−15.7% and −21.1%, P < .046). ConclusionsStatin use is associated with lower long-term mortality among patients undergoing EVAR without predisposing to increased sarcopenia.

Cardiovascular magnetic resonance predicts all-cause mortality in pulmonary hypertension associated with heart failure with preserved ejection fraction

This study aimed to determine the prognostic value of cardiovascular magnetic resonance (CMR) in patients with heart failure with preserved ejection fraction and associated pulmonary hypertension (pulmonary hypertension-HFpEF). Patients with pulmonary hypertension-HFpEF were recruited from the ASPIRE registry and underwent right heart catheterisation (RHC) and CMR. On RHC, the inclusion criteria was a mean pulmonary artery pressure (MPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure > 15 mmHg and, on CMR, a left atrial volume > 41 ml/m2 with left ventricular ejection fraction > 50%. Cox regression was performed to evaluate CMR against all-cause mortality. In this study, 116 patients with pulmonary hypertension-HFpEF were identified. Over a mean follow-up period of 3 ± 2 years, 61 patients with pulmonary hypertension-HFpEF died (53%). In univariate regression, 11 variables demonstrated association to mortality: indexed right ventricular (RV) volumes and stroke volume, right ventricular ejection fraction (RVEF), indexed RV mass, septal angle, pulmonary artery systolic/diastolic area and its relative area change. In multivariate regression, only three variables were independently associated with mortality: RVEF (HR 0.64, P < 0.001), indexed RV mass (HR 1.46, P < 0.001) and IV septal angle (HR 1.48, P < 0.001). Our CMR model had 0.76 area under the curve (P < 0.001) to predict mortality. This study confirms that pulmonary hypertension in patients with HFpEF is associated with a poor prognosis and we observe that CMR can risk stratify these patients and predict all-cause mortality. When patients with HFpEF develop pulmonary hypertension, CMR measures that reflect right ventricular afterload and function predict all-cause mortality.

On the (in)stability of sunspots

Context.The stability of sunspots is one of the long-standing unsolved puzzles in the field of solar magnetism and the solar cycle. The thermal and magnetic structure of the sunspot beneath the solar surface is not accessible through observations, thus processes in these regions that contribute to the decay of sunspots can only be studied through theoretical and numerical studies.Aims.We study the effects that destabilise and stabilise the flux tube of a simulated sunspot in the upper convection zone. The depth-varying effects of fluting instability, buoyancy forces, and timescales on the flux tube are analysed.Methods.We analysed a numerical simulation of a sunspot calculated with the MURaM code. The simulation domain has a lateral extension of more than 98 Mm × 98 Mm and extends almost 18 Mm below the solar surface. The analysed data set of 30 hours shows a stable sunspot at the solar surface. We studied the evolution of the flux tube at defined horizontal layers (1) by means of the relative change in perimeter and area, that is, its compactness; and (2) with a linear stability analysis.Results.The simulation shows a corrugation along the perimeter of the flux tube (sunspot) that proceeds fastest at a depth of about 8 Mm below the solar surface. Towards the surface and towards deeper layers, the decrease in compactness is damped. From the stability analysis, we find that above a depth of 2 Mm, the sunspot is stabilised by buoyancy forces. The spot is least stable at a depth of about 3 Mm because of the fluting instability. In deeper layers, the flux tube is marginally unstable. The stability of the sunspot at the surface affects the behaviour of the field lines in deeper layers by magnetic tension. Therefore the fluting instability is damped at depths of about 3 Mm, and the decrease in compactness is strongest at a depth of about 8 Mm. The more vertical orientation of the magnetic field and the longer convective timescale lead to slower evolution of the corrugation process in layers deeper than 10 Mm.Conclusions.The formation of large intrusions of field-free plasma below the surface destabilises the flux tube of the sunspot. This process is not visible at the surface, where the sunspot is stabilised by buoyancy forces. The onset of sunspot decay occurs in deeper layers, while the sunspot still appears stable in the photosphere. The intrusions eventually lead to the disruption and decay of the sunspot.

Insulin, but Not Metformin, Supports Wound Healing Process in Rats with Streptozotocin-Induced Diabetes.

PurposeOptimal glycemic control is crucial for proper wound healing in patients with diabetes. However, it is not clear whether other antidiabetic drugs support wound healing in mechanisms different from the normalization of blood glucose control. We assessed the effect of insulin and metformin administration on the wound healing process in rats with streptozotocin-induced diabetes.MethodsThe study was conducted on 200 male Wistar rats with streptozotocin-induced diabetes. In the last phase of the study, 45 rats, with the most stable glucose levels in the range of 350–500 mg/dL, were divided into three groups: group I received human non-protamine insulin subcutaneously (5 IU/kg body mass) once a day, group II received metformin intragastrically (500 mg/kg b.m.), and group III (control) was given saline subcutaneously. After 14 days of antidiabetic treatment, a 2 cm × 2 cm thin layer of skin was cut from each rat’s dorsum and a 4 cm disk with a hole in its center was sewn in to stabilize the skin and standardize the healing process. The wound healing process was followed up for 9 days, with assessment every 3 days. Biopsy samples were subjected to hematoxylin and eosin staining and immunohistochemical assays.ResultsAnalysis of variance revealed significant influence of treatment type (insulin, control, or metformin) on the relative change in wound surface area. The wound healing process in rats treated with insulin was more effective than in the metformin and control groups. Wound tissue samples taken from the insulin-treated animals presented significantly lower levels of inflammatory infiltration. Immunohistochemical assessment showed the greatest density of centers of proliferation Ki-67 in insulin-treated animals.ConclusionThese results suggest that an insulin-based treatment is more beneficial than metformin, in terms of accelerating the wound healing process in an animal model of streptozocin-induced diabetes.

Calculation of real growth current using variable electroactive area obtained during polypyrrole synthesis

Among the electrochemical methods, potentiostatic electrosynthesis is the most common method for polymer deposition. In this case, it is possible to avoid undesirable reactions occurring by controlling the synthesis potential. However, this method does not control the kinetics itself, since the measured current values are not real, due to the fact that the polymer surface area changes considerably during the polymerization. In this way, it is essential to develop a method to normalize the current using instantaneous area values to have precise data about the polymer growth. Then, this work describes a method to calculate the electroactive area change during the electrochemical polymerization. For this purpose, PPy films were synthesized electrochemically at different potentials to study their effect on the synthesis process. Electrochemical impedance data was taken in several growth charges to characterize the growth curve completely. Also, electrochemical quartz crystal microbalance (EQCM) and scanning electron microscopy (SEM) were used. Analyzing the impedance complemented with EQCM data, it was possible to obtain the relative area change during the polymer formation. Furthermore, with this information, it was possible to understand the steps that occur during the synthesis and relate them to the measured current curve, which was impossible before, since it is a function of an unknown area. Therefore, it has been observed that depending on the potential applied on potentiostatic synthesis, the deposition mechanism changes, which consequently modifies the polymer morphology, as well as electrochemical properties.

Serum copeptin and NT-proBNP is associated with central aortic stiffness and flow hemodynamics in adolescents with type 1 diabetes: A pilot study.

Cardiovascular disease (CVD) is the major cause of mortality in type 1 diabetes (T1D). Biomarkers, N-terminal pro-brain natriuretic peptide (NT-proBNP) and copeptin have been linked with measures of CVD, but their relationship in adolescents with T1D remains incompletely understood. Accordingly, we examined the associations between NT-proBNP and copeptin and hemodynamic markers of central aortic stiffness in adolescents with T1D. In this pilot study, forty-nine pubertal adolescents with T1D (mean age 17 ± 2 years, median [Q1-Q3] Tanner Stage 5 [5, 5] and HbA1c 8.5 ± 1.5%), from the EMERALD study, were assessed for copeptin and NT-proBNP, and indices of central aortic stiffness non-invasively assessed by MRI. Pearson correlations and generalized linear regression models, adjusting for confounders, were applied to examine the relationships between biomarkers and vascular measures. Copeptin correlated independently with both ascending aortic (AA) (β ± SE: -4.28 ± 1.87, p = 0.03) and descending aortic (DA) relative area change (RAC) (-3.41 ± 1.55, p = 0.04). NT-proBNP was independently associated with DA time-averaged wall shear stress (WSSTA) (0.87 ± 0.25, p = 0.001) and DA maximum wall shear stress (WSSmax) (2.45 ± 1.00, p = 0.02). Serum copeptin and NT-proBNP may be associated with central aortic stiffness and elevated WSS in youth with T1D, potentially offering a non-invasive way to identify and monitor the development of early CVD in an at-risk population.