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Ivan Pećin,1,2 Željko Reiner1,2 1Zagreb School of Medicine, University of Zagreb, Zagreb, Croatia; 2Division of Metabolic Diseases, Department of Internal Medicine, University Hospital Center, Zagreb, CroatiaCorrespondence: Željko ReinerDivision of Metabolic Diseases, Department of Internal Medicine, University Hospital Center Zagreb Kispaticeva 12, Zagreb, 10 000, CroatiaTel + 385 1 2388772Fax + 385 1 2388623Email zreiner@kbc-zagreb.hrAbstract: Atherosclerotic cardiovascular diseases (ASCVD) are still the leading cause of morbidity and mortality in most developed countries and even more in developing countries. Dyslipidemia is a well known main risk factor for ASCVD. Lipid-lowering treatment, particularly lowering LDL-cholesterol (LDL-C), can decrease the risk for ASCVD. New data and guidelines based upon them suggest that we should go with LDL-C levels as low as we can. Therefore, conventional lipid lowering agents (statins and statins+ezetimibe) are not enough mainly because of poor compliance and statin intolerance which is in the real world mostly pseudo-intolerance. PCSK9 inhibitors provided a new hope to further decrease LDL-C but are still expensive, they have to be injected subcutaneously twice a month and their long-lasting adverse effects are not known. Therefore, there is a constant need to develop novel, more potent, more safe, less expensive, more user friendly regimens of hypolipemic agents (bempedoic acid, selective PPAR alpha receptor modulators etc). One of the ways to overcome poor compliance and increase the potency of therapy with less adverse effects are fixed combinations of established drugs (statin+ezetimibe). The future of hypolipemic agents is based on antisense therapy, ie. the use of specific oligonucleotide sequences blocking the translation of the selected protein (targeting apolipoprotein CIII, lipoprotein (a), apolipoprotein B) or RNA silencing technique (PCSK9 mRNA) and are in various stages of clinical trials. Some of them are almost ready to use in everyday clinical practice. High risk and very high risk patients (eg. familial hypercholesterolemia, familial severe chylomicronemia syndrome) will benefit most. The aim of this review is to inform about novel hypolipemic agents – potent and safe drugs for dyslipidemia which should reduce the risk of ASCVD.Keywords: dyslipidemia, novel hypolipemic drugs, cardiovascular risk, LDL-cholesterol, triglycerides, inclisiran, PCSK9 inhibitors, pemafibrate, bempedoic acid, ANGPTL3, pelacarsen

Abstract Key message We analyzed stem growth responses of Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) to severe drought in 2003/04 and 2018. The results showed high drought tolerance in sandy, loamy, and most silty soils, with limitations on clayey soils. This study indicates the susceptibility of Douglas-firs with shallow root systems to extreme drought and the importance of deep rooting for high drought resilience. Context Although Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) is considered a more drought-tolerant substitute for Norway spruce (Picea abies (L.) Karst.) in Europe, there is considerable uncertainty about the drought tolerance of Douglas-fir under climate change, specifically concerning soil properties. Aims This study aimed to assess the influence of soil texture, plant-available water capacity, and rooting characteristics on the interannual stem growth response of Douglas-fir when exposed to severe drought. Methods Along a soil texture gradient from sand to clay, we selected seven closely spaced sites at elevations of approximately 500 m a.s.l. in southern Germany. Mixed-effects models were used to analyze the effects of soil physical and rooting characteristics on growth response indices (resistance, recovery, resilience) related to the severe to extreme droughts in 2003/04 and 2018. Results Douglas-fir showed high drought tolerance in sandy, loamy, and most silty soils. However, the results suggest a higher drought stress risk on clayey soils, as well as at specific silty sites with shallow root systems. A higher effective rooting depth increased the resilience of Douglas-fir during the extreme drought in 2018. Conclusion Douglas-fir demonstrated its drought tolerance in most soil textures. In addition, this study supports the need for combined above- and below-ground investigations on factors influencing drought tolerance and the importance of rooting for drought resilience.

IntroductionDouglas-fir (Pseudotsuga menziesii (Mirb.) Franco) is considered an important non-native substitute tree species in Europe, especially for Norway spruce (Picea abies (L.) Karst.), mainly due to its higher drought tolerance. However, Douglas-fir has also shown increasing mortality in certain regions of the world. One of the main reasons is the increase in drought and heat periods due to climate change. There is still a need for research on the influence of important soil properties and rooting characteristics on the drought tolerance of Douglas-fir. Therefore, we analyzed the influence of soil texture, plant-available water capacity (PAWC), fine root density, and effective rooting depth on water status and thus drought stress in Douglas-fir during the extreme drought of 2018.MethodsWe selected seven closely spaced sites along a soil texture gradient from sand to clay at an elevation of ca. 500 m a.s.l. in southern Germany and determined soil physical and rooting characteristics. Water status parameters and growth duration were derived from dendrometer data at five Douglas-firs per site. The influence of soil and rooting characteristics on these drought stress-related parameters was analyzed using mixed-effects models. The focus was on two summer drought periods in 2018.Results and discussionIn the initial stage of the extreme summer drought of 2018 (in June), a higher PAWC and a higher fine root density reduced drought stress. However, these influences were no longer noticeable in the later stage of drought (in August), probably due to deeper soil desiccation. In August, a higher effective rooting depth reduced drought stress. Soil texture had a significant influence, particularly on growth duration. This study provides information on site selection for Douglas-fir cultivation under the predicted increase in severe drought, showing the importance of deep and intensive rooting, and points to the need for combined above- and belowground investigations for a better understanding of the drought response patterns of tree species.

IntroductionSoil drought during summer in Central Europe has become more frequent and severe over the last decades. European forests are suffering increasing damage, particularly Norway spruce. Douglas-fir (Pseudotsuga menziesii (Mirbel) Franco), a non-native tree species, is considered as a promising alternative to build drought-resilient forests. The main goal of this study was to investigate the intraannual radial stem growth and sap flow performance of Douglas-fir along a precipitation gradient across Germany under severe drought.Material and methodsSap flow and stem radial changes of up to ten trees each at four sites with different precipitation regimes were measured in combination with volumetric soil water content during the growing season of 2022. Measurements of stem radial changes were used to calculate the trees’ stem water deficit, a proxy for tree water status and drought stress.ResultsThe severe summer drought of 2022 led to an early growth cessation and a significant reduction in daily sap flow at all four sites monitored. We could identify a site-specific threshold in soil water availability ranging between 21.7 and 29.6% of relative extractable water (REW) under which stem water reserves cannot be replenished and thereby inhibiting radial growth. We could also demonstrate that at this threshold, sap flow is heavily reduced to between 43.5 and 53.3%, and for a REW below 50%, sap flow linearly decreases by 1.1–2.0% per 1% reduction in REW. This reduction tends to follow the humidity gradient, being more pronounced at the most oceanic characterized site and suggesting an adaptation to site conditions. Even though Douglas-fir is considered to be more drought stress resistant than Norway spruce, growth and sap flow are greatly reduced by severe summer drought, which became more frequent in recent years and their frequency and intensity is likely to increase.ConclusionsOur results suggest that timber production of Douglas-fir in Central Europe will decline considerably under projected climate change, and thus pointing to site specific growth constraints for a so far promising non-native tree species in Europe.

Depth filtration is a widespread technique for the separation of airborne particles. The evolution of the pressure difference within this process is determined to a significant extent by the filter structure. Simulations are an important tool for optimizing the filter structure, allowing the development of filter materials having high filtration efficiencies and low pressure differences. Because of the large number of physical phenomena and the complex structure of filter materials, simulations of the filtration kinetics are, however, challenging. In this context, one-dimensional models are advantageous for the calculation of the filtration kinetics of depth filters, due to their low computation requirements. In this work, an approach for combining a one-dimensional model with microstructural data of filter materials is presented. This enables more realistic modeling of the filtration process. Calculations were performed on a macroscopic as well as microscopic level and compared to experimental data. With the suggested approach, the influence of a measured microstructure on the results was examined and predictability was improved. Especially for small research departments and for the development of optimized filter materials adapted to specific separation tasks, this approach provides a valuable tool.

Abstract We present discrete (2‐h resolution) multi‐year (2008–2017) in situ measurements of seasonal vegetation growth and soil biophysical properties from two sites on Alaska's North Slope, USA, representing dry and wet sedge tundra. We examine measurements of vertical active soil layer temperature and soil moisture profiles (freeze/thaw status), woody shrub vegetation physiological activity, and meteorological site data to assess interrelationships within (and between) these two study sites. Vegetation phenophases (cold de‐hardening start, physiological function start, stem growth start, stem growth end, physiological function end, cold hardening completion) were found to have greater interannual day of year (DOY) occurrence variability at the dry site compared with the wet site. At the dry site, vegetation activity begins on average ~7 days earlier and ends ~11 days earlier. The mean active stem growth window lasts ~54 days for the dry site and ~51 days for the wet site. Vegetation, in both tundra environments, began cold de‐hardening functions (warm season prep) prior to atmospheric temperatures warming above 0°C. Similar results were found related to the critical soil freeze/thaw/transition dates; the dry site had a DOY phenophase occurrence range that was 8 days larger than that of the wet site. A longer continuous summer thaw period was captured at the wet site by ~26 days throughout the active layer. In addition, the dry site was measured to have longer spring and fall soil isothermal conditions than the wet site by ~9 and 5 days throughout the active layer. These results show that the dry site's willow shrub vegetation physiology and soil condition phenology is more variable than the wet site. Alongside the in situ data, a remote sensing product from NASA's MEaSUREs program was utilized; our research indicates that the AMSR‐derived satellite product is more precise over the wet tundra site with critical date alignment between remote sensing observations and in situ measurements ranging from ~4 to 11 days. Furthermore, the AMSR product was shown to preemptively estimate land surface condition change during the spring transition for both tundra types while lagging during the fall transition and freeze‐up periods.

The microscopic diffusion and the low frequency density of states (VDOS) of PIM-EA-TB(CH3) are investigated by inelastic and quasi-elastic neutron scattering where also the demethylated counterpart of PIM-EA-TB(H2) is considered. These intrinsic microporous polymers are characterized by large BET surface area values of several hundred m2/g and pore sizes between 0.5 and 2 nm. Detailed comparison is made to the archetype of polymers of intrinsic microporosity, PIM-1, and polynorbornenes also bearing a microporosity. Due to the wavelength of neutrons, the diffusion and vibrations can be addressed on microscopic length and time scales. From the inelastic neutron scattering experiments the low frequency density of states (VDOS) is estimated which shows excess contributions to the Debye-type VDOS known as Boson peak. It was found that the maximum frequency of the Boson peak decreases with increasing microporosity characterized by the BET surface area. However, besides the BET surface area, additional factors such as the backbone stiffness govern the maximum frequency of the Boson peak. Further the mean squared displacement related to microscopic motions was estimated from elastic fixed window scans. At temperatures above 175 K, the mean squared displacement PIM-EA-TB(CH3) is higher than that for the demethylated counterpart PIM-EA-TB(H2). The additional contribution found for PIM-EA-TB(CH3) is ascribed to the rotation of the methyl group in this polymer because the only difference between the two structures is that PIM-EA-TB(CH3) has methyl groups where PIM-EA-TB(H2) has none. A detailed comparison of the molecular dynamics is also made to that of PIM-1 and the microporous polynorbornene PTCNSi1. The manuscript focuses on the importance of vibrations and the localized molecular mobility characterized by the microscopic diffusion on the gas transport in polymeric separation membranes. In the frame of the random gate model localized fluctuations can open or close bottlenecks between pores to enable the diffusion of gas molecules.

To improve the representativeness of a real microstructural cut-out for modeling purposes, a numerical method named as “boundary pixel color alteration (BPCA)” is presented to modify measured 2D microstructure cut-outs. Its physical background is related to the phase growth. For the application, the precondition is that the representativeness of the microstructure is already satisfied to a certain extent. This method resolves the problem that the phase composition of a small cut-out can have a large discrepancy to the real one. The main idea is to change the pixel color among neighboring pixels belonging to different phases. Our process simultaneously maintains most of the characteristics of the original morphology and is applicable for nearly all kinds of multi-phase or polycrystalline metallic alloys, as well. From our axisymmetric finite element (FE) simulations (ABAQUS ) applied with 2D real microstructures, it shows that the volume ratios of microstructural phases, as a function of the structure position to the symmetric axis, converge to phase area ratios in the 2D cut-out, even though the axisymmetric element volume is position dependent. A mathematical proof provides the reason for the aforementioned convergence. As examples to achieve real compositions and to numerically prove the aforementioned convergence, four different materials including multiphase polycrystals are implemented. An improvement of the predicted FE result is presented for the application of a modified microstructure (with a higher representativeness) compared to the original one.

The sensitivity of Earth’s wetlands to observed shifts in global precipitation and temperature patterns and their ability to produce large quantities of methane gas are key global change questions. We present a microwave satellite-based approach for mapping fractional surface water (FW) globally at 25-km resolution. The approach employs a land cover-supported, atmospherically-corrected dynamic mixture model applied to 20+ years (1992–2013) of combined, daily, passive/active microwave remote sensing data. The resulting product, known as Surface WAter Microwave Product Series (SWAMPS), shows strong microwave sensitivity to sub-grid scale open water and inundated wetlands comprising open plant canopies. SWAMPS’ FW compares favorably (R2 = 91%–94%) with higher-resolution, global-scale maps of open water from MODIS and SRTM-MOD44W. Correspondence of SWAMPS with open water and wetland products from satellite SAR in Alaska and the Amazon deteriorates when exposed wetlands or inundated forests captured by the SAR products were added to the open water fraction reflecting SWAMPS’ inability to detect water underneath the soil surface or beneath closed forest canopies. Except for a brief period of drying during the first 4 years of observation, the inundation extent for the global domain excluding the coast was largely stable. Regionally, inundation in North America is advancing while inundation is on the retreat in Tropical Africa and North Eurasia. SWAMPS provides a consistent and long-term global record of daily FW dynamics, with documented accuracies suitable for hydrologic assessment and global change-related investigations.

Abstract Findings BMI was increased (>25) in 22% of young healthy subjects. Increased cholesterol values (>5.0 mmol/L) were found in 23% of subjects, LDL-C (>3.0 mmol/L) in 23%, triglycerides (>1.7 mmol/L) in 11% of subjects. We found statistically significant differences in subjects' weight (p = 0.015), BMI (p = 0.023), and waist-hip ratio (WHR) (p = 0.015) in regard to their diet type; subjects with Mediterranean diet had the lowest values compared to those on continental and mixed diet. Significant associations were found for: LPL genetic polymorphic variant and abdominal obesity (p = 0.013), APO epsilon4 allele and hypercholesterolemia (p = 0.003), and ESR1-TA long allele and hypercholesterolemia (p = 0.011). Background Human obesity is a multifactorial syndrome influenced also by genetic factors. Among gene variants found to be involved in body weight regulation and development of obesity, particular attention has been paid to polymorphisms in genes associated with obesity-related metabolic disorders. We explored the association of genetic polymorphisms of: estrogen receptor alpha (ESR1-TA repeats); interleukin-6 (IL-6 G-174C); apolipoprotein E (APO epsilon2, epsilon3, epsilon4); lipoprotein lipase Pvu II (LPL P+/-), with clinical variables: gender, age, body mass index (BMI), diet type and biological variables: triglycerides, cholesterol, HDL-C, LDL-C, CRP, homocysteine, urate, and glucose in 105 healthy young subjects (20-35 yrs) of Croatian origin. Methods Genotyping of IL-6, LPL was performed by PCR-RFLP, of APOE by real-time PCR, and of ESR1 by PCR and capillary electrophoresis. Association analyses were performed of alleles and genotypes with biological variables. Conclusion ESR-1, LPL, and APO E genetic polymorphic variants could represent predictive genetic risk markers for obesity-related metabolic disorders in young healthy subjects. Mediterranean type of diet is also an important protective factor against abdominal obesity.

• We studied the effect of Hp genotypes on ischemic stroke and atherosclerosis in males and females. • Presence of hypertension, HDL, CRP, age and male gender increased the risk of stroke. • Genotype Hp2-2 was statistically significantly associated with ischemic stroke. • We can point to the Hp 2–2 genotype as genetic risk factor for prediction of atherosclerosis in patients with IS. Ischemic stroke (IS) is multifactorial disease and therefore different genes and proteins play a role in its development. Haptoglobin (Hp) removes free hemoglobin and protects from iron-induced oxidative damage, inflammatory response, atherosclerosis and cerebrovascular diseases. The aim of this study was to investigate Hp genetic variants in patients with carotid atherosclerotic lesions and IS. A total of 121 subjects with IS participated in the study, 81 male and 40 female. Among 121 patients with IS, 79 had diffuse atherosclerotic plaques and stenosis. Hp genotype was statistically significantly associated with CDFI neck carotid artery stenosis findings (p = 0.006). Patients with Hp1-2 genotype had statistically significantly larger odds for atherosclerotic changes compared to those with Hp1-1 genotype, as well as those with Hp2-2 genotype. This study has shown an association of the Hp2-2 genotype and atherosclerosis in patients with IS, indicating Hp2-2 genotype as a genetic biomarker for precision medicine and personalized healthcare. [ABSTRACT FROM AUTHOR]