Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy.

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date. Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl). Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.

Increasing the Stability of Isolated and Dense High-Aspect-Ratio Nanopillars Fabricated Using UV-Nanoimprint Lithography.

Structural anti-reflective coating and bactericidal surfaces, as well as many other effects, rely on high-aspect-ratio (HAR) micro- and nanostructures, and thus, are of great interest for a wide range of applications. To date, there is no widespread fabrication of dense or isolated HAR nanopillars based on UV nanoimprint lithography (UV-NIL). In addition, little research on fabricating isolated HAR nanopillars via UV-NIL exists. In this work, we investigated the mastering and replication of HAR nanopillars with the smallest possible diameters for dense and isolated arrangements. For this purpose, a UV-based nanoimprint lithography process was developed. Stability investigations with capillary forces were performed and compared with simulations. Finally, strategies were developed in order to increase the stability of imprinted nanopillars or to convert them into nanoelectrodes. We present UV-NIL replication of pillars with aspect ratios reaching up to 15 with tip diameters down to 35 nm for the first time. We show that the stability could be increased by a factor of 58 when coating them with a 20 nm gold layer and by a factor of 164 when adding an additional 20 nm thick layer of SiN. The coating of the imprints significantly improved the stability of the nanopillars, thus making them interesting for a wide range of applications.

Mastering of NIL Stamps with Undercut T-Shaped Features from Single Layer to Multilayer Stamps.

Biomimetic structures such as structural colors demand a fabrication technology of complex three-dimensional nanostructures on large areas. Nanoimprint lithography (NIL) is capable of large area replication of three-dimensional structures, but the master stamp fabrication is often a bottleneck. We have demonstrated different approaches allowing for the generation of sophisticated undercut T-shaped masters for NIL replication. With a layer-stack of phase transition material (PTM) on poly-Si, we have demonstrated the successful fabrication of a single layer undercut T-shaped structure. With a multilayer-stack of silicon oxide on silicon, we have shown the successful fabrication of a multilayer undercut T-shaped structures. For patterning optical lithography, electron beam lithography and nanoimprint lithography have been compared and have yielded structures from 10 µm down to 300 nm. The multilayer undercut T-shaped structures closely resemble the geometry of the surface of a Morpho butterfly, and may be used in future to replicate structural colors on artificial surfaces.

Mortality after cardiopulmonary resuscitation on a medical ICU : A sex-specific outcome analysis.

BACKGROUND: Performing cardiopulmonary resuscitation (CPR) and postresuscitation care in the intensive care unit (ICU) are standardized procedures; however, there is evidence suggesting sex-dependent differences in clinical management and outcome variables after cardiac arrest (CA). METHODS: A prospective analysis of patients who were hospitalized at a medical ICU after CPR between December 2018 and March 2020 was conducted. Exclusion criteria were age < 18 years, hospital length of stay < 24 h and traumatic CA. The primary study endpoint was mortality after 6 months and the secondary endpoint neurological outcome assessed by cerebral performance category (CPC). Differences between groups were calculated by using U­tests and χ2-tests, for survival analysis both univariate and multivariable Cox regression were fitted. RESULTS: A total of 106 patients were included and the majority were male (71.7%). No statistically significant difference regarding 6­month mortality between sexes could be shown (hazard risk, HR 0.68, 95% confidence interval, CI 0.35-1.34; p = 0.27). Neurological outcome was also similar between both groups (CPC 1 88% in both sexes after 6 months; p = 1.000). There were no statistically significant differences regarding general characteristics, pre-existing diseases, as well as the majority of clinical and laboratory parameters or measures performed on the ICU. CONCLUSION: In a single center CPR database no statistically significant sex-specific differences regarding post-resuscitation care, survival and neurological outcome after 6 months were observed.

Nanoimprinted multifunctional nanoprobes for a homogeneous immunoassay in a top-down fabrication approach.

Multifunctional nanoparticles are discussed as versatile probes for homogeneous immunoassays for in-vitro diagnostics. Top-down fabrication allows to combine and tailor magnetic and plasmonic anisotropic properties. The combination of nanoimprint lithography, thin film deposition, and lift-off processing provides a top-down fabrication platform, which is both flexible and reliable. Here, we discuss the material compositions and geometrical designs of monodisperse multicomponent nanoparticles and their consequences on optical and magnetic properties. The rotational hydrodynamics of nanoparticles is measured and considered under the influence of magnetic shape anisotropy in the framework of the Stoner-Wohlfarth theory. The plasmon-optical properties are explained by discrete-dipole finite-element simulations. Rotational dynamical measurements of imprinted nanoprobes for two test proteins demonstrate the applicability as highly sensitive biomolecular nanoprobes.

The Diagnostic and Therapeutic Value of Multimarker Analysis in Heart Failure. An Approach to Biomarker-Targeted Therapy.

Background: Heart failure is a pathophysiological state, which is still associated with high morbidity and mortality despite established therapies. Diverse well-known biomarkers fail to assess the variety of individual pathophysiology in the context of heart failure. Methods: An analysis of prospective, multimarker-specific therapeutic approaches to heart failure based on studies in current literature was performed. A total of 159 screened publications in the field of biomarkers in heart failure were hand-selected and found to be eligible for this study by a team of experts. Results: Established biomarkers of the inflammatory axis, matrix remodeling, fibrosis and oxidative stress axis, as well as potential therapeutic interventions were investigated. Interaction with end organs, such as cardio-hepatic, cardio-renal and cardio-gastrointestinal interactions show the complexity of the syndrome and could be of further therapeutic value. MicroRNAs are involved in a wide variety of physiologic and pathophysiologic processes in heart failure and could be useful in diagnostic as well as therapeutic setting. Conclusion: Based on our analysis by a biomarker-driven approach in heart failure therapy, patients could be treated more specifically in long term with a consideration of different aspects of heart failure. New studies evaluating a multimarker - based therapeutic approach could lead in a decrease in the morbidity and mortality of heart failure patients.

Plasmon-Assisted Direction- and Polarization-Sensitive Organic Thin-Film Detector.

Utilizing Bragg surface plasmon polaritons (SPPs) on metal nanostructures for the use in optical devices has been intensively investigated in recent years. Here, we demonstrate the integration of nanostructured metal electrodes into an ITO-free thin film bulk heterojunction organic solar cell, by direct fabrication on a nanoimprinted substrate. The nanostructured device shows interesting optical and electrical behavior, depending on angle and polarization of incidence and the side of excitation. Remarkably, for incidence through the top electrode, a dependency on linear polarization and angle of incidence can be observed. We show that these peculiar characteristics can be attributed to the excitation of dispersive and non-dispersive Bragg SPPs on the metal-dielectric interface on the top electrode and compare it with incidence through the bottom electrode. Furthermore, the optical and electrical response can be controlled by the organic photoactive material, the nanostructures, the materials used for the electrodes and the epoxy encapsulation. Our device can be used as a detector, which generates a direct electrical readout and therefore enables the measuring of the angle of incidence of up to 60° or the linear polarization state of light, in a spectral region, which is determined by the active material. Our results could furthermore lead to novel organic Bragg SPP-based sensor for a number of applications.

Heart-Type Fatty Acid-Binding Protein (H-FABP) and its Role as a Biomarker in Heart Failure: What Do We Know So Far?

BACKGROUND: Heart failure (HF) remains one of the leading causes of death to date despite extensive research funding. Various studies are conducted every year in an attempt to improve diagnostic accuracy and therapy monitoring. The small cytoplasmic heart-type fatty acid-binding protein (H-FABP) has been studied in a variety of disease entities. Here, we provide a review of the available literature on H-FABP and its possible applications in HF. Methods: Literature research using PubMed Central was conducted. To select possible studies for inclusion, the authors screened all available studies by title and, if suitable, by abstract. Relevant manuscripts were read in full text. RESULTS: In total, 23 studies regarding H-FABP in HF were included in this review. CONCLUSION: While, algorithms already exist in the area of risk stratification for acute pulmonary embolism, there is still no consensus for the routine use of H-FABP in daily clinical practice in HF. At present, the strongest evidence exists for risk evaluation of adverse cardiac events. Other future applications of H-FABP may include early detection of ischemia, worsening of renal failure, and long-term treatment planning.

Differences in biocompatibility of microneedles from cyclic olefin polymers with human endothelial and epithelial skin cells.

Microneedles are promising devices for transdermal delivery and diagnostic applications, due to their minimally invasive and painless nature of application. However, so far, applications are limited to small scale research projects. Material selection and production for larger projects remain a challenge. In vitro testing using human cell culture could bridge the gap between cost effective screening of suitable materials and concerns for safety and ethics. In this study, materials were tested for effects on viability and morphology of human endothelial cells and keratinocytes. In addition, materials were assessed for their potential to influence cellular differentiation and barrier formation. Elution-based testing of inflammatory markers revealed no negative effects in all applied tests, whereas the assessment of differentiation markers on cells in direct contact with the material showed differences and allowed the selection of candidate materials for future medical device applications. This study illustrates that elution-based biocompatibility testing can paint an incomplete picture. Advanced staining techniques and cell types specific for the application of the medical device improve material selection to reduce and replace animal testing at an early stage in the development process. © 2018 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 505-512, 2019.

Multifunctional Nanostructures and Nanopocket Particles Fabricated by Nanoimprint Lithography.

Nanostructured surfaces and nanoparticles are already widely employed in many different fields of research, and there is an ever-growing demand for reliable, reproducible and scalable nanofabrication methods. This is especially valid for multifunctional nanomaterials with physical properties that are tailored for specific applications. Here, we report on the fabrication of two types of nanomaterials. Specifically, we present surfaces comprising a highly uniform array of elliptical pillars as well as nanoparticles with the shape of nanopockets, possessing nano-cavities. The structures are fabricated by nanoimprint lithography, physical and wet-chemical etching and sputter deposition of thin films of various materials to achieve a multifunctional nanomaterial with defined optical and magnetic properties. We show that the nanopockets can be transferred to solution, yielding a nanoparticle dispersion. All fabrication steps are carefully characterized by microscopic and optical methods. Additionally, we show optical simulation results that are in good agreement with the experimentally obtained data. Thus, this versatile method allows to fabricate nanomaterials with specific tailor-made physical properties that can be designed by modelling prior to the actual fabrication process. Finally, we discuss possible application areas of these nanomaterials, which range from biology and medicine to electronics, photovoltaics and photocatalysis.

Giant cross polarization in a nanoimprinted metamaterial combining a fishnet with its Babinet complement.

We present a large area (1 cm2) nanoimprinted metamaterial comprising a fishnet structure and its Babinet complement, which shows giant cross polarization. When illuminated with s-polarized light, the reflected beam can be p-polarized up to 96%, depending on the azimuthal orientation of the sample. This experimental result is close to the result of numerical simulations, which predict 98.7% of cross-polarization. It is further shown, that 95-100% cross polarization is only achieved in the case when the fishnet is combined with its Babinet complement. Each structure alone (either an ordinary fishnet or a plane with metallic rectangles only) shows substantially less polarization conversion.