Search

Infections are one of the main complications in arthroplasties. These infections are difficult to treat because the bacteria responsible for them settle in the prosthesis and form a biofilm that does not allow antimicrobials to reach the infected area. This study is part of a research project aimed at developing 3D-printed spacers (temporary prostheses) capable of incorporating antibacterials for the personalized treatment of arthroplasty infections. The main objective of this research was to analyze the impact of the layer thickness of 3D-printed constructs based on polylactic acid (PLA) for improved treatment of infections in arthroplasty. The focus is on the following parameters: resistance, morphology, drug release, and the effect of antibacterials incorporated in the printed temporary prostheses. The resistance studies revealed that the design and layer thickness of a printed spacer have an influence on its resistance properties. The thickness of the layer used in printing affects the amount of methylene blue (used as a model drug) that is released. Increasing layer thickness leads to a greater release of the drug from the spacer, probably as a result of higher porosity. To evaluate antibacterial release, cloxacillin and vancomycin were incorporated into the constructs. When incorporated into the 3D construct, both antibacterials were released, as evidenced by the growth inhibition of Staphylococcus aureus. In conclusion, preliminary results indicate that the layer thickness during the three-dimensional (3D) printing process of the spacer plays a significant role in drug release.

The rat protoparvovirus H-1 (H-1PV) is an oncolytic virus known for its anticancer properties in laboratory models of various human tumors, including non-Hodgkin lymphomas (NHL) of B-cell origin. However, H-1PV therapeutic potential against hematological malignancies of T-cell origin remains underexplored. The aim of the present study was to conduct a pilot preclinical investigation of H-1PV-mediated oncolytic effects in cutaneous T-cell lymphoma (CTCL), a type of NHL that is urgently calling for innovative therapies. We demonstrated H-1PV productive infection and induction of oncolysis in both classically grown CTCL suspension cultures and in a novel, in vivo-relevant, heterotypic spheroid model, but not in healthy donor controls, including peripheral blood mononuclear cells (PBMCs). H-1PV-mediated oncolysis of CTCL cells was not prevented by Bcl-2 overexpression and was accompanied by increased extracellular ATP release. In CTCL spheroid co-cultures with PBMCs, increased spheroid infiltration with immune cells was detected upon co-culture treatment with the virus. In conclusion, our preclinical data show that H-1PV may hold significant potential as an ingenious viroimmunotherapeutic drug candidate against CTCL.

Age-related conditions, such as sarcopenia, cause physical disabilities for an increasing section of society. At the neuromuscular junction, the postsynaptic-derived neurotrophic factors brain-derived neurotrophic factor (BDNF) and neurotrophin 4 (NT-4) have neuroprotective functions and contribute to the correct regulation of the exocytotic machinery. Similarly, presynaptic muscarinic signalling plays a fundamental modulatory function in this synapse. However, whether or not these signalling pathways are compromised in ageing neuromuscular system has not yet been analysed. The present study analyses, through Western blotting, the differences in expression and activation of the main key proteins of the BDNF/NT-4 and muscarinic pathways related to neurotransmission in young versus ageing Extensor digitorum longus (EDL) rat muscles. The main results show an imbalance in several sections of these pathways: (i) a change in the stoichiometry of BDNF/NT-4, (ii) an imbalance of Tropomyosin-related kinase B receptor (TrkB)-FL/TrkB-T1 and neurotrophic receptor p 75 (p75NTR), (iii) no changes in the cytosol/membrane distribution of phosphorylated downstream protein kinase C (PKC)βI and PKCε, (iv) a reduction in the M2-subtype muscarinic receptor and P/Q-subtype voltage-gated calcium channel, (v) an imbalance of phosphorylated mammalian uncoordinated-18-1 (Munc18-1) (S313) and synaptosomal-associated protein 25 (SNAP-25) (S187), and (vi) normal levels of molecules related to the management of acetylcholine (Ach). Based on this descriptive analysis, we hypothesise that these pathways can be adjusted to ensure neurotransmission rather than undergoing negative alterations caused by ageing. However, further studies are needed to assess this hypothetical suggestion. Our results contribute to the understanding of some previously described neuromuscular functional age-related impairments. Strategies to promote these signalling pathways could improve the neuromuscular physiology and quality of life of older people.

Pregnancy is a contributor to the obesity epidemic in women, probably through postpartum weight retention (PPWR), weight gain (PPWG), or a combination of both (PPWR + WG). The contribution of these patterns of postpartum weight change to long-term maternal health remains understudied. In a secondary analysis of 361 women from the prospective cohort PROGRESS, we evaluated the associations between patterns of weight change one year after delivery and cardiometabolic risk factors at six years postpartum. Using principal component analysis, we grouped cardiometabolic risk factors into: (1) body mass index (BMI), waist circumference (WC), homeostatic model assessment of insulin resistance (HOMA-IR), high-density lipoprotein cholesterol (HDL-c), triglycerides (TG), and glucose; (2) systolic (SBP) and diastolic blood pressure (DBP); and (3) low-density lipoprotein cholesterol and total cholesterol. Using path analysis, we studied direct (patterns of weight change-outcomes) and indirect associations through BMI at six years postpartum. Around 60% of women returned to their pregestational weight (reference) by one year postpartum, 6.6% experienced PPWR, 13.9% PPWG, and 19.9% PPWR + WG. Women with PPWR + WG, vs. the reference, had higher BMI and WC at six years (2.30 kg/m2, 95% CI [1.67, 2.93]; 3.38 cm [1.14, 5.62]). This was also observed in women with PPWR (1.80 kg/m2 [0.80, 2.79]; 3.15 cm [−0.35, 6.65]) and PPWG (1.22 kg/m2 [0.53, 1.92]; 3.32 cm [0.85, 5.78]). PPWR + WG had a direct association with HOMA-IR (0.21 units [0.04, 0.39]). The three patterns of weight change, vs. the reference, had significant indirect associations with HOMA-IR, glucose, TG, HDL-c, SBP, and DBP through BMI at six years. In conclusion, women with PPWR + WG are at high-risk for obesity and insulin resistance. Interventions targeting women during pregnancy and the first year postpartum may have implications for their long-term risk of obesity and cardiovascular disease.

Metabolic products of the intestinal microbiome such as trimethylamine N-oxide (TMAO) that accumulate in renal failure (gut-derived uremic toxins, GDUTs) affect atherosclerosis and increase cardiovascular risk. We hypothesized that patients on a Mediterranean diet and those consuming lower amounts of dietary precursors would have lower levels of GDUTs. Patients attending vascular prevention clinics completed a Harvard Food Frequency Questionnaire (FFQ) and had plasma levels of TMAO, p-cresylsulfate, hippuric acid, indoxyl sulfate, p-cresyl glucuronide, phenyl acetyl glutamine, and phenyl sulfate measured by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Carotid plaque burden was measured by ultrasound; CKD-Epi equations were used to estimate the glomerular filtration rate. In total, 276 patients completed the study. Even moderate renal function significantly increased plasma GDUTs, which were significantly associated with higher carotid plaque burden. There was no significant difference in plasma levels of any GDUT associated with a Mediterranean diet score or with intake of dietary precursors. In omnivorous patients with vascular disease, the intake of dietary precursors of intestinal metabolites or adherence to a Mediterranean diet did not change plasma GDUT. Approaches other than diet, such as probiotics and repopulation of the intestinal microbiome, may be required to mitigate the adverse effects of GDUTs.

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer’s patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

The primacy of endozoochory for the maintenance and expansion of many woody plant populations is well known, but seed dispersal is not well understood for most species. This is especially true for rare species, where small population size and low fruit production can limit field- or observation-based experiments. Additionally, the effect of environmental heterogeneity on disperser movement is rarely investigated but has been shown to improve estimates of plant population spatial patterns and dynamics. We used simulation experiments to explore the effects of environmental heterogeneity and disperser movement on Lindera subcoriacea seed dispersal, a rare shrub from the southeastern United States with avian-dispersed seeds. Our experiments incorporated environmental heterogeneity and simulated disperser movement for five bird species, based on either landscape permeability or straight path rules. We anticipated that permeability-based movement would result in greater dispersal distances and seed dispersal effectiveness, which characterizes both quantity and quality. Generally, we did not find differences in seed dispersal between permeability and straight path experiments. However, we did find that permeability-based experiments had greater deposition into suitable habitat during flight (23 vs. 1%). These rare but longer distance depositions may be especially important for plants that are influenced by gap or interpopulation dynamics. We also found consistently greater dispersal into high quality habitats regardless of disperser species in permeability experiments, implying that incorporating species-specific assessments of landscape utilization (occupancy) could influence the effectiveness of seed dispersal. Our study suggests that including environmental heterogeneity in seed dispersal models can provide additional insights not provided by avian parameters (e.g., gut capacity, seed retention time, and flight speed) commonly used to inform dispersal models.

Flooding in urban areas is expected to become even more common due to climatic changes, putting pressure on cities to implement effective response measures. Practical mechanisms for assessing flood risk have become highly desired, but existing solutions have been devoted to evaluating only specific cities and consider only limited risk perspectives, constraining their general applicability. This article presents an innovative approach for assessing the flood risk of delimited urban areas by exploiting geospatial information from publicly available databases, providing a method that is applicable to any city in the world and requiring minimum configurations. A set of mathematical equations is defined for numerically assessing risk levels based on elevation, slope, and proximity to rivers, while the existence of emergency-related urban infrastructure is considered as a risk reduction factor. Then, computed risk levels are used to classify areas, allowing easy visualisation of flood risk for a city. This smart city approach not only serves as a valuable tool for assessing the expected flood risk based on different parameters but also facilitates the implementation of cutting-edge strategies to effectively mitigate critical situations, ultimately enhancing urban resilience to flood-related disaster.

Fiber-reinforced plywood is a composite material that combines the natural strength and rigidity of plywood with the added durability and resilience provided by reinforcing fibers. This type of plywood is designed to offer improved characteristics over standard plywood, including enhanced strength, stiffness, resistance to impact and moisture, and environmental degradation. By integrating reinforcing fibers, such as glass, carbon, or natural fibers (like flax, bamboo, or hemp) into or onto plywood, manufacturers can create a material that is better suited for applications where traditional plywood might fall short or when a decrease in product weight or savings in wood raw material are necessary. This report reviews the current progress in fiber-reinforced plywood in the context of plywood as a construction material to better understand the potential gains in plywood applications, mechanical parameters, and material savings. It is found that a simple and cost-effective procedure of fiber reinforcement allows for substantial improvements in plywood’s mechanical properties, typically to the extent of 10–40%. It is suggested that the wider adoption of fiber-reinforced plywood, especially in load- and impact-bearing applications, would greatly contribute to enhanced durability and longevity of the material while also allowing for more sustainable use of raw wood material.

Light Detection and Ranging systems serve as robust tools for creating three-dimensional representations of the Earth’s surface. These representations are known as point clouds. Point cloud scene segmentation is essential in a range of applications aimed at understanding the environment, such as infrastructure planning and monitoring. However, automating this process can result in notable challenges due to variable point density across scenes, ambiguous object shapes, and substantial class imbalances. Consequently, manual intervention remains prevalent in point classification, allowing researchers to address these complexities. In this work, we study the elements contributing to the automatic semantic segmentation process with deep learning, conducting empirical evaluations on a self-captured dataset by a hybrid airborne laser scanning sensor combined with two nadir cameras in RGB and near-infrared over a 247 km2 terrain characterized by hilly topography, urban areas, and dense forest cover. Our findings emphasize the importance of employing appropriate training and inference strategies to achieve accurate classification of data points across all categories. The proposed methodology not only facilitates the segmentation of varying size point clouds but also yields a significant performance improvement compared to preceding methodologies, achieving a mIoU of 94.24% on our self-captured dataset.

Wild and forest fires pose a threat to forests and thereby, in extension, to wild life and humanity. Recent history shows an increase in devastating damages caused by fires. Traditional fire detection systems, such as video surveillance, fail in the early stages of a rural forest fire. Such systems would see the fire only when the damage is immense. Novel low-power smoke detection units based on gas sensors can detect smoke fumes in the early development stages of fires. The required proximity is only achieved using a distributed network of sensors interconnected via 5G. In the context of battery-powered sensor nodes, energy efficiency becomes a key metric. Using AI classification combined with XAI enables improved confidence regarding measurements. In this work, we present both a low-power gas sensor for smoke detection and a system elaboration regarding energy-efficient communication schemes and XAI-based evaluation. We show that leveraging edge processing in a smart way combined with buffered data samples in a 5G communication network yields optimal energy efficiency and rating results.

Recovering phosphorus (P) through combustion from waste streams, like wastewater sludge and animal manure, offers a promising solution. This research explores the P release patterns in different ashes derived from secondary raw materials, using a long-term soil incubation lasting 160 days. The study evaluated the P release dynamics in five types of ashes from enhanced biological phosphorus removal (EBPR) systems and pig slurry burned at different temperatures. According to the results, a primary effect was observed on P bioavailability during the initial incubation period. All tested ashes release more than 50% of the total P applied between days 5 and 10. Ashes from EBPR exhibited higher P release than those from pig manure, indicating ash origin as a key factor in P release. Additionally, combustion temperature was crucial, with higher temperatures resulting in increased P release rates. Furthermore, the Pearson correlation revealed a strong relationship between the characteristics of the ashes and the amount of P release. Overall, these findings suggest that ashes could be a valuable P-source for agriculture avoiding the process of wet chemical P extraction, thus reducing both economic and environmental costs.

According to contemporary research, there exists an imbalance within the disciplines of Science, Technology, Engineering, and Mathematics (STEM), wherein certain subjects are lacking representation due to the neglect or omission of mathematical elements. The purpose of this study is to address this issue through the analysis of an established learning sequence that has been well-tested to promote mathematical skills. We adapted the selected biology-based learning sequence to foster mathematical problem solving and conducted it with a school class. The qualitative analysis of the recorded video footage of this adapted learning sequence revealed that the modified task effectively stimulated mathematical problem-solving skills. This successful adaptation demonstrates one approach through which mathematics can be strengthened and effectively utilized in STEM subjects.

One of the problems that most seriously affects oenology today is enzymatic browning, especially when grapes are infected by grey rot. We studied the capacity of glutathione (GSH) and a specific inactivated dry yeast rich in glutathione (IDY-GSH) to protect white grape must from browning compared to that of sulphur dioxide (SO2). The results indicate that SO2 drastically reduces the oxygen consumption rate (by around 72%), protects hydroxycinnamic acids from oxidation and prevents grape must against browning even in the presence of laccase. Specifically, the presence of SO2 reduced the colour’s blue–yellow component (b*) by around 91% in control conditions and around 76% in the presence of laccase. GSH, pure or in the form of IDY-GSH, also reduces the oxygen consumption rate (by 23% and 36%, respectively) but to a lesser extent than SO2. GSH also favours the formation of grape reaction product (GRP) from hydroxycinnamic acids and effectively protects grape must against browning in healthy grape conditions. Specifically, the presence of GSH reduced b* by around 81% in control conditions. Nevertheless, in the presence of laccase, it was not effective enough, reducing b* by around 39% in the case of pure GSH and 24% in the case of IDY-GSH. Therefore, both forms of GSH can be considered as interesting alternative tools to SO2 for preventing browning in white grape must, but only when the grapes are healthy.

Background: The analysis of substrates of polymorphic cytochrome P450 (CYP) enzymes is important information to enable drug–drug interactions (DDIs) analysis and the relevance of pharmacogenetics in this context in large datasets. Our aim was to compare different approaches to assess the substrate properties of drugs for certain polymorphic CYP2 enzymes. Methods: A standardized manual method and an automatic method were developed and compared to assess the substrate properties for the metabolism of drugs by CYP2D6, 2C9, and 2C19. The automatic method used a matching approach to three freely available resources. We applied the manual and automatic methods to a large real-world dataset deriving from a prospective multicenter study collecting adverse drug reactions in emergency departments in Germany (ADRED). Results: In total, 23,878 medication entries relating to 895 different drugs were analyzed in the real-world dataset. The manual method was able to assess 12.2% (n = 109) of drugs, and the automatic method between 12.1% (n = 109) and 88.9% (n = 796), depending on the resource used. The CYP substrate classifications demonstrated moderate to almost perfect agreements for CYP2D6 and CYP2C19 (Cohen’s Kappa (κ) 0.48–0.90) and fair to moderate agreements for CYP2C9 (κ 0.20–0.48). Conclusion: A closer look at different classifications between methods revealed that both methods are prone to error in different ways. While the automated method excels in time efficiency, completeness, and actuality, the manual method might be better able to identify CYP2 substrates with clinical relevance.

This work presents an innovative honeycomb cell geometry design with enhanced in-plane energy absorption under quasi-static lateral loads. Numerical and experimental compression tests results under axial and lateral loads are analyzed. The proposed cell geometry was designed to overcome the limitations posed by standard hexagonal honeycombs, which show relatively low stiffness and energy absorption under loads that have a significant lateral component. To achieve this, the new cell geometry was designed with internal diagonal walls to support the external walls, increasing its stiffness and impact energy absorption in comparison with the hexagonal cell. 3D-printed unit-cell specimens made from ABS thermoplastic material were subjected to experimental quasi-static compression tests, in both lateral and axial directions. Energy absorption was compared to that of the standard hexagonal cell, with the same mass and height. Finite element models were developed and validated using experimental data. Results show that the innovative geometry absorbs approximately 15% more energy under lateral compression, while maintaining the same level of energy absorption of the standard hexagonal cell in the axial direction. The present study demonstrates that the proposed cell geometry has the potential to substitute the standard hexagonal honeycomb in applications where significant lateral loads are present.

Preterm birth (defined as birth

The ability to disperse has continually shaped both the distribution and diversification of biota, and it affects the survival of the species with respect to wide-ranging habitat loss. As a response, organisms unable to spread by their own means often developed surrogate dispersal strategies. Pseudoscorpions possess small body sizes and cannot actively disperse over large distances and geographic barriers; therefore, they have adopted other ecological strategies. They are either sedentary and remain confined to stable environments or passively disperse via phoresy and are capable of inhabiting a wide variety of habitats, including temporary ones. In this paper, we use barcoding data to investigate the genetic diversity of four widely distributed and relatively morphologically uniform Cheliferidae genera Chelifer, Dactylochelifer, Rhacochelifer and Hysterochelifer. We aim to (i) test whether the genera harbor cryptic diversity and (ii) evaluate whether the genetic structure of the species parallels their dispersal capabilities and habitat preferences (i.e., ecological strategies). In general, we uncovered independent lineages within all analyzed genera, which indicates their need for a thorough and integrative taxonomic revision. More specifically, we detected a varying degree of genetic structuring among the lineages. Known phoretic species, as well as some species and delimited lineages that are not known to use this manner of dispersal, showed a complete lack of geographical structure and shared haplotypes over large distances, while other taxa had restricted distributions. We argue that genetic structure can be used as a proxy to evaluate species’ dispersal manner and efficacy. Our results also suggest that taxa inhabiting stable environments might use phoresy for their dispersal.

Research has demonstrated that when learning mechanics, students’ conceptions (SCs) improve gradually (1) and are often activated depending on problem features (2). The aim of this study is to combine these two research lines to investigate how different task characteristics affect the activation of SCs at different levels of sophistication. Data were collected from N = 356 students using a paper–pencil test in which conceptual and contextual task characteristics (CCTCs) are varied systematically across ordered multiple-choice items. Answer options were constructed according to the four levels of a force and motion learning progression. Results, obtained using quantitative methods (e.g., Rasch analysis and regression), demonstrate that the effects of CCTCs may differ at different levels of SCs. For the direction of problem, for example, activating the correct conception, assuming force proportional to acceleration, seems to be easier in tasks asking for the resulting motion. However, activating more appropriate conceptions regarding lower levels, e.g., assuming force proportional to velocity, compared to a rather undifferentiated understanding of force and motion, seems to be easier in tasks asking for the forces. Results of our study can be used for choosing tasks with specific CCTCs to support conceptual change along specific steps of a learning path.

We often interact with our environment through manual handling of objects and exploration of their properties. Object properties (OP), such as texture, stiffness, size, shape, temperature, weight, and orientation provide necessary information to successfully perform interactions. The human haptic perception system plays a key role in this. As virtual reality (VR) has been a growing field of interest with many applications, adding haptic feedback to virtual experiences is another step towards more realistic virtual interactions. However, integrating haptics in a realistic manner, requires complex technological solutions and actual user-testing in virtual environments (VEs) for verification. This review provides a comprehensive overview of recent wearable haptic devices (HDs) categorized by the OP exploration for which they have been verified in a VE. We found 13 studies which specifically addressed user-testing of wearable HDs in healthy subjects. We map and discuss the different technological solutions for different OP exploration which are useful for the design of future haptic object interactions in VR, and provide future recommendations.

Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Transcriptome analysis was performed, comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily and the retinas of 10 additional db/db mice that received vehicle eye drops. Ten non-diabetic mice (db/+) were used as a control group. The Gene Ontology (GO) and Reactome databases were used to perform the gene set enrichment analysis (GSEA) in order to explore the most enriched biological pathways among the groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission is the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesicle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of the macromolecule biosynthetic process with positive regulation of cell communication, which provides beneficial effects for the neuronal metabolism. This study suggests that topical administration of sitagliptin ameliorates the abnormalities on presynaptic and postsynaptic signal transmission during experimental DR and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.

The article is devoted to the optimization of the degassing parameters of the AlSi9Cu3(Fe) alloy. The alloy was degassed with a solid degasser (Ecosal) and nitrogen or argon. The variable parameters were time and type of degasser. The test castings were made in permanent molds with an internal diameter of 25 mm and a length of 150 mm. The effect of the degassing time and the amount of degasser on the mechanical properties, as well as the hydrogen content and density index were investigated. The ALU SPEED TESTER developed by FMA was used to test the hydrogen content and the density index. Magmasoft software was used to design the geometry of the test castings. A significant effect of the solid degasser and degassing time on both the density index and the hydrogen content was demonstrated. Replacing nitrogen with argon did not bring any significant improvement in the above-mentioned parameters. The effect of degassing parameters on the mechanical properties of the EN AC-46000 alloy was much less significant, but was still visible. The optimal degassing parameters needed to obtain the highest strength parameters of the EN AC-46000 gravity die castings were determined.

Temporary mechanical circulatory support (tMCS) is a life-saving treatment option for patients in cardiogenic shock (CS), but many aspects such as patient selection, initiation threshold and optimal modality selection remain unclear. This study describes a standard operating procedure (SOP) for tMCS allocation for CS patients and presents outcome data before and after implementation. Data from 421 patients treated for CS with tMCS between 2018 and 2021 were analyzed. In 2019, we implemented a new SOP for allocating CS patients to tMCS modalities. The association between the time of SOP implementation and the 30-day and 1-year survival as well as hospital discharge was evaluated. Of the 421 patients included, 189 were treated before (pre-SOP group) and 232 after implementation of the new SOP (SOP group). Causes of CS included acute myocardial infarction (n = 80, 19.0%), acute-on-chronic heart failure in patients with dilated or chronic ischemic heart failure (n = 139, 33.0%), valvular cardiomyopathy (n = 14, 3.3%) and myocarditis (n = 5, 1.2%); 102 patients suffered from postcardiotomy CS (24.2%). The SOP group was further divided into an SOP-adherent (SOP-A) and a non-SOP-adherent group (SOP-NA). The hospital discharge rate was higher in the SOP group (41.7% vs. 29.7%), and treating patients according to the SOP was associated with an improved 30-day survival (56.9% vs. 38.9%, OR 2.21, 95% CI 1.01–4.80, p = 0.044). Patient allocation according to the presented SOP significantly improved 30-day survival.

In recent years, cities are experiencing changes in the ways of moving around, increasing the use of micromobility vehicles. Bicycles are the most widespread transport mode and, therefore, cyclists’ behaviour, safety, and comfort have been widely studied. However, the use of other personal mobility vehicles is increasing, especially e-scooters, and related studies are scarce. This paper proposes a low-cost open-source data acquisition system to be installed on an e-scooter. This system is based on Raspberry Pi and allows collecting speed, acceleration, and position of the e-scooter, the lateral clearance during meeting and overtaking manoeuvres, and the vibrations experienced by the micromobility users when riding on a bike lane. The system has been evaluated and tested on a bike lane segment to ensure the accuracy and reliability of the collected data. As a result, the use of the proposed system allows highway engineers and urban mobility planners to analyse the behaviour, safety, and comfort of the users of e-scooters. Additionally, the system can be easily adapted to another micromobility vehicle and used to assess pavement condition and micromobility users’ riding comfort on a cycling network when the budget is limited.

Nowadays, science, technology, engineering, and mathematics (STEM) play a critical role in a nation’s global competitiveness and prosperity. Thus, there is a need to educate students in these subjects to meet the current and future demands of personal life and society. While applications, especially in science, engineering, and technology, are directly obvious, mathematics underpins the other STEM disciplines. It is recognized that mathematics is the foundation for all other STEM disciplines; the role of mathematics in classrooms is not clear yet. Therefore, the question arises: What is the current role of mathematics in secondary STEM classrooms? To answer this question, we conducted a systematic literature review based on three publication databases (Web of Science, ERIC, and EBSCO Teacher Referral Center). This literature review paper is intended to contribute to the current state of the role of mathematics in STEM education in secondary classrooms. Through the search, starting with 1910 documents, only 14 eligible documents were found. In these, mathematics is often seen as a minor matter and a means to an end in the eyes of science educators. From this, we conclude that the role of mathematics in the STEM classroom should be further strengthened. Overall, the paper highlights a major research gap, and proposes possible initial solutions to close it.

Objective: To identify circulating miRNAs associated with ovarian endometriosis (OMA), and to analyze candidate genes targeted by these miRNAs. Methods: Putative regulating miRNAs were identified through an original bioinformatics approach. We first queried the miRWalk 2.0 database to collect putative miRNA targets. Then, we matched it to a transcriptomic dataset of OMA. Moving from gene expression in the tissue to possible alterations in the patient plasma, a selection of these miRNAs was quantified by qRT-PCR in plasma samples from 93 patients with isolated OMA and 95 patients surgically checked as free from endometriosis. Then, we characterized the genes regulated by more than one miRNA and validated them by immunohistochemistry and transfection experiments on endometrial cell primary cultures obtained from endometrial biopsies of 10 women with and without endometriosis with miRNA mimics. Stromal and epithelial cells were isolated and cultured separately and gene expression levels were measured by RT-qPCR. Results: Eight miRNAs were identified by bioinformatics analysis. Two of them were overexpressed in plasma from OMA patients: let-7b-5p and miR-92a-3p (p < 0.005). Three miRNAs, let-7b and miR-92a-3p, and miR-93-5p potentially targeted KIAA1324, an estrogen-responsive gene and one of the most downregulated genes in OMA. Transfection experiments with mimics of these two miRNAs showed a strong decrease in KIAA1324 expression, up to 40%. Immunohistochemistry revealed a moderate-to-intense staining for KIAA1324 in the eutopic endometrium and a faint-to-moderate staining in the ectopic endometrium for half of the samples, which is concordant with the transcriptomic data. Discussion and Conclusion: Our results suggested that KIAA1324 might be involved in endometriosis through the downregulating action of two circulating miRNAs. As these miRNAs were found to be overexpressed, their quantification in plasma could provide a tool for an early diagnosis of endometriosis.

Selection for the number of living pigs on day 11 (L11) aims to reduce piglet mortality and increase litter size simultaneously. This approach could be sub-optimal, especially for organic pig breeding. This study evaluated the effect of selecting for a trait by separating it into two traits. Genetic parameters for L11, the total number born (TNB), and the number of dead piglets at day 11 (D11) were estimated using data obtained from an organic pig population in Denmark. Based on these estimates, two alternative breeding schemes were simulated. Specifically, selection was made using: (1) a breeding goal with L11 only versus (2) a breeding goal with TNB and D11. Different weightings for TNB and D11 were tested. The simulations showed that selection using the first breeding scheme (L11) produced lower annual genetic gain (0.201) compared to the second (TNB and D11; 0.207). A sensitivity analysis showed that the second scheme performed better because it exploited differences in heritability, and accounted for genetic correlations between the two traits. When the second breeding scheme placed more emphasis on D11, D11 declined, whereas genetic gain for L11 remained high (0.190). In conclusion, selection for L11 could be optimized by separating it into two correlated traits with different heritability, reducing piglet mortality and enhancing L11.

Hyperglycemia-induced oxidative stress plays a key role in the impairment of the retinal neurovascular unit, an early event in the pathogenesis of DR. The aim of this study was to assess the antioxidant properties of topical administration (eye drops) of sitagliptin in the diabetic retina. For this purpose, db/db mice received sitagliptin or vehicle eye drops twice per day for two weeks. Age-matched db/+ mice were used as the control group. We evaluated retinal mRNA (RT-PCR) and protein levels (Western blotting and immunohistochemistry) of different components from both the antioxidant system (NRF2, CAT, GPX, GR, CuZnSOD, and MnSOD) and the prooxidant machinery (PKC and TXNIP). We also studied superoxide levels (dihydroethidium staining) and oxidative damage to DNA/RNA (8-hydroxyguanosine immunostaining) and proteins (nitrotyrosine immunostaining). Finally, NF-кB translocation and IL-1β production were assessed through Western blotting and/or immunohistochemistry. We found that sitagliptin protected against diabetes-induced oxidative stress by reducing superoxide, TXNIP, PKC, and DNA/RNA/protein oxidative damage, and it prevented the downregulation of NRF2 and antioxidant enzymes, with the exception of catalase. Sitagliptin also exerted anti-inflammatory effects, avoiding both NF-кB translocation and IL-1β production. Sitagliptin prevents the diabetes-induced imbalance between ROS production and antioxidant defenses that occurs in diabetic retinas.

Despite improved therapeutic and clinical outcomes for patients with localized diseases, outcomes for pediatric and AYA sarcoma patients with high-grade or aggressive disease are still relatively poor. With advancements in next generation sequencing (NGS), precision medicine now provides a strategy to improve outcomes in patients with aggressive disease by identifying biomarkers of therapeutic sensitivity or resistance. The integration of NGS into clinical decision making not only increases the accuracy of diagnosis and prognosis, but also has the potential to identify effective and less toxic therapies for pediatric and AYA sarcomas. Genome and transcriptome profiling have detected dysregulation of the CDK4/6 cell cycle regulatory pathway in subpopulations of pediatric and AYA OS, RMS, and EWS. In these patients, the inhibition of CDK4/6 represents a promising precision medicine-guided therapy. There is a critical need, however, to identify novel and promising combination therapies to fight the development of resistance to CDK4/6 inhibition. In this review, we offer rationale and perspective on the promise and challenges of this therapeutic approach.

Valosin-containing protein (VCP) acts as a key regulator of cellular protein homeostasis by coordinating protein turnover and quality control. Mutations in VCP lead to (cardio-)myopathy and neurodegenerative diseases such as inclusion body myopathy with Paget’s disease of the bone and frontotemporal dementia (IBMPFD) or amyotrophic lateral sclerosis (ALS). To date, due to embryonic lethality, no constitutive VCP knockout animal model exists. Here, we generated a constitutive CRISPR/Cas9-induced vcp knockout zebrafish model. Similar to the phenotype of vcp morphant knockdown zebrafish embryos, we found that vcp-null embryos displayed significantly impaired cardiac and skeletal muscle function. By ultrastructural analysis of skeletal muscle cells and cardiomyocytes, we observed severely disrupted myofibrillar organization and accumulation of inclusion bodies as well as mitochondrial degeneration. vcp knockout was associated with a significant accumulation of ubiquitinated proteins, suggesting impaired proteasomal function. Additionally, markers of unfolded protein response (UPR)/ER-stress and autophagy-related mTOR signaling were elevated in vcp-deficient embryos, demonstrating impaired proteostasis in VCP-null zebrafish. In conclusion, our findings demonstrate the successful generation of a stable constitutive vcp knockout zebrafish line that will enable characterization of the detailed mechanistic underpinnings of vcp loss, particularly the impact of disturbed protein homeostasis on organ development and function in vivo.

There was an error in the original publication [...]

The inter-fiber failure of glass fiber-reinforced epoxy specimens with four different fiber angles was analyzed. Flat specimens were subjected to static and fatigue loading considering different load levels and load ratios. Damage investigation in terms of crack density measurement was performed by transmitted white light imaging using a digital camera and LED illumination from the back of the specimen on a servo-hydraulic testing machine. Static and fatigue results were examined with respect to crack initiation and crack growth, considering the special case of bonding yarns parallel to the fiber directions. The bonding yarns act as stress concentrations, influencing the early cracking behavior, and complicate the detectability of cracks growing underneath or next to the bonding yarns. In cyclic loading, the influence of load level, load ratio, mean stress, fiber orientation, and ply thickness was the focus of the experimental campaign. Cyclic cracking behavior in terms of initiation and growth was analyzed based on the applied loading conditions and laminate configurations. It was found that halving the ply thickness nearly doubled the amount of microcracks in case of high loads. For low loads, no such effect was observed up to 5×105 loading cycles. Experimental findings on individual crack growth confirmed that crack interaction started for crack spacings less than four times the ply thickness and that subsequent crack growth shifted into regions of larger local crack spacing.

Genome-wide association studies are a robust means of identifying candidate genes that regulate economically important traits in farm animals. The aim of this study is to identify single-nucleotide polymorphisms (SNPs) and candidate genes potentially related to carcass depth and hind leg circumference in Simmental beef cattle. We performed Illumina Bovine HD Beadchip (~670 k SNPs) and next-generation sequencing (~12 million imputed SNPs) analyses of data from 1252 beef cattle, to which we applied a linear mixed model. Using a statistical threshold (p = 0.05/number of SNPs identified) and adopting a false discovery rate (FDR), we identified many putative SNPs on different bovine chromosomes. We identified 12 candidate genes potentially annotated with the markers identified, including CDKAL1 and E2F3, related to myogenesis and skeletal muscle development. The identification of such genes in Simmental beef cattle will help breeders to understand and improve related traits, such as meat yield.

Ischemic conditioning and exercise have been suggested for protecting against brain ischemia-reperfusion injury. However, the endogenous protective mechanisms stimulated by these interventions remain unclear. Here, in a comprehensive translational study, we investigated the protective role of extracellular vesicles (EVs) released after remote ischemic conditioning (RIC), blood flow restricted resistance exercise (BFRRE), or high-load resistance exercise (HLRE). Blood samples were collected from human participants before and at serial time points after intervention. RIC and BFRRE plasma EVs released early after stimulation improved viability of endothelial cells subjected to oxygen-glucose deprivation. Furthermore, post-RIC EVs accumulated in the ischemic area of a stroke mouse model, and a mean decrease in infarct volume was observed for post-RIC EVs, although not reaching statistical significance. Thus, circulating EVs induced by RIC and BFRRE can mediate protection, but the in vivo and translational effects of conditioned EVs require further experimental verification.

A high consumption of discretionary foods and drinks has been associated with increased risk of multiple adverse health outcomes, including risk of overweight and dental caries. The family-based cluster randomized intervention study “Are you too sweet?” aimed at reducing the intake of discretionary foods and drinks in a population of children starting pre-school. As part of the intervention a new short web-based sugar-rich food screener (SRFS), was developed to make the parents and the school health nurses aware of the children’s intake of discretionary foods and drinks. In addition to the short assessment tool the parents also completed a validated web-based 7-day dietary record for the children. In the present study, estimates for intake of discretionary foods and drinks from the two assessment tools were compared (n = 80). There was significant correlation between estimates from the two assessment tools, but the SRFS provided lower estimates for intake of discretionary foods and drinks compared to the 7-day dietary record. The correlation coefficient between the two assessment tools was 0.49 (p < 0.001) and Kappa coefficient was 0.33. It is concluded that the SRFS can provide a fairly ranking of participants according to their intake of discretionary foods and drinks when compared to a validated 7-day dietary record. The screener may be a useful tool in practical settings, such as school health nurse consultations, in order to gain insight into the child’s sweet intake habits.

Current organic pig-breeding programs use pigs from conventional breeding populations. However, there are considerable differences between conventional and organic production systems. This simulation study aims to evaluate how the organic pig sector could benefit from having an independent breeding program. Two organic pig-breeding programs were simulated: one used sires from a conventional breeding population (conventional sires), and the other used sires from an organic breeding population (organic sires). For maintaining the breeding population, the conventional population used a conventional breeding goal, whereas the organic population used an organic breeding goal. Four breeding goals were simulated: one conventional breeding goal, and three organic breeding goals. When conventional sires were used, genetic gain in the organic population followed the conventional breeding goal, even when an organic breeding goal was used to select conventional sires. When organic sires were used, genetic gain followed the organic breeding goal. From an economic point of view, using conventional sires for breeding organic pigs is best, but only if there are no genotype-by-environment interactions. However, these results show that from a biological standpoint, using conventional sires biologically adapts organic pigs for a conventional production system.

The neurovascular unit (NVU) plays an essential role in the development of diabetic retinopathy (DR). We previously reported that the topical administration (eye drops) of sitagliptin and saxagliptin, two dipeptidyl peptidase-4 inhibitors (DPP-4i), prevents retinal neurodegeneration and vascular leakage in db/db mice. The aim of the present study is to evaluate the minimum effective dose of the topical administration of these DPP-4i. For this purpose, sitagliptin and saxagliptin were tested at different concentrations (sitagliptin: 1 mg/mL, 5 and 10 mg/mL, twice per day; saxagliptin: 1 and 10 mg/mL, once or twice per day) in db/db mice. As end points of efficacy, the hallmarks of NVU impairment were evaluated: reactive gliosis, neural apoptosis, and vascular leakage. These parameters were assessed by immunohistochemistry, cell counting, and the Evans blue method, respectively. Our results demonstrated that the minimum effective dose is 5 mg/mL twice per day for sitagliptin, and 10 mg/mL twice per day for saxagliptin. In conclusion, this study provides useful results for the design of future preclinical regulatory studies and for planning clinical trials.

The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. In total, N = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95%CI 1.02–2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95%CI 1.05–3.76]), and not significant on DOAC treatment (OR 1.52 [95%CI 0.63–3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance.

In poikilothermic vertebrates, seasonality influences different immunological parameters such as leukocyte numbers, phagocytic activity, and antibody titers. This phenomenon has been described in different teleost species, with immunological parameters peaking during warmer months and decreased levels during winter. In this study, the cellular immune responses of rainbow trout (Oncorhynchus mykiss) kept under constant photoperiod and water temperature against intraperitoneally injected Aeromonas salmonicida during the summer and winter were investigated. The kinetics of different leukocyte subpopulations from peritoneal cavity, spleen, and head kidney in response to the bacteria was measured by flow cytometry. Furthermore, the kinetics of induced A. salmonicida-specific antibodies was evaluated by ELISA. Despite maintaining the photoperiod and water temperature as constant, different cell baselines were detected in all organs analyzed. During the winter months, B- and T-cell responses were decreased, contrary to what was observed during summer months. However, the specific antibody titers were similar between the two seasons. Natural antibodies, however, were greatly increased 12 h post-injection only during the wintertime. Altogether, our results suggest a bias toward innate immune responses and potential lymphoid immunosuppression in the wintertime in trout. These seasonal differences, despite photoperiod and water temperature being kept constant, suggest an internal inter-seasonal or circannual clock controlling the immune system and physiology of this teleost fish.

The objective of this study was to use a model to predict breeding values for sires and cows at an early stage of the first lactation of cows and progeny groups in the Iranian Holstein population to enable the early selection of sires. An additional objective was to estimate genetic and phenotypic parameters associated with this model. The accuracy of predicted breeding values was investigated using cross-validation based on sequential genetic evaluations emulating yearly evaluation runs. The data consisted of 2,166,925 test-day records from 456,712 cows calving between 1990 and 2015. (Co)-variance components and breeding values were estimated using a random regression test-day model and the average information (AI) restricted maximum likelihood method (REML). Legendre polynomial functions of order three were chosen to fit the additive genetic and permanent environmental effects, and a homogeneous residual variance was assumed throughout lactation. The lowest heritability of daily milk yield was estimated to be just under 0.14 in early lactation, and the highest heritability of daily milk yield was estimated to be 0.18 in mid-lactation. Cross-validation showed a highly positive correlation of predicted breeding values between consecutive yearly evaluations for both cows and sires. Correlation between predicted breeding values based only on records of early lactation (5–90 days) and records including late lactation (181–305 days) were 0.77–0.87 for cows and 0.81–0.94 for sires. These results show that we can select sires according to their daughters’ early lactation information before they finish the first lactation. This can be used to decrease generation interval and to increase genetic gain in the Iranian Holstein population.

Growing evidence suggests that maternal exposure to ambient fine particulate matter (PM2.5) during pregnancy is associated with preterm birth; however, few studies have examined critical windows of exposure, which can help elucidate underlying biologic mechanisms and inform public health messaging for limiting exposure. Participants included 891 mother–newborn pairs enrolled in a U.S.-based pregnancy cohort study. Daily residential PM2.5 concentrations at a 1 × 1 km2 resolution were estimated using a satellite-based hybrid model. Gestational age at birth was abstracted from electronic medical records and preterm birth (PTB) was defined as 2.5 exposure in relation to the odds of PTB and examined sex-specific associations using stratified models. The mean ± standard deviation PM2.5 level averaged across pregnancy was 8.13 ± 1.10 µg/m3. PM2.5 exposure was not associated with an increased odds of PTB during any gestational week. In sex-stratified models, we observed a marginal increase in the odds of PTB with exposure occurring during gestational week 16 among female infants only. This study does not provide strong evidence supporting an association between weekly exposure to PM2.5 and preterm birth.

Tsetse flies cause major health and economic problems as they transmit trypanosomes causing sleeping sickness in humans (Human African Trypanosomosis, HAT) and nagana in animals (African Animal Trypanosomosis, AAT). A solution to control the spread of these flies and their associated diseases is the implementation of the Sterile Insect Technique (SIT). For successful application of SIT, it is important to establish and maintain healthy insect colonies and produce flies with competitive fitness. However, mass production of tsetse is threatened by covert virus infections, such as the Glossina pallidipes salivary gland hypertrophy virus (GpSGHV). This virus infection can switch from a covert asymptomatic to an overt symptomatic state and cause the collapse of an entire fly colony. Although the effects of GpSGHV infections can be mitigated, the presence of other covert viruses threaten tsetse mass production. Here we demonstrated the presence of two single-stranded RNA viruses isolated from Glossina morsitans morsitans originating from a colony at the Seibersdorf rearing facility. The genome organization and the phylogenetic analysis based on the RNA-dependent RNA polymerase (RdRp) revealed that the two viruses belong to the genera Iflavirus and Negevirus, respectively. The names proposed for the two viruses are Glossina morsitans morsitans iflavirus (GmmIV) and Glossina morsitans morsitans negevirus (GmmNegeV). The GmmIV genome is 9685 nucleotides long with a poly(A) tail and encodes a single polyprotein processed into structural and non-structural viral proteins. The GmmNegeV genome consists of 8140 nucleotides and contains two major overlapping open reading frames (ORF1 and ORF2). ORF1 encodes the largest protein which includes a methyltransferase domain, a ribosomal RNA methyltransferase domain, a helicase domain and a RdRp domain. In this study, a selective RT-qPCR assay to detect the presence of the negative RNA strand for both GmmIV and GmmNegeV viruses proved that both viruses replicate in G. m. morsitans. We analyzed the tissue tropism of these viruses in G. m. morsitans by RNA-FISH to decipher their mode of transmission. Our results demonstrate that both viruses can be found not only in the host’s brain and fat bodies but also in their reproductive organs, and in milk and salivary glands. These findings suggest a potential horizontal viral transmission during feeding and/or a vertically viral transmission from parent to offspring. Although the impact of GmmIV and GmmNegeV in tsetse rearing facilities is still unknown, none of the currently infected tsetse species show any signs of disease from these viruses.

A major obstacle to obtaining cost-effective experimental data on the fatigue life of sandwich panels is the prohibitive amount of time and cost required to carry out millions of cycles. On the other hand, vibration techniques applied to sandwich geometries fail to match the stress patterns that are obtained from standard flexural fatigue tests. To overcome such limitations, a vibration-based fatigue technique is proposed, which entails the use of sandwich specimens whose geometries are optimized to reproduce the stress distribution observed during three point bend loading while vibrating at the first resonant frequency. The proposed vibration technique was experimentally validated. The results, compared with the average number of cycles to failure at different stress ratios obtained via the Three-Point Bending test, showed high levels of accuracy. The proposed method is robust and time effective and indicates the possibility of attaining fatigue lifetime prediction of a wide class of composite elements, such as sandwich panels.

Background: Despite the risk for complications, allograft surveillance after orthotopic heart transplantation (OHT) is performed by cardiac catheterization and biopsies. We investigated the diagnostic and prognostic value of a TDI-derived systolic wall motion analysis of the posterobasal wall of the left ventricle (Sm) as a screening modality in OHT aftercare. Methods: We examined data of 210 eligible patients who underwent OHT between 2010 and 2020. Forty-four patients who had died within the initial hospital stay were excluded. For 166 patients, baseline and follow-up data were analyzed. The mean age at OHT was 46.2 (±11.4) years; 76.5% were male. Results: Within the observational period, 22 (13.3%) patients died. In total, 170 episodes of acute cellular or humoral rejections occurred (84 ISHLT1R; 13 ISHLT2R; 8 ISHLT3R; 65 AMR), and 29 catheterizations revealed cardiac allograft vasculopathy (5 CAV1; 4 CAV2; 20 CAV3). Individual Sm radial/longitudinal remained stable within the follow-up period (11.5 ± 2.2 cm/s; 10.9 ± 2.1 cm/s). Patients with acute rejections and CAV3 showed significant Sm radial/longitudinal reductions (AMR1: 1.6 ± 1.9 cm/s, confidence interval (CI) 0.77–0.243, p < 0.001; 1.8 ± 2.0 cm/s, CI 0.92–0.267, p < 0.001. ISHLT1R: 1.7 ± 1.8 cm/s, CI 1.32–2.08, p < 0.001; 2.0 ± 1.6 cm/s, CI 1.66–2.34, p < 0.001. CAV3: 1.3 ± 2.5 cm/s, CI 0.23–2.43, p < 0.017; 1.4 ± 2.8 cm/s, CI 0.21–2.66, p < 0.021). Lower Sm was associated with a threefold increase in all-cause mortality (hazard ratio (HR) 3.24, CI 1.2–8.76, p = 0.020; HR 2.92, CI 1.19–7.18, p = 0.019). Overall, Sm-triggered surveillance led to 0.75 invasive diagnostics per patient post-OHT year. Conclusions: Sm remained stable in the post-OHT course. Reductions indicated ISHLT1R, AMR1 and CAV3 and were associated with higher all-cause mortality. Sm-triggered surveillance may be referred to as a safe, high-yield screening modality in OHT aftercare.

Pharmacogenomic (PGx) evidence for selective serotonin reuptake inhibitors (SSRIs) continues to evolve. For sites offering testing, maintaining up-to-date interpretations and implementing new clinical decision support (CDS) driven by existing results creates practical and technical challenges. Vanderbilt University Medical Center initiated panel testing in 2010, added CYP2D6 testing in 2017, and released CDS for SSRIs in 2020. We systematically reinterpreted historic CYP2C19 and CYP2D6 genotypes to update phenotypes to current nomenclature and to launch provider CDS and patient-oriented content for SSRIs. Chart review was conducted to identify and recontact providers caring for patients with current SSRI therapy and new actionable recommendations. A total of 15,619 patients’ PGx results were reprocessed. Of the non-deceased patients reprocessed, 21% (n = 3278) resulted in CYP2C19*1/*17 reinterpretations. Among 289 patients with an actionable recommendation and SSRI medication prescription, 31.8% (n = 92) did not necessitate contact of a clinician, while 43.2% (n = 125) resulted in clinician contacted, and for 25% (n = 72) no appropriate clinician was able to be identified. Maintenance of up-to-date interpretations and recommendations for PGx results over the lifetime of a patient requires continuous effort. Reprocessing is a key strategy for maintenance and expansion of PGx content to be periodically considered and implemented.

The effects of surface pretreatment (water and alkali) and modification with silane on moisture sorption, water resistance, and reaction to fire of hemp fiber reinforced polylactic acid (PLA) composites at two fiber loading contents (30 and 50 wt.%) are investigated in this work. Moisture adsorption was evaluated at 30, 50, 75 and 95% relative humidity, and water resistance was determined after a 28-day immersion period. The cone calorimetry technique was used to investigate response to fire. The fiber surface treatment resulted in the removal of cell wall components, which increased fiber individualization and homogeneity as shown in scanning microscopic pictures of the composite cross-section. Although the improved fiber/matrix bonding increased the composite’s water resistance, the different fiber treatments generated equal moisture adsorption results for the 30 wt.% reinforced composites. Overall, increasing the fiber amount from 30 to 50 wt.% increased the composite sensitivity to moisture/water, mainly due to the availability of more hydroxyl groups and to the development of a higher pore volume, but fire protection improved due to a reduction in the rate of thermal degradation induced by the reduced PLA content. The new Oswin’s model predicted the composite adsorption isotherm well. The 30 wt.% alkali and silane treated hemp fiber composite had the lowest overall adsorption (9%) while the 50 wt.% variant produced the highest ignition temperature (181 ± 18 °C).

In the human heart, the energy supplied by the production of ATP is predominately accomplished by ß-oxidation in mitochondria, using fatty acids (FAs) as the primary fuel. Long-chain acylcarnitines (LCACs) are intermediate forms of FA transport that are essential for FA delivery from the cytosol into mitochondria. Here, we analyzed the impact of the LCACs C18 and C18:1 on mitochondrial function and, subsequently, on heart functionality in the in vivo vertebrate model system of zebrafish (Danio rerio). Since LCACs are formed and metabolized in mitochondria, we assessed mitochondrial morphology, structure and density in C18- and C18:1-treated zebrafish and found no mitochondrial alterations compared to control-treated (short-chain acylcarnitine, C3) zebrafish embryos. However, mitochondrial function and subsequently ATP production was severely impaired in C18- and C18:1-treated zebrafish embryos. Furthermore, we found that C18 and C18:1 treatment of zebrafish embryos led to significantly impaired cardiac contractile function, accompanied by reduced heart rate and diminished atrial and ventricular fractional shortening, without interfering with cardiomyocyte differentiation, specification and growth. In summary, our findings provide insights into the direct role of long-chain acylcarnitines on vertebrate heart function by interfering with regular mitochondrial function and thereby energy allocation in cardiomyocytes.

This study investigates the dependence between extreme returns of West Texas Intermediate (WTI) crude oil prices and the Crude Oil Volatility Index (OVX) changes as well as the predictive power of OVX to generate accurate Value at Risk (VaR) forecasts for crude oil. We focus on the COVID-19 pandemic period as the most violate in the history of the oil market. The static and dynamic conditional copula methodology is used to measure the tail dependence coefficient (TDC) between the variables. We found a strong relationship in the tail dependence between negative returns on crude oil and OVX changes and the tail independence for positive returns. The time-varying copula discloses the strongest tail dependence of negative oil price shocks and the index changes during the COVID-19 health crisis. The findings indicate the ability of the OVX index to be a fear gauge with respect to the oil market. However, we cannot confirm the ability of OVX to improve one day-ahead forecasts of the Value at Risk. The impact of investors’ expectations embedded in OVX on VaR forecasts seems to be negligible.

During the development of the nervous system, synaptogenesis occurs in excess though only the appropriate connections consolidate. At the neuromuscular junction, competition between several motor nerve terminals results in the maturation of a single axon and the elimination of the others. The activity-dependent release of transmitter, cotransmitters, and neurotrophic factors allows the direct mutual influence between motor axon terminals through receptors such as presynaptic muscarinic ACh autoreceptors and the tropomyosin-related kinase B neurotrophin receptor. In previous studies, we investigated the synergistic and antagonistic relations between these receptors and their downstream coupling to PKA and PKC pathways and observed a metabotropic receptor-driven balance between PKA (stabilizes multinnervation) and PKC (promotes developmental axonal loss). However, how much does each kinase contribute in the developmental synapse elimination process? A detailed statistical analysis of the differences between the PKA and PKC effects in the synapse elimination could help to explore this point. The present short communication provides this analysis and results show that a similar level of PKA inhibition and PKC potentiation would be required during development to promote synapse loss.

This randomized clinical study examined the influence of the gingival condition—healthy versus mild inflammation—on sulcus representation and possible gingival recession for two gingival displacement procedures prior to conventional impression making. The interventions double cord technique or a kaolin paste containing aluminum chloride were applied to 40 probands. The opposite quadrant served as intrapersonal reference (split-mouth design). Precision impressions were then made. Extraoral digitization of the plaster models resulting from the reference impression prior to gingival displacement, the intervention impression and control impressions were the basis for the computer-aided three-dimensional analysis. After six months, a mild artificial gingivitis was induced, and the contralateral quadrant (cross-over design) was examined for the intervention. The gingivitis deteriorated the sulcus representation for the double cord technique group but did not affect the paste technique group. The gingival condition had no influence on the marginal gingiva height changes. The minor extent of those changes, which were measured up to six months after intervention at the palatal study site, were not considered to be in the clinically relevant range for gingival recession. For healthy gingiva, the cord technique showed superior sulcus representation compared to the paste technique. This advantage was lost to a great extent under the conditions of mild gingivitis.