Validation of an early vascular aging construct model for comprehensive cardiovascular risk assessment using external risk indicators for improved clinical utility: data from the EVasCu study.

BACKGROUND: Cardiovascular diseases (CVDs) remain a major global health concern, necessitating advanced risk assessment beyond traditional factors. Early vascular aging (EVA), characterized by accelerated vascular changes, has gained importance in cardiovascular risk assessment. METHODS: The EVasCu study in Spain examined 390 healthy participants using noninvasive measurements. A construct of four variables (Pulse Pressure, Pulse Wave Velocity, Glycated Hemoglobin, Advanced Glycation End Products) was used for clustering. K-means clustering with principal component analysis revealed two clusters, healthy vascular aging (HVA) and early vascular aging (EVA). External validation variables included sociodemographic, adiposity, glycemic, inflammatory, lipid profile, vascular, and blood pressure factors. RESULTS: EVA cluster participants were older and exhibited higher adiposity, poorer glycemic control, dyslipidemia, altered vascular properties, and higher blood pressure. Significant differences were observed for age, smoking status, body mass index, waist circumference, fat percentage, glucose, insulin, C-reactive protein, diabetes prevalence, lipid profiles, arterial stiffness, and blood pressure levels. These findings demonstrate the association between traditional cardiovascular risk factors and EVA. CONCLUSIONS: This study validates a clustering model for EVA and highlights its association with established risk factors. EVA assessment can be integrated into clinical practice, allowing early intervention and personalized cardiovascular risk management.

Aspartame and Its Microhydrated Aggregates Revealed by Laser Spectroscopy: Water-Sweetener Interactions in the Gas Phase.

The popular sweetener, aspartame, is an agonist of the tongue's sweet taste receptor. How water molecules affect its conformation or which aspartame atoms are more prone to interact with solvent are helpful questions to understand its activity in different environments. Here, the combination of IR-UV spectroscopic techniques with computational simulations has been successfully applied to characterize aspartame·water0-2 clusters, showing that the addition of water molecules simplifies the conformational panorama of aspartame, favoring the formation of folded structures by interaction with the polar part of the molecule.

Static and Dynamic Hand Gestures: A Review of Techniques of Virtual Reality Manipulation.

This review explores the historical and current significance of gestures as a universal form of communication with a focus on hand gestures in virtual reality applications. It highlights the evolution of gesture detection systems from the 1990s, which used computer algorithms to find patterns in static images, to the present day where advances in sensor technology, artificial intelligence, and computing power have enabled real-time gesture recognition. The paper emphasizes the role of hand gestures in virtual reality (VR), a field that creates immersive digital experiences through the Ma blending of 3D modeling, sound effects, and sensing technology. This review presents state-of-the-art hardware and software techniques used in hand gesture detection, primarily for VR applications. It discusses the challenges in hand gesture detection, classifies gestures as static and dynamic, and grades their detection difficulty. This paper also reviews the haptic devices used in VR and their advantages and challenges. It provides an overview of the process used in hand gesture acquisition, from inputs and pre-processing to pose detection, for both static and dynamic gestures.

Advances in Condition Monitoring of Railway Infrastructure.

In recent years, there has been a notable surge in investments directed towards developing new railway lines and revitalising existing ones, reflecting a global commitment to enhance transportation infrastructure [...].

Early vascular aging as an index of cardiovascular risk in healthy adults: confirmatory factor analysis from the EVasCu study.

BACKGROUND: The concept of early vascular aging (EVA) represents a potentially beneficial model for future research into the pathophysiological mechanisms underlying the early manifestations of cardiovascular disease. For this reason, the aims of this study were to verify by confirmatory factor analysis the concept of EVA on a single factor based on vascular, clinical and biochemical parameters in a healthy adult population and to develop a statistical model to estimate the EVA index from variables collected in a dataset to classify patients into different cardiovascular risk groups: healthy vascular aging (HVA) and EVA. METHODS: The EVasCu study, a cross-sectional study, was based on data obtained from 390 healthy adults. To examine the construct validity of a single-factor model to measure accelerated vascular aging, different models including vascular, clinical and biochemical parameters were examined. In addition, unsupervised clustering techniques (using both K-means and hierarchical methods) were used to identify groups of patients sharing similar characteristics in terms of the analysed variables to classify patients into different cardiovascular risk groups: HVA and EVA. RESULTS: Our data show that a single-factor model including pulse pressure, glycated hemoglobin A1c, pulse wave velocity and advanced glycation end products shows the best construct validity for the EVA index. The optimal value of the risk groups to separate patients is K = 2 (HVA and EVA). CONCLUSIONS: The EVA index proved to be an adequate model to classify patients into different cardiovascular risk groups, which could be valuable in guiding future preventive and therapeutic interventions.

Double Hook Perylene Diimide as a New Receptor for PAHs: An Experimental and Theoretical Study.

In a one-step reaction, we prepared a dibenzylamine perylene diimide derivative (PDI). Its double hook structure allows for self-association with a constant of Kd ∼108  M-1 determined by fluorescence. We confirmed its ability to bind PAHs using UV/Vis, fluorescence, and 1 H NMR titrations in CHCl3 . The complex formation signature in UV/vis is a new band at 567 nm. The calculated binding constants (Ka ∼104  M-1 ) follow the trend pyrene>perylene>phenanthrene>naphthalene>anthracene. Theoretical modeling of these systems using DFT ωB97X-D/6-311G(d,p) proved helpful in rationalizing the complex formation and the observed association trend. The distinctive signal in UV/vis is due to a charge transfer in the complex from orbitals in the guest to the host. SAPT(DFT) confirmed that the driving forces in the complex formation are exchange and dispersion (π-π interactions). Still, the recognition ability depends on the electrostatic component of the interaction, a minor fraction.

Reliability of confocal corneal microscopy for measurement of dendritic cell density in suspected small fiber neuropathy.

INTRODUCTION/AIMS: Dendritic cells (DCs) and their contacts with corneal nerves are described in animal models of nerve damage. Dendritic cell density (DCD) is a potential marker of immune activity in suspected small-fiber neuropathy (SFN). Here, we aim to evaluate the intra- and inter-rater reliability of DCD measurements in suspected SFN. METHODS: This retrospective study collected DCD from confocal microscopy images from the corneal sub-basal epithelium of the eye from 48 patients (mean age 49.6 ± 12.1 y, 61% female). Two examiners, each blinded to the other's examinations and measurements, assessed DCD to evaluate inter-rater reliability. For intra-rater reliability, the first examiner performed a second measurement after 14 days. DCs were classified into two cell morphological subtypes: mature and immature. RESULTS: Test-retest reliability for total DCD showed excellent agreement, with an intraclass correlation coefficient of 0.96 and inter-rater reliability intraclass correlation coefficient of 0.77. The immature cell subtype showed excellent intra-rater reliability but lower inter-rater reliability. DISCUSSION: We found that DCD measurements in the corneal sub-basal epithelium are sufficiently reliable for consideration in clinical studies of patients with suspected SFN.

Evaluation of effective coverage for type 2 diabetes in Mexican primary care health information systems: a retrospective registry analysis.

BACKGROUND: As the leading cause of disability and the fourth leading cause of premature death in Mexico, type 2 diabetes (T2D) represents a serious public health concern. The incidence of diabetes has increased dramatically in recent years, and data from the Mexican National Health and Nutrition Survey (ENSANUT) indicate that many people remain undiagnosed. Persistent socioeconomic health care barriers exacerbate this situation, as T2D morbidity and mortality are worsened in vulnerable populations, such as those without social security. We evaluated the performance of public primary health centers (PHCs) in T2D medical attention through the measure of effective coverage (EC, a combined measure of health care need, use, and quality) at national, state, health jurisdiction, and municipality levels. METHODS: This retrospective analysis used blinded data recorded during 2017 in the Non-communicable Diseases National Information System (SIC) and T2D prevalence reported in 2018 ENSANUT to evaluate the EC achieved. We included individuals ≥ 20 years old without social security who did not declare the use of private health care services. Each EC component (need, use, and quality) was estimated based on the Shengelia adapted framework. The Kruskal-Wallis test was applied to evaluate the associations among EC quintiles and demographics. RESULTS: In 2017, 26.5 million individuals, aged ≥ 20 years, without social security, and without the use of private health care services, were under the care of 12,086 PHCs. The national prevalence of T2D was 10.3%, equivalent to 2.6 million people living with T2D in need of primary health care. Large contrasts were seen among EC components between and within Mexican states. We found that only 37.1% of the above individuals received health services at PHCs and of them, 25.8% improved their metabolic condition. The national EC was 9.3%, and the range (by health jurisdiction) was 0.2%-38.6%, representing a large geographic disparity in EC. We found an evident disconnect among need, utilization, and quality rates across the country. CONCLUSIONS: Expansion and improvement of EC are urgently needed to address the growing number of people living with T2D in Mexico, particularly in states with vulnerable populations.

Aggregation of nucleobases and metabolites: Adenine-theobromine trimers.

The selection of cytosine, guanine, thymine, and adenine as components of the information biopolymers was a complex process influenced by several factors. Among them, the intermolecular interactions may have played a determinant role. Thus, a deep understanding of the intermolecular interactions between nucleobases and other prebiotic molecules may help understand the first instants of chemical evolution. Following this hypothesis, we present here a combined spectroscopic and computational study of theobromine2-adenine and thebromine-adenine2 trimers. While adenine is a nucleobase, theobromine was probably part of the prebiotic chemistry. The trimers were formed in jets and probed by a combination of UV and IR spectroscopic techniques. The spectra were interpreted in light of the predictions obtained using density-functional methods. The results suggest the existence of a subtle balance between formation of hydrogen bonds and π-π interactions. Thus, while theobromine2-adenine tends to form complex in stacked structures, theobromine-adenine2 prefers formation of planar structures, maximizing the interaction by hydrogen bonds. The small energy difference between planar and stacked structures highlights the importance of accurately modeling the dispersion forces in the functionals to produce reliable predictions.

Feasibility and outcomes of transjugular intrahepatic portosystemic shunts in infants.

BACKGROUND: Experience with transjugular intrahepatic portosystemic shunts (TIPS) in the pediatric population, especially in infants, is limited. OBJECTIVE: To evaluate the feasibility, efficacy and safety of TIPS placement in infants. MATERIALS AND METHODS: This retrospective non-comparative observational cohort study analyzed all pediatric patients < 12 months of age treated with TIPS while waiting for liver transplant between October 2018 and April 2021. The sample consisted of 10 infants with chronic liver disease. All had refractory ascites and decreased portal vein size. Their mean age ± standard deviation was 5 ± 1 months and their mean weight was 5.4 ± 1.0 kg. We calculated the pediatric end-stage liver disease score and portosystemic gradients before and after TIPS placement. We used ultrasound to check for complications and to assess the presence of ascites. We used paired-sample t-test for the mean comparison of paired variables. RESULTS: Ten TIPS procedures were performed that were technically and hemodynamically successful except for one, in which an extrahepatic portal puncture required surgical repair. Ascites resolved in three infants and was reduced in six. The portal vein size remained stable after TIPS placement. Four infants had early stent thrombosis and two had late stent thrombosis treated with angioplasty or covered stents. CONCLUSION: TIPS placement in infants is a feasible, safe and effective procedure.

A Tailored Approach to Leishmaniases Vaccination: Comparative Evaluation of the Efficacy and Cross-Protection Capacity of DNA vs. Peptide-Based Vaccines in a Murine Model.

Zoonotic leishmaniases are a worldwide public health problem for which the development of effective vaccines remains a challenge. A vaccine against leishmaniases must be safe and affordable and should induce cross-protection against the different disease-causing species. In this context, the DNA vaccine pHisAK70 has been demonstrated to induce, in a murine model, a resistant phenotype against L. major, L. infantum, and L. amazonensis. Moreover, a chimeric multiepitope peptide, HisDTC, has been obtained by in silico analysis from the histone proteins encoded in the DNA vaccine and has showed its ability to activate a potent CD4+ and CD8+ T-cell protective immune response in mice against L. infantum infection. In the present study, we evaluated the plasmid DNA vaccine pHisAK70 in comparison with the peptide HisDTC (with and without saponin) against L. major and L. infantum infection. Our preliminary results showed that both formulations were able to induce a potent cellular response leading to a decrease in parasite load against L. infantum. In addition, the DNA candidate was able to induce better lesion control in mice against L. major. These preliminary results indicate that both strategies are potentially effective candidates for leishmaniases control. Furthermore, it is important to carry out such comparative studies to elucidate which vaccine candidates are the most appropriate for further development.

Genome-wide association study for growth traits in Blanco Orejinegro and Romosinuano cattle.

Growth traits are economically important characteristics for the genetic improvement of local cattle breeds. Genome-wide association studies (GWAS) provide valuable information to enhance the understanding on the genetics of complex traits. The aim of this study was to perform a GWAS to identify genomic regions and genes associated to birth weight, weaning weight adjusted for 240 days, 16 months, and 24 months weight in Romosinuano (ROMO) and Blanco Orejinegro (BON) cattle. A single-step genomic-BLUP was implemented using 596 BON and 569 ROMO individuals that were genotyped with an Illumina BovineSNP50 BeadChip. There were 25 regions of interest identified on different chromosomes, with few of them simultaneously associated with two or more growth traits and some were common to both breeds. The gene mapping allowed to find 173 annotations on these regions, from which 49 represent potential candidate genes with known growth-related functions in cattle and other species. Among the regions that were associated with several growth traits, that at 24 - 27 MB of BTA14, has important candidate genes such as LYPLA1, XKR4, TMEM68 and PLAG1. Another region of interest at 0.40-0.77 Mb of BTA23 was identified in both breeds, containing KHDRBS2 as a potential candidate gene influencing body weight. Future studies targeting these regions could provide more knowledge to uncover the genetic architecture underlying growth traits in BON and ROMO cattle. The genomic regions and genes identified in this study could be used to improve the prediction of genetic merit for growth traits in these creole cattle breeds.

Genomic variability and population structure of six Colombian cattle breeds.

Analyses of the genetic diversity of indigenous cattle are essential for implementing conservation programs, promoting their sustainable use and maintaining productive advantages offered by these breeds in local conditions. The aim of this study was to investigate the genetic diversity and population structure of six Colombian cattle breeds: Blanco Orejinegro (BON), Costeño con Cuernos (CCC), Romosinuano (ROM), Sanmartinero (SAM), Casanareño (CAS), and Hartón del Valle (HDV). Two additional breed groups were included for comparison: Zebu (CEB) and a crossbreed of Colombian cattle breeds × Zebu. Genetic diversity within breeds was analyzed using expected heterozygosity (He), inbreeding coefficient (f), and runs of homozygosity (ROH). Population structure was assessed using model-based clustering (ADMIXTURE) and principal components analysis (PCA). Zebu cattle showed the lowest genetic diversity (He = 0.240). Breeds with the highest genetic diversity level were HDV and BON (He = 0.350 and 0.340, respectively). Inbreeding was lower for Colombian cattle breeds ranging between 0.005 and 0.045. Overall, the largest average genetic distance was found among the group of Colombian cattle breeds and Zebu, while the smallest was found between ROM and CCC. Model-based clustering revealed some level of admixture among HDV and CAS cattle which is consistent with their recent history. The results of the present study provide a useful insight on the genetic structure of Colombian cattle breeds.

Liver Transplantation as Definitive Treatment of Post-cholecystectomy Bile Duct Injury: Experience in a High-volume Repair Center.

OBJECTIVE: To analyze the perioperative and long-term outcomes of patients undergoing LT due to BDI in a tertiary care center. BACKGROUND: BDI is associated with significant morbidity and long-term impact on quality of life. LT represents the only possibility of a cure in patients with BDI who develop SBC. METHODS: Retrospective cohort study from a prospective LT database. Between 2008 and 2019, patients with SBC due to BDI after cholecystectomy and requiring LT were identified. Perioperative and long-term outcomes were analyzed. RESULTS: Among 354 LT, 12 patients underwent LT to treat post-cholecystectomy BDI and accounted for 3.4% of all LT. The median time from BDI to SBC diagnosis was 9.3 years (2.4-14). The mean time from SBC to inclusion on the waitlist was 2.4years (± 2.2). Postoperative complications occurred in 11 patients (91.6%); mainly infectious (9/12 patients, 75%), followed by renal complications (4/12 patients, 33.3%). Only 2 patients developed major complications, which were the patients who died, resulting in a 90-day mortality of 16.7%. After a mean follow-up of 40.3 months (± 42.2) survival at 1, 3, and 5 years was 83%. CONCLUSIONS: Although BDI is an unusual indication for LT worldwide, it accounted for 3.4% of all LT in our center. Although postoperative mortality remains high, LT is the only possibility of a cure, with acceptable long-term outcomes. Early referral to a tertiary care center is essential to avoid long-term complications of BDI, such as SBC.

The Waiting Game - How Cooperation Between Public and Private Hospitals Can Help Reduce Waiting Lists.

Prolonged waiting to access health care is a primary concern for nations aiming for comprehensive effective care, due to its adverse effects on mortality, quality of life, and government approval. Here, we propose two novel bargaining frameworks to reduce waiting lists in two-tier health care systems with local and regional actors. In particular, we assess the impact of 1) trading patients on waiting lists among hospitals, the 2) introduction of the role of private hospitals in capturing unfulfilled demand, and the 3) hospitals' willingness to share capacity on the system performance. We calibrated our models with 2008-2018 Chilean waiting list data. If hospitals trade unattended patients, our game-theoretic models indicate a potential reduction of waiting lists of up to 37%. However, when private hospitals are introduced into the system, we found a possible reduction of waiting lists of up to 60%. Further analyses revealed a trade-off between diagnosing unserved demand and the additional expense of using private hospitals as a back-up system. In summary, our game-theoretic frameworks of waiting list management in two-tier health systems suggest that public-private cooperation can be an effective mechanism to reduce waiting lists. Further empirical and prospective evaluations are needed.

Transcriptomic Profile of Canine DH82 Macrophages Infected by Leishmania infantum Promastigotes with Different Virulence Behavior.

Zoonotic visceral leishmaniosis caused by Leishmania infantum is an endemic disease in the Mediterranean Basin affecting mainly humans and dogs, the main reservoir. The leishmaniosis outbreak declared in the Community of Madrid (Spain) led to a significant increase in human disease incidence without enhancing canine leishmaniosis prevalence, suggesting a better adaptation of the outbreak's isolates by other host species. One of the isolates obtained in the focus, IPER/ES/2012/BOS1FL1 (BOS1FL1), has previously demonstrated a different phenotype than the reference strain MCAN/ES/1996/BCN150 (BCN150), characterized by a lower infectivity when interacting with canine macrophages. Nevertheless, not enough changes in the cell defensive response were found to support their different behavior. Thus, we decided to investigate the molecular mechanisms involved in the interaction of both parasites with DH82 canine macrophages by studying their transcriptomic profiles developed after infection using RNA sequencing. The results showed a common regulation induced by both parasites in the phosphoinositide-3-kinase-protein kinase B/Akt and NOD-like receptor signaling pathways. However, other pathways, such as phagocytosis and signal transduction, including tumor necrosis factor, mitogen-activated kinases and nuclear factor-κB, were only regulated after infection with BOS1FL1. These differences could contribute to the reduced infection ability of the outbreak isolates in canine cells. Our results open a new avenue to investigate the true role of adaptation of L. infantum isolates in their interaction with their different hosts.

Accelerating Reaction Rates of Biomolecules by Using Shear Stress in Artificial Capillary Systems.

Biomimetics is a design principle within chemistry, biology, and engineering, but chemistry biomimetic approaches have been generally limited to emulating nature's chemical toolkit while emulation of nature's physical toolkit has remained largely unexplored. To begin to explore this, we designed biophysically mimetic microfluidic reactors with characteristic length scales and shear stresses observed within capillaries. We modeled the effect of shear with molecular dynamics studies and showed that this induces specific normally buried residues to become solvent accessible. We then showed using kinetics experiments that rates of reaction of these specific residues in fact increase in a shear-dependent fashion. We applied our results in the creation of a new microfluidic approach for the multidimensional study of cysteine biomarkers. Finally, we used our approach to establish dissociation of the therapeutic antibody trastuzumab in a reducing environment. Our results have implications for the efficacy of existing therapeutic antibodies in blood plasma as well as suggesting in general that biophysically mimetic chemistry is exploited in biology and should be explored as a research area.

Exploring Epigenetic Marks by Analysis of Noncovalent Interactions.

Epigenetic marks are modest chemical modifications on DNA and histone proteins that regulate the activation or silencing of genes through modulation of the intermolecular interactions between the DNA strands and the protein machinery. The process is complex and not always well understood. One of the systems studied in greater detail is the epigenetic mark on H3K9: lysine 9 of histone 3. The degree of methylation or acetylation of this histone is linked to silencing or activation of the corresponding gene, but it is not clear which effect each mark has in gene expression. We shed light on this particular methylation process by using density functional theory (DFT) calculations. First, we built a model consisting of a DNA double strand containing three base pairs and a sequence of three amino acids of the histone's tail. Then, we computed the modulation introduced into the intermolecular interactions by each epigenetic modification: from mono- to trimethylation and acetylation. The calculations show that whereas acetylation and trimethylation result in a reduction of the DNA-peptide interaction; non-, mono-, and dimethylation increase the intermolecular interactions. Such observations compare well with the findings reported in the literature, and highlight the correlation between the balance of intermolecular forces and biological properties, simultaneously advancing quantum-mechanical studies of large biochemical systems at molecular level through the use of DFT methods.

Tracking intracellular forces and mechanical property changes in mouse one-cell embryo development.

Cells comprise mechanically active matter that governs their functionality, but intracellular mechanics are difficult to study directly and are poorly understood. However, injected nanodevices open up opportunities to analyse intracellular mechanobiology. Here, we identify a programme of forces and changes to the cytoplasmic mechanical properties required for mouse embryo development from fertilization to the first cell division. Injected, fully internalized nanodevices responded to sperm decondensation and recondensation, and subsequent device behaviour suggested a model for pronuclear convergence based on a gradient of effective cytoplasmic stiffness. The nanodevices reported reduced cytoplasmic mechanical activity during chromosome alignment and indicated that cytoplasmic stiffening occurred during embryo elongation, followed by rapid cytoplasmic softening during cytokinesis (cell division). Forces greater than those inside muscle cells were detected within embryos. These results suggest that intracellular forces are part of a concerted programme that is necessary for development at the origin of a new embryonic life.

Detection of Negative Stress through Spectral Features of Electroencephalographic Recordings and a Convolutional Neural Network.

In recent years, electroencephalographic (EEG) signals have been intensively used in the area of emotion recognition, partcularly in distress identification due to its negative impact on physical and mental health. Traditionally, brain activity has been studied from a frequency perspective by computing the power spectral density of the EEG recordings and extracting features from different frequency sub-bands. However, these features are often individually extracted from single EEG channels, such that each brain region is separately evaluated, even when it has been corroborated that mental processes are based on the coordination of different brain areas working simultaneously. To take advantage of the brain's behaviour as a synchronized network, in the present work, 2-D and 3-D spectral images constructed from common 32 channel EEG signals are evaluated for the first time to discern between emotional states of calm and distress using a well-known deep-learning algorithm, such as AlexNet. The obtained results revealed a significant improvement in the classification performance regarding previous works, reaching an accuracy about 84%. Moreover, no significant differences between the results provided by the diverse approaches considered to reconstruct 2-D and 3-D spectral maps from the original location of the EEG channels over the scalp were noticed, thus suggesting that these kinds of images preserve original spatial brain information.