Development of a recommendation system and data analysis in personalized medicine: an approach towards healthy vascular ageing.

Purpose: Understanding early vascular ageing has become crucial for preventing adverse cardiovascular events. To this respect, recent AI-based risk clustering models offer early detection strategies focused on healthy populations, yet their complexity limits clinical use. This work introduces a novel recommendation system embedded in a web app to assess and mitigate early vascular ageing risk, leading patients towards improved cardiovascular health. Methods: This system employs a methodology that calculates distances within multidimensional spaces and integrates cost functions to obtain personalized optimisation of recommendations. It also incorporates a classification system for determining the intensity levels of the clinical interventions. Results: The recommendation system showed high efficiency in identifying and visualizing individuals at high risk of early vascular ageing among healthy patients. Additionally, the system corroborated its consistency and reliability in generating personalized recommendations among different levels of granularity, emphasizing its focus on moderate or low-intensity recommendations, which could improve patient adherence to the intervention. Conclusion: This tool might significantly aid healthcare professionals in their daily analysis, improving the prevention and management of cardiovascular diseases.

Mucormycosis in Liver Allograft Following Transplant for Secondary Biliary Cirrhosis.

Mucormycosis, a group of opportunistic mycoses caused by Mucorales, present a significant threat to immunocompromised patients. In this report, we present the case of a 57-year-old male patient who underwent liver transplant for secondary biliary cirrhosis following inadvertent bile duct injury. Despite initial satisfactory postoperative evolution, the patient developed fever, and imaging revealed a suspicious lesion. Preliminary culture growth suggested a filamentous fungus, leading to initiation of liposomal amphotericin B. However, the lesion progressed, and a surgical debridement was necessary. During surgery, involvement of the liver dome and diaphragm was observed, and a nonanatomical hepatectomy was performed. Despite efforts, the patient's condition deteriorated, ultimately resulting in multiple organ failure and mortality. This case emphasizes the challenging nature of mucormycosis in livertransplant recipients.

Effectiveness of Extracorporeal Shock Wave Therapy in Treatment of Spasticity of Different Aetiologies: A Systematic Review and Meta-Analysis.

Background: Spasticity is a motor disorder characterised by exaggerated movements of the tendons and accompanied by hyperreflexia and hypertonia. Extracorporeal shock wave therapy (ESWT) is used as a treatment for spasticity, although more evidence is needed on the effectiveness of this therapy in the treatment of spasticity. Therefore, the aim of this study was to assess the effectiveness ESWT in the treatment of upper and lower limbs spasticity in both children and adults through different aetiologies. Methods: A systematic search was performed in different databases from inception to December 2023. Random-effects meta-analysis was used to estimate the efficacy of ESWT on spasticity using the Modified Ashworth Scale. Results: Sixteen studies were included in the systematic review and meta-analysis. The effect of ESWT on spasticity measured with the Modified Ashworth Scale shows a significant decrease in spasticity in the upper limbs and in the lower limbs in adults with chronic stroke and in children with cerebral palsy, is more effective immediately after application, and maintains its effect up to 12 weeks post treatment. Conclusions: These findings are important for clinical practice since they show evidence that ESWT is effective in reducing spasticity in both children and adults.

Effect of Botulinum Toxin Injections in the Treatment of Spasticity of Different Etiologies: An Umbrella Review.

BACKGROUND: Spasticity is a very common neurological sequelae that significantly impacts the quality of life of patients, affecting more than 12 million people worldwide. Botulinum toxin is considered a reversible treatment for spasticity, but due to the large amount of available evidence, synthesis seems necessary. Therefore, we conducted an overview of existing systematic reviews and meta-analyses to evaluate the effect of botulinum toxin injections in the treatment of spasticity of different etiologies. METHODS: A systematic search of different databases, including Pubmed, Scopus, the Cochrane Library, and Web of Science, was performed from inception to February 2024. Standardized mean differences (SMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the effect of botulinum toxin compared to that of the control treatment using the Modified Ashworth Scale (MAS). All the statistical analyses were performed using STATA 15 software. RESULTS: 28 studies were included in the umbrella review. The effect of botulinum toxin injections on spasticity, as measured by the MAS, was significantly lower in all but three studies, although these studies also supported the intervention. The SMDs reported by the meta-analyses ranged from -0.98 to -0.01. CONCLUSION: Botulinum toxin injections were effective at treating spasticity of different etiologies, as indicated by the measurements on the MAS. This implies an improvement in muscle tone and, consequently, in the patient's mobility and quality of life.

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 [...].

Enhancing Control of Leishmania infantum Infection: A Multi-Epitope Nanovaccine for Durable T-Cell Immunity.

Canine leishmaniosis (CanL) is a growing health problem for which vaccination is a crucial tool for the control of disease. The successful development of an effective vaccine against this disease relies on eliciting a robust and enduring T-cell immune response involving the activation of CD4+ Th1 and CD8+ T-cells. This study aimed to evaluate the immunogenicity and prophylactic efficacy of a novel nanovaccine comprising a multi-epitope peptide, known as HisDTC, encapsulated in PLGA nanoparticles against Leishmania infantum infection in the murine model. The encapsulation strategy was designed to enhance antigen loading and sustain release, ensuring prolonged exposure to the immune system. Our results showed that mice immunized with PLGA-encapsulated HisDTC exhibited a significant reduction in the parasite load in the liver and spleen over both short and long-term duration. This reduction was associated with a cellular immune profile marked by elevated levels of pro-inflammatory cytokines, such as IFN-γ, and the generation of memory T cells. In conclusion, the current study establishes that PLGA-encapsulated HisDTC can promote effective and long-lasting T-cell responses against L. infantum in the murine model. These findings underscore the potential utility of multi-epitope vaccines, in conjunction with appropriate delivery systems, as an alternative strategy for CanL control.

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.

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.

Chromosome-Mediated Colistin Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli: Mutation Analysis in the Light of Genetic Background.

Purpose: Colistin resistance mechanisms involving mutations in chromosomal genes associated with LPS modification are not completely understood. Mutations in genes coding for the MgrB regulator frequently account for colistin resistance in Klebsiella pneumoniae, whereas mutations in genes coding for PhoPQ and PmrAB are frequent in E. coli. Our aim was to perform a genetic analysis of chromosomal mutations in colistin-resistant (MIC ≥4 µg/mL) clinical isolates of K. pneumoniae (n = 8) and E. coli (n = 7) of different STs. Methods: Isolates were obtained in a 3-year period in a university hospital in Santiago, Chile. Susceptibility to colistin, aminoglycosides, cephalosporins, carbapenems and ciprofloxacin was determined through broth microdilution. Whole genome sequencing was performed for all isolates and chromosomal gene sequences were compared with sequences of colistin-susceptible isolates of the same sequence types. Results: None of the isolates carried mcr genes. Most of the isolates were susceptible to all the antibiotics analyzed. E. coli isolates were ST69, ST127, ST59, ST131 and ST14, and K. pneumoniae isolates were ST454, ST45, ST6293, ST380 and ST25. All the isolates had mutations in chromosomal genes analyzed. K. pneumoniae had mutations mainly in mgrB gene, whereas E. coli had mutations in pmrA, pmrB and pmrE genes. Most of the amino acid changes in LPS-modifying enzymes of colistin-resistant isolates were found in colistin-susceptible isolates of the same and/or different ST. Eleven of them were found only in colistin-resistant isolates. Conclusion: Colistin resistance mechanisms depend on genetic background, and are due to chromosomal mutations, which implies a lower risk of transmission than plasmid-mediated genes. Colistin resistance is not associated with multidrug-resistance, nor to high-risk sequence types.

Fecal occult blood and calprotectin testing to prioritize primary care patients for colonoscopy referral: The advantage study.

BACKGROUND: Colonoscopy is the gold standard for colorectal cancer (CRC) diagnosis and screening, but endoscopy services are usually overburdened. This study aims to investigate the usefulness of fecal hemoglobin (fHb) and calprotectin (FC) for the identification of patients with high probability of CRC who need urgent referral. METHODS: In a multicenter prospective study, we enrolled symptomatic patients referred from primary care for colonoscopy. Prior to bowel preparation, fHb and FC quantitative tests were performed. The diagnostic performance was estimated for each biomarker/combination. We built a multivariable predictive model based on logistic regression, translated to a nomogram and a risk calculator to assist clinicians in the decision-making process. RESULTS: The study included 1224 patients, of whom 69 (5.6%) had CRC. At the fHb cut-offs of >0 and 10 µg/g, the negative predictive values for CRC were 98.8% (95% confidence interval 97.8%-99.3%) and 98.6% (95%CI 97.7%-99.1%), and the sensitivities were 85.5% (95%CI 75.0%-92.8%) and 79.7% (95%CI 68.3%-88.4%), respectively. When we added the cut-off of 150 µg/g of FC to both fHb thresholds, the sensitivity of fecal tests improved. In the multivariate logistic regression model, the concentration of fHb was an independent predictor for CRC; age and gender were also independently associated with CRC. CONCLUSIONS: fHb and FC are useful as part of a triage tool to identify those symptomatic patients with high probability of CRC. This can be easily applied by physicians to prioritize high-risk patients for urgent colonoscopy.

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.

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.

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.

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.

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.

MIDO GDM: an innovative artificial intelligence-based prediction model for the development of gestational diabetes in Mexican women.

Given the barriers to early detection of gestational diabetes mellitus (GDM), this study aimed to develop an artificial intelligence (AI)-based prediction model for GDM in pregnant Mexican women. Data were retrieved from 1709 pregnant women who participated in the multicenter prospective cohort study 'Cuido mi embarazo'. A machine-learning-driven method was used to select the best predictive variables for GDM risk: age, family history of type 2 diabetes, previous diagnosis of hypertension, pregestational body mass index, gestational week, parity, birth weight of last child, and random capillary glucose. An artificial neural network approach was then used to build the model, which achieved a high level of accuracy (70.3%) and sensitivity (83.3%) for identifying women at high risk of developing GDM. This AI-based model will be applied throughout Mexico to improve the timing and quality of GDM interventions. Given the ease of obtaining the model variables, this model is expected to be clinically strategic, allowing prioritization of preventative treatment and promising a paradigm shift in prevention and primary healthcare during pregnancy. This AI model uses variables that are easily collected to identify pregnant women at risk of developing GDM with a high level of accuracy and precision.

Description of two cultivated and two uncultivated new Salinibacter species, one named following the rules of the bacteriological code: Salinibacter grassmerensis sp. nov.; and three named following the rules of the SeqCode: Salinibacter pepae sp. nov., Salinibacter abyssi sp. nov., and Salinibacter pampae sp. nov.

Current -omics methods allow the collection of a large amount of information that helps in describing the microbial diversity in nature. Here, and as a result of a culturomic approach that rendered the collection of thousands of isolates from 5 different hypersaline sites (in Spain, USA and New Zealand), we obtained 21 strains that represent two new Salinibacter species. For these species we propose the names Salinibacter pepae sp. nov. and Salinibacter grassmerensis sp. nov. (showing average nucleotide identity (ANI) values < 95.09% and 87.08% with Sal. ruber M31T, respectively). Metabolomics revealed species-specific discriminative profiles. Sal. ruber strains were distinguished by a higher percentage of polyunsaturated fatty acids and specific N-functionalized fatty acids; and Sal. altiplanensis was distinguished by an increased number of glycosylated molecules. Based on sequence characteristics and inferred phenotype of metagenome-assembled genomes (MAGs), we describe two new members of the genus Salinibacter. These species dominated in different sites and always coexisted with Sal. ruber and Sal. pepae. Based on the MAGs from three Argentinian lakes in the Pampa region of Argentina and the MAG of the Romanian lake Fara Fund, we describe the species Salinibacter pampae sp. nov. and Salinibacter abyssi sp. nov. respectively (showing ANI values 90.94% and 91.48% with Sal. ruber M31T, respectively). Sal. grassmerensis sp. nov. name was formed according to the rules of the International Code for Nomenclature of Prokaryotes (ICNP), and Sal. pepae, Sal. pampae sp. nov. and Sal. abyssi sp. nov. are proposed following the rules of the newly published Code of Nomenclature of Prokaryotes Described from Sequence Data (SeqCode). This work constitutes an example on how classification under ICNP and SeqCode can coexist, and how the official naming a cultivated organism for which the deposit in public repositories is difficult finds an intermediate solution.

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.

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.