Aloe vera mucilage loaded gelatin electrospun fibers contained in polylactic acid coaxial system and polylactic acid and poly(e-caprolactone) tri-layer membranes for tissue engineering.

BACKGROUND: Polymeric electrospun mats have been used as scaffolds in tissue engineering for the development of novel materials due to its characteristics. The usage of synthetic materials has gone in decline due to environmental problems associated with their synthesis and waste disposal. Biomaterials such as biopolymers have been used recently due to good compatibility on biological applications and sustainability. OBJECTIVE: The purpose of this work is to obtain novel materials based on synthetic and natural polymers for applications on tissue engineering. METHODS: Aloe vera mucilage was obtained, chemically characterized, and used as an active compound contained in electrospun mats. Polymeric scaffolds were obtained in single, coaxial and tri-layer structures, characterized and evaluated in cell culture. RESULTS: Mucilage loaded electrospun fibers showed good compatibility due to formation of hydrogen bonds between polymers and biomolecules from its structure, evidenced by FTIR spectra and thermal properties. Cell viability test showed that most of the obtained mats result on viability higher than 75%, resulting in nontoxic materials, ready to be used on scaffolding applications. CONCLUSION: Mucilage containing fibers resulted on materials with potential use on scaffolding applications due to their mechanical performance and cell viability results.

Macroplastic and Microparticle Pollution in Beach Sediments from Urias Coastal Lagoon (Northwest Mexico).

This study investigates the occurrence and characteristics of macroplastic and polymer microparticles in the Urias coastal lagoon's beach sediments, in northwest Mexico. Coastal lagoons, productive and vulnerable ecosystems, are impacted significantly by anthropogenic activities, leadings to their pollution by various contaminants, including plastics. Our research involved sampling sediments from four sites within the lagoon that were influenced by different human activities such as fishing, aquaculture, thermoelectric power plant operations, industrial operations, and domestic wastewater discharge. Our methodology included collecting macroplastics and beach sediment samples, followed by laboratory analyses to identify the plastic debris' size, shape, color, and chemical composition. The results indicated a notable presence of macroplastic items (144), predominantly bags, styrofoam, and caps made of polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET). The polymer microparticles were mainly fibers, with cotton and polyester as the most common polymers, suggesting a significant contribution from clothing-related waste. The dominant colors of the microparticles were blue and transparent. High densities were observed in areas with slower water exchange. Our findings highlight the urgent need for better waste management practices to mitigate plastic pollution in coastal lagoons, preserving their ecological and economic functions.

Impact of Inherited Thrombophilia in Women with Obstetric Antiphospholipid Syndrome: A Single-Center Study and Literature Review.

Inherited thrombophilia (IT) has been implicated as a potential causal factor of adverse pregnancy outcomes (APOs), including recurrent miscarriage with and without the presence of antiphospholipid syndrome (APS). The aim of this study was to assess the prevalence and impact of IT on fetal-maternal outcomes and thrombotic risk in women within the spectrum of obstetric APS. Three hundred and twenty-eight women with APS-related obstetric morbidity ever pregnant were included. Of these, 74 met the APS classification criteria, 169 were non-criteria (NC)-APS, and 85 were seronegative (SN)-APS. Patients with other autoimmune diseases were excluded. APOs included early pregnancy loss, fetal death, preeclampsia, abruptio placentae, and preterm birth. Successful pregnancy was defined as the achievement of a live newborn. A literature search was also performed. The mean age of the overall group was 33.9 ± 5.3 years, and the patients were followed up for 35 (11-79) months. During the study period, there were 1332 pregnancies. Nearly 14% of the patients had an associated IT. IT patients more frequently received the standard-of-care (SoC) therapy. The presence of IT was not associated with worse maternal-fetal outcomes in patients treated with SoC treatment. Overall, IT patients had a lower frequency of newborns without treatment, especially those without definite APS. In addition, IT did not increase the risk of thrombosis during pregnancy or the postpartum period. A detailed analysis of the literature review identified only four publications related to our study and did not show conclusive evidence of the impact of IT on patients with obstetric APS. The group of women with APS-related obstetric morbidity and IT who did not receive treatment, especially those without definite APS, had a worse prognosis in terms of a live birth. However, with SoC therapy, the prognosis is similar in those patients without IT. The association of IT with APS does not seem to predispose to the development of thrombosis during pregnancy and/or the postpartum period.

Breast Cancer Screening Using Inverse Modeling of Surface Temperatures and Steady-State Thermal Imaging.

Cancer is characterized by increased metabolic activity and vascularity, leading to temperature changes in cancerous tissues compared to normal cells. This study focused on patients with abnormal mammogram findings or a clinical suspicion of breast cancer, exclusively those confirmed by biopsy. Utilizing an ultra-high sensitivity thermal camera and prone patient positioning, we measured surface temperatures integrated with an inverse modeling technique based on heat transfer principles to predict malignant breast lesions. Involving 25 breast tumors, our technique accurately predicted all tumors, with maximum errors below 5 mm in size and less than 1 cm in tumor location. Predictive efficacy was unaffected by tumor size, location, or breast density, with no aberrant predictions in the contralateral normal breast. Infrared temperature profiles and inverse modeling using both techniques successfully predicted breast cancer, highlighting its potential in breast cancer screening.

One-Month Versus Three-Month Dual-Antiplatelet Therapy in High Bleeding Risk Patients With Chronic Kidney Disease.

Shortening the duration of dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) was shown to be effective and safe in patients at high bleeding risk (HBR). We aimed to investigate the effect of 1 versus 3-month DAPT on outcomes after drug-eluting stent in HBR patients with or without chronic kidney disease (CKD). Data from 3 prospective single-arm studies (XIENCE Short DAPT Program) enrolling HBR patients after successful coronary implantation of cobalt-chromium everolimus-eluting stent (XIENCE, Abbott) were analyzed. Subjects were eligible for DAPT discontinuation at 1 or 3 months if free from ischemic events. The primary end point was all-cause death or any myocardial infarction. The key secondary end point was Bleeding Academic Research Consortium Type 2 to 5 bleeding. Outcomes were assessed from 1 to 12 months after PCI. CKD was defined as baseline creatinine clearance <60 ml/min. Of 3,286 patients, 1,432 (43.6%) had CKD. One-month versus 3-month DAPT was associated with a similar 12-month risk of the primary outcome irrespective of CKD status (CKD: 9.5% vs 10.9%, adjusted hazard ratio 0.86, 95% confidence interval 0.60 to 1.22; no-CKD: 6.6% vs 5.6%, adjusted hazard ratio 1.15, 95% confidence interval 0.77 to 1.73; p interaction 0.299). Bleeding Academic Research Consortium 2 to 5 bleeding rates were numerically but not significantly lower with 1-month versus 3-month DAPT in both CKD (9.9% vs 12%) and no-CKD (6.4% vs 9.0%) patients. In conclusion, in HBR patients, 1-month versus 3-month DAPT was associated with a similar risk of ischemic complications and a trend toward fewer bleeding events at 12 months after PCI, irrespective of CKD status.

Y-90 PET/MR imaging optimization with a Bayesian penalized likelihood reconstruction algorithm.

Positron Emission Tomography (PET) imaging after 90 Y liver radioembolization is used for both lesion identification and dosimetry. Bayesian penalized likelihood (BPL) reconstruction algorithms are an alternative to ordered subset expectation maximization (OSEM) with improved image quality and lesion detectability. The investigation of optimal parameters for 90 Y image reconstruction of Q.Clear, a commercial BPL algorithm developed by General Electric (GE), in PET/MR is a field of interest and the subject of this study. The NEMA phantom was filled at an 8:1 sphere-to-background ratio. Acquisitions were performed on a PET/MR scanner for clinically relevant activities between 0.7 and 3.3 MBq/ml. Reconstructions with Q.Clear were performed varying the ß penalty parameter between 20 and 6000, the acquisition time between 5 and 20 min and pixel size between 1.56 and 4.69 mm. OSEM reconstructions of 28 subsets with 2 and 4 iterations with and without Time-of-Flight (TOF) were compared to Q.Clear with ß = 4000. Recovery coefficients (RC), their coefficient of variation (COV), background variability (BV), contrast-to-noise ratio (CNR) and residual activity in the cold insert were evaluated. Increasing ß parameter lowered RC, COV and BV, while CNR was maximized at ß = 4000; further increase resulted in oversmoothing. For quantification purposes, ß = 1000-2000 could be more appropriate. Longer acquisition times resulted in larger CNR due to reduced image noise. Q.Clear reconstructions led to higher CNR than OSEM. A ß of 4000 was obtained for optimal image quality, although lower values could be considered for quantification purposes. An optimal acquisition time of 15 min was proposed considering its clinical use.

Atomic-Scale Description of the Magnetic TiN|FeCo Multilayers.

Motivated by the experimental findings of Wolff et al., we investigated the TiN|FeCo multilayers at the atomic scale. Four different models were employed to investigate the interface, considering both Fe and Co surface terminations of the FeCo compounds. The interface formation energy formalism was employed to study the thermodynamic stability of these models. The results show that an interface mediated by Co atoms is most likely to appear in the experiment. Also, the Fe surface termination is more viable than a Co surface termination. The magnetic moments of Co at the interface are 1.48 µB/atom, which denotes a decay compared to bulk (1.76 µB/atom). Besides, Ti acquires a very small induced magnetization of -0.05 µB/atom. Our proposed atomistic model of the TiN|FeCo multilayer system fits perfectly with the structure obtained in experiments, and it is a step forward in the theoretical-experimental design of wear-resistant coatings with outstanding magnetic and mechanical properties.

Characterization and Implementation of Cocoa Pod Husk as a Reinforcing Agent to Obtain Thermoplastic Starches and Bio-Based Composite Materials.

When the cocoa pod husk (CPH) is used and processed, two types of flour were obtained and can be differentiated by particle size, fine flour (FFCH), and coarse flour (CFCH) and can be used as a possible reinforcement for the development of bio-based composite materials. Each flour was obtained from chopping, drying by forced convection, milling by blades, and sieving using the 100 mesh/bottom according to the Tyler series. Their physicochemical, thermal, and structural characterization made it possible to identify the lower presence of lignin and higher proportions of cellulose and pectin in FFCH. Based on the properties identified in FFCH, it was included in the processing of thermoplastic starch (TPS) from the plantain pulp (Musa paradisiaca) and its respective bio-based composite material using plantain peel short fiber (PPSF) as a reinforcing agent using the following sequence of processing techniques: extrusion, internal mixing, and compression molding. The influence of FFCH contributed to the increase in ultimate tensile strength (7.59 MPa) and higher matrix-reinforcement interaction when obtaining the freshly processed composite material (day 0) when compared to the bio-based composite material with higher FCP content (30%) in the absence of FFCH. As for the disadvantages of FFCH, reduced thermal stability (323.57 to 300.47 °C) and losses in ultimate tensile strength (0.73 MPa) and modulus of elasticity (142.53 to 26.17 MPa) during storage progress were identified. In the case of TPS, the strengthening action of FFCH was not evident. Finally, the use of CFCH was not considered for the elaboration of the bio-based composite material because it reached a higher lignin content than FFCH, which was expected to decrease its affinity with the TPS matrix, resulting in lower mechanical properties in the material.

Microstructural and Electrochemical Study: Pitting Corrosion Mechanism on A390 Al-Si Alloy and Ce-Mo Treatment as a Better Corrosion Protection.

Sulfuric acid anodizing assisted by a hydrothermal sealing with inhibitors [Ce3+-Mo6+] was used to prevent pitting corrosion on spray-deposited hypereutectic Al-Si alloy (A390). An investigation concerning the evaluation of pitting corrosion resistance on the anodic oxide thin film with ions incorporated was carried out in NaCl solution using electrochemical measurements (i.e., potentiodynamic polarization and electrochemical impedance spectroscopy, EIS). The influence of Si phase morphology and size on the growth mechanism of an anodic oxide film was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results were then compared with those for its equivalent IM390 alloy (Al-17Si-4.5Cu-0.6Mg) produced through a conventional process ingot metallurgy, IM. The electrochemical findings indicate that sulfuric acid anodizing followed by a simple hot water sealing treatment was ineffective. In this manner, an intense attack was localized by pitting corrosion that occurred on the anodic oxide film in less than three days, as denoted by characteristic changes in the EIS spectra at the lowest frequencies. Improved results were achieved for Ce-Mo surface modification, which can provide better corrosion resistance on the aluminum alloys because no signs of pits were observed during the corrosion testing.

Modeling the Evolution of S. pombe Populations with Multiple Killer Meiotic Drivers.

Meiotic drivers are selfish genetic loci that can be transmitted to more than half of the viable gametes produced by a heterozygote. This biased transmission gives meiotic drivers an evolutionary advantage that can allow them to spread over generations until all members of a population carry the driver. This evolutionary power can also be exploited to modify natural populations using synthetic drivers known as 'gene drives.' Recently, it has become clear that natural drivers can spread within genomes to birth multicopy gene families. To understand intragenomic spread of drivers, we model the evolution of two or more distinct meiotic drivers in a population. We employ the wtf killer meiotic drivers from Schizosaccharomyces pombe, which are multicopy in all sequenced isolates, as models. We find that a duplicate wtf driver identical to the parent gene can spread in a population unless, or until, the original driver is fixed. When the duplicate driver diverges to be distinct from the parent gene, we find that both drivers spread to fixation under most conditions, but both drivers can be lost under some conditions. Finally, we show that stronger drivers make weaker drivers go extinct in most, but not all, polymorphic populations with absolutely linked drivers. These results reveal the strong potential for natural meiotic drive loci to duplicate and diverge within genomes. Our findings also highlight duplication potential as a factor to consider in the design of synthetic gene drives.

Clinical impact of complex percutaneous coronary intervention in the pre-TAVR workup.

INTRODUCTION AND OBJECTIVES: In patients undergoing percutaneous coronary intervention (PCI) in the workup pre-transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup. METHODS: This was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated. RESULTS: A total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiac death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.31; 95%CI, 1.01-1.71; P=.042). CONCLUSIONS: In TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population.

Investigating the causal association of generalized and abdominal obesity with microvascular complications in patients with type 2 diabetes: A community-based prospective study.

AIM: The paradoxical protective association between overweight/obesity and diabetic microvascular complications (DMC), a phenomenon well-known as the obesity paradox, has been considered a non-causal association based on methodological influences. We aimed to investigate the association of generalized and abdominal obesity, as measured by body mass index (BMI) and waist circumference (WC), respectively, with DMC in patients with type 2 diabetes (T2D), using a causal inference approach. MATERIALS AND METHODS: We enrolled 1436 patients with clinically diagnosed T2D but not DMC at baseline in a community-based prospective cohort in China between 2017 and 2019 and followed them annually until 2022 with new-onset DMC recorded. Marginal structural Cox models with inverse probability weighting were constructed to determine the causal association. Subgroup analyses were performed to identify potential effect modifiers. RESULTS: We observed 360 incident DMC cases, including 109 cases of diabetic nephropathy (DN) and 277 cases of diabetic retinopathy (DR) during four follow-up visits. Multivariable-adjusted hazard ratios (95% confidence intervals) for overall DMC, DN and DR were 1.037 (1.005-1.071), 1.117 (1.062-1.175) and 1.018 (0.980-1.059) for 1 kg/m2 increase in BMI, and 1.005 (0.994-1.017), 1.034 (1.018-1.051) and 1.000 (0.987-1.014) for 1 cm increase in WC, respectively. Similar patterns were observed across the BMI and WC categories, while the positive association appeared to be more pronounced in women. CONCLUSIONS: Generalized but not abdominal obesity was associated with an increased risk for the overall DMC, whereas both obesities were causally related to DN, albeit not DR, in T2D. Routine weight management should not be neglected in diabetes care, particularly in women.

Osteomesopyknosis associated with a novel ALOX5 variant that impacts the RANKL pathway.

BACKGROUND: Bone tissue homeostasis relies on the coordinated activity of the bone-forming osteoblasts and bone-resorbing osteoclasts. Osteomesopyknosis is considered a distinctive rare sclerosing skeletal disorder of unelucidated pathophysiology and presumably autosomal dominant transmission. However, the causal genes are unknown. METHODS: We present a case report encompassing clinical assessments, imaging studies, and whole-exome sequencing analysis, complemented by functional in vitro experiments. RESULTS: This new case of osteomesopyknosis was associated with a missense ALOX5 variant predicted to induce protein misfolding and proteasomal degradation. Transfection experiments demonstrated that the variant was associated with reduced protein levels restored by proteasomal inhibition with bortezomib. Likewise, gene expression analysis showed that the mutated gene was associated with a decreased RANKL/OPG ratio, which is a critical driver of osteoclast precursor differentiation. CONCLUSION: Our data indicate impaired bone resorption as the underlying mechanism of this rare osteosclerosis, implicating ALOX5 pathogenic variants as potential etiological factors.

Interfacial Interactions between Nanoplastics and Biological Systems: toward an Atomic and Molecular Understanding of Plastics-Driven Biological Dyshomeostasis.

Micro- and nano-plastics (NPs) are found in human milk, blood, tissues, and organs and associate with aberrant health outcomes including inflammation, genotoxicity, developmental disorders, onset of chronic diseases, and autoimmune disorders. Yet, interfacial interactions between plastics and biomolecular systems remain underexplored. Here, we have examined experimentally, in vitro, in vivo, and by computation, the impact of polystyrene (PS) NPs on a host of biomolecular systems and assemblies. Our results reveal that PS NPs essentially abolished the helix-content of the milk protein ß-lactoglobulin (BLG) in a dose-dependent manner. Helix loss is corelated with the near stoichiometric formation of ß-sheet elements in the protein. Structural alterations in BLG are also likely responsible for the nanoparticle-dependent attrition in binding affinity and weaker on-rate constant of retinol, its physiological ligand (compromising its nutritional role). PS NP-driven helix-to-sheet conversion was also observed in the amyloid-forming trajectory of hen egg-white lysozyme (accelerated fibril formation and reduced helical content in fibrils). Caenorhabditis elegans exposed to PS NPs exhibited a decrease in the fluorescence of green fluorescent protein-tagged dopaminergic neurons and locomotory deficits (akin to the neurotoxin paraquat exposure). Finally, in silico analyses revealed that the most favorable PS/BLG docking score and binding energies corresponded to a pose near the hydrophobic ligand binding pocket (calyx) of the protein where the NP fragment was found to make nonpolar contacts with side-chain residues via the hydrophobic effect and van der Waals forces, compromising side chain/retinol contacts. Binding energetics indicate that PS/BLG interactions destabilize the binding of retinol to the protein and can potentially displace retinol from the calyx region of BLG, thereby impairing its biological function. Collectively, the experimental and high-resolution in silico data provide new insights into the mechanism(s) by which PS NPs corrupt the bimolecular structure and function, induce amyloidosis and onset neuronal injury, and drive aberrant physiological and behavioral outcomes.

ß-Carotene production from sugarcane molasses by a newly isolated Rhodotorula toruloides L/24-26-1.

Production of carotenoids by yeast fermentation is an advantaged technology due to its easy scaling and safety. Nevertheless, carotenoid production needs an economic culture medium and other efficient yeast stains. The study aims to isolate and identify a yeast strain capable of producing carotenoids using a cost-effective substrate. A new strain was identified as Rhodotorula toruloides L/24-26-1, which can produce carotenoids at different pretreated and unpretreated sugarcane molasses concentrations (40 and 80 g/L). The highest biomass concentration (18.6 ± 0.6 g/L) was reached in the culture using 80 g/L of hydrolyzed molasses. On the other hand, the carotenoid accumulation reached the maximum value using pretreated molasses at 40 g/L (715.4 ± 15.1 µg/g d.w). In this case, the ß-carotene was 1.5 times higher than that on the control medium. The yeast growth in molasses was not correlated with carotenoid production. The most outstanding production of The DPPH, ABTS, and FRAP tests demonstrated the antioxidant activity of the obtained carotenogenic extracts. This research demonstrated the R. toruloides L/24-26-1 strain biotechnological potential for carotenoid compounds. The yeast produces carotenoids with antioxidant activity in an inexpensive medium, such as sulfuric acid pretreated and unpretreated molasses.

[Cardiovascular manifestations in pediatric multisystem inflammatory syndrome associated with COVID-19 in a tertiary care pediatric center in Mexico City]. / Alteraciones cardiovasculares en el síndrome inflamatorio multisistémico pediátrico asociado a COVID-19 en un hospital pediátrico de tercer nivel de la Ciudad de México.

Objective: The objective is to expose the cardiovascular alterations in patients diagnosed with pediatric inflammatory multisystem syndrome (PIMS) associated with COVID-19 during the SARS-CoV-2 pandemic, in order to understand the disease, its evolution, and optimal management upon diagnosis. Method: Retrospective, observational, cross-sectional analytical study of patients diagnosed with PIMS according to the criteria of the World Health Organization at the National Institute of Pediatrics, from March 2020 to December 2021. Results: During the study period, 77 patients with PIMS were diagnosed. The results showed correlation between the shock state and alteration of laboratory markers (platelets 144217.29 ± 139321.6 µL [p < 0.001], procalcitonin 27.37 ± 38.37 ng/ml [p = 0.05] and ferritin 1937.87 ± 2562.63 [p < 0.001]). The ventricular function in patients with shock was significantly lower compared to those without shock (49.6 ± 9.1% vs. 58.1 ± 8.4 %; t-Student p < 0.001), as well as injury to the left coronary artery (p = 0.02). There is a correlation between NT-proBNP and ventricular dysfunction (Kruskal-Wallis p = 0.007). Statistical significance was found in the association between death, elevation of inflammatory markers and ventricular dysfunction (p < 0.001). Conclusions: The cardiovascular alterations observed, in order of frequency, were pericardial effusion (25.7%), myocarditis (15%), mild ventricular dysfunction (13.5%) and small coronary aneurysm with predominance of the left coronary artery and the anterior descending one.

Objetivo: Exponer las alteraciones cardiovasculares en los pacientes diagnosticados con síndrome inflamatorio multisistémico pediátrico (PIMS) asociado a COVID-19 durante la pandemia por SARS-CoV-2 con el fin de comprender la enfermedad, su evolución y el manejo óptimo al diagnóstico. Método: Estudio retrospectivo, observacional, transversal y analítico de pacientes con diagnóstico de PIMS de acuerdo con los criterios de la Organización Mundial de la Salud en el Instituto Nacional de Pediatría, de marzo de 2020 a diciembre de 2021. Resultados: Durante el periodo de estudio se diagnosticaron 77 pacientes con PIMS. Los resultados demostraron una correlación entre el estado de choque y la alteración de los marcadores de laboratorio (plaquetas 144217.29 ± 139321.6 µl [p < 0.001], procalcitonina 27.37 ± 38.37 ng/ml [p = 0.05] y ferritina 1937.87 ± 2562.63 [p < 0.001]). La función ventricular en los pacientes con choque se registró significativamente menor en comparación con aquellos sin choque (49.6 ± 9.1 % vs. 58.1 ± 8.4 %; t de Student p < 0.001), así como lesión en la arteria coronaria izquierda (p = 0.02). Existe una correlación entre el NT-proBNP y la disfunción ventricular (Kruskal-Wallis p = 0.007). Se encontró significancia estadística en la asociación entre fallecimiento, elevación de los marcadores inflamatorios y disfunción ventricular (p < 0.001). Conclusiones: Las alteraciones cardiovasculares observadas fueron, en orden de frecuencia, derrame pericárdico (25.7%), miocarditis (15%), disfunción ventricular leve (13.5%) y aneurisma pequeño coronario con predominio de la arteria coronaria izquierda y la descendente anterior.

Sucrose supplements modulate the Pseudomonas chlororaphis-Arabidopsis thaliana interaction via decreasing the production of phenazines and enhancing the root auxin response.

Management of the plant microbiome may help support food needs for the human population. Bacteria influence plants through enhancing nutrient uptake, metabolism, photosynthesis, biomass production and/or reinforcing immunity. However, information into how these microbes behave under different growth conditions is missing. In this work, we tested how carbon supplements modulate the interaction of Pseudomonas chlororaphis with Arabidopsis thaliana. P. chlororaphis streaks strongly repressed primary root growth, lateral root formation and ultimately, biomass production. Noteworthy, increasing sucrose availability into the media from 0 to 2.4% restored plant growth and promoted lateral root formation in bacterized seedlings. This effect could not be observed by supplementing sucrose to leaves only, indicating that the interaction was strongly modulated by bacterial access to sugar. Total phenazine content decreased in the bacteria grown in high (2.4%) sucrose medium, and conversely, the expression of phzH and pslA genes were diminished by sugar supply. Pyocyanin antagonized the promoting effects of sucrose in lateral root formation and biomass production in inoculated seedlings, indicating that this virulence factor accounts for growth repression during the plant-bacterial interaction. Defence reporter transgenes PR-1::GUS and LOX2::GUS were induced in leaves, while the expression of the auxin-inducible, synthetic reporter gene DR5::GUS was enhanced in the roots of bacterized seedlings at low and high sucrose treatments, which suggests that growth/defence trade-offs in plants are critically modulated by P. chlororaphis. Collectively, our data suggest that bacterial carbon nutrition controls the outcome of the relation with plants.

HMGA1 regulates trabectedin sensitivity in advanced soft-tissue sarcoma (STS): A Spanish Group for Research on Sarcomas (GEIS) study.

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.