Feasibility and Short-Term Outcomes in Liver-First Approach: A Spanish Snapshot Study (the RENACI Project).

(1) Background: The liver-first approach may be indicated for colorectal cancer patients with synchronous liver metastases to whom preoperative chemotherapy opens a potential window in which liver resection may be undertaken. This study aims to present the data of feasibility and short-term outcomes in the liver-first approach. (2) Methods: A prospective observational study was performed in Spanish hospitals that had a medium/high-volume of HPB surgeries from 1 June 2019 to 31 August 2020. (3) Results: In total, 40 hospitals participated, including a total of 2288 hepatectomies, 1350 for colorectal liver metastases, 150 of them (11.1%) using the liver-first approach, 63 (42.0%) in hospitals performing <50 hepatectomies/year. The proportion of patients as ASA III was significantly higher in centers performing ≥50 hepatectomies/year (difference: 18.9%; p = 0.0213). In 81.1% of the cases, the primary tumor was in the rectum or sigmoid colon. In total, 40% of the patients underwent major hepatectomies. The surgical approach was open surgery in 87 (58.0%) patients. Resection margins were R0 in 78.5% of the patients. In total, 40 (26.7%) patients had complications after the liver resection and 36 (27.3%) had complications after the primary resection. One-hundred and thirty-two (89.3%) patients completed the therapeutic regime. (4) Conclusions: There were no differences in the surgical outcomes between the centers performing <50 and ≥50 hepatectomies/year. Further analysis evaluating factors associated with clinical outcomes and determining the best candidates for this approach will be subsequently conducted.

Innate biosignature of treatment failure in human cutaneous leishmaniasis.

The quality and magnitude of the immune and inflammatory responses determine the clinical outcome of Leishmania infection, and contribute to the efficacy of antileishmanial treatments. However, the precise immune mechanisms involved in healing or in chronic immunopathology of human cutaneous leishmaniasis (CL) are not completely understood. Through sequential transcriptomic profiling of blood monocytes (Mo), neutrophils (Nφ), and eosinophils (Eφ) over the course of systemic treatment with meglumine antimoniate, we discovered that a heightened and sustained Type I interferon (IFN) response signature is a hallmark of treatment failure (TF) in CL patients. The transcriptomes of pre-treatment, mid-treatment and end-of-treatment samples were interrogated to identify predictive and prognostic biomarkers of TF. A composite score derived from the expression of 9 differentially expressed genes (common between Mo, Nφ and Eφ) was predictive of TF in this patient cohort for biomarker discovery. Similarly, machine learning models constructed using data from pre-treatment as well as post-treatment samples, accurately classified treatment outcome between cure and TF. Results from this study instigate the evaluation of Type-I IFN responses as new immunological targets for host-directed therapies for treatment of CL, and highlight the feasibility of using transcriptional signatures as predictive biomarkers of outcome for therapeutic decision making.

Enhancing stress measurements accuracy control in the construction of long-span bridges.

This paper introduces new contributions for construction procedures designed to enhance the robustness and precision of stress control in active anchorage and short presetressing units for long-span bridges, particularly addressing potential technical risks. The primary focus is on optimizing stress management for bridge stays, suspension cables, and short prestressing units by emphasizing a unified parameter: stress. The contributions of this research encompass (1) the introduction of advanced load cells for stress control in active anchorages and (2) the implementation of a novel synchronized multi-strain gage load cell network for short prestressing units, crucial in situations where prestressing losses can attain significant magnitudes. To validate these advancements, the authors present (3) a practical experience and results obtained from applying these methodologies in monitoring the structural response during the construction of the Tajo Bridge using the cable-stayed cantilever technique.

Natural resistance to meglumine antimoniate is associated with treatment failure in cutaneous leishmaniasis caused by Leishmania (Viannia) panamensis.

The multifactorial basis of therapeutic response can obscure the relation between antimicrobial drug susceptibility and clinical outcome. To discern the relationship between parasite susceptibility to meglumine antimoniate (SbV) and therapeutic outcome of cutaneous leishmaniasis, risk factors for treatment failure were considered in evaluating this relationship in ninety-one cutaneous leishmaniasis patients and corresponding clinical strains of Leishmania (Viannia) panamensis. Parasite susceptibility to 32 µg SbV/mL (plasma Cmax) was evaluated in primary human macrophages, PBMCs, and U937 macrophages. Early parasitological response to treatment was determined in lesions of a subgroup of patients, and pathogenicity of Sb-resistant and sensitive clinical strains was compared in BALB/c mice. Parasite survival in cell models and patient lesions was determined by qRT-PCR of Leishmania 7SLRNA transcript. Parasite loads in BALB/c mice were quantified by limiting dilution analysis. The disparate Sb-susceptibility of parasite subpopulations distinguished by isoenzyme profiles (zymodemes) was manifest in all cell models. Notably, Sb-resistance defined by parasite survival, was most effectively discerned in U937 macrophages compared with primary human host cells, significantly higher among strains from patients who failed treatment than cured and, significantly associated with treatment failure. Each unit increase in transformed survival rate corresponded to a 10.6-fold rise in the odds of treatment failure. Furthermore, treatment failure was significantly associated with naturally Sb-resistant zymodeme 2.3 strains, which also produced larger lesions and parasite burdens in BALB/c mice than Sb-sensitive zymodeme 2.2 strains. The confounding effect of host risk factors for treatment failure in discerning this association was evidenced in comparing strains from patients with and without the defined risk factors for treatment failure. These results establish the association of natural resistance to meglumine antimoniate with treatment failure, the importance of host risk factors in evaluating drug susceptibility and treatment outcome, and the clinical and epidemiological relevance of natural Sb-resistance in L. (V.) panamensis subpopulations.

The pharmacoepigenetic paradigm in cancer treatment.

Epigenetic modifications, characterized by changes in gene expression without altering the DNA sequence, play a crucial role in the development and progression of cancer by significantly influencing gene activity and cellular function. This insight has led to the development of a novel class of therapeutic agents, known as epigenetic drugs. These drugs, including histone deacetylase inhibitors, histone acetyltransferase inhibitors, histone methyltransferase inhibitors, and DNA methyltransferase inhibitors, aim to modulate gene expression to curb cancer growth by uniquely altering the epigenetic landscape of cancer cells. Ongoing research and clinical trials are rigorously evaluating the efficacy of these drugs, particularly their ability to improve therapeutic outcomes when used in combination with other treatments. Such combination therapies may more effectively target cancer and potentially overcome the challenge of drug resistance, a significant hurdle in cancer therapy. Additionally, the importance of nutrition, inflammation control, and circadian rhythm regulation in modulating drug responses has been increasingly recognized, highlighting their role as critical modifiers of the epigenetic landscape and thereby influencing the effectiveness of pharmacological interventions and patient outcomes. Epigenetic drugs represent a paradigm shift in cancer treatment, offering targeted therapies that promise a more precise approach to treating a wide spectrum of tumors, potentially with fewer side effects compared to traditional chemotherapy. This progress marks a step towards more personalized and precise interventions, leveraging the unique epigenetic profiles of individual tumors to optimize treatment strategies.

Backup Frontal Drainage System for Urgent Tension Pneumocephalus Management After Chronic Subdural Hematoma Surgery: A Retrospective Cohort Study.

OBJECTIVE: To describe a simple variation of burr hole craniostomy for the management of chronic subdural hematoma (CSDH) that uses a frontal drainage system to facilitate timely decompression in the event of tension pneumocephalus and spares the need for additional surgery. METHODS: We conducted a retrospective analysis of 20 patients with CSDH who underwent burr hole craniostomy and 20 patients who underwent the same procedure alongside the placement of a 5fr neonatal feeding tube as a backup drainage for the anterior craniostomy. Depending on the situation, the secondary drain stayed for a maximum of 72 hours to be opened and used in emergency settings for drainage, aspiration, or as a one-way valve with a water seal. RESULTS: The outcomes of 20 patients who underwent this procedure and 20 controls are described. One patient from each group presented tension pneumocephalus. One was promptly resolved by opening the backup drain under a water seal to evacuate pneumocephalus and the other patient had to undergo a re-opening of the craniostomy. CONCLUSIONS: The described variation of burr hole craniostomy represents a low-cost and easy-to-implement technique that can be used for emergency decompression of tension pneumocephalus. It also has the potential to reduce re-operation rates and CSDH recurrence. Prospective controlled research is needed to validate this approach further.

Deceased Donor Liver Transplantation With Hepatic Artery Aneurysm.

Few case reports have documented the long-term outcomes of liver donor aneurysms, illustrating the apprehension of transplant surgeons about using these grafts. However,the presence of an aneurysm in the donor liver should not be an absolute contraindication for its use. As shown in our described patient, such grafts have the potential to achieve good results.

The differential effects of palmitic acid and oleic acid on the metabolic response of hypothalamic astrocytes from male and female mice.

Diets rich in saturated fats are more detrimental to health than those containing mono- or unsaturated fats. Fatty acids are an important source of energy, but they also relay information regarding nutritional status to hypothalamic metabolic circuits and when in excess can be detrimental to these circuits. Astrocytes are the main site of central fatty acid ß-oxidation, and hypothalamic astrocytes participate in energy homeostasis, in part by modulating hormonal and nutritional signals reaching metabolic neurons, as well as in the inflammatory response to high-fat diets. Thus, we hypothesized that how hypothalamic astrocytes process-specific fatty acids participates in determining the differential metabolic response and that this is sex dependent as males and females respond differently to high-fat diets. Male and female primary hypothalamic astrocyte cultures were treated with oleic acid (OA) or palmitic acid (PA) for 24 h, and an untargeted metabolomics study was performed. A clear predictive model for PA exposure was obtained, while the metabolome after OA exposure was not different from controls. The observed modifications in metabolites, as well as the expression levels of key metabolic enzymes, indicate a reduction in the activity of the Krebs and glutamate/glutamine cycles in response to PA. In addition, there were specific differences between the response of astrocytes from male and female mice, as well as between hypothalamic and cerebral cortical astrocytes. Thus, the response of hypothalamic astrocytes to specific fatty acids could result in differential impacts on surrounding metabolic neurons and resulting in varied systemic metabolic outcomes.

Removal of Azo Dyes from Water Using Natural Luffa cylindrica as a Non-Conventional Adsorbent.

Reducing high concentrations of pollutants such as heavy metals, pesticides, drugs, and dyes from water is an emerging necessity. We evaluated the use of Luffa cylindrica (Lc) as a natural non-conventional adsorbent to remove azo dye mixture (ADM) from water. The capacity of Lc at three different doses (2.5, 5.0, and 10.0 g/L) was evaluated using three concentrations of azo dyes (0.125, 0.250, and 0.500 g/L). The removal percent (R%), maximum adsorption capacity (Qm), isotherm and kinetics adsorption models, and pH influence were evaluated, and Fourier-transform infrared spectroscopy and scanning electron microscopy were performed. The maximum R% was 70.8% for 10.0 g L-1Lc and 0.125 g L-1 ADM. The Qm of Lc was 161.29 mg g-1. Adsorption by Lc obeys a Langmuir isotherm and occurs through the pseudo-second-order kinetic model. Statistical analysis showed that the adsorbent dose, the azo dye concentration, and contact time significantly influenced R% and the adsorption capacity. These findings indicate that Lc could be used as a natural non-conventional adsorbent to reduce ADM in water, and it has a potential application in the pretreatment of wastewaters.

miRNA Dynamics for Pest Management: Implications in Insecticide Resistance.

Utilizing chemical agents in pest management in modern agricultural practices has been the predominant approach since the advent of synthetic insecticides. However, insecticide resistance is an emerging issue, as pest populations evolve to survive exposure to chemicals that were once effective in controlling them, underlining the need for advanced and innovative approaches to managing pests. In insects, microRNAs (miRNAs) serve as key regulators of a wide range of biological functions, characterized by their dynamic expression patterns and the ability to target genes. Recent studies are increasingly attributed to the significance of miRNAs in contributing to the evolution of insecticide resistance in numerous insect species. Abundant miRNAs have been discovered in insects using RNA sequencing and transcriptome analysis and are known to play vital roles in regulation at both the transcriptional and post-transcriptional levels. Globally, there is growing research interest in the characterization and application of miRNAs, especially for their potential role in managing insecticide resistance. This review focuses on how miRNAs contribute to regulating insecticide resistance across various insect species. Furthermore, we discuss the gain and loss of functions of miRNAs and the techniques for delivering miRNAs into the insect system. The review emphasizes the application of miRNA-based strategies to studying their role in diminishing insecticide resistance, offering a more efficient and lasting approach to insect management.

Heterostructures coupling ultrathin metal carbides and chalcogenides.

Non-layered transition metal carbides (TMCs) and layered transition metal dichalcogenides (TMDs) are two well-studied material families that have individually received considerable attention over the past century. In recent years, with the shift towards two-dimensional materials and heterostructures, a field has emerged that is focused on the structure and properties of TMC/TMD heterostructures, which through chemical conversion exhibit diverse types of heterostructure configuration that host coupled 2D-3D interfaces, giving rise to exotic properties. In this Review, we highlight experimental and computational efforts to understand the routes to fabricate TMC/TMD heterostructures. Furthermore, we showcase how controlling these heterostructures can lead to emergent electronic transport, optical properties and improved catalytic properties.

Higher Numbers of Family Meals and Social Eating Behavior Are Associated with Greater Self-Esteem among Adolescents: The EHDLA.

BACKGROUND: the aim of this study was to assess the associations of family meals and social eating behavior with self-esteem levels among Spanish adolescents. METHODS: This was a secondary cross-sectional study including 706 participants (aged 12 to 17 years; 56.1% girls) from the Eating Habits and Daily Life Activities (EHDLA) study. The evaluation of the frequency of family meals involved participants providing information in physical education classes on how frequently they, along with other members of their household, had shared meals in the previous week. Social eating behavior was assessed by three different statements: "I usually have dinner with others", "Having at least one meal a day with others (family or friends) is important to me", and "I enjoy sitting down with family or friends for a meal". To assess overall self-esteem, the Rosenberg Self-Esteem Scale was used. RESULTS: In the adjusted models, a positive association was observed between the frequency of family meals and the self-esteem score (unstandardized beta coefficient [B] = 0.06, 95% confidence interval [CI] 0.003 to 0.12, p-adjusted = 0.040). Furthermore, the same positive association was also identified between social eating behavior and the self-esteem score (B = 0.23; 95% CI 0.07 to 0.40, p-adjusted = 0.005). CONCLUSIONS: Although self-esteem is complex and can be influenced by numerous factors, both family meals and social eating behavior may exert a relevant role in adolescents. Encouraging consistent participation in family meals and promoting positive eating practices could be valuable approaches in public health actions targeting the enhancement of self-esteem levels in adolescents.

Synthesis and Characterization of Titanium Nitride-Carbon Composites and Their Use in Lithium-Ion Batteries.

This work focuses on the synthesis of titanium nitride-carbon (TiN-carbon) composites by the thermal decomposition of a titanyl phthalocyanine (TiN(TD)) precursor into TiN. The synthesis of TiN was also performed using the sol-gel method (TiN(SG)) of an alkoxide/urea. The structure and morphology of the TiN-carbon and its precursors were characterized by XRD, FTIR, SEM, TEM, EDS, and XPS. The FTIR results confirmed the presence of the titanium phthalocyanine (TiOPC) complex, while the XRD data corroborated the decomposition of TiOPC into TiN. The resultant TiN exhibited a cubic structure with the FM3-M lattice, aligning with the crystal system of the synthesized TiN via the alkoxide route. The XPS results indicated that the particles synthesized from the thermal decomposition of TiOPC resulted in the formation of TiN-carbon composites. The TiN particles were present as clusters of small spherical particles within the carbon matrix, displaying a porous sponge-like morphology. The proposed thermal decomposition method resulted in the formation of metal nitride composites with high carbon content, which were used as anodes for Li-ion half cells. The TiN-carbon composite anode showed a good specific capacity after 100 cycles at a current density of 100 mAg-1.

Screening and treatment of latent tuberculosis in patients with solid tumors and systemic cancer therapy.

INTRODUCTION: Tuberculosis is one of the infectious diseases with greater morbidity and mortality worldwide. Cancer causes an important immunosuppression with increased risk of infections. There is an enlarged bidirectional incidence between tuberculosis and cancer, mainly due to latent tuberculosis. GUIDELINES REVIEW: There is great discrepancy between recommendations for screening and prophylaxis of latent tuberculosis in patients with solid tumors and systemic cancer therapy among different medical societies and guidelines. Most infectious diseases guidelines recommend it, while most oncology guidelines do not. DISCUSSION: Patients with solid tumours generally have a limited life expectancy and a state of intermittent immunosuppression, resulting in a lower risk of tuberculosis reactivation than other risky populations. There is a lack of prospective and retrospective studies analysing the benefit of screening and prophylaxis in this population. The first step is to study the incidence of active tuberculosis in this population to estimate the real magnitude of the problem.

Navigating the waves in Colombia: a cohort study of inpatient care during four COVID-19 waves.

INTRODUCTION: Understanding the intricate dynamics between different waves of the COVID-19 pandemic and the corresponding variations in clinical outcomes is essential for informed public health decision-making. Comprehensive insights into these fluctuations can guide resource allocation, healthcare policies, and the development of effective interventions. This study aimed to compare the characteristics and clinical outcomes of COVID-19 at peak transmission points by including all patients attended during the first four pandemic waves in a referral center in Colombia. MATERIAL AND METHODS: In a prospective observational study of 2733 patients, clinical and demographic data were extracted from the Fundacion Valle de Lili's COVID-19 Registry, focusing on ICU admission, Invasive Mechanical Ventilation (IMV), length of hospital stay, and mortality. RESULTS: Our analysis unveiled substantial shifts in patient care patterns. Notably, the proportion of patients receiving glucocorticoid therapy and experiencing secondary infections exhibited a pronounced decrease across waves (p < 0.001). Remarkably, there was a significant reduction in ICU admissions (62.83% vs. 51.23% vs. 58.23% vs. 46.70 %, p < 0.001), Invasive Mechanical Ventilation (IMV) usage (39.25% vs. 32.22% vs. 31.22% vs. 21.55 %, p < 0.001), and Length of Hospital Stay (LOS) (9 vs. 8 vs. 8 vs. 8 days, p < 0.001) over the successive waves. Surprisingly, hospital mortality remained stable at approximately 18‒20 % (p > 0.05). Notably, vaccination coverage with one or more doses surged from 0 % during the initial waves to 66.71 % in the fourth wave. CONCLUSIONS: Our findings emphasize the critical importance of adapting healthcare strategies to the evolving dynamics of the pandemic. The reduction in ICU admissions, IMV utilization, and LOS, coupled with the rise in vaccination rates, underscores the adaptability of healthcare systems. Hospital mortality's persistence may warrant further exploration of treatment strategies. These insights can inform public health responses, helping policymakers allocate resources effectively and tailor interventions to specific phases of the pandemic.

Novel B cell subsets as potential biomarkers in Idiopathic Inflammatory Myopathies: insights into disease pathogenesis and disease activity.

Idiopathic inflammatory myopathies are a heterogeneous group of rare autoimmune disorders characterized by progressive muscle weakness and the histopathologic findings of inflammatory infiltrates in muscle tissue. Although their pathogenesis remains indefinite, the association of autoantibodies with clinical manifestations and the evidence of high effectiveness of depleting therapies suggest that B cells could be implicated. Therefore, we explored the landscape of peripheral B cells in this disease by multiparametric flow cytometry, finding significant numerical decreases in memory and double negative subsets, as well as an expansion of the naïve compartment relative to healthy controls, that contribute to defining disease-associated B cell subset signatures and correlating with different clinical features of patients. Additionally, we determined the potential value of these subsets as diagnostic biomarkers, thus positioning B cells as neglected key elements possibly participating in idiopathic inflammatory myopathies onset or development.

Cardiovascular event in a cohort of rheumatoid arthritis patients in Castilla-La Mancha: Utility of carotid ultrasound.

Rheumatoid Arthritis (RA) has a mortality rate 1,3 to 3 times higher than the general population, with cardiovascular mortality accounting for 40-50% of cases. Currently, cardiovascular disease is considered an extraarticular manifestation of RA (OR: 1,5-4,0). Ultrasound measurement of the intima-media thickness (IMT) of the common carotid artery and the presence of atherosclerotic plaques (AP) is a non-invasive method and a surrogate marker of subclinical arteriosclerosis. OBJECTIVE: To determine if subclinical arteriosclerosis findings through carotid ultrasound can serve as a good predictor of cardiovascular events (CVE) development in a cohort of RA patients over a 10-year period. METHODOLOGY: A cohort of RA patients seen in the Rheumatology outpatient clinic of a hospital in Castilla La Mancha in 2013 was evaluated. A prospective evaluation for the development of CVE over the following 10 years was conducted, and its correlation with previous ultrasound findings of IMT and AP was analyzed. RESULTS: Eight (24%) patients experienced a CVE. Three (9%) had heart failure, three (9%) had a stroke, and two (6%) experienced acute myocardial infarction. RA patients who developed a CVE had a higher IMT (0,97 +/- 0.08 mm) compared to the RA patients without CV complications (0,74 +/- 0.15 mm) (p = 0,003). The presence of IMT ≥ 0.9 mm and AP had a relative risk of 12,25 (p = 0,012) and 18,66 (p = 0,003), respectively, for the development of a CVE. CONCLUSIONS: Carotid ultrasound in RA patients may allow for early detection of subclinical atherosclerosis before the development of CVE, with IMT ≥ 0.9 mm being the most closely associated finding with CVE, unaffected by age.

Genome-Based Taxonomy of Species in the Pseudomonas syringae and Pseudomonas lutea Phylogenetic Groups and Proposal of Pseudomonas maioricensis sp. nov., Isolated from Agricultural Soil.

Species in the phylogenetic group Pseudomonas syringae are considered the most relevant plant pathogenic bacteria, but their taxonomy is still controversial. Twenty named species are validated in the current taxonomy of this group and in recent years many strains have been genome-sequenced, putative new species have been proposed and an update in the taxonomy is needed. A taxonomic study based on the core-genome phylogeny, genomic indices (ANI and GGDC) and gene content (phyletic pattern and Jaccard index) have been applied to clarify the taxonomy of the group. A phylogenomic analysis demonstrates that at least 50 phylogenomic species can be delineated within the group and that many strains whose genomes have been deposited in the databases are not correctly classified at the species level. Other species names, like "Pseudomonas coronafaciens", have been proposed but are not validated yet. One of the putative new species is taxonomically described, and the name Pseudomonas maioricensis sp. nov. is proposed. The taxonomies of Pseudomonas avellanae and Pseudomonas viridiflava are discussed in detail as case studies. Correct strain identification is a prerequisite for many studies, and therefore, criteria are given to facilitate identification.

Anti-Inflammatory and Cytotoxic Compounds Isolated from Plants of Euphorbia Genus.

Euphorbia is a large genus of the Euphorbiaceae family. Around 250 species of the Euphorbia genus have been studied chemically and pharmacologically; different compounds have been isolated from these species, especially diterpenes and triterpenes. Several reports show that several species have anti-inflammatory activity, which can be attributed to the presence of diterpenes, such as abietanes, ingenanes, and lathyranes. In addition, it was found that some diterpenes isolated from different Euphorbia species have anti-cancer activity. In this review, we included compounds isolated from species of the Euphorbia genus with anti-inflammatory or cytotoxic effects published from 2018 to September 2023. The databases used for this review were Science Direct, Scopus, PubMed, Springer, and Google Scholar, using the keywords Euphorbia with anti-inflammatory or cytotoxic activity. In this review, 68 studies were collected and analyzed regarding the anti-inflammatory and anti-cancer activities of 264 compounds obtained from 36 species of the Euphorbia genus. The compounds included in this review are terpenes (95%), of which 68% are diterpenes, especially of the types ingenanes, abietanes, and triterpenes (approximately 15%).