Targeting strategies with lipid vectors for nucleic acid supplementation therapy in Fabry disease: a systematic review.

Fabry disease (FD) results from a lack of activity of the lysosomal enzyme α-Galactosidase A (α-Gal A), leading to the accumulation of glycosphingolipids in several different cell types. Protein supplementation by pDNA or mRNA delivery presents a promising strategy to tackle the underlying genetic defect in FD. Protein-coding nucleic acids in FD can be either delivered to the most affected sites by the disease, including heart, kidney and brain, or to specialized organs that can act as a production factory of the enzyme, such as the liver. Lipid-based systems are currently at the top of the ranking of non-viral nucleic acid delivery systems, and their versatility allows the linking to the surface of a wide range of molecules to control their biodistribution after intravenous administration. This systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement guidelines and provides an overview and discussion of the targeting ligands that have been employed so far to actively vectorize intravenously administered non-viral vectors based on lipid carriers to clinically relevant organs in the treatment of FD, for protein-coding nucleic acid (pDNA and mRNA) supplementation. Among the thirty-two studies included, the majority focus on targeting the liver and brain. The targeting of the heart has been reported to a lesser degree, whereas no articles addressing kidney-targeting have been recorded. Although a great effort has been made to develop organ-specific nucleic acid delivery systems, the design of active-targeted carriers with high quality, good clinical translation, and large-scale manufacturing capacity is still challenging.

Fish skin grafts versus standard of care on wound healing of chronic diabetic foot ulcers: A systematic review and meta-analysis.

INTRODUCTION: This study will explore the effectiveness of fish skin grafts (FSG) in ulcer healing in diabetic foot disease compared to standard of care (SOC). METHODS: The systematic review and meta-analysis were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard. The electronic databases of PubMed, EMBASE, and Web of Science (WoS) internet were searched for the outcome rate of complete ulcer healing. The risk of bias assessment was conducted using the tool recommended by the Cochrane Collaboration. Statistical analysis included the individual and combined result of the studies, heterogeneity test, the effect size, sensitivity analysis, and publication bias tests. RESULTS: Five randomised controlled trials (RCTs) with a total of 411 patients were included in this study. This meta-analysis showed a higher rate of complete ulcer healing in groups receiving fish skin grafts (OR = 3.34, 95% CI 2.14-5.20, p < 0.01, I2 = 0%) compared to control groups. CONCLUSION: Fish skin grafts have been shown to be more effective for achieving complete ulcer healing compared to current conventional treatments in diabetic foot disease.

Plants from Arid and Semi-Arid Zones of Mexico Used to Treat Respiratory Diseases: A Review.

Medicinal plants have been a traditional remedy for numerous ailments for centuries. However, their usage is limited due to a lack of evidence-based studies elucidating their mechanisms of action. In some countries, they are still considered the first treatment due to their low cost, accessibility, and minor adverse effects. Mexico is in second place, after China, in inventoried plants for medicinal use. It has around 4000 species of medicinal plants; however, pharmacological studies have only been carried out in 5% of its entirety. The species of the Mexican arid zones, particularly in semi-desert areas, exhibit outstanding characteristics, as their adverse growing conditions (e.g., low rainfall and high temperatures) prompt these plants to produce interesting metabolites with diverse biological activities. This review explores medicinal plants belonging to the arid and semi-arid zones of Mexico, focusing on those that have stood out for their bioactive potential, such as Jatropha dioica, Turnera diffusa, Larrea tridentata, Opuntia ficus-indica, Flourensia cernua, Fouquieria splendes, and Prosopis glandulosa. Their extraction conditions, bioactive compounds, mechanisms of action, and biological efficacy are presented, with emphasis on their role in the treatment of respiratory diseases. Additionally, current research, novel applications, and perspectives concerning medicinal plants from these zones are also discussed.

Validity of bioelectric impedance analysis for body composition assessment in interstitial lung disease patients.

BACKGROUND: changes in body composition (BC) are common in interstitial lung disease, which leads to an increased risk of complications and infections, and are associated with poor quality of life and worse outcomes. BC assessment is important to identify malnutrition and sarcopenia. However, gold-standard techniques are not available in all clinical settings. AIMS: this study aimed to evaluate the agreement and reliability of body composition estimated by bioelectric impedance analysis (BIA) and measured using dual-energy x-ray absorptiometry (DEXA) in women with interstitial lung disease. METHODS: this is a cross-sectional study. BC (fat mass and appendicular skeletal muscle mass) were assessed using BIA multifrequency and DEXA in standardized conditions. Agreement and reliability between techniques were evaluated using Bland-Altman plots and the intraclass correlation coefficient (ICC). RESULTS: a total of 50 women were evaluated. No differences were observed for FM (BIA, 25.8 ± 10.2 kg and DEXA, 26.3 ± 10.0 kg, p = 0.77) and ASMM (BIA, 14.1 ± 2.7 kg and DEXA, 13.9 ± 2.3 kg, p = 0.83). Based on ICC, good reliability was observed for FM (ICC, 0.98) and ASMM (ICC, 0.93). CONCLUSION: BC estimated by BIA showed good agreement and reliability with DEXA measurements. In the absence of this method, BIA can replace the DEXA technique for body composition assessment.

Cardiac Rehabilitation Increases Plasma Klotho Levels.

Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. -49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. -17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.

Resolvin D2 attenuates LPS-induced macrophage exhaustion.

Early in sepsis, a hyperinflammatory response is dominant, but later, an immunosuppressive phase dominates, and the host is susceptible to opportunistic infections. Anti-inflammatory agents may accelerate the host into immunosuppression, and few agents can reverse immunosuppression without causing inflammation. Specialized pro-resolving mediators (SPMs) such as resolvin D2 (RvD2) have been reported to resolve inflammation without being immunosuppressive, but little work has been conducted to examine their effects on immunosuppression. To assess the effects of RvD2 on immunosuppression, we established a model of macrophage exhaustion using two lipopolysaccharide (LPS) treatments or hits. THP-1 monocyte-derived macrophages were first treated with RvD2 or vehicle for 1 h. One LPS hit increased NF-κB activity 11-fold and TNF-α release 60-fold compared to unstimulated macrophages. RvD2 decreased LPS-induced NF-κB activity and TNF-α production but increased bacterial clearance. Two LPS hits reduced macrophage bacterial clearance and decreased macrophage NF-κB activity (45%) and TNF-α release (75%) compared to one LPS hit, demonstrating exhaustion. RvD2 increased NF-κB activity, TNF-α release, and bacterial clearance following two LPS hits compared to controls. TLR2 inhibition abolished RvD2-mediated changes. In a mouse sepsis model, splenic macrophage response to exogenous LPS was reduced compared to controls and was restored by in vivo administration of RvD2, supporting the in vitro results. If RvD2 was added to monocytes before differentiation into macrophages, however, RvD2 reduced LPS responses and increased bacterial clearance following both one and two LPS hits. The results show that RvD2 attenuated macrophage suppression in vitro and in vivo and that this effect was macrophage-specific.

Atherogenic Index as a Cardiovascular Biomarker in Mexican Workers from Marginalized Urban Areas Occupationally Exposed to Metals.

BACKGROUND: Cardiovascular disease (CVD) is one of the main causes of death and disability worldwide. The etiology of CVD is often associated with multiple risk factors, with environmental factors receiving considerable attention. Individuals with precarious jobs are among the groups most affected by chronic exposure to environmental pollutants. AIM: This study aimed to evaluate occupational exposure to heavy metals among individuals in precarious job settings and investigate atherogenic indices as biomarkers of cardiovascular risk. METHODS: A total of 137 workers participated in this cross-sectional study conducted in three work environments in San Luis Potosi, Mexico. Urine and blood samples were collected to assess metal exposure and biochemical profiles, including atherogenic indices. RESULTS: The results showed that workers in the brick sector exhibited the highest levels of metal exposure, particularly arsenic (44.06 µg/L), followed by stonecutters and garbage collectors (24.7 and 16.9 µg/L, respectively). Similarly, Castelli risk index (CRI) and the atherogenic index of plasma (AIP) were higher in brickmakers (3.883 and 0.499) compared to stonecutters (3.285 and 0.386) and garbage collectors (3.329 and 0.367). CONCLUSIONS: Evidence of exposure to heavy metals was observed in the three populations, in addition to the fact that individuals with greater exposure to arsenic also exhibited higher CRI and AIP.

Telomere length as biomarker of nutritional therapy for prevention of type 2 diabetes mellitus development in patients with coronary heart disease: CORDIOPREV randomised controlled trial.

BACKGROUND: Telomere Length (TL), a marker of cellular aging, holds promise as a biomarker to elucidate the molecular mechanism of diabetes. This study aimed to investigate whether shorter telomeres are associated with a higher risk of type 2 diabetes mellitus (T2DM) incidence in patients with coronary heart disease; and to determine whether the most suitable dietary patterns, particularly a Mediterranean diet or a low-fat diet, can mitigate the development of diabetes in these patients after a follow-up period of five years. METHODS: The CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study) was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive two healthy diets. Clinical investigators were masked to treatment assignment; participants were not. Quantitative-PCR was used to assess TL measurements. FINDINGS: 1002 patients (59.5 ± 8.7 years and 82.5% men) were enrolled into Mediterranean diet (n = 502) or a low-fat diet (n = 500) groups. In this analysis, we included all 462 patients who did not have T2DM at baseline. Among them, 107 patients developed T2DM after a median of 60 months. Cox regression analyses showed that patients at risk of short telomeres (TL < percentile 20th) are more likely to experience T2DM than those at no risk of short telomeres (HR 1.65, p-value 0.023). In terms of diet, patients at high risk of short telomeres had a higher risk of T2DM incidence after consuming a low-fat diet compared to patients at no risk of short telomeres (HR 2.43, 95CI% 1.26 to 4.69, p-value 0.008), while no differences were observed in the Mediterranean diet group. CONCLUSION: Patients with shorter TL presented a higher risk of developing T2DM. This association could be mitigated with a specific dietary pattern, in our case a Mediterranean diet, to prevent T2DM in patients with coronary heart disease. TRIAL REGISTRATION: Clinicaltrials.gov number NCT00924937.

Design of New Bis(1,2,3-triazol-1-yl)methane-Based Nitrogen Ligands: Synthesis and Coordination Chemistry.

The reaction between bis(1,2,3-triazol-1-yl)methane derivatives and nBuLi and various aldehydes, yielded novel neutral ligand precursors incorporating alcohol functional groups. The resulting compounds exhibited distinct characteristics depending on the steric hindrance of the aldehyde employed. In instances where aromatic aldehydes were utilized, functionalization occurred at the methine group bridging both triazole rings. Conversely, the use of pivalic aldehyde prompted functionalization at the C5 position of the triazole ring. These compounds were subsequently employed as ligand precursors in the synthesis of organometallic aluminum and zinc complexes, yielding dinuclear complexes with high efficiency. The structural elucidation of all compounds was accomplished through spectroscopic methods and validated by X-ray crystallography. Preliminary catalytic investigations into the coupling reaction of cyclohexene oxide and CO2 revealed that aluminum and zinc complexes catalyzed the selective formation of polyether and polycarbonate materials, respectively.

Applicability of the Barcelona scale to assess the quality of cleanliness of mucosa at esophagogastroduodenoscopy / Aplicabilidad de la escala Barcelona para valorar la calidad de la limpieza de la mucosa en la esofagogastroduodenoscopia

Background and objectives There are few scales with prospective validation for the assessment of the upper gastrointestinal mucosal cleanliness during an esophagogastroduodenoscopy (EGD). The aim of this study was to develop a valid and reproducible cleanliness scale for use during an EGD. Methods We developed a cleanliness scale (Barcelona scale) with a score (0–2 points) of five segments of the upper gastrointestinal tract with thorough cleaning techniques (esophagus, fundus, body, antrum, and duodenum). First, 125 photos (25 of each area) were assessed, and a score was assigned to each image by consensus among 7 experts endoscopists. Subsequently, 100 of the 125 images were selected and the inter- and intra-observer variability of 15 previously trained endoscopists was evaluated using the same images at two different times. Results In total, 1500 assessments were performed. In 1336/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.83 (0.45–0.96). In the second evaluation, in 1330/1500 observations (89%) there was agreement with the consensus score, with a mean kappa value of 0.82 (0.45–0.93). The intra-observer variability was 0.89 (0.76–0.99). Conclusions The Barcelona cleanliness scale is a valid measure and reproducible with minimal training. Its application in clinical practice is a significant step to standardize the quality of the EGD. (AU)

Introducción Existen pocas escalas validadas prospectivamente para evaluar la limpieza de la mucosa esofagogastroduodenal durante la endoscopia digestiva alta (EDA). El objetivo de este estudio fue desarrollar una escala válida y reproducible para su uso en la realización de una EDA. Métodos Desarrollamos una escala de limpieza (escala Barcelona) en la que se aplicó una puntuación de 0 a 2 a cinco áreas del tracto digestivo superior (esófago, fundus, cuerpo, antro y duodeno) después de haber realizado todas las maniobras de lavado necesarias. Inicialmente, se evaluaron 125 fotos (25 de cada área) y se asignó una puntuación (de 0 a 2) a cada una por consenso entre siete endoscopistas. Posteriormente, se seleccionaron 100 de las 125 fotografías y se evaluó la variabilidad inter e intraobservador de 15 endoscopistas previamente formados utilizando las mismas imágenes en dos momentos diferentes. Resultados Se efectuaron un total de 1.500 observaciones. En 1.336/1.500 de ellas (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,83 (0,45-0,96). En la segunda evaluación, en 1.330/1.500 observaciones (89%) hubo coincidencia con la puntuación del consenso, siendo el valor medio de kappa de 0,82 (mínimo 0,45 y máximo 0,93). La variabilidad intraobservador fue de 0,89 (0,76-0,99). Conclusiones La escala de limpieza Barcelona es una medida válida y reproducible con un mínimo entrenamiento. Su uso en la práctica clínica podría ser un paso significativo para estandarizar la calidad de la EDA. (AU)

Direct oral challenge for immediate and non-immediate beta-lactam allergy in children: A real-world multicenter study.

BACKGROUND: Allergy to beta-lactam antibiotics (BLA) is frequently suspected in children, but a drug provocation test (DPT) rules it out in over 90% of cases. Direct oral DPT (DODPT), without skin or other previous tests, is increasingly been used to delabel non-immediate BLA reactions. This real-world study aimed to assess the safety and effectiveness of DODPT in children with immediate and non-immediate reactions to BLAs. METHODS: Ambispective registry study in children (<15 years), attended between 2016 and 2023 for suspected BLA allergy in 15 hospitals in Spain that routinely perform DODPT. RESULTS: The study included 2133 patients with generally mild reactions (anaphylaxis 0.7%). Drug provocation test with the implicated BLA was performed in 2014 patients (94.4%): 1854 underwent DODPT (86.9%, including 172 patients with immediate reactions). One hundred forty-five (7.2%) had symptoms associated with DPT, although only four reactions were severe: two episodes of anaphylaxis and two of drug-induced enterocolitis syndrome, which resolved rapidly with treatment. Of the 141 patients with mild reactions in the first DPT, a second DPT was considered in 87 and performed in 57, with 52 tolerating it without symptoms. Finally, BLA allergy was ruled out in 90.9% of the sample, confirmed in 3.4%, and remained unverified, usually due to loss to follow-up, in 5.8%. CONCLUSIONS: Direct oral DPT is a safe, effective procedure even in immediate mild reactions to BLA. Many reactions observed in DPT are doubtful and require confirmation. Severe reactions are exceptional and amenable to treatment. Direct oral DPT can be considered for BLA allergy delabeling in pediatric primary care.

Cannabidiol reduces intraventricular hemorrhage brain damage, preserving myelination and preventing blood brain barrier dysfunction in immature rats.

Intraventricular hemorrhage (IVH) is an important cause of long-term disability in extremely preterm infants, with no current treatment. This study assessed the potential neuroprotective effects of cannabidiol (CBD) in an IVH model using immature rats. IVH was induced in 1-day-old (P1) Wistar rats by left periventricular injection of Clostridial collagenase. Some rats received CBD prenatally (10 â€‹mg/kg i.p. to the dam) and then 5 â€‹mg/kg i.p. 6, 30 and 54 â€‹h after IVH (IVH+CBD, n â€‹= â€‹30). Other IVH rats received vehicle (IVH+VEH, n â€‹= â€‹34) and vehicle-treated non-IVH rats served as controls (SHM, n â€‹= â€‹29). Rats were humanely killed at P6, P14 or P45. Brain damage (motor and memory performance, area of damage, Lactate/N-acetylaspartate ratio), white matter injury (ipsilateral hemisphere and corpus callosum volume, oligodendroglial cell density and myelin basic protein signal), blood-brain barrier (BBB) integrity (Mfsd2a, occludin and MMP9 expression, gadolinium leakage), inflammation (TLR4, NFκB and TNFα expression, infiltration of pro-inflammatory cells), excitotoxicity (Glutamate/N-acetylspartate ratio) and oxidative stress (protein nitrosylation) were then evaluated. CBD prevented the long-lasting motor and cognitive consequences of IVH, reduced brain damage in the short- and long-term, protected oligodendroglial cells preserving adequate myelination and maintained BBB integrity. The protective effects of CBD were associated with the modulation of inflammation, excitotoxicity and oxidative stress. In conclusion, in immature rats, CBD reduced IVH-induced brain damage and its short- and long-term consequences, showing robust and pleiotropic neuroprotective effects. CBD is a potential candidate to ameliorate IVH-induced immature brain damage.

Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, non-randomized, multicenter GEM-SELIBORDARA study.

The treatment landscape for multiple myeloma has significantly evolved in the last decade. Notwithstanding, a large proportion of patients continue to relapse and novel combinations continue to be needed. In this phase 2 study, selinexor, a first-in-class inhibitor of exportin-1 was evaluated in combination with standard daratumumab-bortezomib-dexamethasone (DVd), for the treatment of relapsed and refractory multiple myeloma (RRMM). The aim of the trial was to assess the efficacy and safety of the combination of selinexor with DVd (S-DVd). A total of 57 patients were enrolled in the two parts of the study. Part 1 enrolled a heavily pretreated population with at least 3 prior lines of therapy and part 2 enrolled an early relapse population with at least 1 prior therapy. The primary endpoint was complete response (CR) rate in part 2 and overall response rate (ORR) in part 1. In the latter, 24 patients were treated with a median of 3 prior lines. Overall response rate (ORR) was 50% with 2 CR. Median progressionfree survival (PFS) was 7 months. In part 2, 33 patients were enrolled, with a median of 1 prior lines. ORR was 82% and CR or better was 33%. Median PFS was 24 months. In lenalidomide refractory patients, a median PFS of 22.1 months was observed. Thrombocytopenia was the most common hematological adverse event (69%; grade 3-4: 34%) and nausea, the most frequent nonhematological AE (38%; grade 3-4: 6%). 62% of the patients required dose modifications. In summary, although the primary endpoint of the study was not met, the combination of S-DVd showed encouraging clinical efficacy with a generally manageable safety profile representing a potential option for the treatment of RRMM patients.

Bibliometric analysis on cannibalism/infanticide and maternal aggression towards pups in laboratory rodents.

Animal welfare has evolved during the past decades to improve not only the quality of life of laboratory rodents but also the quality and reproducibility of scientific investigations. Bibliometric analysis has become an important tool to complete the current knowledge with academic databases. Our objective was to investigate whether scientific research on cannibalism/infanticide is connected with maternal aggression towards the offspring in laboratory rodents. To carry out our research, we performed a specific search for published articles on each concept. Results were analyzed in the open-source environment RStudio with the package Bibliometrix. We obtained 253 and 134 articles for the first search (cannibalism/infanticide) and the second search (maternal aggression towards the pups) respectively. We observed that the interest in infanticide/cannibalism started in the 1950s, while researchers started showing interest in maternal aggression towards the pups 30 years later. Our analyses indicated that maternal aggression had better citations in scientific literature. In addition, although our results showed some common features (e.g. oxytocin or medial preoptic area in the brain), we observed a gap between cannibalism/infanticide and maternal aggression towards the pups with only 14 published articles in common for both the searches. Therefore, we recommend researchers to combine both concepts in further investigations in the context of cannibalism for better dissemination and higher impact in laboratory rodents' welfare research.

How 'hidden hearing loss' noise exposure affects neural coding in the inferior colliculus of rats.

Exposure to brief, intense sound can produce profound changes in the auditory system, from the internal structure of inner hair cells to reduced synaptic connections between the auditory nerves and the inner hair cells. Moreover, noisy environments can also lead to alterations in the auditory nerve or to processing changes in the auditory midbrain, all without affecting hearing thresholds. This so-called hidden hearing loss (HHL) has been shown in tinnitus patients and has been posited to account for hearing difficulties in noisy environments. However, much of the neuronal research thus far has investigated how HHL affects the response characteristics of individual fibres in the auditory nerve, as opposed to higher stations in the auditory pathway. Human models show that the auditory nerve encodes sound stochastically. Therefore, a sufficient reduction in nerve fibres could result in lowering the sampling of the acoustic scene below the minimum rate necessary to fully encode the scene, thus reducing the efficacy of sound encoding. Here, we examine how HHL affects the responses to frequency and intensity of neurons in the inferior colliculus of rats, and the duration and firing rate of those responses. Finally, we examined how shorter stimuli are encoded less effectively by the auditory midbrain than longer stimuli, and how this could lead to a clinical test for HHL.

Prevalence of virulence- and antibiotic resistance-associated genotypes and phenotypes in Staphylococcus aureus strains from the food sector compared to clinical and cow mastitis isolates.

Background: Infections by the pathogen Staphylococcus aureus currently represent one of the most serious threats to human health worldwide, especially due to the production of enterotoxins and the ability to form biofilms. These structures and the acquisition of antibiotic resistance limit the action of antibiotics and disinfectants used to combat this microorganism in the industry and the clinic. Methods: This work reports a comparative phenotypic and genotypic study of 18 S. aureus strains from different origins: clinical samples, milk from mastitic cows and food industry surfaces, most of which were isolated in Northern Spain. Results: Genetically, the strains were very diverse but, in most cases, a closer proximity was observed for those from the same source. Notably, the average number of virulence genes was not significantly different in strains from the food sector. Of the 18 strains, 10 coded for at least one enterotoxin, and four of them carried 6 or 7 enterotoxin genes. The latter were all veterinary or clinical isolates. Most strains carried prophages, plasmids and/or pathogenicity islands. Regarding antibiotic resistance, although phenotypically all strains showed resistance to at least one antibiotic, resistance genes were only identified in 44.5% of strains, being mastitis isolates those with the lowest prevalence. Virulence-related phenotypic properties such as haemolytic activity, staphyloxanthin production, biofilm-forming capacity and spreading ability were widely distributed amongst the isolates. Conclusions: Our results indicate that production of virulence factors, antibiotic resistance and biofilm formation can be found in S. aureus isolates from diverse environments, including the food industry, although some of these traits are more prevalent in strains isolated from infections in cows or humans. This emphasizes on the importance of monitoring the spread of these determinants not only in samples from the clinical environment, but also along the food chain, a strategy that falls under the prism of a one-health approach.

Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines.

Dendritic cells (DCs) serve as professional antigen-presenting cells (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular and humoral responses against tumor and infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, and have been intensively investigated specifically in the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects the elderly population (those aged over 65), which usually presents a high rate of therapeutic failure and an unfavorable prognosis. In this review, we examine the current state of development and progress of vaccines in AML. The findings evidence the possible administration of DC-based vaccines as an adjuvant treatment in AML following initial therapy. Furthermore, the therapy demonstrates promising outcomes in preventing or delaying tumor relapse and exhibits synergistic effects when combined with other treatments during relapses or disease progression. On the other hand, the remarkable success observed with RNA vaccines for COVID-19, delivered in lipid nanoparticles, has revealed the efficacy and effectiveness of these types of vectors, prompting further exploration and their potential application in AML, as well as other neoplasms, loading them with tumor RNA.