Reducing variability in nasal surgery outcomes through computational fluid dynamics and advanced 3D virtual surgery techniques.

Objectives: This study aims to delineate the specific impact of using computational fluid dynamics (CFD) and 3D virtual surgery techniques in otolaryngology surgery, focusing on their roles in enhancing the precision of nasal surgery and optimizing future patient outcomes. The central objective was to assess whether these advanced technologies could reduce variability in surgical approaches and decision-making among specialists, thereby improving the consistency and efficacy of patient care in cases of nasal obstruction. Methods and results: Our methodology involved a detailed analysis of pre- and post-operative scenarios using CFD feedback. Six otolaryngologists participated, employing virtual surgery techniques on two patients with diagnosed nasal obstruction. The CFD analysis focused on quantifying key airflow parameters: right nasal flow rate (QR), left nasal flow rate (QL), flow symmetry (Ф), and bilateral nasal resistance (R). These parameters were meticulously compared before and after the application of CFD feedback to evaluate changes in surgical planning and outcomes. Quantitative analysis revealed a notable decrease in the standard deviation of the measured parameters among the specialists post-CFD feedback, indicating reduced variability in surgical approaches. Specifically, for Patient #1 the standard deviation for QR values dropped from 0.694 L/min to 0.602 L/min, and for QL values from 0.676 L/min to 0.584 L/min, and for Patient #2, the standard deviation for QR values decreased from 2.204 L/min to 0.958 L/min, and for QL values from 2.295 L/min to 1.014 L/min. Moreover, the variability range, represented by the differences between the maximum and minimum values for Ф and R, diminished significantly. Post-operative average values for all parameters showed a convergence towards ideal basal levels, suggesting a more uniform and effective surgical strategy across different surgeons. Conclusions: Both integration of CFD and 3D virtual surgery techniques in otolaryngology can substantially reduce variability in surgical planning and decision-making, ultimately leading to improved patient outcomes. These advanced tools have the potential to standardize the diagnosis and treatment of nasal pathologies, contributing to more effective and consistent care. Future research in this area should focus on larger patient cohorts and further exploration of the potential benefits and applications of CFD and virtual surgery in otolaryngology.

Biomedical and ecosafety assessment of marine fish collagen capped silver nanoparticles.

In the rapidly evolving landscape of silver nanoparticles (Ag NPs) synthesis, the focus has predominantly been on plant-derived sources, leaving the realm of biological or animal origins relatively uncharted. Breaking new ground, our study introduces a pioneering approach: the creation of Ag NPs using marine fish collagen, termed ClAg NPs, and offers a comprehensive exploration of their diverse attributes. To begin, we meticulously characterized ClAg NPs, revealing their spherical morphology, strong crystalline structure, and average diameter of 5 to 100 nm. These NPs showed potent antibacterial activity, notably against S. aureus (gram-positive), surpassing their efficacy against S. typhi (gram-negative). Additionally, ClAg NPs effectively hindered the growth of MRSA biofilms at 500 µg/mL. Impressively, they demonstrated substantial antioxidant capabilities, out performing standard gallic acid. Although higher concentrations of ClAg NPs induced hemolysis (41.804 %), lower concentrations remained non hemolytic. Further evaluations delved into the safety and potential applications of ClAg NPs. In vitro cytotoxicity studies on HEK 293 and HeLa cells revealed dose-dependent toxicity, with IC50 of 75.28 µg/mL and 79.13 µg/mL, respectively. Furthermore, ClAg NPs affected seed germination, root, and shoot lengths in Mung plants, underscoring their relevance in agriculture. Lastly, zebrafish embryo toxicity assays revealed notable effects, particularly at 500 µg/mL, on embryo morphology and survival rates at 96 hpf. In conclusion, our study pioneers the synthesis and multifaceted evaluation of ClAg NPs, offering promise for their use as versatile nano therapeutics in the medical field and as high-value collagen-based nanobiomaterial with minimal environmental impact.

Immunizing hearts: exploring the vaccination frontier in heart failure management.

Heart failure (HF) is a widespread clinical condition that affects numerous individuals globally and is a leading cause of hospitalization, particularly in the elderly population. Despite efforts to manage HF using various pharmacological and nonpharmacological interventions, mortality and hospitalization rates remain alarmingly high. Preventive vaccination has emerged as a key measure endorsed by cardiology societies for reducing the morbidity and mortality associated with HF. This study undertakes an extensive review of existing literature to explore the role of vaccination in managing HF, focusing specifically on the immunological pathways involved and potential benefits offered by immunization in this context. This article highlights the role of various vaccines, including influenza, pneumococcal, and COVID-19 vaccines, in reducing HF-related hospitalization, mortality, and overall disease burden. Additionally, this article will delve into specific vaccines that have shown promise in HF management, such as influenza, pneumococcal, and COVID-19 vaccines, along with the rationale for their use, clinical trials, meta-analyses, and real-world data supporting their effectiveness in patients with HF. This article also considers potential challenges and obstacles to widespread vaccination in individuals with HF, which include vaccine hesitancy, accessibility, and adverse events related to vaccines.

Hydrogel-Based Microneedle as a Drug Delivery System.

The skin is considered the largest and most accessible organ in the human body, and allows the use of noninvasive and efficient strategies for drug administration, such as the transdermal drug delivery system (TDDS). TDDSs are systems or patches, with the ability and purpose to deliver effective and therapeutic doses of drugs through the skin. Regarding the specific interaction between hydrogels (HG) and microneedles (MNs), we seek to find out how this combination would be applied in the context of drug delivery, and we detail some possible advantages of the methods used. Depending on the components belonging to the HG matrix, we can obtain some essential characteristics that make the combination of hydrogels-microneedles (HG-MNs) very advantageous, such as the response to external stimuli, among others. Based on multiple characteristics provided by HGMNs that are depicted in this work, it is possible to obtain unique properties that include controlled, sustained, and localized drug release, as well as the possibility of a synergistic association between the components of the formulation and the combination of more than one bioactive component. In conclusion, a system based on HG-MNs can offer many advantages in the biomedical field, bringing to light a new technological and safe system for improving the pharmacokinetics and pharmacodynamics of drugs and new treatment perspectives.

Bacterial Polyhydroxyalkanoates-based Therapeutics-delivery Nanosystems.

Microbial polyhydroxyalkanoates (PHAs) are bio-based aliphatic biopolyester produced by bacteria as an intracellular storage material of carbon and energy under stressed conditions. PHAs have been paid attention to due to their unique and impressive biological properties including high biodegradability, biocompatibility, low cytotoxicity, and different mechanical properties. Under this context, the development of drug-delivery nanosystems based on PHAs has been revealed to have numerous advantages compared with synthetic polymers that included biocompatibility, biodegradability, non-toxic, and low-cost production, among others. In this review article, we present the available state of the art of PHAs. Moreover, we discussed the potential benefits, weaknesses, and perspectives of PHAs to the develop drug delivery systems.

Delivery Systems in Ocular Retinopathies: The Promising Future of Intravitreal Hydrogels as Sustained-Release Scaffolds.

Slow-release delivery systems are needed to ensure long-term sustained treatments for retinal diseases such as age-related macular degeneration and diabetic retinopathy, which are currently treated with anti-angiogenic agents that require frequent intraocular injections. These can cause serious co-morbidities for the patients and are far from providing the adequate drug/protein release rates and required pharmacokinetics to sustain prolonged efficacy. This review focuses on the use of hydrogels, particularly on temperature-responsive hydrogels as delivery vehicles for the intravitreal injection of retinal therapies, their advantages and disadvantages for intraocular administration, and the current advances in their use to treat retinal diseases.

Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19.

BACKGROUND: The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs). OBJECTIVE: To determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19. DESIGN: Retrospective cohort. SETTING: Eight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN). TARGET POPULATION: Adults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020. MEASUREMENTS: We randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs. RESULTS: Two hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p < 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error. LIMITATIONS: Results are limited by available documentation and do not capture communication between providers and patients. CONCLUSION: Among PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.

Moringa oleifera gum capped MgO nanoparticles: Synthesis, characterization, cyto- and ecotoxicity assessment.

Nano-based drug delivery research is increasing due to the therapeutic applications for human health care. However, traditional chemical capping-based synthesis methods lead to unwanted toxicity effects. Hence, there is an urgent need for green synthesis-based and biocompatible synthesis methods. The current work describes for the first time the green synthesis of Moringa gum-capped MgO nanoparticles (Mgm-MgO NPs). Their antioxidant activity, hemolysis potential, cytotoxicity, phytotoxicity, toxicity by chorioallantoic membrane (CAM) chick embryo assay and in vivo toxicity in zebrafish embryos were described. The Mgm-MgO NPs exhibited significant antioxidant activity. The Mgm-MgO NPs at 500 µg/ml produced significant hemolysis (72.54 %), while lower concentrations did not. Besides, the cytotoxicity assessment of the Mgm-MgO NPs was conducted in PA-1 cells from human ovarian teratocarcinoma by MTT assay. The Mgm-MgO NPs (0.1-500 µg/ml) considerably reduced the viability of PA-1 cells. Furthermore, Mgm-MgO NPs had no significant effect on seed germination but had a significant effect on root and shoot length of mungbean (Vigna radiata). Additionally, the CAM assay was used to analyze the antiangiogenic potential of Mgm-MgO NPs, exhibiting no significant alterations after 72 h. Finally, the zebrafish embryotoxicity assay revealed that the Mgm-MgO NPs (0.1-500 µg/ml) did not affect morphology, mortality or survival rate.

Intracellular Delivery of Anti-Kirsten Rat Sarcoma Antibodies Mediated by Polymeric Micelles Exerts Strong In Vitro and In Vivo Anti-Tumorigenic Activity in Kirsten Rat Sarcoma-Mutated Cancers.

The Kirsten rat sarcoma viral oncogene (KRAS) is one of the most well-known proto-oncogenes, frequently mutated in pancreatic and colorectal cancers, among others. We hypothesized that the intracellular delivery of anti-KRAS antibodies (KRAS-Ab) with biodegradable polymeric micelles (PM) would block the overactivation of the KRAS-associated cascades and revert the effect of its mutation. To this end, PM-containing KRAS-Ab (PM-KRAS) were obtained using Pluronic F127. The feasibility of using PM for antibody encapsulation as well as the conformational change of the polymer and its intermolecular interactions with the antibodies was studied, for the first time, using in silico modeling. In vitro, encapsulation of KRAS-Ab allowed their intracellular delivery in different pancreatic and colorectal cancer cell lines. Interestingly, PM-KRAS promoted a high proliferation impairment in regular cultures of KRAS-mutated HCT116 and MIA PaCa-2 cells, whereas the effect was neglectable in non-mutated or KRAS-independent HCT-8 and PANC-1 cancer cells, respectively. Additionally, PM-KRAS induced a remarkable inhibition of the colony formation ability in low-attachment conditions in KRAS-mutated cells. In vivo, when compared with the vehicle, the intravenous administration of PM-KRAS significantly reduced tumor volume growth in HCT116 subcutaneous tumor-bearing mice. Analysis of the KRAS-mediated cascade in cell cultures and tumor samples showed that the effect of PM-KRAS was mediated by a significant reduction of the ERK phosphorylation and a decrease in expression in the stemness-related genes. Altogether, these results unprecedently demonstrate that the delivery of KRAS-Ab mediated by PM can safely and effectively reduce the tumorigenicity and the stemness properties of KRAS-dependent cells, thus bringing up new possibilities to reach undruggable intracellular targets.

Rational Design of Hydrogels for Cationic Antimicrobial Peptide Delivery: A Molecular Modeling Approach.

In light of the growing bacterial resistance to antibiotics and in the absence of the development of new antimicrobial agents, numerous antimicrobial delivery systems over the past decades have been developed with the aim to provide new alternatives to the antimicrobial treatment of infections. However, there are few studies that focus on the development of a rational design that is accurate based on a set of theoretical-computational methods that permit the prediction and the understanding of hydrogels regarding their interaction with cationic antimicrobial peptides (cAMPs) as potential sustained and localized delivery nanoplatforms of cAMP. To this aim, we employed docking and Molecular Dynamics simulations (MDs) that allowed us to propose a rational selection of hydrogel candidates based on the propensity to form intermolecular interactions with two types of cAMPs (MP-L and NCP-3a). For the design of the hydrogels, specific building blocks were considered, named monomers (MN), co-monomers (CM), and cross-linkers (CL). These building blocks were ranked by considering the interaction with two peptides (MP-L and NCP-3a) as receptors. The better proposed hydrogel candidates were composed of MN3-CM7-CL1 and MN4-CM5-CL1 termed HG1 and HG2, respectively. The results obtained by MDs show that the biggest differences between the hydrogels are in the CM, where HG2 has two carboxylic acids that allow the forming of greater amounts of hydrogen bonds (HBs) and salt bridges (SBs) with both cAMPs. Therefore, using theoretical-computational methods allowed for the obtaining of the best virtual hydrogel candidates according to affinity with the specific cAMP. In conclusion, this study showed that HG2 is the better candidate for future in vitro or in vivo experiments due to its possible capacity as a depot system and its potential sustained and localized delivery system of cAMP.

Perspectives toward the Development of Advanced Materials Based on Bacterial Polysaccharides.

Bacteria and their enzymatic machinery, also called bacterial cell factories, produce a diverse variety of biopolymers, such as polynucleotides, polypeptides and polysaccharides, with different and fundamental cellular functions. Polysaccharides are the most widely used biopolymers, especially in biotechnology. This type of biopolymer, thanks to its physical and chemical properties, can be used to create a wide range of advanced bio-based materials, hybrid materials and nanocomposites for a variety of exciting biomedical applications. In contrast to synthetic polymers, bacterial polysaccharides have several advantages, such as biocompatibility, biodegradability, low immunogenicity, and non-toxicity, among others. On the other hand, the main advantage of bacterial polysaccharides compared to polymers extracted from other natural sources is that their physicochemical properties, such as purity, porosity, and malleability, among others, can be adapted to a specific application with the use of biotechnological tools and/or chemical modifications. Another great reason for using bacterial polysaccharides is due to the possibility of developing advanced materials from them using bacterial factories that can metabolize raw materials (recycling of industrial and agricultural wastes) that are readily available and in large quantities. Moreover, through this strategy, it is possible to curb environmental pollution. In this article, we project the desire to move towards large-scale production of bacterial polysaccharides taking into account the benefits, weaknesses and prospects in the near future for the development of advanced biological materials for medical and pharmaceutical purposes.

Smart and eco-friendly N-isopropylacrylamide and cellulose hydrogels as a safe dual-drug local cancer therapy approach.

Local cancer treatment by in situ injections of thermo-responsive hydrogels (HG) offers several advantages over conventional systemic anti-cancer treatments. In this work, a biodegradable and multicompartmental HG composed of N-isopropylacrylamide, cellulose, citric acid, and ceric ammonium nitrate was developed for the controlled release of hydrophilic (doxorubicin) and hydrophobic (niclosamide) drugs. The formulation presented ideal properties regarding thermo-responsiveness, rheological behavior, drug release profile, biocompatibility, and biological activity in colon and ovarian cancer cells. Cellulose was found to retard drugs release rate, being only 4 % of doxorubicin and 30 % of niclosamide released after 1 week. This low release was sufficient to cause cell death in both cell lines. Moreover, HG demonstrated a proper injectability, in situ prevalence, and safety profile in vivo. Overall, the HG properties, together with its natural and eco-friendly composition, create a safe and efficient platform for the local treatment of non-resectable tumors or tumors requiring pre-surgical adjuvant therapy.

Comparative Study of Three Dyes' Adsorption onto Activated Carbon from Chenopodium quinoa Willd and Quillaja saponaria.

The present study shows porous activated carbon obtained from Chenopodium quinoa Willd and Quillaja saponaria and their use as potential adsorbents to remove three types of dyes from aqueous solutions. The adsorption results were compared with commercial charcoal to check their efficiency. All porous carbon materials were activated using carbon dioxide and steam and fully characterized. Moreover, the steam-activated samples exhibited a high total pore volume with a BET surface area of around 800 m2 g−1. Batch adsorption experiments showed that commercial charcoal is the charcoal that offered the best adsorption efficiency for tartrazine and sunset yellow FCF. However, in the case of crystal violet, all activated carbons obtained from Chenopodium quinoa Willd and Quillaja saponaria showed the best captures, outperforming commercial charcoal. Molecular dockings of the dyes on the commercial charcoal surface were performed using AutoDock Vina. The kinetic results of the three isotherm's models for the present data follow the order: Langmuir~Freundlich > Temkin.

Genomic prediction for canopy height and dry matter yield in alfalfa using family bulks.

Genomic selection (GS) has proven to be an effective method to increase genetic gain rates and accelerate breeding cycles in many crop species. However, its implementation requires large investments to phenotype of the training population and for routine genotyping. Alfalfa (Medicago sativa L.) is one of the major cultivated forage legumes, showing high-quality nutritional value. Alfalfa breeding is usually carried out by phenotypic recurrent selection and is commonly done at the family level. The application of GS in alfalfa could be simplified and less costly by genotyping and phenotyping families in bulks. For this study, an alfalfa reference population composed of 142 full-sib and 35 half-sib families was bulk-genotyped using target enrichment sequencing and phenotyped for dry matter yield (DMY) and canopy height (CH) in Florida, USA. Genotyping of the family bulks with 17,707 targeted probes resulted in 114,945 single-nucleotide polymorphisms. The markers revealed a population structure that matched the mating design, and the linkage disequilibrium slowly decayed in this breeding population. After exploring multiple prediction scenarios, a strategy was proposed including data from multiple harvests and accounting for the G×E in the training population, which led to a higher predictive ability of up to 38 and 24% for DMY and CH, respectively. Although this study focused on the implementation of GS in alfalfa families, the bulk methodology and the prediction schemes used herein could guide future studies in alfalfa and other crops bred in bulks.

Marine polysaccharide laminarin embedded ZnO nanoparticles and their based chitosan capped ZnO nanocomposites: Synthesis, characterization and in vitro and in vivo toxicity assessment.

In the current scenario where more and more products containing nanomaterials are on the technological or pharmaceutical market, it is crucial to have a thorough knowledge of their toxicity before proposing possible applications. A proper analysis of the toxicity of the nanoproducts should include both in vitro and in vivo biological approaches and should consider that the synthesis and purification methods of nanomaterials may affect such toxicity. In the current work, the green synthesis of laminarin embedded ZnO nanoparticles (Lm-ZnO NPs) and their based chitosan capped ZnO nanocomposites (Ch-Lm-ZnO NCmps) is described for the first time. Furthermore, the evaluation of their in vitro cytotoxicity, phytotoxicity, and in vivo (Zebrafish embryo) toxicity was described. First, the green synthesized Lm-ZnO NPs and Ch-Lm-ZnO NCmps were fully physicochemically characterized. Lm-ZnO NPs were greatly agglomerated and had a spindle morphology ranging from 100 to 350 nm, while Ch-Lm-ZnO NCmps had irregular rod shape with flake-like structure clusters randomly aggregated with diverse sizes ranging from 20 to 250 nm. The in vitro cytotoxicity assessment of the green synthesized Lm-ZnO NPs and Ch-Lm-ZnO NCmps was carried out in normal human dermal fibroblasts (HDF) cells and human colon cancer (HT-29) cells by MTT assay. Lm-ZnO NPs and Ch-Lm-ZnO NCmps (0.1-500 µg/mL), significantly inhibited the viability of both cell lines, revealing dose-dependent cytotoxicity. Besides, the Lm-ZnO NPs and Ch-Lm-ZnO NCmps significantly affected seed germination and roots and shoots length of mung (Vigna radiata). Moreover, the zebrafish embryo toxicity of Lm-ZnO NPs and Ch-Lm-ZnO NCmps among the various concentrations used (0.1-500 µg/mL) caused deformities, increased mortality and decreased the survival rate of zebrafish embryo dose-dependently.

The mid-secretory endometrial transcriptomic landscape in endometriosis: a meta-analysis.

STUDY QUESTION: Do women with endometriosis have a different endometrial gene expression profile at the time of embryo implantation than women without endometriosis? SUMMARY ANSWER: The endometrial gene expression profile of women with endometriosis differs from that of women without endometriosis at the mid-secretory phase, although the differences are small. WHAT IS KNOWN ALREADY: About 50% of women with endometriosis suffer infertility. Several molecular studies have suggested impaired endometrial receptivity in women with endometriosis, while others have detected no dysregulation of endometrial receptivity. Nevertheless, the previous endometrial transcriptome studies comparing women with and without endometriosis have been performed in small sample size with limited statistical power. We set out to systematically search and compile data of endometrial gene expression signatures at the receptive phase in women with endometriosis versus control women. Based on the obtained data, we conducted a meta-analysis of differentially expressed genes in order to raise the power of the analysis for identifying the molecular profiles of receptive phase endometria in endometriosis. STUDY DESIGN SIZE DURATION: A systematic literature search was conducted up to February 2022 following PRISMA criteria and included PubMed, Cochrane and Web of Science databases. For the systematic search, the term 'endometriosis' was paired with the terms 'transcriptomics', 'transcriptome', 'gene expression', 'RNA-seq', 'sequencing' and 'array', by using the Boolean operator 'AND' to connect them. Articles written in English were screened and interrogated for data extraction. PARTICIPANTS/MATERIALS SETTING METHODS: A meta-analysis was performed on the selected studies to extract the differentially expressed genes described at the mid-secretory phase in women with endometriosis versus women without endometriosis in natural cycles, using the robust rank aggregation method. In total, transcriptome data of 125 women (78 patients and 47 controls) were meta-analysed, with a special focus on endometrial receptivity-specific genes based on commercial endometrial receptivity tests. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 8 studies were eligible for the quantitative meta-analysis, gathering transcriptome data from the mid-secretory phase endometria of 125 women. A total of 7779 differentially expressed transcripts between the study groups were retrieved (3496 up-regulated and 4283 down-regulated) and were meta-analysed. After stringent multiple correction, there was no differential expression of any single molecule in the endometrium of women with endometriosis versus controls, while enrichment analysis detected that the pathways of chemotaxis and locomotion are dysregulated in endometriosis. Further analysis of endometrial receptivity-specific genes highlighted dysregulation of C4BPA, MAOA and PAEP and enrichment of immune and defence pathways in women with endometriosis. LIMITATIONS REASONS FOR CAUTION: Most of the studies included into the meta-analysis were relatively small and had different study designs, which might have contributed to a bias. WIDER IMPLICATIONS OF THE FINDINGS: The current meta-analysis supports the hypothesis that endometrial receptivity is altered in women with endometriosis, although the changes are small. The molecules and pathways identified could serve as future biomarkers and therapeutical targets in detecting and treating endometriosis-associated infertility. STUDY FUNDING/COMPETING INTERESTS: The authors declare no competing interests. This work was supported by the Spanish Ministry of Education, Culture and Sport [grant FPU15/01193] and the Margarita Salas program for the Requalification of the Spanish University system [grant UJAR01MS]; Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and European Regional Development Fund (FEDER): grants RYC-2016-21199 and ENDORE SAF2017-87526-R; Programa Operativo FEDER Andalucía (B-CTS-500-UGR18; A-CTS-614-UGR20); the Junta de Andalucía [BIO-302; and PAIDI P20_00158]; the University of Jaén [PAIUJA-EI_CTS02_2017]; the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES), and by the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/UGR; the Estonian Research Council (grant PRG1076); Horizon 2020 innovation (ERIN, grant no. EU952516) of the European Commission and Enterprise Estonia (grant EU48695). TRIAL REGISTRATION NUMBER: The systematic review was registered at PROSPERO (identifier: CRD42020122054).

[Identification of epithelial-mesenchymal transition markers (EMT) by immunohistochemistry in pediatric osteosarcoma and association with clinical outcomes]. / Identificación de marcadores de transición epitelio-mesénquima (TEM) por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos.

The epithelial-mesenchymal transition (EMT) is the ability of epithelial and mesenchymal cells to exchange phenotypes transiently. Its identification in carcinomatous cells has been associated with aggressive clinical phenotypes. In sarcomas, this ability is under study. OBJECTIVE: to evaluate the expression of two transcription factors involved in EMT by immunohistochemistry in pediatric osteosarcoma and its association with clinical outcomes. PATIENTS AND METHOD: A retrospective cohort study in children under 18 years of age with osteosarcoma diagnosis. Immunohistochemistry was performed for Snail and Twist-1 expressions from samples collected at the time of diagnosis. Correlations between immunohistochemistry and the clinical outcomes and overall survival were performed. RESULTS: 53 patients were included. There were 26 positive cytoplasmic cases (49.1%) in Snail expression and were correlated with the presence of multiple metastases (p = 0.02) and distant bone metastases (p = 0.01). On the other hand, 45 cases (84.9%) were positive in Twist-1 expression in the nuclear location, showing no association with the analyzed clinical variables. CONCLUSIONS: Snail and Twist-1 were frequently expressed in pediatric cases of osteosarcoma. Cytoplasmic Snail was correlated with the presence of multiple metastatic disease and distant bone metastases. The positivity of both markers suggests the activation of these proteins as regulators of EMT events in this tumor, suggesting a role in the phenomena related to the clinical presentation of the disease.

Cost-Effectiveness of Molecular Method Diagnostic for Rapid Detection of Antibiotic-Resistant Bacteria.

OBJECTIVES: This study aimed to perform a cost-effectiveness analysis (CEA) of the molecular diagnostic method (MM) associated with conventional diagnostic method (CM) compared with the CM alone, for the detection of resistant profile in bacteremia, from the perspective of the Brazilian Public Health System, in intensive care units setting. METHODS: The clinical parameters regarding methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Gram-negative bacteria (CRGNB), and vancomycin-resistant Enterococcus spp. (VRE) infections were collected from searches on PubMed, Scopus, and SciELO, using specific keywords. Data on direct medical costs to treat these infections were collected according to Brazilian Public Health System perspective from Brazilian databases, in tables of 2018 to 2019. CEA was performed after building a dynamic model, which was calibrated and validated according to international recommendations. The incremental cost-effectiveness ratio of the MM + CM compared with the CM was calculated using the outcomes "avoided death" and "avoided resistant infections." One-way sensitivity analyses were performed. RESULTS: This CEA demonstrated that the MM + CM was dominant in all scenarios. Estimates showed that for MRSA, CRGNB, and VRE infections, every avoided death would lead to savings of Brazilian real (R$) 4.9 million ($937 301), R$2.2 million ($419 899), and R$1.3 million ($248 919), respectively. The same infections assessed by avoided resistant infections savings were projected to be R$24 964 ($4686), R$40 260 ($7558), and R$23 867 ($4480). CONCLUSIONS: MM leads to cost reduction and increased benefits, optimizing the use of financial resources on the health system in the intensive care unit setting, in bacteremia caused by MRSA, CRGNB, and VRE.