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Proteus mirabilis, a microorganism distributed in soil, water, and animals, is clinically known for causing urinary tract infections in humans. However, recent studies have linked it to skin infections in broiler chickens, termed avian cellulitis, which poses a threat to animal welfare. While Avian Pathogenic Escherichia coli (APEC) is the primary cause of avian cellulitis, few cases of P. mirabilis involvement are reported, raising questions about the factors facilitating such occurrences. This study employed a pan-genomic approach to investigate whether unique genes exist in P. mirabilis strains causing avian cellulitis. The genome of LBUEL-A33, a P. mirabilis strain known to cause this infection, was assembled, and compared with other P. mirabilis strains isolated from poultry and other sources. Additionally, in silico serogroup analysis was conducted. Results revealed numerous genes unique to the LBUEL-A33 strain. No function in cellulitis was identified for these genes, and in silico investigation of the virulence potential of LBUEL-A33's exclusive proteins proved inconclusive. These findings support that multiple factors are necessary for P. mirabilis to cause avian cellulitis. Furthermore, this species likely employs its own unique arsenal of virulence factors, as many identified mechanisms are analogous to those of E. coli. While antigenic gene clusters responsible for serogroups were identified, no clear trend was observed, and the gene cluster of LBUEL-A33 did not show homology with any sequenced Proteus serogroups. These results reinforce the understanding that this disease is multifactorial, necessitating further research to unravel the mechanisms and underpin the development of control and prevention strategies.
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BACKGROUND: Proteasome assembly chaperone 3 (PSMG3), a subunit of proteasome, has been found to be associated with lung cancer. However, the role of PSMG3 in other cancers has not been elucidated. The objective of this study was to explore the immune role of PSMG3 in pan-cancer and confirm the oncogenic significance in liver hepatocellular carcinoma (LIHC). METHODS: We examined the differential expression of PSMG3 across various cancer types using data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. We investigated the prognostic value of PSMG3 and examined its relationship with tumor mutation burden (TMB), microsatellite instability (MSI), and immune infiltration. The functional enrichment analysis was performed to explore the potential molecular mechanism of PSMG3. To elucidate the biological function of PSMG3, we conducted in vitro experiments using liver cancer cell lines. RESULTS: PSMG3 was highly expressed in most cancers. The high PSMG3 expression value of PSMG3 was closely related to poor prognosis. We observed correlations between PSMG3 and TMB, and MSI immune infiltration. PSMG3 may be involved in metabolic reprogramming, cell cycle, and PPAR pathways. The over-expression of PSMG3 promoted the proliferation, migration, and invasion capabilities of liver cancer cells. CONCLUSION: Our study demonstrated that PSMG3 was a pivotal oncogene in multiple cancers. PSMG3 contributed to the progression and immune infiltration in pan-cancer, especially in LIHC.
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The pan-immune-inflammation value (PIV), calculated as (neutrophil × platelet × monocyte)/lymphocyte count, may be useful for estimating survival in breast cancer patients. To determine the prognostic value of PIV for overall survival in breast cancer patients in Lima, Peru. A retrospective cohort study was conducted. 97 breast cancer patients diagnosed between January 2010 and December 2016 had their medical records analyzed. The primary dependent variable was overall survival, and the key independent variable was the PIV, divided into high (≥ 310) and low (< 310) groups. Patient data included demographics, treatment protocols and other clinical variables. Statistical analysis involved Kaplan-Meier survival curves and Cox proportional hazards modeling. Patients with a PIV ≥ 310 had significantly lower 5-year survival functions (p = 0.004). Similar significant differences in survival were observed for clinical stage III-IV (p = 0.015), hemoglobin levels < 12 mg/Dl (p = 0.007), histological grade (p = 0.019), and nuclear grade (p < 0.001); however, molecular classification did not show a significant survival difference (p = 0.371). The adjusted Hazard Ratios showed that PIV ≥ 310 was significantly associated with poor outcome (5.08, IC95%: 1.52-16.92). While clinical stage and hemoglobin levels were associated with survival in the unadjusted model. These factors did not maintain significance after adjustment. PIV is an independent predictor of reduced survival in Peruvian breast cancer patients.
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Neoplasias de la Mama , Humanos , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/patología , Femenino , Perú/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Adulto , Inflamación , Anciano , Estimación de Kaplan-Meier , Monocitos/inmunología , Modelos de Riesgos Proporcionales , Neutrófilos/inmunologíaRESUMEN
PURPOSE: This study aimed to further evaluate the potential value of Pan-Immune-Inflammation Value (PIV) as a prognostic marker in patients with laryngeal and pharyngeal tumors. METHODS: A total of 545 patients with laryngeal and pharyngeal tumors who underwent surgery at Qilu Hospital of Shandong University were included. We determined the optimal cutoff of PIV and divided the patients into two groups. The relationship between PIV and clinicopathological features was explored by the chi-square test and the Mann-Whitney U test. Survival analysis and Cox regression analysis were used to evaluate the relationship between PIV and overall survival (OS) and disease-free survival (DFS). We also compared the prognostic predictive value of PIV with other inflammation-related markers. Finally, we developed a simple scoring prediction model based on several independent prognostic parameters. RESULTS: We found that PIV was statistically associated with clinicopathological features such as tumor stage (p < 0.001), node stage (p = 0.001), postoperative chemotherapy (p = 0.026), and vascular thrombosis (p = 0.027). Survival analysis demonstrated a significant correlation between elevated PIV and reduced OS and DFS (p < 0.0001). Multivariate Cox regression analysis further confirmed PIV as a prognostic indicator (HR 2.507; 95% CI 1.343-4.681; p = 0.004), which is superior to SII, NLR, MLR and PLR. Three of the independent prognostic factors screened by multivariate Cox regression analysis were selected to be used to create a scoring system with a concordance index of 0.756. CONCLUSIONS: Elevated PIV is associated with poor prognosis in patients with laryngeal and pharyngeal tumors, suggesting that PIV may be an important adjunctive indicator for assessing patient prognosis. REGISTRATION INFORMATION: Registration number: KYLL-202307-001, date: July 2023.
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Candida auris is an emerging multidrug-resistant and opportunistic pathogenic yeast. Whole-genome sequencing analysis has defined five major clades, each from a distinct geographic region. The current study aimed to examine the genome of the C. auris 20-1498 strain, which is the first isolate of this fungus identified in Mexico. Based on whole-genome sequencing, the draft genome was found to contain 70 contigs. It had a total genome size of 12.86 Mbp, an N50 value of 1.6 Mbp, and an average guanine-cytosine (GC) content of 45.5%. Genome annotation revealed a total of 5432 genes encoding 5515 proteins. According to the genomic analysis, the C. auris 20-1498 strain belongs to clade IV (containing strains endemic to South America). Of the two genes (ERG11 and FKS1) associated with drug resistance in C. auris, a mutation was detected in K143R, a gene located in a mutation hotspot of ERG11 (lanosterol 14-α-demethylase), an antifungal drug target. The focus on whole-genome sequencing and the identification of mutations linked to the drug resistance of fungi could lead to the discovery of new therapeutic targets and new antifungal compounds.
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BACKGROUND: Cuproptosis, as a unique modality of regulated cell death, requires the involvement of ubiquitin-binding enzyme UBE2D2. However, the prognostic and immunotherapeutic values of UBE2D2 in pan-cancer remain largely unknown. METHODS: Using UCSC Xena, TIMER, Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) databases, we aimed to explore the differential expression pattern of UBE2D2 across multiple cancer types and to evaluate its association with patient prognosis, clinical features, and genetic variations. The association between UBE2D2 and immunotherapy response was assessed by gene set enrichment analysis, tumor microenvironment, immune gene co-expression and drug half maximal inhibitory concentration (IC50) analysis. RESULTS: The mRNA and protein levels of UBE2D2 were markedly elevated in most cancer types, and UBE2D2 exhibited prognostic significance in liver hepatocellular carcinoma (LIHC), kidney chromophobe (KICH), uveal melanomas (UVM), cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), and kidney renal papillary cell carcinoma (KIRP). UBE2D2 expression was correlated with clinical features, tumor mutation burden, microsatellite instability, and anti-tumor drug resistance in several tumor types. Gene enrichment analysis showed that UBE2D2 was significantly associated with immune-related pathways. The expression level of UBE2D2 was correlated with immune cell infiltration, including CD4 + T cellsãMacrophages M2ãCD8 + T cells in pan-cancer. PDCD1, CD274 and CTLA4 expression levels were positively correlated with UBE2D2 level in multiple cancers. CONCLUSIONS: We comprehensively investigated the potential value of UBE2D2 as a prognostic and immunotherapeutic predictor for pan-cancer, providing a novel insight for cancer immunotherapy.
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Biomarcadores de Tumor , Neoplasias , Microambiente Tumoral , Enzimas Ubiquitina-Conjugadoras , Humanos , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Enzimas Ubiquitina-Conjugadoras/genética , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Inmunoterapia , Femenino , Melanoma/genética , Melanoma/inmunología , Melanoma/tratamiento farmacológico , Melanoma/patología , Neoplasias Renales/genética , Neoplasias Renales/patología , Neoplasias Renales/inmunología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/inmunología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/inmunología , Neoplasias Hepáticas/metabolismo , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Antígeno CTLA-4/genética , Neoplasias de la Úvea , Antígeno B7-H1RESUMEN
Rabies, a fatal zoonotic viral disease affecting mammals, including humans, remains a significant global health concern, particularly in low-income countries. The disease, primarily transmitted through infected animal saliva, prompts urgent diagnosis for timely post-exposure prophylaxis (PEP). The gold standard diagnostic test, direct fluorescent antibody test (dFAT), while sensitive, suffers from limitations such as subjective interpretation and high costs. As a confirmatory technique, the LN34 Pan-Lyssavirus RT-qPCR assay has emerged as a promising tool for universal Lyssavirus detection. This study evaluated its performance using 130 rabies virus isolates representing eleven Brazilian variants and 303 clinical samples from surveillance operations. The LN34 assay demonstrated 100% sensitivity and 98% specificity compared to dFAT. Additionally, it detected all samples, including those missed by dFAT, indicating superior sensitivity. The assay's specificity was confirmed through Sanger nucleotide sequencing, with only a minimal false-positive rate. Comparative analysis revealed higher accuracy and concordance with dFAT than traditional rabies tissue culture infection tests (RTCIT). False-negative RTCIT results were attributed to low viral load or suboptimal sampling. These findings underscore the LN34 assay's utility as a confirmatory technique, enhancing rabies surveillance and control in Brazil. Its widespread adoption could significantly improve diagnostic sensitivity, crucial for effective PEP and public health interventions.
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Virus de la Rabia , Rabia , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Rabia/diagnóstico , Rabia/veterinaria , Rabia/virología , Brasil , Virus de la Rabia/genética , Virus de la Rabia/aislamiento & purificación , Virus de la Rabia/clasificación , Humanos , Animales , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Lyssavirus/genética , Lyssavirus/aislamiento & purificación , Lyssavirus/clasificación , ARN Viral/genética , Carga ViralRESUMEN
Marine macroalgae are the habitat of epiphytic bacteria and provide several conditions for a beneficial biological interaction to thrive. Although Bacillus is one of the most abundant epiphytic genera, genomic information on marine macroalgae-associated Bacillus species remains scarce. In this study, we further investigated our previously published genome of the epiphytic strain Bacillus altitudinis 19_A to find features that could be translated to potential metabolites produced by this microorganism, as well as genes that play a role in its interaction with its macroalgal host. To achieve this goal, we performed a pan-genome analysis of Bacillus sp. and a codon bias assessment, including the genome of the strain Bacillus altitudinis 19_A and 29 complete genome sequences of closely related Bacillus strains isolated from soil, marine environments, plants, extreme environments, air, and food. This genomic analysis revealed that Bacillus altitudinis 19_A possessed unique genes encoding proteins involved in horizontal gene transfer, DNA repair, transcriptional regulation, and bacteriocin biosynthesis. In this comparative analysis, codon bias was not associated with the habitat of the strains studied. Some accessory genes were identified in the Bacillus altitudinis 19_A genome that could be related to its epiphytic lifestyle, as well as gene clusters for the biosynthesis of a sporulation-killing factor and a bacteriocin, showing their potential as a source of antimicrobial peptides. Our results provide a comprehensive view of the Bacillus altitudinis 19_A genome to understand its adaptation to the marine environment and its potential as a producer of bioactive compounds.
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SUMMARY: The calcium-activated chloride channel (CLCA2) performs a vital function in the intricate process of tumorigenesis. Using a bioinformatics analysis system, we conducted a pan-cancer investigation on CLCA2 to explore its association with tumor prognosis and its involvement in immunology. In order to achieve this objective, we examined the prognostic significance and expression level of CLCA2 in multiple cancer types using the TIMER and Sangerbox databases. The analysis of protein interaction networks revealed proteins linked to CLCA2. To investigate the potential biological functions and enrichment pathways of CLCA2 in cancer, the SangerBox and GSCA databases were utilized. Furthermore, the expression of CLCA2 in different cancer subtypes was evaluated during the analysis. Various functional conditions of cancer cells were then compared with CLCA2 in the CancerSEA database. Using online tools like TISIDB and Assistant for Clinical Bioinformatics, the investigation explored the link between CLCA2 and immune subtypes. Additionally, it assessed immune cell infiltration as part of the analysis. In addition, the application of GDSA was employed to investigate the predictive significance of CLCA2 in relation to drug sensitivity. The research outcomes uncovered abnormal expression patterns of CLCA2 in diverse tumor categories, with its expression level demonstrating a correlation with distinct subtypes of tumors. Strong associations have been observed between enhanced patient survival rates and CLCA2 in specific tumor types. There is a noteworthy connection observed among diverse tumor types, immune cell infiltration, immune subtypes, and CLCA2. The enrichment analysis of KEGG indicates that there may exist a connection between the expression of CLCA2 and renin secretion, pancreatic secretion, as well as other pathways in pan-cancer. CLCA2 appears to primarily activate pathways such as EMT (epithelial-mesenchymal transition), RAS/MAPK, RTK, apoptosis, TSC/mTOR, and PI3K/ AKT in pan-cancer. On the other hand, it seems to inhibit pathways like cell cycle, DNA damage, hormone AR, and hormone ER. Through single-cell functional analysis, it has been confirmed that CLCA2 is associated with diverse cellular functional states, encompassing DNA repair, EMT, hypoxia, invasion, metastasis, and quiescence. Furthermore, a substantial correlation has been observed between the expression of CLCA2 and drug sensitivity towards bosutinib, tipifarnib-P1, as well as other therapeutic agents. This research affirms that various cancer types express CLCA2 and its involvement in tumor advancement and immune penetration. CLCA2 possesses the capability to function as a noteworthy biomarker and target for therapeutic intervention in diverse cancer forms.
El canal de cloruro activado por calcio (CLCA2) desempeña una función vital en el proceso de tumorigénesis. Utilizando un sistema de análisis bioinformático, llevamos a cabo una investigación pan-cáncer en CLCA2 para explorar su asociación con el pronóstico tumoral y su participación en la inmunología. Para lograr este objetivo, examinamos la importancia pronóstica y el nivel de expresión de CLCA2 en múltiples tipos de cáncer utilizando las bases de datos TIMER y Sangerbox. El análisis de las redes de interacción de proteínas reveló proteínas vinculadas a CLCA2. Para investigar las posibles funciones biológicas y las vías de enriquecimiento de CLCA2 en el cáncer, se utilizaron las bases de datos SangerBox y GSCA. Además, durante el análisis se evaluó la expresión de CLCA2 en diferentes subtipos de cáncer. Luego se compararon varias condiciones funcionales de las células cancerosas con CLCA2 en la base de datos CancerSEA. Utilizando herramientas en línea como TISIDB y Assistant for Clinical Bioinformatics, la investigación exploró el vínculo entre CLCA2 y los subtipos inmunes. Además, evaluó la infiltración de células inmunitarias como parte del análisis y se empleó la aplicación de GDSA para investigar la importancia predictiva de CLCA2 en relación con la sensibilidad al fármaco. Los resultados de la investigación descubrieron patrones de expresión anormales de CLCA2 en diversas categorías de tumores, y su nivel de expresión demuestra una correlación con distintos subtipos de tumores. Se han observado fuertes asociaciones entre mayores tasas de supervivencia de los pacientes y CLCA2 en tipos de tumores específicos. Se observa una conexión notable entre diversos tipos de tumores, infiltración de células inmunitarias, subtipos inmunitarios y CLCA2. El análisis de enriquecimiento de KEGG indica que puede existir una conexión entre la expresión de CLCA2 y la secreción de renina, la secreción pancreática y otras vías en el pancáncer. CLCA2 parece activar principalmente vías como EMT (transición epitelial-mesenquimatosa), RAS/MAPK, RTK, apoptosis, TSC/mTOR y PI3K/AKT en pan-cáncer. Por otro lado, parece inhibir vías como el ciclo celular, el daño del ADN, la hormona AR y la hormona ER. Mediante análisis funcional unicelular, se ha confirmado que CLCA2 está asociado con diversos estados funcionales celulares, que abarcan la reparación del ADN, la EMT, la hipoxia, la invasión, la metástasis y la inactividad. Además, se ha observado una correlación sustancial entre la expresión de CLCA2 y la sensibilidad al fármaco hacia bosutinib, tipifarnib-P1, así como a otros agentes terapéuticos. Esta investigación indica que varios tipos de cáncer expresan CLCA2 y su participación en el avance tumoral y la penetración inmune. CLCA2 posee la capacidad de funcionar como un biomarcador notable y como un objetivo para la intervención terapéutica en diversas formas de cáncer.
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Humanos , Canales de Cloruro/metabolismo , Neoplasias/metabolismo , Pronóstico , Biomarcadores de Tumor , Canales de Cloruro/inmunología , Genómica , Estimación de Kaplan-Meier , Neoplasias/genética , Neoplasias/inmunologíaRESUMEN
ABSTRACT Background: Pan-immuno-inflammation value is a new and comprehensive index that reflects both the immune response and systemic inflammation in the body. Objective: The aim of this study was to investigate the prognostic relevance of pan-immuno-inflammation value in predicting in-hospital mortality in acute pulmonary embolism patients and to compare it with the well-known risk scoring system, pulmonay embolism severity index, which is commonly used for a short-term mortality prediction in such patients. Methods: In total, 373 acute pulmonary embolism patients diagnosed with contrast-enhanced computed tomography were included in the study. Detailed cardiac evaluation of each patient was performed and pulmonary embolism severity index and pan-immuno-inflammation value were calculated. Results: In total, 60 patients died during their hospital stay. The multivariable logistic regression analysis revealed that baseline heart rate, N-terminal pro-B-type natriuretic peptide, lactate dehydrogenase, pan-immuno-inflammation value, and pulmonary embolism severity index were independent risk factors for in-hospital mortality in acute pulmonay embolism patients. When comparing with pulmonary embolism severity index, pan-immuno-inflammation value was non-inferior in terms of predicting the survival status in patients with acute pulmonay embolism. Conclusion: In our study, we found that the PIV was statistically significant in predicting in-hospital mortality in acute pulmonay embolism patients and was non-inferior to the pulmonary embolism severity index. (Rev Invest Clin. 2024;76(2):97-102)
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BACKGROUND: Transmembrane protein 92 (TMEM92) has been implicated in the facilitation of tumor progression. Nevertheless, comprehensive analyses concerning the prognostic significance of TMEM92, as well as its role in immunological responses across diverse cancer types, remain to be elucidated. METHODS: In this study, data was sourced from a range of publicly accessible online platforms and databases, including TCGA, GTEx, UCSC Xena, CCLE, cBioPortal, HPA, TIMER2.0, GEPIA, CancerSEA, GDSC, exoRBase, and ImmuCellAI. We systematically analyzed the expression patterns of TMEM92 at both mRNA and protein levels across diverse human organs, tissues, extracellular vesicles (EVs), and cell lines associated with multiple cancer types. Subsequently, analyses were conducted to determine the relationship between TMEM92 and various parameters such as prognosis, DNA methylation, copy number variation (CNV), the tumor microenvironment (TME), immune cell infiltration, genes with immunological relevance, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR), and half-maximal inhibitory concentration (IC50) values. RESULTS: In the present study, we observed a pronounced overexpression of TMEM92 across a majority of cancer types, which was concomitantly associated with a less favorable prognosis. A notable association emerged between TMEM92 expression and both DNA methylation and CNV. Furthermore, a pronounced relationship was discerned between TMEM92 expression, the TME, and the degree of immune cell infiltration. Intriguingly, while TMEM92 expression displayed a positive correlation with macrophage presence, it inversely correlated with the infiltration level of CD8 + T cells. Concurrently, significant associations were identified between TMEM92 and the major histocompatibility complex, TMB, MSI, and MMR. Results derived from Gene Set Enrichment Analysis and Gene Set Variation Analysis further substantiated the nexus of TMEM92 with both immune and metabolic pathways within the oncogenic context. CONCLUSIONS: These findings expanded the understanding of the roles of TMEM92 in tumorigenesis and progression and suggest that TMEM92 may have an immunoregulatory role in several malignancies.
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Proteínas de la Membrana , Neoplasias , Microambiente Tumoral , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Variaciones en el Número de Copia de ADN , Metilación de ADN , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Regulación Neoplásica de la Expresión Génica , Linfocitos Infiltrantes de Tumor/inmunología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Inestabilidad de Microsatélites , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Neoplasias/metabolismo , Pronóstico , Microambiente Tumoral/inmunologíaRESUMEN
The purpose of this review is to highlight the most important aspects of the anatomical and functional uniqueness of the human brain. For this, a comparison is made between our brains and those of our closest ancestors (chimpanzees and bonobos) and human ancestors. During human evolution, several changes occurred in the brain, such as an absolute increase in brain size and number of cortical neurons, in addition to a greater degree of functional lateralization and anatomical asymmetry. Also, the cortical cytoarchitecture became more diversified and there was an increase in the number of intracortical networks and networks extending from the cerebral cortex to subcortical structures, with more neural networks being invested in multisensory and sensory-motor-affective-cognitive integration. These changes permitted more complex, flexible and versatile cognitive abilities and social behavior, such as shared intentionality and symbolic articulated language, which, in turn, made possible the formation of larger social groups and cumulative cultural evolution that are characteristic of our species.
Esta revisão se propõe a relatar os aspectos mais importantes da singularidade anatômica e funcional do cérebro humano. Para isso, faz-se uma comparação entre o nosso cérebro e os de nossos parentes evolutivos mais próximos (chimpanzés e bonobos) e os ancestrais humanos. Durante a evolução humana ocorreu aumento absoluto do tamanho do cérebro e do número de neurônios corticais cerebrais, maior grau de lateralização funcional e assimetria anatômica cerebral, citoarquitetura cortical mais diversificada e aumento das redes neurais intracorticais e do córtex cerebral para as estruturas subcorticais acompanhada de mudança em direção ao investimento de redes neurais na integração multissensorial e sensório-motora-afetiva-cognitiva. Essas mudanças possibilitaram capacidades cognitivas e comportamentos sociais complexos, flexíveis e versáteis, destacando-se a intencionalidade compartilhada e a linguagem articulada simbólica, que permitiram a formação de grupos sociais maiores e a evolução cultural cumulativa característica de nossa espécie.
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Background: Pan-immuno-inflammation value (PIV) is a new and comprehensive index that reflects both the immune response and systemic inflammation in the body. Objective: The aim of this study was to investigate the prognostic relevance of PIV in predicting in-hospital mortality in acute pulmonary embolism (PE) patients and to compare it with the well-known risk scoring system, PE severity index (PESI), which is commonly used for a short-term mortality prediction in such patients. Methods: In total, 373 acute PE patients diagnosed with contrast-enhanced computed tomography were included in the study. Detailed cardiac evaluation of each patient was performed and PESI and PIV were calculated. Results: In total, 60 patients died during their hospital stay. The multivariable logistic regression analysis revealed that baseline heart rate, N-terminal pro-B-type natriuretic peptide, lactate dehydrogenase, PIV, and PESI were independent risk factors for in-hospital mortality in acute PE patients. When comparing with PESI, PIV was non-inferior in terms of predicting the survival status in patients with acute PE. Conclusion: In our study, we found that the PIV was statistically significant in predicting in-hospital mortality in acute PE patients and was non-inferior to the PESI.
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Mortalidad Hospitalaria , Inflamación , Embolia Pulmonar , Índice de Severidad de la Enfermedad , Humanos , Embolia Pulmonar/mortalidad , Masculino , Femenino , Anciano , Persona de Mediana Edad , Enfermedad Aguda , Pronóstico , Factores de Riesgo , Tomografía Computarizada por Rayos X , Anciano de 80 o más Años , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , L-Lactato Deshidrogenasa/sangre , Biomarcadores , Valor Predictivo de las Pruebas , Modelos LogísticosRESUMEN
Forkhead Box O1 (FOXO1) has been reported to play important roles in many tumors. However, FOXO1 has not been studied in pan-cancer. The purpose of this study was to reveal the roles of FOXO1 in pan-cancer (33 cancers in this study). Through multiple public platforms, a pan-cancer analysis of FOXO1 was conducted to obtained FOXO1 expression profiles in various tumors to explore the relationship between FOXO1 expression and prognosis of these tumors and to disclose the potential mechanism of FOXO1 in these tumors. FOXO1 was associated with the prognosis of multiple tumors, especially LGG (low grade glioma), OV (ovarian carcinoma), and KIRC (kidney renal clear cell carcinoma). FOXO1 might play the role of an oncogenic gene in LGG and OV, while playing the role of a cancer suppressor gene in KIRC. FOXO1 expression had a significant correlation with the infiltration of some immune cells in LGG, OV, and KIRC. By combining FOXO1 expression and immune cell infiltration, we found that FOXO1 might influence the overall survival of LGG through the infiltration of myeloid dendritic cells or CD4+ T cells. Functional enrichment analysis and gene set enrichment analysis showed that FOXO1 might play roles in tumors through immunoregulatory interactions between a lymphoid and a non-lymphoid cell, TGF-beta signaling pathway, and transcriptional misregulation in cancer. FOXO1 was associated with the prognosis of multiple tumors, especially LGG, OV, and KIRC. In these tumors, FOXO1 might play its role via the regulation of the immune microenvironment.
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We analyzed the pan-genome and gene content modulation of the most diverse genome data set of the Mycobacterium tuberculosis complex (MTBC) gathered to date. The closed pan-genome of the MTBC was characterized by reduced accessory and strain-specific genomes, compatible with its clonal nature. However, significantly fewer gene families were shared between MTBC genomes as their phylogenetic distance increased. This effect was only observed in inter-species comparisons, not within-species, which suggests that species-specific ecological characteristics are associated with changes in gene content. Gene loss, resulting from genomic deletions and pseudogenization, was found to drive the variation in gene content. This gene erosion differed among MTBC species and lineages, even within M. tuberculosis, where L2 showed more gene loss than L4. We also show that phylogenetic proximity is not always a good proxy for gene content relatedness in the MTBC, as the gene repertoire of Mycobacterium africanum L6 deviated from its expected phylogenetic niche conservatism. Gene disruptions of virulence factors, represented by pseudogene annotations, are mostly not conserved, being poor predictors of MTBC ecotypes. Each MTBC ecotype carries its own accessory genome, likely influenced by distinct selective pressures such as host and geography. It is important to investigate how gene loss confer new adaptive traits to MTBC strains; the detected heterogeneous gene loss poses a significant challenge in elucidating genetic factors responsible for the diverse phenotypes observed in the MTBC. By detailing specific gene losses, our study serves as a resource for researchers studying the MTBC phenotypes and their immune evasion strategies.IMPORTANCEIn this study, we analyzed the gene content of different ecotypes of the Mycobacterium tuberculosis complex (MTBC), the pathogens of tuberculosis. We found that changes in their gene content are associated with their ecological features, such as host preference. Gene loss was identified as the primary driver of these changes, which can vary even among different strains of the same ecotype. Our study also revealed that the gene content relatedness of these bacteria does not always mirror their evolutionary relationships. In addition, some genes of virulence can be variably lost among strains of the same MTBC ecotype, likely helping them to evade the immune system. Overall, our study highlights the importance of understanding how gene loss can lead to new adaptations in these bacteria and how different selective pressures may influence their genetic makeup.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Filogenia , Tuberculosis/microbiología , Genómica , Factores de Virulencia/genéticaRESUMEN
ABSTRACT BACKGROUND: To the best of our knowledge, this is the first study to evaluate the effectiveness of specific concentrations of antibiofilm agents, such as N-acetyl cysteine (NAC), rifampicin, and ozone, for the treatment of pan-resistant Klebsiella pneumoniae (PRKp). OBJECTIVES: We evaluated the effectiveness of antibiofilm agents, such as NAC, rifampicin, and ozone, on biofilm formation in PRKp at 2, 6, 24, and 72 h. DESIGN AND SETTING: This single-center experimental study was conducted on June 15, 2017, and July 15, 2018, at Istanbul Faculty of Medicine, Istanbul University, Turkey. METHODS: Biofilm formation and the efficacy of these agents on the biofilm layer were demonstrated using colony counting and laser-screened confocal microscopy. RESULTS: NAC at a final concentration of 2 μg/mL was administered to bacteria that formed biofilms (24 h), and no significant decrease was detected in the bacterial counts of all isolates (all P > 0.05). Rifampicin with a final concentration of 0.1 μg/mL was administered to bacteria that formed biofilm (24 h), and no significant decrease was detected in bacterial count (all P > 0.05). Notably, ozonated water of even 4.78 mg/L concentration for 72 h decreased the bacterial count by ≥ 2 log10. CONCLUSION: Different approaches are needed for treating PRKp isolates. We demonstrate that PRKp isolates can be successfully treated with higher concentrations of ozone.
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ABSTRACT The purpose of this review is to highlight the most important aspects of the anatomical and functional uniqueness of the human brain. For this, a comparison is made between our brains and those of our closest ancestors (chimpanzees and bonobos) and human ancestors. During human evolution, several changes occurred in the brain, such as an absolute increase in brain size and number of cortical neurons, in addition to a greater degree of functional lateralization and anatomical asymmetry. Also, the cortical cytoarchitecture became more diversified and there was an increase in the number of intracortical networks and networks extending from the cerebral cortex to subcortical structures, with more neural networks being invested in multisensory and sensory-motor-affective-cognitive integration. These changes permitted more complex, flexible and versatile cognitive abilities and social behavior, such as shared intentionality and symbolic articulated language, which, in turn, made possible the formation of larger social groups and cumulative cultural evolution that are characteristic of our species.
RESUMO Esta revisão se propõe a relatar os aspectos mais importantes da singularidade anatômica e funcional do cérebro humano. Para isso, faz-se uma comparação entre o nosso cérebro e os de nossos parentes evolutivos mais próximos (chimpanzés e bonobos) e os ancestrais humanos. Durante a evolução humana ocorreu aumento absoluto do tamanho do cérebro e do número de neurônios corticais cerebrais, maior grau de lateralização funcional e assimetria anatômica cerebral, citoarquitetura cortical mais diversificada e aumento das redes neurais intracorticais e do córtex cerebral para as estruturas subcorticais acompanhada de mudança em direção ao investimento de redes neurais na integração multissensorial e sensório-motora-afetiva-cognitiva. Essas mudanças possibilitaram capacidades cognitivas e comportamentos sociais complexos, flexíveis e versáteis, destacando-se a intencionalidade compartilhada e a linguagem articulada simbólica, que permitiram a formação de grupos sociais maiores e a evolução cultural cumulativa característica de nossa espécie.
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ABSTRACT The Pan American Health Organization (PAHO) and its Member States have been leading the efforts to eradicate wild poliovirus in the Region of Americas since smallpox's successful elimination in 1971. The region became the first to be certified free of wild poliovirus in 1994. However, in July 2022, an unvaccinated patient with no recent travel history was diagnosed with poliomyelitis in the United States of America. In response to the emergence of a circulating vaccine-derived poliovirus in the United States, PAHO established the Polio Incident Management Support Team. This team has been coordinating response efforts, focusing on: coordination, planning, and monitoring; risk communication and community engagement; surveillance and case investigation; vaccination; and rapid response. In this paper, we identified and documented best practices observed following establishment of the Incident Management Support Team (September 2022-2023) through a comprehensive review and analysis of various data sources and country-specific data from the polio surveillance dashboard. The aim was to share these best practices, highlighting technical support and implementation of polio measures by Member States. Despite several challenges, the Americas region remains polio-free. Polio risk is declining, with a July 2023 assessment showing fewer countries at medium, high, and very high risk. This progress reflects improved immunization coverage, surveillance, containment, health determinants, and outbreak preparedness and response. The PAHO Polio Incident Management Support Team has played a key role in supporting these efforts.
RESUMEN La Organización Panamericana de la Salud (OPS) y sus Estados Miembros han liderado los esfuerzos para erradicar el poliovirus salvaje en la Región de las Américas desde la eliminación exitosa de la viruela en 1971. En 1994, la Región fue la primera en obtener la certificación de libre del poliovirus salvaje. Sin embargo, en julio del 2022, se diagnosticó poliomielitis a un paciente de Estados Unidos de América no vacunado y sin antecedentes de viajes recientes. Para responder a la aparición de un poliovirus circulante derivado de la vacuna en ese país, la OPS creó el equipo de apoyo a la gestión de incidentes de poliomielitis. Este equipo ha asumido la coordinación de los esfuerzos de respuesta y se ha centrado en la coordinación, la planificación y seguimiento; la comunicación de riesgos y la participación de la comunidad; la vigilancia e investigación de casos; la vacunación; y la respuesta rápida. En este artículo, se determinan y documentan las mejores prácticas observadas después de la creación del equipo de apoyo a la gestión de incidentes (septiembre del 2022-2023) mediante una revisión y un análisis pormenorizados de datos procedentes de diversas fuentes y de datos específicos de los países del panel de vigilancia de la poliomielitis. El objetivo fue poner en común estas mejores prácticas y resaltar el apoyo técnico y la aplicación de medidas contra la poliomielitis por parte de los Estados Miembros. A pesar de los diversos desafíos, la Región de las Américas se mantiene libre de poliomielitis. El riesgo de esta enfermedad es cada vez menor, y la evaluación de julio del 2023 muestra una disminución del número de países con un riesgo medio, alto o muy alto. Este progreso refleja la mejora de la cobertura de inmunización, la vigilancia, la contención, los determinantes de la salud y la preparación y respuesta ante brotes. El equipo de apoyo a la gestión de incidentes relacionados con la poliomielitis de la OPS ha desempeñado un papel fundamental para brindar apoyo a estas iniciativas.
RESUMO Desde a eliminação bem-sucedida da varíola em 1971, a Organização Pan-Americana da Saúde (OPAS) e seus Estados Membros têm estado à frente de iniciativas para erradicar o poliovírus selvagem na Região das Américas. Em 1994, a região foi a primeira do mundo a ser certificada como livre do poliovírus selvagem. Entretanto, em julho de 2022, um paciente não vacinado e sem histórico de viagens recentes foi diagnosticado com poliomielite nos Estados Unidos da América. Em resposta ao surgimento de um poliovírus derivado de vacina circulante nos Estados Unidos, a OPAS criou a Equipe de Apoio à Gestão de Incidentes de Poliomielite. A equipe vem administrando os esforços de resposta, concentrando-se em: coordenação, planejamento e monitoramento; comunicação de risco e envolvimento da comunidade; vigilância e investigação de casos; vacinação; e resposta rápida. Neste documento, identificamos e documentamos as melhores práticas observadas após a criação da Equipe de Apoio à Gestão de Incidentes (setembro de 2022 a 2023) por meio de uma revisão e análise abrangentes de diversas fontes de dados e dados específicos de cada país fornecidos por meio do painel de vigilância da poliomielite. O objetivo foi compartilhar essas melhores práticas, destacando o apoio técnico e a implementação de medidas contra a poliomielite pelos Estados Membros. Apesar de vários desafios, a Região das Américas continua livre da poliomielite. Um levantamento de julho de 2023 demonstrou que o risco da poliomielite vem diminuindo, com menos países com risco médio, alto ou muito alto. Essa evolução é resultado de melhoras na cobertura vacinal, vigilância, contenção, preparação, determinantes de saúde e resposta a surtos. A Equipe de Apoio à Gestão de Incidentes de Poliomielite da OPAS foi fundamental para apoiar esses esforços.
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RESUMEN El desarrollo de la salud pública en América Latina durante el siglo XX combinó, desde el principio, el marco de la medicina social sobre los orígenes sociales, políticos y ambientales de la enfermedad con los aportes del trabajo de campo de la antropología médica. A pesar de la hegemonía del modelo médico, el surgimiento del marco de la medicina preventiva legitimó aún más la participación de los científicos sociales en el estudio de la multicausalidad de la enfermedad. Sin embargo, las limitaciones que trajo consigo la falta de contextualización histórica y política del modelo de la medicina preventiva dieron paso al movimiento latinoamericano de medicina social, basado en el materialismo histórico, y al desarrollo tanto de la epidemiología crítica como de la antropología médica crítica.
ABSTRACT The development of public health in Latin America during the 20th century combined, early on, the social medicine framework on the social, political, and environmental origins of disease with the contributions of medical anthropological fieldwork. Despite the hegemony of the medical model, the surge of the preventive medicine framework further legitimized the involvement of social scientists in the study of the multicausality of disease. However, the limitations brought by the preventive medicine model's lack of historical and political contextualization gave way to the Latin American social medicine movement, which was grounded in historical materialism, and the development of both critical epidemiology and critical medical anthropology.
RESUMO Desde o início, a evolução da saúde pública na América Latina ao longo do século XX combinou o marco teórico da medicina social sobre as origens sociais, políticas e ambientais das doenças com as contribuições derivadas do trabalho de campo da antropologia médica. Apesar da hegemonia do modelo médico, o surgimento do modelo de medicina preventiva legitimou ainda mais a participação dos cientistas sociais no estudo da multicausalidade das doenças. Entretanto, as limitações causadas pela falta de contextualização histórica e política do modelo de medicina preventiva abriram espaço para o movimento latino-americano de medicina social, fundamentado no materialismo histórico, e para o desenvolvimento da epidemiologia crítica e da antropologia médica crítica.
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El objetivo del presente trabajo es analizar el desempeño deportivo de la delegación chilena en los Juegos Panamericanos celebrados entre los años 1951 y 2023, haciendo uso de datos retrospectivos y proyectivos a través de series temporales de tiempo. Para esto se empleó un diseño cuantitativo, no experimental y longitudinal de tendencias y un método de suavización exponencial simple, que utiliza promedios históricos y que permite realizar una predicción o comportamiento futuro basado en una media ponderada de los valores actuales y de los pasados. A partir de los resultados obtenidos, fue posible concluir que, en las últimas décadas, la ubicación de Chile en el ranking de los Juegos Panamericanos se ha estabilizado en torno a un onceavo lugar, posición pronosticada para Santiago 2023. Manteniéndose condiciones similares, el desempeño deportivo general y específico no tendría un quiebre exponencial de la tendencia y los resultados no resultan favorables, específicamente en lo que respecta a la obtención de medallas de oro y la posición general de la delegación.
The objective of this paper is to analyze the sports performance of the Chilean delegation in the Pan American Games held between 1951 and 2023, using retrospective and projective data through time series. For this purpose, a quantitative, non-experimental and longitudinal design of trends and a simple exponential smoothing method was used, which uses historical averages and allows a prediction or future behavior based on a weighted average of current and past values. From the results obtained, it was possible to conclude that, in recent decades, Chile's position in the Pan American Games ranking has stabilized around eleventh place, a position predicted for Santiago 2023. Maintaining similar conditions, the general and specific sporting performance would not have an exponential break in the trend and the results are not favorable, specifically in terms of obtaining gold medals and the overall position of the delegation.
O objetivo deste artigo é analisar o desempenho esportivo da delegação chilena nos Jogos Pan-Americanos realizados entre 1951 e 2023, usando dados retrospectivos e projetivos por meio de séries temporais. Para isso, foi utilizado um desenho quantitativo, não experimental e longitudinal de tendências e um método de suavização exponencial simples, que utiliza médias históricas e permite uma previsão do comportamento futuro com base em uma média ponderada dos valores atuais e passados. Com base nos resultados obtidos, foi possível concluir que, nas últimas décadas, a posição do Chile no ranking dos Jogos Pan-Americanos se estabilizou em torno do 11º lugar, posição prevista para Santiago 2023. Mantendo-se condições semelhantes, o desempenho esportivo geral e específico não teria uma quebra exponencial na tendência e os resultados não são favoráveis, especificamente em termos de conquista de medalhas de ouro e posição geral da delegação.