Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 234
Filtrar
1.
Pathogens ; 13(9)2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39338979

RESUMEN

Wetlands are ecosystems that are essential to ecological balance and biodiversity; nevertheless, human activity is a constant threat to them. Excess nutrients are caused by intensive livestock and agricultural operations, pollution, and population growth, which in turn leads to uncontrolled microbiological development. This impairment in water quality can constitute a risk to animal, human, and environmental health. To thoroughly characterize the microbial communities, shotgun metagenomics was used to characterize the taxonomic and functional pattern of microorganisms that inhabit urban wetlands in the Los Lagos Region of Chile. The main objective was to identify microorganisms of veterinary relevance, assess their potential antibiotic resistance, and characterize the main virulence mechanism. As expected, a high diversity of microorganisms was identified, including bacteria described as animal or human pathogens, such as Pasteurella multocida, Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli. Also, a diverse repertory of antimicrobial-resistant genes (ARGs) was detected in metagenomic assembled sequences and inside the sequence of mobile genetic elements, genes that confer mainly resistance to beta-lactams, consistent with the families of antibiotics most used in Chile. In addition, a diverse collection of virulence mechanisms was also identified. Given the significance of the relationship between environmental, animal, and human health-a concept known as One Health-there is a need to establish molecular surveillance programs that monitor the environmental biohazard elements using molecular tools. This work is the first report of the presence of these harmful biological elements in urban wetlands subjected to anthropogenic pressure, located in the south of Chile.

2.
R Soc Open Sci ; 11(6): 240530, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39100162

RESUMEN

Habitat fragmentation can negatively impact wildlife populations by simplification of ecological interactions, but little is known about how these impacts extend to host-associated symbiotic communities. The symbiotic communities of amphibians play important roles in anti-pathogen defences, particularly against the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). In this study, we analyse the role of macroparasitic helminth communities in concert with microbial communities in defending the host against Bd infection within the context of forest fragmentation. We found that skin microbial and helminth communities are disrupted at fragmented habitats, while gut microbiomes appear more resilient to environmental change. We also detected potential protective roles of helminth diversity and anti-pathogen microbial function in limiting Bd infection. Microbial network analysis revealed strong patterns of structure in both skin and gut communities, with helminths playing central roles in these networks. We reveal consistent roles of microbial and helminth diversity in driving host-pathogen interactions and the potential implications of fragmentation on host fitness.

3.
Antibiotics (Basel) ; 13(7)2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39061361

RESUMEN

Antimicrobial resistance has been stated to be a global health problem. In Chile, the use of antibiotics should be declared by medical prescription, but it is unknown what happens to the drugs once the treatment ends. Among the possibilities for their disposal are the trash or the drain; regardless of which scenario arises, antibiotics could accumulate in the environment, stimulating the emergence of antimicrobial resistance mechanisms and their transfer between microorganisms. Unfortunately, sometimes wastewater ends up in bodies of water, due to the dragging of elements by rain, or by the presence of illegal water discharges. In this work, shotgun metagenomics was used to elucidate the functional and microbial composition of biohazard elements in the bay of Puerto Varas City, Chile. As expected, a high diversity of microorganisms was found, including bacterial elements described as human or animal pathogens. Also, a diverse repertory of antimicrobial resistant genes (ARGs) was detected, which confers mainly resistance to macrolides, beta-lactams, and tetracyclines, consistent with the families of antibiotics most used in Chile. Similar ARGs were identified in DNA mobile elements. In addition, we tested the antimicrobial susceptibility in 14 bacterial strains isolated from Llanquihue Lake. This is the first report of the presence of genomic elements that could constitute a health problem, considering the importance of the interconnection between environmental, animal, and human health, a concept known as One Health.

4.
Oncol Lett ; 28(1): 303, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38774453

RESUMEN

NK2 homeobox 1 (NKX2-1) copy number alterations (CNAs) are frequently observed in lung cancer. However, little is known about the complete landscape of focal alterations in NKX2-1 copy number (CN), their clinical significance and their therapeutic implications in non-small cell lung cancer (NSCLC). The correlations between NKX2-1 expression and EGFR driver mutations and programmed death ligand 1 (PD-L1) co-expression were studied using immunohistochemistry and PCR from the tumors of recruited Filipino patients (n=45). Clinical features of NSCLC with NKX2-1 CNAs were resolved at the tumor and clonal levels using the molecular profiles of patients with lung adenocarcinoma and lung squamous cell carcinoma from The Cancer Genome Atlas (n=1,130), and deconvoluted single-cell RNA-seq data from the Bivona project (n=1,654), respectively. Despite a significant and positive correlation between expression and CN (r=0.264; P<0.001), NKX2-1 CNAs exerted a stronger influence on the combined EGFR and PD-L1 status of NSCLC tumors than expression. NKX2-1 CN gain was prognostic of favorable survival (P=0.018) and a better response to targeted therapy. NKX2-1 CN loss predicted a worse survival (P=0.041). Mutational architecture in the Y-chromosome differentiated the two prognostic groups. There were 19,941 synonymous mutations and 1,408 genome-wide CN perturbations associated with NKX2-1 CNAs. Tumors with NKX2-1 CN gain expressed lymphocyte markers more heterogeneously than those with CN loss. Higher expression of tumor-infiltrating lymphocyte gene signatures in CN gain was prognostic of longer disease-free survival (P=0.005). Tumors with NKX2-1 CN gain had higher B-cell (P<0.001) and total T-cell estimates (P=0.003). NKX2-1 CN loss was associated with immunologically colder tumors due to higher M2 macrophage infiltrates (P=0.011) and higher expression of immune checkpoint proteins, CD274 (P=0.025), VTCN1 (P<0.001) and LGALS9 (P=0.002). In conclusion, NKX2-1 CNAs are associated with tumors that exhibit clinically diverse characteristics, and with unique oncogenic, immunological and prognostic signatures.

6.
BMC Neurol ; 24(1): 108, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38566012

RESUMEN

BACKGROUND: Effective interventions for Multiple Sclerosis require timely treatment optimization which usually involves switching disease modifying therapies. The patterns of prescription and the reasons for changing treatment in people with MS, especially in low prevalence populations, are unknown. OBJECTIVES: To describe the persistence, reasons of DMT switches and prescription patterns in a cohort of Colombian people with MS. METHODS: We conducted a retrospective observational study including patients with confirmed MS with at least one visit at our centre. We estimated the overall incidence rate of medication changes and assessed the persistence on medication with Kaplan-Meier survival estimates for individual medications and according to efficacy and mode of administration. The factors associated with changing medications were assessed using adjusted Cox proportional-hazards models. The reasons for switching medication changes were described, and the prescription patterns were assessed using network analysis, with measures of centrality. RESULTS: Seven hundred one patients with MS were included. Mean age was 44.3 years, and 67.9% were female. Mean disease duration was 11.3 years and 84.5% had relapsing MS at onset, with median EDSS of 1.0. Treatment was started in 659 (94%) of the patients after a mean of 3 years after MS symptom onset. Among them, 39.5% maintained their initial DMT, 29.9% experienced a single DMT change, while 18.7% went through two, and 11.9% had three or more DMT changes until the final follow-up. The total number of treatment modifications reached 720, resulting in an incidence rate of 1.09 (95% confidence interval: 1.01-1.17) per patient per year The median time to change after the first DMT was 3.75 years, and was not different according to the mode of administration or efficacy classification. The main reasons for changing DMT were MS activity (relapses, 56.7%; MRI activity, 18.6%), followed by non-serious adverse events (15.3%) and disability (11.1%). Younger age at MS onset, care under our centre and insurer status were the main determinants of treatment change. Network analysis showed that interferons and fingolimod were the most influential DMTs. CONCLUSIONS: A majority of patients switch medications, mostly due to disease activity, and in association with age and insurer status.


Asunto(s)
Esclerosis Múltiple Recurrente-Remitente , Esclerosis Múltiple , Pueblos Sudamericanos , Humanos , Femenino , Adulto , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/epidemiología , Clorhidrato de Fingolimod/uso terapéutico , Estudios Retrospectivos , Modelos de Riesgos Proporcionales , Esclerosis Múltiple Recurrente-Remitente/tratamiento farmacológico
8.
Neurol Sci ; 45(1): 55-63, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37697027

RESUMEN

After a stroke, several mechanisms of neural plasticity can be activated, which may lead to significant recovery. Rehabilitation therapies aim to restore surviving tissue over time and reorganize neural connections. With more patients surviving stroke with varying degrees of neurological impairment, new technologies have emerged as a promising option for better functional outcomes. This review explores restorative therapies based on brain-computer interfaces, robot-assisted and virtual reality, brain stimulation, and cell therapies. Brain-computer interfaces allow for the translation of brain signals into motor patterns. Robot-assisted and virtual reality therapies provide interactive interfaces that simulate real-life situations and physical support to compensate for lost motor function. Brain stimulation can modify the electrical activity of neurons in the affected cortex. Cell therapy may promote regeneration in damaged brain tissue. Taken together, these new approaches could substantially benefit specific deficits such as arm-motor control and cognitive impairment after stroke, and even the chronic phase of recovery, where traditional rehabilitation methods may be limited, and the window for repair is narrow.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/terapia , Encéfalo , Plasticidad Neuronal/fisiología , Corteza Cerebral , Recuperación de la Función
9.
Transl Lung Cancer Res ; 12(9): 1896-1911, 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37854154

RESUMEN

Background: The tumor immune microenvironment influences tumor evolution in non-small cell lung cancer (NSCLC). Yet, the prognostic value of programmed death-ligand 1 (PD-L1) in epidermal growth factor receptor (EGFR)-mutant NSCLC remains controversial. Additionally, prognostic studies in Filipinos with EGFR-mutant NSCLC remain unexplored to this day. Methods: We prospectively studied the outcomes of EGFR-mutant NSCLC in Filipino cohort, and retrospectively verified the survival trend using The Cancer Genome Atlas (TCGA) cohort. Kaplan-Meier method and generalized linear regression were used to assess survival. Expression and DNA methylation of cluster of differentiation 274 (CD274, gene that codes for PD-L1) were examined from TCGA tumor profiles. Pearson's correlation was used to correlate PD-L1 expression with outcomes associated with occurrence of EGFR mutations, tyrosine kinase inhibitor (TKI) types, and programmed cell death protein 1 (PD-1) expression. Proteome network analysis was used to examine the correlation between drug resistance and PD-L1. Results: PD-L1 positivity was associated with significantly longer progression-free survival (PFS; P=0.0096) but had a significantly contrasting influence in the overall survival (OS; P=0.0011). PD-L1 positivity (in both protein and RNA) was associated with longer median OS (mOS) in exon21 L858R, whereas, negativity was associated with longer mOS in exon19 deletion (exon19del). Stratification (high, low, negative) of PD-L1 expression lacked significant prognostic value (all P>0.05). PD-L1/CD274 expression (P<0.05) and DNA methylation (P<0.001) vary significantly among NSCLC subtypes and in different disease stages. Erlotinib treatment produced the longest median progression-free survival (mPFS; 874 days) relative to other EGFR-TKIs (137-311 days). PD-L1 lacked a significant correlation with EGFR-TKIs. Consistent with the immune-regulation activities of PD-1, higher expression leads to relatively shorter mOS. PD-1 correlated positively with PD-L1 expression and occurrence of exon21 L858R. Conclusions: PD-L1 differentially influenced the outcomes of Filipinos with EGFR-mutant NSCLC. NSCLC subtypes, disease stage, and PD-1 expression may impact the collective outcomes associated with PD-L1 and EGFR-sensitizing mutations.

10.
11.
Commun Biol ; 6(1): 941, 2023 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-37709833

RESUMEN

By altering the abundance, diversity, and distribution of species-and their pathogens-globalization may inadvertently select for more virulent pathogens. In Brazil's Atlantic Forest, a hotspot of amphibian biodiversity, the global amphibian trade has facilitated the co-occurrence of previously isolated enzootic and panzootic lineages of the pathogenic amphibian-chytrid (Batrachochytrium dendrobatidis, 'Bd') and generated new virulent recombinant genotypes ('hybrids'). Epidemiological data indicate that amphibian declines are most severe in hybrid zones, suggesting that coinfections are causing more severe infections or selecting for higher virulence. We investigated how coinfections involving these genotypes shapes virulence and transmission. Overall, coinfection favored the more virulent and competitively superior panzootic genotype, despite dampening its transmission potential and overall virulence. However, for the least virulent and least competitive genotype, coinfection increased both overall virulence and transmission. Thus, by integrating experimental and epidemiological data, our results provide mechanistic insight into how globalization can select for, and propel, the emergence of introduced hypervirulent lineages, such as the globally distributed panzootic lineage of Bd.


Asunto(s)
Coinfección , Humanos , Coinfección/epidemiología , Biodiversidad , Bosques , Genotipo , Virulencia/genética
12.
Epilepsy Behav ; 146: 109383, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37549466

RESUMEN

INTRODUCTION: Adverse drug reactions (ADRs) to antiseizure therapy can worsen the quality of life, reduce adherence, and potentially lead to treatment discontinuation and uncontrolled seizures. OBJECTIVES: The aim of the study was to develop a prognostic model for ADRs to antiseizure therapy in adult patients with epilepsy from Colombia. METHODS: This case-control study included adult patients with epilepsy, who were separated into two groups: one group with ADRs to antiseizure therapy (cases), as determined by a complete evaluation conducted by an epileptologist, and another group without ADRs (controls). Variables were analyzed to identify statistical differences between the two groups and were then selected to construct a prognostic model using logistic regression. The Bonferroni method was applied for multiple comparisons. RESULTS: Three hundred fifty-four patients with epilepsy were studied. One hundred and fifty (42%) patients had ADRs and 204 (57%) patients did not have ADs. A total of 362 ADRs were reported, with a third of them being general symptoms and most frequently occurring with older-generation antiseizure drugs (58%). Female sex, drug-resistant epilepsy, LEV, and CZP were risk factors, whereras the presence of tumoral etiology, absence of seizure triggers, and VPA were identified as protective factors. A prognostic model was constructed using previously reported risk factors for ADRs to antiseizure therapy and other variables available in this population study. In the multivariable analysis, the number of previously used antiseizure drugs (1, 2, or ≥3), TPM, CZP, LEV, PHT, and female sex were predictors of ADRs. The corrected p-values were estimated by the Bonferroni method; however, not all the variables achieved statistical significance with this adjustment. CONCLUSIONS: In adult patients with epilepsy from Colombia, we found that the number of previously used antiseizure drugs, TPM, CZP, LEV, PHT, and female sex were predictive factors for ADRs to antiseizure therapy.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Epilepsia , Humanos , Adulto , Femenino , Anticonvulsivantes/efectos adversos , Estudios de Casos y Controles , Colombia/epidemiología , Calidad de Vida , Epilepsia/tratamiento farmacológico , Epilepsia/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/tratamiento farmacológico
13.
PeerJ ; 11: e15556, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465150

RESUMEN

Skin microbial communities are an essential part of host health and can play a role in mitigating disease. Host and environmental factors can shape and alter these microbial communities and, therefore, we need to understand to what extent these factors influence microbial communities and how this can impact disease dynamics. Microbial communities have been studied in amphibian systems due to skin microbial communities providing some resistance to the amphibian chytrid fungus, Batrachochytrium dendrobatidis. However, we are only starting to understand how host and environmental factors shape these communities for amphibians. In this study, we examined whether amphibian skin bacterial communities differ among host species, host infection status, host developmental stage, and host habitat. We collected skin swabs from tadpoles and adults of three Ranid frog species (Lithobates spp.) at the Mianus River Gorge Preserve in Bedford, New York, USA, and used 16S rRNA gene amplicon sequencing to determine bacterial community composition. Our analysis suggests amphibian skin bacterial communities change across host developmental stages, as has been documented previously. Additionally, we found that skin bacterial communities differed among Ranid species, with skin communities on the host species captured in streams or bogs differing from the communities of the species captured on land. Thus, habitat use of different species may drive differences in host-associated microbial communities for closely-related host species.


Asunto(s)
Quitridiomicetos , Microbiota , Animales , ARN Ribosómico 16S/genética , Quitridiomicetos/genética , Anuros/genética , Ranidae/genética , Microbiota/genética , Bacterias/genética
14.
Am J Hematol ; 98(8): 1204-1213, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37151135

RESUMEN

Data on the effect of booster SARS-CoV-2 vaccination are mainly focused on humoral immunogenicity, while the kinetics of vaccine-induced cellular response and its correlation with effectiveness in hematologic patients are less explored. Our aim was to evaluate the longitudinal cellular and humoral immunogenicity induced by two and three doses of the mRNA-1273 SARS-CoV-2 vaccine in 270 patients with hematologic malignancies, and its relationship with the severity of breakthrough SARS-CoV-2 infection. Results indicate that at 23 weeks after the second dose, the seroconversion rate declined from 68.5% to 59.3%, with a reduction in median anti-S titers from 1577 to 456 BAU/mL, mainly in patients over 65 years of age or chronic lymphocytic leukemia (CLL) patients undergoing active therapy. Cellular immunogenicity, however, remained positive in 84.4% of cases. A third vaccine dose seroconverted 42.7% (41/96) and triggered cellular response in 36.7% (11/30) of previously negative patients. Notably, only 7.2% (15/209) of patients failed to develop both humoral and cellular response. Active therapy, anti-CD20 antibodies, lymphopenia, hypogammaglobulinemia, and low CD19+ cell count were associated with poor humoral response, while active disease, GvHD immunosuppressive therapy, lymphopenia, and low CD3+ , CD4+ , CD56+ cell count determined an impaired cellular response. After 13.8 months of follow-up, the incidence of SARS-CoV-2 infection was 24.8% (67/270), including 6 (9%) severe/critical cases associated with a weaker cellular (median interferon gamma (IFN-γ) 0.19 vs. 0.35 IU/mL) and humoral response (median anti-S titer <4.81 vs. 788 BAU/mL) than asymptomatic/mild cases. In conclusion, SARS-CoV-2 booster vaccination improves humoral response and COVID-19 severity is associated with impaired vaccine-induced immunogenicity.


Asunto(s)
COVID-19 , Neoplasias Hematológicas , Linfopenia , Humanos , Vacunas contra la COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Vacunación , Neoplasias Hematológicas/terapia , Anticuerpos , Anticuerpos Antivirales
15.
J Neurovirol ; 29(2): 237-240, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36867345

RESUMEN

A new outbreak of monkeypox has been reported worldwide with CNS complications like encephalitis or myelitis being extremely rare. We present a case of a 30-year-old man with PCR-confirmed diagnosis of monkeypox who developed rapid neurological deterioration with extensive inflammatory involvement of the brain and spinal cord on MRI. Because of the clinical and radiological resemblance to acute disseminated encephalomyelitis (ADEM), it was decided to indicate treatment with high-dose corticosteroids for 5 days (without concomitant antiviral management due to lack of availability in our country). Given the poor clinical and radiological response, 5 days of immunoglobulin G were administered. During follow-up the patient's clinical condition improved, physiotherapy was started and all associated medical complications were controlled. To our knowledge, this is the first reported monkeypox case with severe CNS complications treated with steroids and immunoglobulin in the absence of specific antiviral treatment.


Asunto(s)
Encefalomielitis Aguda Diseminada , Encefalomielitis , Mpox , Masculino , Humanos , Adulto , Mpox/complicaciones , Mpox/tratamiento farmacológico , Encefalomielitis Aguda Diseminada/complicaciones , Encefalomielitis Aguda Diseminada/diagnóstico por imagen , Encefalomielitis Aguda Diseminada/tratamiento farmacológico , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Antivirales/uso terapéutico , Encefalomielitis/diagnóstico por imagen , Encefalomielitis/tratamiento farmacológico , Encefalomielitis/complicaciones
16.
Biochim Biophys Acta Gene Regul Mech ; 1866(2): 194910, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36731791

RESUMEN

It has become increasingly clear in the last few years that gene expression in eukaryotes is not a linear process from mRNA synthesis in the nucleus to translation and degradation in the cytoplasm, but works as a circular one where the mRNA level is controlled by crosstalk between nuclear transcription and cytoplasmic decay pathways. One of the consequences of this crosstalk is the approximately constant level of mRNA. This is called mRNA buffering and happens when transcription and mRNA degradation act at compensatory rates. However, if transcription and mRNA degradation act additively, enhanced gene expression regulation occurs. In this work, we analyzed new and previously published genomic datasets obtained for several yeast mutants related to either transcription or mRNA decay that are not known to play any role in the other process. We show that some, which were presumed only transcription factors (Sfp1) or only decay factors (Puf3, Upf2/3), may represent examples of RNA-binding proteins (RBPs) that make specific crosstalk to enhance the control of the mRNA levels of their target genes by combining additive effects on transcription and mRNA stability. These results were mathematically modeled to see the effects of RBPs when they have positive or negative effects on mRNA synthesis and decay rates. We found that RBPs can be an efficient way to buffer or enhance gene expression responses depending on their respective effects on transcription and mRNA stability.


Asunto(s)
Regulación de la Expresión Génica , Proteínas de Saccharomyces cerevisiae , Transcripción Genética , Estabilidad del ARN/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
17.
Lung Cancer ; 176: 121-131, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36634573

RESUMEN

TTF-1-expressing non-small cell lung cancer (NSCLC) is one of the most prevalent lung cancer types worldwide. However, theparadoxical activity of TTF-1 in both lung carcinogenesis and tumor suppression is believed to be context-dependentwhich calls for a deeper understanding about the pathological expression of TTF-1. In addition, the expression circuitry of TTF-1-target genes in NSCLC has not been well examined which necessitates to revisit the involvement of TTF-1- in a multitude of oncologic pathways. We used RNA-seq and clinical data of patients from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), including ChIP-seq data from different NSCLC cell lines, and mapped the proteome of NSCLC tumor. Our analysis showed significant variability in TTF-1 expression among NSCLC,and further clarified that this variability is orchestrated at the transcriptional level. We also found that high TTF-1 expression could negatively influence the survival outcomes of stage 1 LUAD which may be attributed to growth factor receptor-driven activation of mitogenic and angiogenic pathways. Mechanistically, TTF-1 may also control the genes associated with pathways involved in acquired TKI drug resistance or response to immune checkpoint inhibitors. Lastly, proteome-based biomarker discovery in stage 1 LUAD showed that TTF-1 positivity is potentially associated with the upregulation of several oncogenes which includes interferon proteins, MUC1, STAT3, and EIF2AK2. Collectively, this study highlights the potential involvement of TTF-1 in cell proliferation, immune evasion, and angiogenesis in early-stage NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Factor Nuclear Tiroideo 1 , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Proteínas Nucleares/genética , Proteoma , Factor Nuclear Tiroideo 1/genética
18.
Cancer Immunol Immunother ; 72(6): 1405-1415, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36445410

RESUMEN

BACKGROUND: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma. METHODS: Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety. RESULTS: Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3+ infiltrates. Surprisingly, the baseline cell density of CD3+CD8- T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179). CONCLUSIONS: These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment. TRIAL REGISTRATION NUMBER: NCT02565992.


Asunto(s)
Melanoma , Virus Oncolíticos , Humanos , Animales , Cabras , Anticuerpos Monoclonales Humanizados/efectos adversos , Melanoma/tratamiento farmacológico , Microambiente Tumoral
19.
Anim Microbiome ; 4(1): 69, 2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36582011

RESUMEN

Microbial diversity positively influences community resilience of the host microbiome. However, extinction risk factors such as habitat specialization, narrow environmental tolerances, and exposure to anthropogenic disturbance may homogenize host-associated microbial communities critical for stress responses including disease defense. In a dataset containing 43 threatened and 90 non-threatened amphibian species across two biodiversity hotspots (Brazil's Atlantic Forest and Madagascar), we found that threatened host species carried lower skin bacterial diversity, after accounting for key environmental and host factors. The consistency of our findings across continents suggests the broad scale at which low bacteriome diversity may compromise pathogen defenses in species already burdened with the threat of extinction.

20.
Salud ment ; 45(6): 303-308, Nov.-Dec. 2022. tab
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1432207

RESUMEN

Abstract Introduction Indigenous populations are considered a vulnerable minority and have characteristics such as poverty, difficulties to access food, housing, and educational backwardness; these conditions make them prone to alcohol consumption problems. Dependence on alcohol consumption probably arises as a symbol of protest, challenge, and response to social anguish, which has in turn repercussions in marginal population sectors that have conditions of fragility due to exploitation and discrimination, such as indigenous people. Objective To know the effect of perceived discrimination on alcohol consumption in Mexican indigenous population. Method Research design was descriptive, correlational check-model, with a sample of 362 adults from two indigenous communities. Results A simple linear regression model was performed, which shows a significant effect in the entire model (F[248] = 78.312, p = .001), which explains 49% of the variance of alcohol consumption. A significant positive influence was also found from the perceived discrimination variable (β = .626, p < .001) on alcohol consumption. Discussion and conclusion The studied indigenous communities had characteristics that the literature highlights as risk factors for developing addictive behaviors of alcohol consumption. These results coincide with those of the National Commission for the Development of Indigenous Peoples. Indigenous population present discrimination problems that are associated with alcohol consumption problems.


Resumen Introducción Las poblaciones indígenas se consideran minoritarias y vulnerables, y se caracterizan por su pobreza, dificultad para acceder a la alimentación, la vivienda y el rezago educativo. Estas condiciones los vuelven propensos a presentar problemas de consumo de alcohol. La dependencia al consumo de alcohol surge probablemente como símbolo de protesta, reto y respuesta a la angustia social, lo cual repercute en los sectores poblacionales marginales que poseen condiciones de fragilidad por la explotación y discriminación como los pueblos indígenas. Objetivo Conocer el efecto de la discriminación percibida en el consumo de alcohol en poblaciones indígenas mexicanas. Método El diseño del estudio fue descriptivo, correlacional de comprobación de modelo, con una muestra de 362 adultos de dos comunidades indígenas. Resultados Se realizó el modelo de regresión lineal simple el cual muestra efecto significativo en la totalidad del modelo (F[248] = 78.312, p = .001), explica el 49% de la varianza del consumo de alcohol, además se encontró influencia positiva significativa de la variable discriminación percibida (β = .626, p < .001) sobre el consumo de alcohol. Discusión y conclusión Las comunidades indígenas estudiadas poseen características que la literatura destaca como factores de riesgo para desarrollar conductas adictivas de consumo de alcohol, estos resultados coinciden con lo expuesto por la Comisión Nacional para el Desarrollo de los Pueblos Indígenas. Las poblaciones indígenas presentan problemas de discriminación que se asocian con los problemas de consumo de alcohol.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...