Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 85
Filtrar
1.
Cell Mol Life Sci ; 81(1): 219, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758230

RESUMO

HMGA1 is a structural epigenetic chromatin factor that has been associated with tumor progression and drug resistance. Here, we reported the prognostic/predictive value of HMGA1 for trabectedin in advanced soft-tissue sarcoma (STS) and the effect of inhibiting HMGA1 or the mTOR downstream pathway in trabectedin activity. The prognostic/predictive value of HMGA1 expression was assessed in a cohort of 301 STS patients at mRNA (n = 133) and protein level (n = 272), by HTG EdgeSeq transcriptomics and immunohistochemistry, respectively. The effect of HMGA1 silencing on trabectedin activity and gene expression profiling was measured in leiomyosarcoma cells. The effect of combining mTOR inhibitors with trabectedin was assessed on cell viability in vitro studies, whereas in vivo studies tested the activity of this combination. HMGA1 mRNA and protein expression were significantly associated with worse progression-free survival of trabectedin and worse overall survival in STS. HMGA1 silencing sensitized leiomyosarcoma cells for trabectedin treatment, reducing the spheroid area and increasing cell death. The downregulation of HGMA1 significantly decreased the enrichment of some specific gene sets, including the PI3K/AKT/mTOR pathway. The inhibition of mTOR, sensitized leiomyosarcoma cultures for trabectedin treatment, increasing cell death. In in vivo studies, the combination of rapamycin with trabectedin downregulated HMGA1 expression and stabilized tumor growth of 3-methylcholantrene-induced sarcoma-like models. HMGA1 is an adverse prognostic factor for trabectedin treatment in advanced STS. HMGA1 silencing increases trabectedin efficacy, in part by modulating the mTOR signaling pathway. Trabectedin plus mTOR inhibitors are active in preclinical models of sarcoma, downregulating HMGA1 expression levels and stabilizing tumor growth.


Assuntos
Proteína HMGA1a , Sarcoma , Trabectedina , Trabectedina/farmacologia , Humanos , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Sarcoma/genética , Sarcoma/metabolismo , Proteína HMGA1a/metabolismo , Proteína HMGA1a/genética , Animais , Linhagem Celular Tumoral , Camundongos , Antineoplásicos Alquilantes/farmacologia , Antineoplásicos Alquilantes/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Prognóstico , Feminino , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/patologia , Leiomiossarcoma/genética , Leiomiossarcoma/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Colorectal Dis ; 26(1): 120-129, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38010046

RESUMO

AIM: Management of diverticulitis with abscess formation in immunosuppressed patients (IMS) remains unclear. The main objective of the study was to assess short- and long-term outcomes between IMS and immunocompetent patients (IC). The secondary aim was to identify risk factors for emergency surgery. METHODS: A nationwide retrospective cohort study was performed at 29 Spanish referral centres between 2015-2019 including consecutive patients with first episode of diverticulitis classified as modified Hinchey Ib or II. IMS included immunosuppressive therapy, biologic therapy, malignant neoplasm with active chemotherapy and chronic steroid therapy. A multivariate analysis was performed to identify independent risk factors to emergency surgery in IMS. RESULTS: A total of 1395 patients were included; 118 IMS and 1277 IC. There were no significant differences in emergency surgery between IMS and IC (19.5% and 13.5%, p = 0.075) but IMS was associated with higher mortality (15.1% vs. 0.6%, p < 0.001). Similar recurrent episodes were found between IMS and IC (28% vs. 28.2%, p = 0.963). Following multivariate analysis, immunosuppressive treatment, p = 0.002; OR: 3.35 (1.57-7.15), free gas bubbles, p < 0.001; OR: 2.91 (2.01-4.21), Hinchey II, p = 0.002; OR: 1.88 (1.26-2.83), use of morphine, p < 0.001; OR: 3.08 (1.98-4.80), abscess size ≥5 cm, p = 0.001; OR: 1.97 (1.33-2.93) and leucocytosis at third day, p < 0.001; OR: 1.001 (1.001-1.002) were independently associated with emergency surgery in IMS. CONCLUSION: Nonoperative management in IMS has been shown to be safe with similar treatment failure than IC. IMS presented higher mortality in emergency surgery and similar rate of recurrent diverticulitis than IC. Identifying risk factors to emergency surgery may anticipate emergency surgery.


Assuntos
Doença Diverticular do Colo , Diverticulite , Humanos , Abscesso/etiologia , Abscesso/terapia , Doença Diverticular do Colo/terapia , Doença Diverticular do Colo/complicações , Estudos Retrospectivos , Recidiva Local de Neoplasia/complicações , Diverticulite/complicações
3.
Int J Mol Sci ; 24(13)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37445592

RESUMO

Parkinson's disease is a neurodegenerative disorder characterized by oxidative stress and immune activation in the nigro-striatal pathway. Simvastatin regulates cholesterol metabolism and protects from atherosclerosis disease. Simvastatin-tween 80 was administered 7 days before sterotaxic intrastriatal administration of MPP+ (1-methyl-4-phenylpyridine) in rats. Fluorescent lipidic product formation, dopamine levels, and circling behavior were considered damage markers. Twenty-four hours and six days after, the animal group lesioned with MPP+ showed significant damage in relation to the control group. Animals pretreated with simvastatin significantly reduced the MPP+-induced damage compared to the MPP+ treated group. As apoptosis promotes neuroinflammation and neuronal degeneration in Parkinson's disease, and since there is not currently a proteomic map of the nigro-striatum of rats and assuming a high homology among the identified proteins in other rat tissues, we based the search for rat protein homologs related to the establishment of inflammation response. We demonstrate that most proteins related to inflammation decreased in the simvastatin-treated rats. Furthermore, differential expression of antioxidant enzymes in striated tissue of rat brains was found in response to simvastatin. These results suggest that simvastatin could prevent striatal MPP+-induced damage and, for the first time, suggest that the molecular mechanisms involved in this have a protective effect.


Assuntos
Doença de Parkinson , Ratos , Animais , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Sinvastatina/farmacologia , Sinvastatina/uso terapêutico , Sinvastatina/metabolismo , Proteômica , Substância Negra/metabolismo , Dopamina/metabolismo , 1-Metil-4-fenilpiridínio/farmacologia , Corpo Estriado/metabolismo , Modelos Animais de Doenças
4.
Parasitol Res ; 121(7): 2065-2078, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35524789

RESUMO

The invasive nature of Toxoplasma gondii is closely related to the properties of its cytoskeleton, which is constituted by a group of diverse structural and dynamic components that play key roles during the infection. Even if there have been numerous reports about the composition and function of the Toxoplasma cytoskeleton, the ultrastructural organization of some of these components has not yet been fully characterized. This study used a detergent extraction process and several electron microscopy contrast methods that allowed the successful isolation of the cytoskeleton of Toxoplasma tachyzoites. This process allowed for the conservation of the structures known to date and several new structures that had not been characterized at the ultrastructural level. For the first time, characterization was achieved for a group of nanofibers that allow the association between the polar apical ring and the conoid as well as the ultrastructural characterization of the apical cap of the parasite. The ultrastructure and precise location of the peripheral rings were also found, and the annular components of the basal complex were characterized. Finally, through immunoelectron microscopy, the exact spatial location of the subpellicular network inside the internal membrane system that forms the pellicle was found. The findings regarding these new structures contribute to the knowledge concerning the biology of the Toxoplasma gondii cytoskeleton. They also provide new opportunities in the search for therapeutic strategies aimed at these components with the purpose of inhibiting invasion and thus parasitism.


Assuntos
Toxoplasma , Citoesqueleto/ultraestrutura , Microscopia Eletrônica , Microscopia Imunoeletrônica , Microtúbulos , Toxoplasma/ultraestrutura
5.
Pol J Pathol ; 73(4): 364-370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36946274

RESUMO

Atypical spindle cell lipomatous tumour (ASCLT) is a benign neoplasm that presents a variable proportion of atypical spindle and adipocytic cells, frequently expressing CD34, and embedded in myxoid or collagenous matrix. An important feature is a constant lack of either MDM2 or CDK4 amplification. It typically arises in the extremities. The retroperitoneum is a rare site of involvement. We report a case of a retroperitoneal ASCLT in a 62-year-old male. A differential diagnosis of ASCLT from the other mesenchymal, spindle-cell, and lipomatous tumours is crucial for optimal treatment and significantly influences the prognosis. A diagnosis should be warranted by the immunohistochemistry and molecular findings.


Assuntos
Lipoma , Lipossarcoma , Masculino , Humanos , Pessoa de Meia-Idade , Lipossarcoma/patologia , Lipoma/patologia , Imuno-Histoquímica , Diagnóstico Diferencial , Biomarcadores Tumorais
6.
Adv Funct Mater ; 31(22)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-36213489

RESUMO

Advanced wound scaffolds that integrate active substances to treat chronic wounds have gained significant recent attention. While wound scaffolds and advanced functionalities have previously been incorporated into one medical device, the wirelessly triggered release of active substances has remained the focus of many research endeavors. To combine multiple functions including light-triggered activation, anti-septic, angiogenic, and moisturizing properties, we have developed a 3D printed hydrogel patch encapsulating vascular endothelial growth factor (VEGF) decorated with photoactive and antibacterial tetrapodal zinc oxide (t-ZnO) microparticles. To achieve the smart release of VEGF, t-ZnO was modified by chemical treatment and activated through UV/visible light exposure. This process would also make the surface rough and improve protein adhesion. The elastic modulus and degradation behavior of the composite hydrogels, which must match the wound healing process, were adjusted by changing t-ZnO concentrations. The t-ZnO-laden composite hydrogels can be printed with any desired micropattern to potentially create a modular elution of various growth factors. The VEGF decorated t-ZnO-laden hydrogel patches showed low cytotoxicity and improved angiogenic properties while maintaining antibacterial functions in vitro. In vivo tests showed promising results for the printed wound patches, with less immunogenicity and enhanced wound healing.

7.
Environ Res ; 191: 109960, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33181973

RESUMO

Breast cancer is one of the most common malignancies and the second leading cause of death in women. Despite efforts for its early detection, its worldwide incidence continues to increase. Thus, identification of risk factors for its development and new targets for its therapy are of vital importance. Environmental pollutants derived from human activity have been associated with predisposition to the development of cancer. Bisphenol A (BPA) is an endocrine disruptor compound (EDC) widely used in the manufacture of polycarbonates, and it has affinity for the estrogen receptor (ER). Scientific evidence has proposed an association between increased incidence of breast cancer and BPA exposure at lower doses. Among worldwide concerns with BPA exposure, different industries proceeded to replace BPA with analogs such as bisphenol S (BPS), which is now employed in products labelled as BPA-free. Nevertheless, recent studies exhibit that its exposure results in altered mammary gland development and morphogenesis; and promotes breast cancer cell proliferation. Of note, most of the effects of both BPA and BPS have been performed in estrogen-dependent breast cancer models. However, gaps in knowledge still exist on the roles and mechanisms that both compounds, specifically BPS, may play in cancer initiation and development in hormone-dependent and other types of breast cancer. Thus, the aim of the present study was to deepen the understanding of biological targets modulated by these ubiquitous pollutants in different breast cancer cell lines, representing two scenarios of this pathology: hormone-dependent and hormone-independent breast cancer. Results point out that both compounds induced proliferation in ER positive cells, not showing this effect in the ER-negative breast cancer cells. Different targets modified at the proteomic level in both breast cancer scenarios were also identified. Stem cell markers (eg. CD44) and invasion proteins (eg. MMP-14) were importantly increased by BPA and BPS in ER-positive breast cancer cells. In contrast, growth factors and associated receptors such as EGFR and TGF-ß were induced by BPS in the ER-negative breast cancer cells; both pollutants induced an increase of vascular endothelial growth factor (VEGF) protein secretion. This finding suggests that the use of BPS must be considered with more caution than BPA, since it can act independently of the presence of the hormonal receptor. These findings show new evidence that BPA and BPS exposure can contribute to breast cancer development and progression. Our results suggest that both BPA and BPS must be considered equally as outstanding risk factors for this pathology.


Assuntos
Neoplasias da Mama , Poluentes Ambientais , Compostos Benzidrílicos/toxicidade , Neoplasias da Mama/induzido quimicamente , Poluentes Ambientais/toxicidade , Feminino , Humanos , Fenóis , Fenótipo , Proteômica , Sulfonas , Fator A de Crescimento do Endotélio Vascular
8.
Parasitol Res ; 118(6): 1899-1918, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30949853

RESUMO

After host cell invasion, Toxoplasma secretes a variety of dense granule proteins (GRA proteins) from its secretory dense granules, which are involved in the biogenesis of the parasitophorous vacuole (PV). TgGRA8I is predicted to contain proline-rich domains, which are structural features of some cytoskeleton-related proteins. In agreement with this observation, previous proteomic analyses revealed the presence of TgGRA8I in the Toxoplasma sub-pellicular cytoskeleton. In the present study, we show (1) by docking analyses that TgGRA8I may interact with both Toxoplasma ß-tubulin and actin; (2) by immunoelectron microscopy, proteomic, biochemical, and cellular approaches that TgGRA8I associates with sub-pellicular microtubules and actin at the parasite sub-pellicular cytoskeleton; (3) that type I parasites (RH strain) lacking the GRA8 gene (RHΔku80Δgra8) exhibit loss of conoid extrusion, diminished cell infection, and egress capabilities, and that these motility impairments were likely due to important alterations in their sub-pellicular cytoskeleton, in particular their sub-pellicular microtubules and meshwork. Parasites lacking the GRA4 gene (RHΔku80Δgra4) did not show modifications in the organization of the sub-pellicular cytoskeleton. Collectively, these results demonstrated that TgGRA8I is a dense granule protein that, besides its role in the formation of the PV, contributes to the organization of the parasite sub-pellicular cytoskeleton and motility. This is the first proline-rich protein described in the Toxoplasma cytoskeleton, which is a key organelle for both the parasite motility and the invasion process. Knowledge about the function of cytoskeleton components in Toxoplasma is fundamental to understand the motility process and the host cell invasion mechanism. Refining this knowledge should lead to the design of novel pharmacological strategies for the treatment against toxoplasmosis.


Assuntos
Actinas/metabolismo , Antígenos de Protozoários/metabolismo , Movimento Celular/genética , Citoesqueleto/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Toxoplasma/patogenicidade , Tubulina (Proteína)/metabolismo , Animais , Antígenos de Protozoários/genética , Transporte Biológico , Microscopia Imunoeletrônica , Microtúbulos/metabolismo , Simulação de Acoplamento Molecular , Proteômica , Proteínas de Protozoários/genética , Vesículas Secretórias/metabolismo , Toxoplasma/genética , Toxoplasmose/parasitologia , Toxoplasmose/patologia , Vacúolos/parasitologia
9.
Parasitol Res ; 117(2): 547-563, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29308550

RESUMO

The biochemical and structural changes that occur during the conversion of Toxoplasma gondii tachyzoites to bradyzoites and the formation of tissue cyst are not well understood. Maintaining cells infected with T. gondii type II and III strains under stress conditions induces the tachyzoite-bradyzoite in vitro differentiation, along with the formation of cyst-like structures. However, due to the long exposure to such conditions required to induce the differentiation, the severe damages in the host cell and the low encystation frequency, it has been difficult to dissect in more detail these processes. Here, we successfully induced the in vitro formation of Toxoplasma cysts-like structures from tachyzoites of the type I RH strain by treating with mycophenolic acid, an inhibitor of the inosine monophosphate dehydrogenase. Mycophenolic acid is a drug widely used for HXGPRT positive selection of Toxoplasma mutant strains along with xanthine incubation in the culture medium; under such conditions, formation of tissue cysts has not been reported. We show that the exposure of extracellular tachyzoites to mycophenolic acid in absence of xanthine, followed by host cell invasion, triggered their differentiation into cyst-like structures. The differential expression of CST1, BAG1, and SAG1 molecules, as well as the structural modifications of infected cells, was characterized during the formation of cyst-like structures in vitro. These findings will allow the characterization of signaling pathways involved in tachyzoite to bradyzoite conversion and formation of tissue cysts.


Assuntos
Ácido Micofenólico/farmacologia , Toxoplasma/efeitos dos fármacos , Toxoplasma/crescimento & desenvolvimento , Diferenciação Celular/efeitos dos fármacos , Humanos , Estágios do Ciclo de Vida/efeitos dos fármacos , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Transdução de Sinais/efeitos dos fármacos , Toxoplasma/genética , Toxoplasma/metabolismo , Toxoplasmose/parasitologia
10.
Parasitol Res ; 115(5): 2081-96, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26888289

RESUMO

Quinoxalinone derivatives, identified as VAM2 compounds (7-nitroquinoxalin-2-ones), were evaluated against Toxoplasma gondii tachyzoites of the RH strain. The VAM2 compounds were previously synthesized based on the design obtained from an in silico prediction with the software TOMOCOMD-CARDD. From the ten VAM2 drugs tested, several showed a deleterious effect on tachyzoites. However, VAM2-2 showed the highest toxoplasmicidal activity generating a remarkable decrease in tachyzoite viability (in about 91 %) and a minimal alteration in the host cell. An evident inhibition of host cell invasion by tachyzoites previously treated with VAM2-2 was observed in a dose-dependent manner. In addition, remarkable alterations were observed in the pellicle parasite, such as swelling, roughness, and blebbing. Toxoplasma motility was inhibited, and subpellicular cytoskeleton integrity was altered, inducing a release of its components to the soluble fraction. VAM2-2 showed a clear and specific deleterious effect on tachyzoites viability, structural integrity, and invasive capabilities with limited effects in host cells morphology and viability. VAM2-2 minimum inhibitory concentration (MIC50) was determined as 3.3 µM ± 1.8. Effects of quinoxalinone derivatives on T. gondii provide the basis for a future therapeutical alternative in the treatment of toxoplasmosis.


Assuntos
Quinoxalinas/farmacologia , Toxoplasma/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Citoesqueleto , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Toxoplasma/fisiologia , Toxoplasma/ultraestrutura , Toxoplasmose/parasitologia
11.
Nurs Inq ; 23(4): 358-367, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27550888

RESUMO

The role played by witnesses of bullying in nursing settings remains little studied, despite their potential relevance in explaining the onset and development of bullying. The objective of this study was to develop a model to account for witnesses' intention to help and helping behaviour in response to bullying in a nursing setting. Three hundred and thirty-seven witnesses completed self-report measures of variables predicting intention to help and helping behaviour. A full structural model was constructed using structural equation modelling. The intention to help victims was elicited by tension, group identity, support to peers' initiative to intervene and absence of fear of retaliation. However, engagement in helping behaviour was only predicted by the absence of fear of retaliation. This study shows that witnesses of bullying in nursing settings do not remain impassive, but their experienced discomfort and intention to help victims is not sufficient to predict helping behaviour. Fear of possible retaliation if intervening in favour of victims constitutes a crucial factor explaining witnesses' hesitation to help victims. Several implications for the implementation of policies directed at eradicating bullying in nursing settings are discussed.


Assuntos
Bullying/prevenção & controle , Medo/psicologia , Comportamento de Ajuda , Intenção , Recursos Humanos de Enfermagem Hospitalar/psicologia , Humanos , Responsabilidade Social , Estigma Social , Inquéritos e Questionários
12.
Thorax ; 70(11): 1054-61, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26310452

RESUMO

BACKGROUND: Compliance with continuous positive airway pressure (CPAP) therapy is essential in patients with obstructive sleep apnoea (OSA), but adequate control is not always possible. This is clinically important because CPAP can reverse the morbidity and mortality associated with OSA. Telemedicine, with support provided via a web platform and video conferences, could represent a cost-effective alternative to standard care management. AIM: To assess the telemedicine impact on treatment compliance, cost-effectiveness and improvement in quality of life (QoL) when compared with traditional face-to-face follow-up. METHODS: A randomised controlled trial was performed to compare a telemedicine-based CPAP follow-up strategy with standard face-to-face management. Consecutive OSA patients requiring CPAP treatment, with sufficient internet skills and who agreed to participate, were enrolled. They were followed-up at 1, 3 and 6 months and answered surveys about sleep, CPAP side effects and lifestyle. We compared CPAP compliance, cost-effectiveness and QoL between the beginning and the end of the study. A Bayesian cost-effectiveness analysis with non-informative priors was performed. RESULTS: We randomised 139 patients. At 6 months, we found similar levels of CPAP compliance, and improved daytime sleepiness, QoL, side effects and degree of satisfaction in both groups. Despite requiring more visits, the telemedicine group was more cost-effective: costs were lower and differences in effectiveness were not relevant. CONCLUSIONS: A telemedicine-based strategy for the follow-up of CPAP treatment in patients with OSA was as effective as standard hospital-based care in terms of CPAP compliance and symptom improvement, with comparable side effects and satisfaction rates. The telemedicine-based strategy had lower total costs due to savings on transport and less lost productivity (indirect costs). TRIAL REGISTER NUMBER: NCT01716676.


Assuntos
Teorema de Bayes , Pressão Positiva Contínua nas Vias Aéreas/economia , Gerenciamento Clínico , Apneia Obstrutiva do Sono/terapia , Telemedicina/métodos , Pressão Positiva Contínua nas Vias Aéreas/métodos , Análise Custo-Benefício , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Qualidade de Vida , Sono , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/psicologia , Telemedicina/economia
13.
Gastroenterol Hepatol ; 38(8): 484-90, 2015 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-25843813

RESUMO

INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Numerous studies have reported the association between GIST and other neoplasms. OBJECTIVES: The aim of this study was to investigate the possible association between GIST and other tumors in a genetically isolated population. METHODS: A retrospective study was conducted of patients with GIST between 2002 and 2009 at our center. Epidemiological, pathological and family data in patients with GIST alone (group A) were compared with those in patients with GIST associated with other neoplasms (group B). A possible common genetic mechanism was investigated between GIST and associated malignancies by testing the detection of the immunohistochemical marker, CD117, in all tumors. RESULTS: Twenty-two patients with GIST were identified, 10 in group A (45%) and 12 in group B (55%). In group B, the associated tumor was malignant in 6 patients (50%) and benign in another 6 (50%). Of the 22 patients with GIST, 8 (36%) had a family history of malignancies. Of these 8 patients, 7 (87.5%) were in group B (p=0.03) and 3 (37.5%) showed the same pathological type of neoplasm as their relatives. All GIST were positive for CD117 whereas associated malignancies were negative for this marker. CONCLUSION: We did not find immunohistochemical positivity for CD117 in malignancies associated with GIST. Given the special characteristics of the study population, the association between GIST and associated malignancies may be incidental.


Assuntos
Neoplasias Gastrointestinais/genética , Tumores do Estroma Gastrointestinal/genética , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Saúde da Família , Feminino , Efeito Fundador , Neoplasias Gastrointestinais/química , Neoplasias Gastrointestinais/etnologia , Tumores do Estroma Gastrointestinal/química , Tumores do Estroma Gastrointestinal/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/análise , Neoplasias Primárias Múltiplas/etnologia , Neoplasias Primárias Múltiplas/genética , Segunda Neoplasia Primária/etnologia , Segunda Neoplasia Primária/genética , Proteínas Proto-Oncogênicas c-kit/análise , Estudos Retrospectivos , Espanha/epidemiologia
14.
Epidemiologia (Basel) ; 5(2): 167-186, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38651389

RESUMO

Our goal was to determine the cellular immune response (CIR) in a sample of the Borriana COVID-19 cohort (Spain) to identify associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals aged 18 and older, including 36 individuals naïve to the SARS-CoV-2 infection and 189 infected patients. We employed flow-cytometry-based immunoassays for intracellular cytokine staining, using Wuhan and BA.2 antigens, and chemiluminescence microparticle immunoassay to detect SARS-CoV-2 antibodies. Logistic regression models were applied. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3%, respectively. No difference in CIR was found between naïve and infected patients. Patients who experienced sequelae exhibited a higher CIR than those without. A positive correlation was observed between TCR and anti-spike IgG levels. Factors positively associated with the TCR included blood group A, number of SARS-CoV-2 vaccine doses received, and anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and blood group B. These findings contribute valuable insights into the nuanced immune landscape shaped by SARS-CoV-2 infection and vaccination.

15.
Artigo em Inglês | MEDLINE | ID: mdl-36767805

RESUMO

Although gender roles have continued to evolve, stereotypical perceptions about men and women persist. From a traditional perspective, men are viewed as aggressive, competitive, and dominant, whereas women are expected to be pretty, affectionate, and passive. The relevance of gender stereotypes lies in the way such expectations reinforce gender inequality and discrimination. Gender stereotyping is also linked to an increased acceptance of gender-based violence, as such conceptions are based on the premise that women are subordinate to men. The current study uses data from the Barometer on Youth and Gender, conducted by the Centro Reina Sofía in 2021 (N = 1201), to analyze the potential associations among gender stereotyping, support for feminism, and acceptance of gender-based violence among young people in Spain (15-29 years old). The results show that young people ascribe, to some extent, stereotypical characteristics to women and men and point to the existence of gender-based occupational stereotypes. Our results shed light on the role that gender stereotyping plays in support for feminism and the acceptance of gender-based violence. They also provide valuable information about the magnitude of gender-stereotypical perceptions among young men and women.


Assuntos
Violência de Gênero , Estereotipagem , Masculino , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Feminismo , Agressão , Espanha , Identidade de Gênero
16.
J Neuroimmunol ; 383: 578179, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37657130

RESUMO

The 2020-21 West Nile Virus (WNV) outbreak in Andalusia, Spain, was the largest reported in the country, with eight cases of West Nile Neuroinvasive Disease (WNND) diagnosed in a tertiary hospital. Diagnosis of WNND is based on detecting WNV RNA, viral isolation, or demonstrating a specific immune response against the virus, with additional tests used to support the diagnosis. Treatment remains supportive, with variable outcomes. The potential efficacy of plasma exchange (PLEX) in select cases raises the possibility of an autoimmune component secondary to infectious pathology of the central nervous system. The influence of climate change on the expansion of WNV into new regions is a significant concern. It is crucial for physicians practicing in high-risk areas to be knowledgeable about the disease for early prevention and effective control measures.


Assuntos
Febre do Nilo Ocidental , Vírus do Nilo Ocidental , Humanos , Vírus do Nilo Ocidental/genética , Febre do Nilo Ocidental/epidemiologia , Febre do Nilo Ocidental/diagnóstico , Espanha/epidemiologia , Sistema Nervoso Central/patologia , Surtos de Doenças
17.
Environ Pollut ; 337: 122551, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37714400

RESUMO

Outdoor air pollution is responsible for the exacerbation of respiratory diseases in humans. Particulate matter with an aerodynamic diameter ≤2.5 µm (PM2.5) is one of the main components of outdoor air pollution, and solvent extracted organic matter (SEOM) is adsorbed to the main PM2.5 core. Some of the biological effects of black carbon and polycyclic aromatic hydrocarbons, which are components of PM2.5, are known, but the response of respiratory cell lineages to SEOM exposure has not been described until now. The aim of this study was to obtain SEOM from PM2.5 and analyze the molecular and proteomic effects on human type II pneumocytes. PM2.5 was collected from Mexico City in the wildfire season and the SEOM was characterized to be exposed on human type II pneumocytes. The effects were compared with benzo [a] pyrene (B[a]P) and hydrogen peroxide (H2O2). The results showed that SEOM induced a decrease in surfactant and deregulation in the molecular protein and lipid pattern analyzed by reflection-Fourier transform infrared (ATR-FTIR) spectroscopy on human type II pneumocytes after 24 h. The molecular alterations induced by SEOM were not shared by those induced by B[a]P nor H2O2, which highlights specific SEOM effects. In addition, proteomic patterns by quantitative MS analysis revealed a downregulation of 171 proteins and upregulation of 134 proteins analyzed in the STRING database. The deregulation was associated with positive regulation of apoptotic clearance, removal of superoxide radicals, and positive regulation of heterotypic cell-cell adhesion processes, while ATP metabolism, nucleotide process, and cellular metabolism were also affected. Through this study, we conclude that SEOM extracted from PM2.5 exerts alterations in molecular patterns of protein and lipids, surfactant expression, and deregulation of metabolic pathways of type II pneumocytes after 24 h of exposure in absence of cytotoxicity, which warns about apparent SEOM silent effects.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Células Epiteliais Alveolares/química , Peróxido de Hidrogênio/análise , Proteômica , Monitoramento Ambiental/métodos , Poluição do Ar/análise , Material Particulado/toxicidade , Material Particulado/análise , Tensoativos/análise
18.
Skin Appendage Disord ; 9(2): 147-150, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36937164

RESUMO

Introduction: Although Hutchinson's sign can appear associated with benign conditions, dermoscopic findings of non-melanoma eponychium pigmentation have not yet been described in the literature. We report for the first time to our knowledge the dermoscopic findings of an acral nevus located in the proximal nail fold as well as its clinical-dermoscopic-histologic correlation. Case Report: A twenty-year-old patient presented with a homogeneous longitudinal melanonychia on the left-hand thumb, with benign dermoscopic pattern, and an irregular, 6-mm, dark-brown hyperpigmented macule on the adjacent eponychium (Hutchinson's sign). The eponychium lesion showed on dermoscopy two irregular brown-black pigmented blotches, with superimposed parallel brown lines on a brushy distribution, with a thicker terminal end. The histopathologic examination of the proximal nail fold was performed, revealing scattered nevus cells in the epidermal basal layer and dermal-epidermal junction thecae, without any atypia or mitosis. These features were consistent with nevus of the proximal nail fold. Discussion: Previous descriptions of benign hyponychium's pigmentations, despite the malignant appearance of the overlying melanonychia, were reported to have a similar dermoscopic pattern, known as longitudinal brushy pigmentation. This newly described dermoscopic sign on the eponychium may help distinguish Hutchinson's sign related to subungual melanoma to non-melanoma Hutchinson's sign.

19.
Surgery ; 174(3): 492-501, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37385866

RESUMO

BACKGROUND: To assess short- and long-term outcomes from non-surgical management of diverticulitis with abscess formation and to develop a nomogram to predict emergency surgery. METHODS: This nationwide retrospective cohort study was performed in 29 Spanish referral centers, including patients with a first episode of a diverticular abscess (modified Hinchey Ib-II) from 2015 to 2019. Emergency surgery, complications, and recurrent episodes were analyzed. Regression analysis was used to assess risk factors, and a nomogram for emergency surgery was designed. RESULTS: Overall, 1,395 patients were included (1,078 Hinchey Ib and 317 Hinchey II). Most (1,184, 84.9%) patients were treated with antibiotics without percutaneous drainage, and 194 (13.90%) patients required emergency surgery during admission. Percutaneous drainage (208 patients) was associated with a lower risk of emergency surgery in patients with abscesses of ≥5 cm (19.9% vs 29.3%, P = .035; odds ratio 0.59 [0.37-0.96]). The multivariate analysis showed that immunosuppression treatment, C-reactive protein (odds ratio: 1.003; 1.001-1.005), free pneumoperitoneum (odds ratio: 3.01; 2.04-4.44), Hinchey II (odds ratio: 2.15; 1.42-3.26), abscess size 3 to 4.9 cm (odds ratio: 1.87; 1.06-3.29), abscess size ≥5 cm (odds ratio: 3.62; 2.08-6.32), and use of morphine (odds ratio: 3.68; 2.29-5.92) were associated with emergency surgery. A nomogram was developed with an area under the receiver operating characteristic curve of 0.81 (95% confidence interval: 0.77-0.85). CONCLUSION: Percutaneous drainage must be considered in abscesses ≥5 cm to reduce emergency surgery rates; however, there are insufficient data to recommend it in smaller abscesses. The use of the nomogram could help the surgeon develop a targeted approach.


Assuntos
Abscesso Abdominal , Diverticulite , Humanos , Abscesso/cirurgia , Abscesso/complicações , Estudos Retrospectivos , Abscesso Abdominal/etiologia , Abscesso Abdominal/terapia , Nomogramas , Diverticulite/cirurgia , Drenagem/efeitos adversos
20.
Epidemiologia (Basel) ; 4(1): 63-73, 2023 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-36810454

RESUMO

Our objective was to estimate the incidence of COVID-19 and the ABO blood Groups in the mass-gathering events (MGEs) during the Falles Festival in Borriana (Spain) from 6-10 March 2020. We conducted a population-based retrospective cohort study and measured anti-SARS-CoV-2 antibodies and the ABO of participants. We performed laboratory COVID-19 tests and obtained the ABO in 775 subjects (72.8% of the original exposed cohort): O-group (45.2%), A-group (43.1%), B-group (8.5%) and AB-group (3.4%). Adjusted for confounding factors, including COVID-19 exposure during the MGEs, attack rates of COVID-19 for each ABO group were 55.4%, 59.6%, 60.2%, and 63.7%. The adjusted relative risks were for O-group 0.93 (95% Confidence Interval [CI] 0.83-1.04), for A-group 1.06 (95% CI 0.94-1.18), for B-group 1.04 (95%CI 0.88-1.24), and for AB-group 1.11 (95% CI 0.81-1.51) with no significant differences. Conclusions: Our results suggest no effect of ABO on COVID-19 incidence. We observed weak but not significant protection of the O-group and not a significantly greater infection risk for the remaining groups compared with the O-group. More studies are needed to resolve the controversies regarding the association between ABO and COVID-19.

SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa