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1.
JCO Precis Oncol ; 8: e2300713, 2024 May.
Article in English | MEDLINE | ID: mdl-38810175

ABSTRACT

PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.


Subject(s)
Protein Kinase Inhibitors , Pyrazoles , Humans , Child , Male , Female , Adolescent , Pyrazoles/therapeutic use , Child, Preschool , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Receptor, trkA/genetics , Receptor, trkA/antagonists & inhibitors , Brain Neoplasms/drug therapy , Brain Neoplasms/genetics , Sarcoma/drug therapy , Sarcoma/genetics , Neuroblastoma/drug therapy , Neuroblastoma/genetics , Infant , Receptor, trkB/genetics , Receptor, trkC/genetics , Clinical Trials as Topic
2.
Am J Physiol Cell Physiol ; 326(4): C1203-C1211, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38581656

ABSTRACT

Cardiometabolic diseases are often associated with heightened levels of angiotensin II (Ang II), which accounts for the observed oxidative stress, inflammation, and fibrosis. Accumulating evidence indicates a parallel upregulation of dipeptidyl dipeptidase 4 (DPP4) activity in cardiometabolic diseases, with its inhibition shown to mitigate oxidative stress, inflammation, and fibrosis. These findings highlight an overlap between the pathophysiological mechanisms used by Ang II and DPP4. Recent evidence demonstrates that targeted inhibition of DPP4 prevents the rise in Ang II and its associated molecules in experimental models of cardiometabolic diseases. Similarly, inhibitors of the angiotensin I-converting enzyme (ACE) or Ang II type 1 receptor (AT1R) blockers downregulate DPP4 activity, establishing a bidirectional relationship between DPP4 and Ang II. Here, we discuss the current evidence supporting the cross talk between Ang II and DPP4, along with the potential mechanisms promoting this cross regulation. A comprehensive analysis of this bidirectional relationship across tissues will advance our understanding of how DPP4 and Ang II collectively promote the development and progression of cardiometabolic diseases.


Subject(s)
Angiotensin II , Cardiovascular Diseases , Humans , Dipeptidyl Peptidase 4 , Peptidyl-Dipeptidase A , Receptor, Angiotensin, Type 1 , Inflammation , Fibrosis , Angiotensin I
3.
Nutrients ; 16(8)2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38674787

ABSTRACT

Given the changes in the digestive tract post-bariatric surgery, adapting to a new pattern of eating behavior becomes crucial, with special attention to the specifics of chewing mechanics. This study aimed to investigate the association between self-perception of chewing, chewing behavior, and the presence of gastrointestinal symptoms in preoperative patients undergoing bariatric surgery. Sixty adult candidates for bariatric surgery at a public hospital in Belém (Brazil) were analyzed. Participants predominantly exhibited unilateral chewing patterns (91.6%), a fast chewing rhythm (73.3%), a large food bolus (80%), liquid intake during meals (36.7%), and 41.7% reported that chewing could cause some issue. Significant associations were found between the perception of causing problems and chewing scarcity (p = 0.006), diarrhea (p = 0.004), absence of slow chewing (p = 0.048), and frequent cutting of food with front teeth (p = 0.034). These findings reveal a relationship between the perception of chewing problems and chewing scarcity, presence of diarrhea, and fast chewing.


Subject(s)
Bariatric Surgery , Mastication , Self Concept , Humans , Female , Male , Adult , Middle Aged , Feeding Behavior/psychology , Gastrointestinal Diseases/psychology , Gastrointestinal Diseases/etiology , Diarrhea/etiology , Brazil , Cross-Sectional Studies , Obesity, Morbid/surgery , Obesity, Morbid/psychology
4.
Am J Physiol Cell Physiol ; 326(6): C1573-C1589, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38557357

ABSTRACT

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) reduce blood pressure (BP) in patients with hypertension, yet the precise molecular mechanisms remain elusive. SGLT2i inhibits proximal tubule (PT) NHE3-mediated sodium reabsorption in normotensive rodents, yet no hypotensive effect is observed under this scenario. This study examined the effect of empagliflozin (EMPA) on renal tubular sodium transport in normotensive and spontaneously hypertensive rats (SHRs). It also tested the hypothesis that EMPA-mediated PT NHE3 inhibition in normotensive rats is associated with upregulation of distal nephron apical sodium transporters. EMPA administration for 14 days reduced BP in 12-wk-old SHRs but not in age-matched Wistar rats. PT NHE3 activity was inhibited by EMPA treatment in both Wistar and SHRs. In Wistar rats, EMPA increased NCC activity, mRNA expression, protein abundance, and phosphorylation levels, but not in SHRs. SHRs showed higher NKCC2 activity and an abundance of cleaved ENaC α and γ subunits compared with Wistar rats, none of which were affected by EMPA. Another set of male Wistar rats was treated with EMPA, the NCC inhibitor hydrochlorothiazide (HCTZ), and EMPA combined with HCTZ or vehicle for 14 days. In these rats, BP reduction was observed only with combined EMPA and HCTZ treatment, not with either drug alone. These findings suggest that NCC upregulation counteracts EMPA-mediated inhibition of PT NHE3 in male normotensive rats, maintaining their baseline BP. Moreover, the reduction of NHE3 activity without further upregulation of major apical sodium transporters beyond the PT may contribute to the BP-lowering effect of SGLT2i in experimental models and patients with hypertension.NEW & NOTEWORTHY This study suggests that reduced NHE3-mediated sodium reabsorption in the renal proximal tubule may account, at least in part, for the BP-lowering effect of SGLT2 inhibitors in the setting of hypertension. It also demonstrates that chronic treatment with SGLT2 inhibitors upregulates NCC activity, phosphorylation, and expression in the distal tubule of normotensive but not hypertensive rats. SGLT2 inhibitor-mediated upregulation of NCC seems crucial to counteract proximal tubule natriuresis in subjects with normal BP.


Subject(s)
Benzhydryl Compounds , Glucosides , Hypertension , Rats, Inbred SHR , Rats, Wistar , Sodium-Glucose Transporter 2 Inhibitors , Sodium-Hydrogen Exchanger 3 , Up-Regulation , Animals , Male , Sodium-Hydrogen Exchanger 3/metabolism , Sodium-Hydrogen Exchanger 3/genetics , Sodium-Hydrogen Exchanger 3/antagonists & inhibitors , Hypertension/drug therapy , Hypertension/metabolism , Hypertension/physiopathology , Glucosides/pharmacology , Benzhydryl Compounds/pharmacology , Up-Regulation/drug effects , Rats , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Blood Pressure/drug effects , Solute Carrier Family 12, Member 3/metabolism , Solute Carrier Family 12, Member 3/genetics , Kidney Tubules, Proximal/drug effects , Kidney Tubules, Proximal/metabolism , Kidney/metabolism , Kidney/drug effects
5.
Res Sq ; 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38410476

ABSTRACT

Clinical data revealed that KRAS mutant tumors, while initially sensitive to treatment, rapidly bypass KRAS dependence to acquire a drug-tolerant phenotype. However, the mechanisms underlying the transition from a drug-sensitive to a drug-tolerant state still elude us. Here, we show that global chromatin reorganization is a recurrent and specific feature of KRAS-dependent cells that tolerated KRAS silencing. We show that KRAS-dependent cells undergo G0/G1 cell cycle arrest after KRAS silencing, presenting a transcriptomic signature of quiescence. Proteomic analysis showed upregulated chromatin-associated proteins and transcription-associated biological processes. Accordingly, these cells shifted euchromatin/heterochromatin states, gained topologically associating domains, and altered the nanoscale physical organization of chromatin, more precisely by downregulating chromatin packing domains, a feature associated with the induction of quiescence. In addition, they also accumulated transcriptional alterations over time leading to a diversification of biological processes, linking chromatin alterations to transcriptional performance. Overall, our observations pinpoint a novel molecular mechanism of tolerance to KRAS oncogenic loss driven not by specific gene alterations but by global reorganization of genomic information, in which cells transition chromatin domain structure towards a more quiescent state and gain transcriptional reprogramming capacity.

6.
Rev Enferm UFPI ; 12(1): e3902, 2023-12-12. tab
Article in English, Portuguese | LILACS, BDENF - Nursing | ID: biblio-1525434

ABSTRACT

Objetivo: Analisar as estratégias de treinamento em segurança do paciente para profissionais de saúde no contexto da atenção primária. Métodos: Trata-se de uma revisão integrativa conduzida nas bases de dados Medical Literature Analysis and Retrieval System Online, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Base de Dados de Enfermagem, Web of Sciencee Scopus, com os descritores "Capacitação Profissional", "Segurança do Paciente" e "Atenção Primária à Saúde". Resultados: Foram identificados 390 estudos nas bases de dados, os quais resultaram em uma amostra final de seis artigos para a composição da revisão. Estes foram publicados entre os anos de 2017 e 2019, desenvolvidos em países da Europa, da América do Norte e Oceania. Conclusão: Descaram-se como estratégias de treinamento os seguintes itens: workshop, implementação de programa de segurança medicamentosa, identificação de fatores-chave para elevação da qualidade, feedback e aprendizagem através de erros. Descritores: Capacitação Profissional; Atenção Primária à Saúde; Segurança do Paciente; Pessoal de Saúde


Objective: To analyze patient safety training strategies for health professionals in the context of primary care.Methods: This is an integrative review conducted in the Medical Literature Analysis and Retrieval System Online, Latin American and Caribbean Center on Health Sciences Information, Base de Dados de Enfermagem, Web of Science and Scopus databases, with the descriptors "Professional Training", "Patient Safety" and "Primary Health Care". Results: A total of 390 studies were identified in the databases, which resulted in a final sample of six articles for the composition of the review. These were published between the years 2017 and 2019, developed in countries in Europe, North America and Oceania. Conclusion: The following items were described as training strategies: workshop, implementation of a medication safety program, identification of key factors for quality improvement, feedback and learning through errors.Descriptors:Professional Training; Primary Health Care; Patient Safety; Health Personnel


Subject(s)
Primary Health Care , Health Personnel , Professional Training , Patient Safety
7.
Front Oncol ; 13: 1237170, 2023.
Article in English | MEDLINE | ID: mdl-37746264

ABSTRACT

Purpose: Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%-90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics. Methods: A total of 266 medulloblastomas from seven different institutions from Brazil (n=211), Portugal (n=38), and Argentina (n=17) were evaluated. Following RNA and DNA isolation from formalin-fixed, paraffin-embedded (FFPE) tumor tissues, the molecular classification and CTNNB1 mutation analysis were performed by nCounter and Sanger sequencing, respectively. Results: WNT-activated medulloblastomas accounted for 15% (40/266) of the series. We observed that 73% of WNT-activated medulloblastomas harbored CTNNB1 mutations. CTNNB1 wild-type cases (27%) were more prevalent in female individuals and suggested to be associated with a worse outcome. Among the CTNNB1 wild-type cases, the available analysis of family history revealed two cases with familiar adenomatous polyposis, harboring APC germline variants. Conclusion: We observed a lower incidence of CTNNB1 mutations in WNT-activated medulloblastomas in our Latin-Iberian cohort compared to frequencies previously described in other populations. Considering that CTNNB1 wild-type cases may exhibit APC germline mutations, our study suggests a higher incidence (~30%) of hereditary WNT-activated medulloblastomas in the Latin-Iberian population.

8.
Microbiol Res ; 277: 127503, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37748260

ABSTRACT

Many pathogenic organisms need to reach either an intracellular compartment or the cytoplasm of a target cell for their survival, replication or immune system evasion. Intracellular pathogens frequently penetrate into the cell through the endocytic and phagocytic pathways (clathrin-mediated endocytosis, phagocytosis and macropinocytosis) that culminates in fusion with lysosomes. However, several mechanisms are triggered by pathogenic microorganisms - protozoan, bacteria, virus and fungus - to avoid destruction by lysosome fusion, such as rupture of the phagosome and thereby release into the cytoplasm, avoidance of autophagy, delaying in both phagolysosome biogenesis and phagosomal maturation and survival/replication inside the phagolysosome. Here we reviewed the main data dealing with phagosome maturation and evasion from lysosomal killing by different bacteria, protozoa, fungi and virus.


Subject(s)
Lysosomes , Phagocytosis , Lysosomes/microbiology , Phagosomes/metabolism , Phagosomes/microbiology , Endocytosis , Immune Evasion
9.
Front Immunol ; 14: 1175275, 2023.
Article in English | MEDLINE | ID: mdl-37275853

ABSTRACT

Ethanol abuse is a risk factor for the development of pneumonia caused by Streptococcus pneumoniae, a critical pathogen for public health. The aim of this article was to investigate the inflammatory mechanisms involved in pneumococcal pneumonia that may be associated with chronic ethanol exposure. Male C57BL6/J-Unib mice were exposed to 20% (v/v) ethanol for twelve weeks and intranasally infected with 5x104 CFU of S. pneumoniae. Twenty-four hours after infection, lungs, bronchoalveolar lavage and blood samples were obtained to assess the consequences of chronic ethanol exposure during infection. Alcohol-fed mice showed increased production of nitric oxide and CXCL1 in alveoli and plasma during pneumococcal pneumonia. Beside this, ethanol-treated mice exhibited a decrease in leukocyte infiltration into the alveoli and reduced frequency of severe lung inflammation, which was associated with an increase in bacterial load. Curiously, no changes were observed in survival after infection. Taken together, these results demonstrate that chronic ethanol exposure alters the inflammatory response during S. pneumoniae lung infection in mice with a reduction in the inflammatory infiltrate even in the presence of higher levels of the chemoattractant CXCL1.


Subject(s)
Pneumonia, Pneumococcal , Male , Mice , Animals , Pneumonia, Pneumococcal/microbiology , Ethanol/adverse effects , Nitric Oxide , Bronchoalveolar Lavage Fluid , Streptococcus pneumoniae , Leukocytes
10.
Front Immunol ; 14: 1128352, 2023.
Article in English | MEDLINE | ID: mdl-37090737

ABSTRACT

Introduction: People with hazardous alcohol use are more susceptible to viral, bacterial, and fungal infections due to the effect of alcohol on immune system cell function. Metabolized ethanol reduces NAD+ to NADH, affecting critical metabolic pathways. Here, our aim was to investigate whether alcohol is metabolized by bone marrow cells and if it impacts the metabolic pathways of leukocyte progenitor cells. This is said to lead to a qualitative and quantitative alteration of key metabolites which may be related to the immune response. Methods: We addressed this aim by using C57BL/6 mice under chronic ethanol administration and evaluating the metabolomic profile of bone marrow total cells by gas chromatography-coupled mass spectrometry (GC-MS). Results: We identified 19 metabolites. Our data demonstrated that chronic ethanol administration alters the metabolomic profile in the bone marrow, resulting in a statistically diminished abundance of five metabolites in ethanol-treated animals: uracil, succinate, proline, nicotinamide, and tyrosine. Discussion: Our results demonstrate for the first time in the literature the effects of alcohol consumption on the metabolome content of hematopoietic tissue and open a wide range of further studies to investigate mechanisms by which alcohol compromises the cellular function of the immune system.


Subject(s)
Bone Marrow , Ethanol , Mice , Animals , Mice, Inbred C57BL , Ethanol/pharmacology , Metabolomics/methods , Metabolome
11.
Cells ; 11(16)2022 08 11.
Article in English | MEDLINE | ID: mdl-36010567

ABSTRACT

KRAS mutations have been shown to extend their oncogenic effects beyond the cancer cell, influencing the tumor microenvironment. Herein, we studied the impact of mutant KRAS on the modulation of the pro-tumorigenic properties of cancer-associated fibroblasts (CAFs), including α-SMA expression, TGFß1 and HGF production, extracellular matrix components and metalloproteinases expression as well as collagen contraction and migration capacities. To do so, CCD-18Co normal-like colon fibroblasts were challenged with conditioned media from control and KRAS silenced colorectal cancer (CRC) cells. Our results showed that the mutant KRAS CRC cell-secreted factors were capable of turning normal-like fibroblasts into CAF-like by modulating the α-SMA expression, TGFß1 and HGF production and migration capacity. Oncogenic KRAS played a secondary role as its silencing did not completely impair the capacity of CRC cells to modulate most of the fibroblast properties analyzed. In summary, our work suggests that mutant KRAS does not play a major role in controlling the CRC cell-secreted factors that modulate the behavior of fibroblasts. The fact that CRC cells retain the capacity to modulate the pro-tumorigenic features of fibroblasts independently of KRAS silencing is likely to negatively impact their response to KRAS inhibitors, thus standing as a putative mechanism of resistance to KRAS inhibition with potential therapeutical relevance.


Subject(s)
Cancer-Associated Fibroblasts , Colorectal Neoplasms , Cancer-Associated Fibroblasts/metabolism , Carcinogenesis/pathology , Colorectal Neoplasms/pathology , Fibroblasts/metabolism , Humans , Phenotype , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Tumor Microenvironment
12.
Cells ; 11(13)2022 06 21.
Article in English | MEDLINE | ID: mdl-35805073

ABSTRACT

Understanding how mutant KRAS signaling is modulated by exogenous stimuli is of utmost importance to elucidate resistance mechanisms underlying pathway inhibition failure, and to uncover novel therapeutic targets for mutant KRAS patients. Hence, aiming at perceiving KRAS-autonomous versus -non autonomous mechanisms, we studied the response of two mutant KRAS colorectal cancer cell lines (HCT116 and LS174T) upon KRAS silencing and treatment with rhTGFß1-activated fibroblasts secretome. A proteomic analysis revealed that rhTGFß1-activated fibroblast-secreted factors triggered cell line-specific proteome alterations and that mutant KRAS governs 43% and 38% of these alterations in HCT116 and LS174T cells, respectively. These KRAS-dependent proteins were localized and displayed molecular functions that were common to both cell lines (e.g., extracellular exosome, RNA binding functions). Moreover, 67% and 78% of the KRAS-associated proteome of HCT116 and LS174T cells, respectively, was controlled in a KRAS-non-autonomous manner, being dependent on fibroblast-secreted factors. In HCT116 cells, KRAS-non-autonomously controlled proteins were mainly involved in proteoglycans in cancer, p53, and Rap1 signaling pathways; whereas in LS174T cells, they were associated with substrate adhesion-dependent cell-spreading and involved in metabolic processes. This work highlights the context-dependency of KRAS-associated signaling and reinforces the importance of integrating the tumor microenvironment in the study of KRAS-associated effects.


Subject(s)
Colorectal Neoplasms , Proteome , Cell Line, Tumor , Colorectal Neoplasms/pathology , Humans , Mutation/genetics , Proteome/metabolism , Proteomics , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Tumor Microenvironment
13.
Life Sci ; 305: 120757, 2022 Sep 15.
Article in English | MEDLINE | ID: mdl-35780844

ABSTRACT

AIMS: Emerging evidence suggests the existence of a crosstalk between dipeptidyl peptidase 4 (DPP4) and the renin-angiotensin system (RAS). Therefore, combined inhibition of DPP4 and RAS may produce similar pharmacological effects rather than being additive. This study tested the hypothesis that combining an inhibitor of DPP4 with an angiotensin II (Ang II) receptor blocker does not provide additional cardioprotection compared to monotherapy in heart failure (HF) rats. MAIN METHODS: Male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were assigned into four groups and received vehicle (water), vildagliptin, valsartan, or both drugs, for four weeks by oral gavage. KEY FINDINGS: Vildagliptin and valsartan in monotherapy reduced LV hypertrophy, alleviated cardiac interstitial fibrosis, and improved systolic and diastolic function in HF rats, with no additional effect of combination treatment. HF rats displayed higher cardiac and serum DPP4 activity and abundance than sham. Surprisingly, not only vildagliptin but also valsartan in monotherapy downregulated the catalytic function and expression levels of systemic and cardiac DPP4. Moreover, vildagliptin and valsartan alone or in combination comparably upregulate the components of the cardiac ACE2/Ang-(1-7)/MasR while downregulating the ACE/Ang II/AT1R axis. SIGNIFICANCE: Vildagliptin or valsartan alone is as effective as combined to treat cardiac dysfunction and remodeling in experimental HF. DPP4 inhibition downregulates classic RAS components, and pharmacological RAS blockade downregulates DPP4 in the heart and serum of HF rats. This interplay between DPP4 and RAS may affect HF progression and pharmacotherapy.


Subject(s)
Dipeptidyl Peptidase 4 , Heart Failure , Animals , Dipeptidyl Peptidase 4/metabolism , Heart Failure/drug therapy , Male , Rats , Rats, Wistar , Renin-Angiotensin System , Valsartan/pharmacology , Valsartan/therapeutic use , Vildagliptin/pharmacology , Vildagliptin/therapeutic use
14.
Int J Cancer ; 151(10): 1810-1823, 2022 11 15.
Article in English | MEDLINE | ID: mdl-35869872

ABSTRACT

Genetic alterations influence the malignant potential of cancer cells, and so does the tumor microenvironment. Herein, we combined the study of KRAS oncogenic effects in colorectal cancer cells with the influence of fibroblast-derived factors. Results revealed that mutant KRAS regulates cell fate through both autonomous and nonautonomous signaling mechanisms. Specifically, processes such as proliferation and cell-cell aggregation were autonomously controlled by mutant KRAS independently of the stimulation with fibroblasts conditioned media. However, cancer cell invasion revealed to be a KRAS-dependent nonautonomous effect, resulting from the cooperation between fibroblast-derived HGF and mutant KRAS regulation of C-MET expression. C-MET downregulation upon KRAS silencing rendered cells less responsive to HGF and thus less invasive. Yet, in one cell line, KRAS inhibition triggered invasion upon stimulation with fibroblasts conditioned media. Inhibition of PIK3CA oncogene did not promote invasion, thus showing a KRAS-specific effect. Moreover, the invasive capacity also depended on the HGF-C-MET axis. Overall, our study awards oncogenic KRAS an important role in modulating the response to fibroblast-secreted factors either by promoting or impairing invasion, and depicts the HGF-C-MET axis as a putative therapeutic target to impair the invasive properties of mutant KRAS cancer cells.


Subject(s)
Colorectal Neoplasms , Hepatocyte Growth Factor , Cell Line, Tumor , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Colorectal Neoplasms/pathology , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Fibroblasts/pathology , Hepatocyte Growth Factor/genetics , Hepatocyte Growth Factor/metabolism , Humans , Proto-Oncogene Proteins c-met/genetics , Proto-Oncogene Proteins c-met/metabolism , Proto-Oncogene Proteins p21(ras)/genetics , Proto-Oncogene Proteins p21(ras)/metabolism , Tumor Microenvironment
15.
Front Cell Infect Microbiol ; 12: 898619, 2022.
Article in English | MEDLINE | ID: mdl-35719346

ABSTRACT

Aspergillus fumigatus is a ubiquitous and saprophytic filamentous fungus and the main etiologic agent of aspergillosis. Infections caused by A. fumigatus culminate in a strong inflammatory response that can evolve into respiratory failure and may be lethal in immunocompromised individuals. In the last decades, it has been demonstrated that extracellular vesicles (EVs) elicit a notable biological response in immune cells. EVs carry a variety of biomolecules, therefore are considered potential antigen delivery vehicles. The role of EVs as a strategy for modulating an effective response against infections caused by A. fumigatus remains unexplored. Here we investigate the use of EVs derived from A. fumigatus as an immunization tool to induce a more robust immune response to A. fumigatus pulmonary infection. In order to investigate that, male C57BL/6 mice were immunized with two doses of EVs and infected with A. fumigatus. Pre-exposure of mice to EVs was able to induce the production of specific IgG serum for fungal antigens. Besides that, the immunization with EVs reduced the neutrophilic infiltrate into the alveoli, as well as the extravasation of total proteins and the production of proinflammatory mediators IL-1ß, IL-6, and CXCL-1. In addition, immunization prevented extensive lung tissue damage and also improved phagocytosis and fungus clearance. Noteworthy, immunization with EVs, associated with subclinical doses of Amphotericin B (AmB) treatment, rescued 50% of mice infected with A. fumigatus from lethal fungal pneumonia. Therefore, the present study shows a new role for A. fumigatus EVs as host inflammatory response modulators, suggesting their use as immunizing agents.


Subject(s)
Aspergillosis , Extracellular Vesicles , Pulmonary Aspergillosis , Animals , Aspergillus fumigatus , Disease Models, Animal , Male , Mice , Mice, Inbred C57BL
17.
Rev. Enferm. Atual In Derme ; 96(37): 1-14, Jan-Mar. 2022.
Article in Portuguese | BDENF - Nursing | ID: biblio-1378449

ABSTRACT

Objetivo: Analisar a literatura científica acerca da incidência de Lesão Por Esforço Repetitivo/Distúrbios Osteomusculares Relacionados ao Trabalho em trabalhadores de enfermagem e identificar as estratégias formuladas para a diminuição da sua incidência nos serviços de saúde. Método:Estudo do tipo revisão integrativa. A busca dos artigos ocorreuno período de janeiro a março de 2021, na Biblioteca Eletrônica Científica Online, na Biblioteca Virtual em Saúde e nas bases de dados Web of Science, Pubmed, Scopus, Cochrane e Cinahl. Resultados:Foram incluídos 21 artigos, os quais foram elencados em duas categorias, a saber:incidência de transtornos traumáticos cumulativos em profissionais de enfermagem eestratégias voltadas para a prevenção e/ou combate ao desenvolvimento de transtornos traumáticos cumulativos em profissionais de enfermagem. Os estudos expressaram umaelevada incidência de transtornos traumáticos cumulativos em profissionais de enfermagem, principalmente em auxiliares e técnicos, evidenciando o perfil e as dificuldades enfrentadas pelo trabalhador acometido com essas afecções.Poucos estudos foram incluídos nas estratégias de prevenção e/ou combate ao desenvolvimento desses transtornos, reforçando a necessidade de realização de estudos clínicos a fim de melhorias da ergonomia no ambiente laboral. Conclusão:As evidências destapesquisa contribuem para que os profissionais e os gestores dos serviços de saúde possam conhecer o conteúdo produzido na literatura acerca dos transtornos traumáticos cumulativos mais incidentes nos profissionais de enfermagem, possibilitando a formulação de intervenções direcionadas a sua prevenção e controle.


Objective: To analyze the scientific literature on the incidence of Repetitive Strain Injury/Work-Related Musculoskeletal Disorders in nursing workers and identify the strategies formulated to reduce its incidence in health services.Method: An integrative review study. The search for articles took place from January to March 2021, in the Online Scientific Electronic Library, in the Virtual Health Library and in the Web of Science, Pubmed, Scopus, Cochrane and Cinahl databases. Results: 21 articles were included, which were listed in two categories, namely: incidence of cumulative traumatic disorders in nursing professionals and strategies aimed at preventing and/or combating the development of cumulative traumatic disorders in nursing professionals. The studies expressed a high incidence of cumulative traumatic disorders innursing professionals, especially assistants and technicians, evidencing the profile and difficulties faced by workers affected by these conditions. Few studies were included in strategies to prevent and/or combat the development of these disorders, reinforcing the need to carry out clinical studies in order to improve ergonomics in the work environment.Conclusions:The evidence of this research contributes so that professionals and managers of health services can learn about the content produced in the literature about cumulative traumatic disorders most incidents in nursing professionals, enabling the formulation of interventions aimed at their prevention and control.


Objetivo: Analizar la literatura científica sobre la incidencia de Lesiones por Esfuerzo Repetitivo/Trastornos Musculoesqueléticos Relacionados con el Trabajo en trabajadores de enfermería e identificar las estrategias formuladas para reducir su incidencia en los servicios de salud. Método: Estudio de revisión integradora. La búsqueda de artículos se realizó de enero a marzo de 2021, en la Biblioteca Electrónica Científica en Línea, en la Biblioteca Virtual en Salud y en las bases de datos Web of Science, Pubmed, Scopus, Cochrane y Cinahl.Resultados: Se incluyeron 21 artículos, que fueron catalogados en dos categorías, a saber: incidencia de trastornos traumáticos acumulativos en profesionales de enfermería y estrategias dirigidas a prevenir y/o combatir el desarrollo de trastornos traumáticos acumulativos en profesionales de enfermería. Los estudios expresaron una alta incidencia de trastornos traumáticos acumulativos en los profesionales de enfermería, especialmente auxiliares y técnicos, evidenciando el perfil y las dificultades enfrentadas por los trabajadores afectados por esas condiciones. Pocos estudios se incluyeron en las estrategias para prevenir y/o combatir el desarrollo de estos trastornos, lo que refuerza la necesidad de realizar estudios clínicos para mejorar la ergonomía en el ambiente de trabajo. Conclusión: La evidencia de esta investigación contribuye para que los profesionales y gestores de los servicios de salud conozcan el contenido producido en la literatura sobre los trastornos traumáticos acumulativos más incidentes en los profesionales de enfermería, posibilitando la formulación de intervenciones dirigidas a su prevención y control.


Subject(s)
Humans , Male , Female , Cumulative Trauma Disorders , Incidence , Nursing , Health Strategies , Disease Prevention
18.
Rev. enferm. atenção saúde ; 11(1): 202249, jan.-abr. 2022. ilus.
Article in English, Spanish, Portuguese | BDENF - Nursing | ID: biblio-1381916

ABSTRACT

Objetivo: analisar a produção científica quanto a assistência de enfermagem ao paciente em uso de Cateter de Swan-Ganz e ao conhecimento dos enfermeiros relacionado a esse dispositivo. Método: revisão integrativa da literatura, com busca realizada no mês de junho e finalizada em julho de 2020, nas bases de dados da Web of Science, PubMed, LILACS e SCIELO. Resultados: Identificou-se nas produções científicas que para a prestação da assistência de enfermagem, torna-se importante a expertise do profissional em remover o cateter; o monitoramento da pressão arterial pulmonar; higienização da pele, curativo adicional, dentre outras ações. O conhecimento dos enfermeiros foi considerado insatisfatório e também foram relatadas dificuldades na interpretação das informações relacionadas ao uso do cateter. Conclusão: os cuidados de enfermagem ao paciente em uso deste cateter correspondem ao monitoramento e interpretação dos parâmetros, prevenção de infecção associada ao cateter e sua remoção. Evidencia-se dificuldades entre os enfermeiros na interpretação dos dados coletados, apontando a necessidade de aprimoramento dos conhecimentos (AU).


Objective: to analyze the scientific production regarding nursing care to patients using the Swan-Ganz catheter and nurses' knowledge about this device. Method: integrative literature review, with a search conducted in June and finalized in July 2020, in the Web of Science, PubMed, LILACS and SCIELO databases. Results: the sample comprised six studies, which were categorized according to the corpus of the study as: assistance regarding Swan-Ganz catheter care and nurses' knowledge about this device. It was identified in the scientific productions that for the provision of nursing care, it is important the professional's expertise to remove the catheter; the monitoring of pulmonary arterial pressure; the cleaning of the skin, additional dressing, among other actions. The nurses' knowledge was considered unsatisfactory, and difficulties in interpreting the information related to catheter use were also reported. Conclusion: nursing care to patients using this catheter corresponds to the monitoring and interpretation of parameters, prevention of infection associated with the catheter and its removal. Evidencia-se dificuldades entre os enfermeiros na interpretação dos dados coletados, apontando a necessidade de aprimoramento dos conhecimentos (AU).


Objetivo: analizar la producción científica sobre la atención del enfermero al paciente que usa catéter de Swan-Ganz y el conocimiento de los enfermeros relacionado con este dispositivo. Método: revisión integradora de la literatura, la búsqueda se realizó en junio y julio de 2020, en las bases de datos de Web of Science, PubMed, LILACS y SCIELO. Resultados: la muestra estuvo compuesta por seis estudios, que fueron categorizados según el corpus del estudio en: atención sobre cómo realizar los cuidados del catéter de Swan-Ganz y conocimiento de los enfermeros sobre este dispositivo. Se identificó en los resultados científicos que, para la atención sanitaria, es importante la experiencia del profesional en la remoción del catéter; el monitoreo de la presión arterial pulmonar; la higienización de la piel, un apósito adicional, entre otras cosas. El conocimiento de los enfermeros se consideró insatisfactorio y también se manifestaron dificultades para interpretar la información relacionada con el uso del catéter. Conclusión: la atención de enfermería al paciente que usa este catéter implica el monitoreo y la interpretación de los parámetros, la prevención de la infección asociada al catéter y su remoción. Se observó que los enfermeros tenían dificultades para interpretar los datos obtenidos y se señaló que es necesario que mejoren sus conocimientos (AU).


Subject(s)
Humans , Catheterization, Swan-Ganz , Knowledge , Nurses , Nursing Care
19.
Esc. Anna Nery Rev. Enferm ; 26: e20210455, 2022. tab
Article in Portuguese | LILACS, BDENF - Nursing | ID: biblio-1384924

ABSTRACT

RESUMO Objetivo avaliar o conhecimento, a atitude e a prática de universitários intercambistas provenientes do continente africano acerca das Infecções Sexualmente Transmissíveis. Método estudo transversal, realizado de dezembro de 2019 a março de 2020, em universidade pública internacional brasileira localizada no Ceará. A amostra foi constituída por 150 estudantes africanos de diferentes cursos de graduação. Utilizou-se do inquérito de Conhecimento, Atitude e Prática. Resultados os universitários apresentaram conhecimento satisfatório acerca da forma de transmissão das Infecções Sexualmente Transmissíveis, porém, com deficiências a respeito das hepatites virais. Identificou-se associação entre sexo e atitude acerca do uso de preservativo em relação sexual com parceria fixa (p=0,042). No que se refere às práticas, houve associação entre sexo e uso do preservativo na primeira relação sexual (p=0,001), ter mais que um parceiro (p=0,001) e mais que dez parceiros em toda a vida (0,007). No que se relaciona às práticas sexuais nos últimos 12 meses, observou-se associação estatística entre ter relações sexuais com mais de um parceiro sexual e sexo do participante (p=0,001). Conclusão e implicações para a prática enfatiza-se a importância de a universidade pesquisada realizar atividades de educação em saúde que abordem Infecções Sexualmente Transmissíveis, bem como de extensão universitária, que envolvam alunos imigrantes africanos.


RESUMEN Objetivo evaluar el conocimiento, la actitud y la práctica de estudiantes de intercambio del continente africano sobre las Infecciones de Transmisión Sexual. Método estudio transversal, realizado de diciembre de 2019 a marzo de 2020, en una universidad pública internacional brasileña ubicada en Ceará. La muestra estuvo compuesta por 150 estudiantes africanos de diferentes cursos de pregrado. Se utilizó la encuesta de Conocimiento, Actitud y Práctica. Resultados los universitarios mostraron conocimientos satisfactorios sobre la transmisión de Infecciones de Transmisión Sexual, sin embargo, con deficiencias sobre las hepatitis virales. Se identificó asociación entre el sexo y la actitud sobre el uso del preservativo en las relaciones sexuales con pareja estable (p=0,042). En cuanto a las prácticas, hubo asociación entre sexo y uso de preservativo en la primera relación sexual (p=0,001), tener más de una pareja (p=0,001) y tener más de diez parejas en la vida (0,007). En cuanto a las prácticas sexuales en los últimos 12 meses, hubo asociación estadística entre tener sexo con más de una pareja sexual y el género del participante (p=0,001). Conclusión e implicaciones para la práctica se destaca la importancia de que la universidad investigada realice actividades de educación en salud que aborden las Infecciones de Transmisión Sexual, así como actividades de extensión universitaria, involucrando estudiantes inmigrantes africanos.


ABSTRACT Objective to evaluate the knowledge, attitude and practice of university exchange students from the African continent about Sexually Transmitted Infections. Method a cross-sectional study, conducted from December 2019 to March 2020, in a public international Brazilian university located in Ceará. The sample consisted of 150 African students from different undergraduate courses. It was used the survey of Knowledge, Attitude and Practice. Results the students showed satisfactory knowledge about the form of transmission of Sexually Transmitted Infections, however, with deficiencies regarding viral hepatitis. An association between sex and attitude about condom use in sexual intercourse with a fixed partner was identified (p=0.042). Regarding the practices, there was an association between sex and condom use in the first sexual relation (p=0.001), having more than one partner (p=0.001) and more than ten partners in the whole life (0.007). Regarding sexual practices in the last 12 months, there was a statistical association between having sex with more than one sexual partner and the participant's sex (p=0.001). Conclusion and implications for practice the importance of the university researched carrying out health education activities that address Sexually Transmitted Infections, as well as university extension activities that involve African immigrant students, is emphasized.


Subject(s)
Humans , Male , Female , Adult , Young Adult , Students , Sexually Transmitted Diseases/prevention & control , Sexually Transmitted Diseases/transmission , Health Knowledge, Attitudes, Practice , Black People , Student Health , Cross-Sectional Studies , Africa/ethnology , Emigrants and Immigrants
20.
Espaç.saúde ; 22: 1-16, 03/12/2021. ilus, tab
Article in Portuguese | LILACS | ID: biblio-1353772

ABSTRACT

A presente pesquisa teve como objetivo avaliar o desenvolvimento das competências gerais em cursos de bacharelado em Educação Física, tendo sido estudadas duas Instituições de Ensino Superior do Estado do Paraná. Foi utilizado o instrumento elaborado e validado por De Matia para a avaliação das competências gerais nos cursos da saúde. A amostra total foi de 263 respondentes. Quando comparamos as respostas dos professores à autoavaliação pelos graduandos, observamos escores menores em todas as dimensões estudadas. Os graduandos dos primeiros períodos se avaliam pior do que aqueles em períodos mais avançados do curso. Os professores percebem graduandos do sexo feminino, mais hábeis na postura inovadora e crítica, e os graduandos destacam colegas do sexo feminino como mais hábeis na interação com seus pares e sociedade. Conclui-se que os graduandos envolvidos na pesquisa estão desenvolvendo parcialmente as competências gerais fundamentais para a sua atuação profissional.


This study aimed to evaluate the development of general competences in Physical Education Undergraduate Courses in two Higher Education Institutions in an inland city of the State of Paraná. The instrument developed and validated by De Matia was used to assess general skills in health courses. The total sample consisted of 263 respondents. The comparison of the professors' answers to the students self-evaluation shows lower scores in all the dimensions studied. Undergraduate students of the first terms haver worse self-evaluations when compared to those in more advanced periods of the course. The professors perceive female students as more skilled in their innovative and critical posture, and the students highlight that female students are more skilled in interaction with their peers and society. It is concluded that the undergraduate students involved in the research are partially developing the general basic competences for their professional performance.


Esta investigación tuvo como objetivo evaluar el desarrollo de las competencias generales en los Cursos de Graduación en Educación Física - Bachillerato en instituciones de educación superior públicas y privadas de una ciudad en el interior del estado de Paraná. El instrumento desarrollado y validado por De Matia se utilizó para evaluar las competencias generales en los cursos de salud. La muestra total fue de 263 encuestados. Las respuestas de los maestros en comparación con los estudiantes son más bajas en todas las dimensiones estudiadas. Los graduados de los primeros períodos se evalúan peor que aquellos en períodos más avanzados del curso. Los profesores perciben que las alumnas, son más habilidosas y tienen una postura innovadora y crítica, y los alumnos destacan las alumnas, más capacitadas para interactuar con sus pares y la sociedad. Se concluye que los graduandos involucrados en la investigación, desarrollan parcialmente las competencias generales básicas.


Subject(s)
Humans , Physical Education and Training , Students , Competency-Based Education
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