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1.
Psicosom. psiquiatr ; (28): 18-28, Ene-Mar, 2024. tab
Artigo em Espanhol | IBECS | ID: ibc-231741

RESUMO

Introducción: Existe evidencia sobre una asociación directa entre la Violencia Machista/Violencia de Género (VdG) y el suicidio, e incluso se señala que la VdG es el principal factor precipitante para que una mujer realice una tentativa suicida. Además, se ha demostrado que las mujeres con enfermedades mentales crónicas sufren especialmente más violencia que la población en general. Sin embargo, existen relativamente pocos datos sobre la capacidad de detección de VdG de los servicios de urgencias. En Catalunya, el Programa Código Riesgo de Suicidio (CRS) atendió a 12.596 persones con episodios de conducta suicida y ha demostrado su eficacia en nuestro hospital. Objetivo principal: Cuantificar el grado de detección de la VdG de nuestros registros sanitarios en mujeres visitadas en el servicio urgencias de nuestro hospital por ideación y/o tentativa suicida y que han sido incluidas en el Programa CRS. Hipótesis principal: La detección actual de VdG en las mujeres es <10%. Metodología: Estudio descriptivo retrospectivo basado en registros electrónicos sanitarios. Se identificaron todas las mujeres que habían estado en seguimiento telefónico en los últimos 12 meses por haber acudido al servicio de urgencias de nuestro Hospital por ideación y/o intento suicida. El período de análisis incluyó del 1 de enero al 31 de diciembre de 2020. Se realizó una revisión completa de todos los informes de alta de estas mujeres visitadas en urgencias y de los registros clínicos de todos los profesionales (médicos, psiquiatrías, enfermeras...) disponibles en la historia clínica informatizada. Se realizó un análisis descriptivo simple de los datos. Resultados: Durante el período de estudio, se detectaron cuatro casos de violencia machista/VdG (1,92%) y dos casos de violencia familiar entre las 208 mujeres que se visitaron por ideación y/o intento autolítico...(AU)


Introduction: There is evidence of a direct association between interpersonal partner/sexist/gender violence (IPV) and suicide, and it is even pointed out that IPV is the main precipitating factor for a woman to make a suicide attempt. In addition, it has been shown that women with chronic mental illness suffer especially more violence than the general population. However, there is relatively little data on the IPV detection capacity of emergency departments. In Catalonia, the Suicide Risk Code Program (CRS) treated 12,596 people with episodes of suicidal behaviour and has demonstrated its effectiveness in our hospital. Main objective: To quantify the degree of detection of IPV in our health records in women visited in the emergency department of our hospital for suicidal ideation and/or attempt and who have been included in the CRS Program.Main hypothesis: Current detection of IPV in women is <10%. Methodology: Retrospective descriptive study based on electronic health records. All the women who had been in telephone follow-up in the last 12 months for having gone to the emergency department of our hospital for suicidal ideation and/or attempt were identified. The analysis period included from January 1 to December 31, 2020. A complete review of all the discharge reports of the women visited in the emergency room and of all the clinical records of all the professionals (doctors, psychiatrists, nurses...) available in the computerized medical record was carried out. A simple descriptive analysis of the data was performed. Results: During the study period, four cases of IPV (1.92%) and two cases of family violence were detected among the 208 women who were visited for suicidal ideation and/or attempt. All the women who were detected with IPV were recommended to visit the Women’s Care Center, but it is unknown if they were actually referred to other professionals or if they actually attended...(AU)


Assuntos
Humanos , Masculino , Feminino , Violência de Gênero , Androcentrismo , Suicídio , Violência por Parceiro Íntimo , Tentativa de Suicídio , Serviços Médicos de Emergência , Psiquiatria , Saúde Mental , Estudos Retrospectivos , Epidemiologia Descritiva
2.
J Transl Med ; 21(1): 582, 2023 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-37649088

RESUMO

Over the last five decades, breast density has been associated with increased risk of developing breast cancer. Mammographically dense breasts are considered those belonging to the heterogeneously dense breasts, and extremely dense breasts subgroups according to the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS). There is a statistically significant correlation between the increased mammographic density and the presence of more glandular tissue alone. However, the strength of this correlation is weak. Although the mechanisms driving breast density-related tumor initiation and progression are still unknown, there is evidence suggesting that certain molecular pathways participating in epithelial-stromal interactions may play a pivotal role in the deposition of fibrillar collagen, increased matrix stiffness, and cell migration that favor breast density and carcinogenesis. This article describes these molecular mechanisms as potential "landscapers" for breast density-related cancer. We also introduce the term "Breast Compactness" to reflect collagen density of breast tissue on chest CT scan and the use of breast stiffness measurements as imaging biomarkers for breast cancer screening and risk stratification.


Assuntos
Neoplasias da Mama , Radiologia , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Fatores de Risco
3.
J Transl Med ; 21(1): 274, 2023 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-37085817

RESUMO

The periphery of malignant tumors and the leading edge of fibrotic tissue have analogous metabolic pathways. Both use glycolysis as the primary source of energy to produce biomass with consequential acidification of the microenvironment. A low PH has been shown to increase the ability of cancer cells to invade the surrounding tissue in both in vitro and in vivo studies. The pH-dependent activation of TGF-B leading to myofibroblast activation is an important step in the initiation and progression of fibrosis. Markers of accelerated cell proliferation have also been reported in the periphery of malignant tumors and the leading edge of fibrosis. Understanding the shared molecular and metabolic characteristics of these conditions may explain the increased prevalence of cancer among patients with fibrosis.


Assuntos
Neoplasias , Fibrose Pulmonar , Humanos , Fibrose Pulmonar/patologia , Diferenciação Celular , Fator de Crescimento Transformador beta/metabolismo , Fibrose , Neoplasias/patologia , Miofibroblastos/metabolismo , Fibroblastos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral
4.
Mol Oncol ; 17(7): 1302-1323, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36808875

RESUMO

Oestrogen receptor-alpha (ERα) positivity is intimately associated with the development of hormone-dependent breast cancers. A major challenge in the treatment of these cancers is to understand and overcome the mechanisms of endocrine resistance. Recently, two distinct translation programmes using specific transfer RNA (tRNA) repertoires and codon usage frequencies were evidenced during cell proliferation and differentiation. Considering the phenotype switch of cancer cells to more proliferating and less-differentiated states, we can speculate that the changes in the tRNA pool and codon usage that likely occur make the ERα coding sequence no longer adapted, impacting translational rate, co-translational folding and the resulting functional properties of the protein. To verify this hypothesis, we generated an ERα synonymous coding sequence whose codon usage was optimized to the frequencies observed in genes expressed specifically in proliferating cells and then investigated the functional properties of the encoded receptor. We demonstrate that such a codon adaptation restores ERα activities to levels observed in differentiated cells, including: (a) an enhanced contribution exerted by transactivation function 1 (AF1) in ERα transcriptional activity; (b) enhanced interactions with nuclear receptor corepressor 1 and 2 [NCoR1 and NCoR2 (also known as SMRT) respectively], promoting repressive capability; and (c) reduced interactions with SRC proto-oncogene, non-receptor tyrosine kinase (Src) and phosphoinositide 3-kinase (PI3K) p85 kinases, inhibiting MAPK and AKT signalling pathway.


Assuntos
Neoplasias , Receptores de Estrogênio , Receptores de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Mutação Silenciosa , Linhagem Celular Tumoral , Códon/genética , Neoplasias/genética
5.
J Transl Med ; 21(1): 59, 2023 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717924
6.
Rev. colomb. ortop. traumatol ; 37(1): 1-10, 2023. tab
Artigo em Espanhol | LILACS, COLNAL | ID: biblio-1532265

RESUMO

Introducción: la fractura de cadera en adultos mayores constituye un problema de salud importante, ya que está asociada a mayor morbilidad y mortalidad. Por esta razón, se han creado protocolos de ortogeriatría para su abordaje, los cuales reportan resultados favorables.Objetivo: evaluar los desenlaces adversos perioperatorios en adultos mayores con fractura de cadera antes y después de la implementación de un protocolo de evaluación geriátrica integral (EGI).Metodología: estudio de casos y controles realizado en 136 pacientes (casos: 43; controles: 93) >65 años con fractura de cadera que fueron atendidos en un hospital de referencia entre 2020 y 2021 (casos), y 2015 y 2017 (controles). Se determinaron diferencias entre grupos mediante un análisis bivariado usando las pruebas de chi cuadrado o exacta de Fisher en variables categóricas, y las pruebas t de student o de Wilcoxon de los rangos con signo en variables continuas según la distribución de los datos.Resultados: los desenlaces adversos perioperatorios ocurrieron en el 62,7% de los casos y el 84,0% de los controles (p=0,007; OR:0,32; IC95%:0,13-0,73). La mediana de duración de la estancia hospitalaria fue 10 y 17 días en los casos y controles, respectivamente (RIQ: 8-14; RIQ 11-26), mientras que el tiempo entre el ingreso a urgencias y la cirugía fue 7 días (RIQ:5-11) y 11 días (RIQ:8-17), respectivamente (p=0.002). Conclusiones: la implementación de la EGI redujo los desenlaces adversos por fractura de cadera, principal-mente la duración de la estancia hospitalaria y el tiempo entre el ingreso y la cirugía, donde se observaron diferencias estadísticamente significativas entre ambos grupos


Introduction: Hip fracture in elderly patients is a major health concern, as it is associated with increased morbidity and mortality. For this reason, orthogeriatric protocols have been created to approach it, reporting favorable outcomes.Objective: To evaluate adverse perioperative outcomes in elderly patients with hip fractures before and after the implementation of a comprehensive geriatric assessment (CGA) protocol.Methodology: Case-control study performed on 136 patients (cases: 43; controls: 93) >65 years old with a hip fracture, who were treated at a referral hospital between 2020 and 2021 (cases) and 2015 and 2017 (controls). Differences between groups were determined through bivariate analysis using Fisher's chi-square or exact tests on categorical variables, and Student's t-test or Wilcoxon signed-rank test on continuous variables depending on the distribution of the data.Results: Adverse perioperative outcomes occurred in 62.7% of cases and 84.0% of controls (p=0.007; OR:0.32; 95%CI:0.13-0.73). The median length of hospital stay was 10 and 17 days in cases and controls, respectively (IQR: 8-14; IQR 11-26), while the time between ED admission and surgery was 7 days (IQR:5-11) and 11 days (IQR:8-17), respectively (p=0.002).Conclusions: The implementation of the CGA protocol reduced adverse outcomes associated with hip fracture, mainly the length of hospital stay and the time between admission and surgery, in which statistically significant differences were observed between both groups

7.
Front Oncol ; 11: 728519, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912703

RESUMO

PURPOSE: Stereotactic body radiation therapy (SBRT) is considered standard of care for medically inoperable early stage non-small cell lung cancer (ES-NSCLC). Central tumor location is a known risk factor for severe SBRT related toxicity. Bronchoscopy allows for visualization of the central airways prior to treatment. Five fraction SBRT approaches have been advocated to mitigate treatment induced toxicity. In this report, we examine the mature clinical outcomes of a diverse cohort of ES-NSCLC patients with both peripheral and central tumors treated with a conservative 5 fraction SBRT approach and evaluate the role of lobar gross endobronchial disease (LGED) in predicting overall survival and treatment-related death. METHODS: Medically inoperable biopsy-proven, lymph node-negative ES-NSCLC patients were treated with SBRT. Bronchoscopy was completed prior to treatment in all centrally located cases. The Kaplan-Meier method was used to estimate overall survival (OS), local control (LC), regional control (RC), distant metastasis free survival (DMFS) and disease-free survival (DFS). Overall survival was stratified based on clinical stage, histology, tumor location and LGED. Toxicities were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. RESULTS: From December 2010 to December 2015, 50 consecutive patients were treated uniformly with a 50 Gy in 5 fraction SBRT approach (tumor BED10 ≥ 100 Gy) and followed for a minimum of 5 years or until death. At a median follow up of 42 months for all patients, 3-year OS was 50%. Three-year OS did not statistically differ between stage I and stage II disease (51% vs. 47%; p=0.86), adenocarcinoma and squamous cell carcinoma (50% vs. 45%; p=0.68), or peripheral and central tumors (56% vs. 45%; p=0.46). Five central tumors were found to have LGED, and 3-year OS for this cohort was quite poor at 20%. Cox regression analysis identified LGED as a predictor of OS while controlling for age, stage and location (OR:4.536, p-value=0.038). Despite the relatively low dose delivered, treatment likely contributed to the death of 4 patients with central tumors. Lobar gross endobronchial disease was an independent predictor for grade 5 pulmonary toxicity (n=4, p=0.007). Specifically, 3 of the 5 patients with LGED developed fatal radiation-induced bronchial stricture. Three-year LC, RC, DMFS and DFS results for the group were similar to contemporary studies at 90%, 90%, 82% and 65%. CONCLUSIONS: Central location of ES-NSCLC is a well-established predictor for severe SBRT-related toxicity. Here we identify LGED as a significant predictor of poor overall survival and grade 5 pulmonary toxicity. The relatively high rates of severe treatment-related toxicity seen in patients with central ES-NSCLC may be due in part to LGED. Underlying LGED may cause irreparable damage to the lobar airway, unmitigated by SBRT treatment thus increasing the risk of severe treatment-related toxicity. These findings should be verified in larger data sets. Future prospective central ES-NSCLC clinical trials should require staging bronchoscopy to identify LGED and further assess its clinical significance.

8.
Clin Geriatr Med ; 37(4): 523-532, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34600719

RESUMO

Perceptions of illness, pain, and death are not static. They vary among populations according to their cultural and biological characteristics. Older black and Hispanic/Latinx women are unique in their approach to health care with respect to mentation, mobility, medication adherence, and what matters to them. It is the complexity of these components, which affect the ability of these women to age gracefully.


Assuntos
Negro ou Afro-Americano , Hispânico ou Latino , Feminino , Humanos , Adesão à Medicação
9.
Front Mol Biosci ; 8: 643701, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33796548

RESUMO

Cellular tRNAs appear today as a diverse population of informative macromolecules with conserved general elements ensuring essential common functions and different and distinctive features securing specific interactions and activities. Their differential expression and the variety of post-transcriptional modifications they are subject to, lead to the existence of complex repertoires of tRNA populations adjusted to defined cellular states. Despite the tRNA-coding genes redundancy in prokaryote and eukaryote genomes, it is surprising to note the absence of genes coding specific translational-active isoacceptors throughout the phylogeny. Through the analysis of different releases of tRNA databases, this review aims to provide a general summary about those "missing tRNA genes." This absence refers to both tRNAs that are not encoded in the genome, as well as others that show critical sequence variations that would prevent their activity as canonical translation adaptor molecules. Notably, while a group of genes are universally missing, others are absent in particular kingdoms. Functional information available allows to hypothesize that the exclusion of isodecoding molecules would be linked to: 1) reduce ambiguities of signals that define the specificity of the interactions in which the tRNAs are involved; 2) ensure the adaptation of the translational apparatus to the cellular state; 3) divert particular tRNA variants from ribosomal protein synthesis to other cellular functions. This leads to consider the "missing tRNA genes" as a source of putative non-canonical tRNA functions and to broaden the concept of adapter molecules in ribosomal-dependent protein synthesis.

10.
PLoS One ; 15(10): e0240580, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33045024

RESUMO

Human serum albumin presents in its primary structure only one free cysteine (Cys34) which constitutes the most abundant thiol of plasma. An antioxidant role can be attributed to this thiol, which is located in domain I of the protein. Herein we expressed domain I as a secretion protein using the yeast Pichia pastoris. In the initial step of ammonium sulfate precipitation, a brown pigment co-precipitated with domain I. Three chromatographic methods were evaluated, aiming to purify domain I from the pigment and other contaminants. Purification was achieved by cation exchange chromatography. The protein behaved as a non-covalent dimer. The primary sequence of domain I and the possibility of reducing Cys34 to the thiol state while avoiding the reduction of internal disulfides were confirmed by mass spectrometry. The reactivity of the thiol towards the disulfide 5,5´-dithiobis(2-nitrobenzoate) was studied and compared to that of full-length albumin. A ~24-fold increase in the rate constant was observed for domain I with respect to the entire protein. These results open the door to further characterization of the Cys34 thiol and its oxidized derivatives.


Assuntos
Antioxidantes/química , Cisteína/genética , Albumina Sérica Humana/genética , Compostos de Sulfidrila/química , Cromatografia por Troca Iônica , Cisteína/química , Expressão Gênica/genética , Humanos , Domínios Proteicos/genética , Multimerização Proteica , Saccharomycetales/genética , Albumina Sérica Humana/química
11.
Case Rep Pediatr ; 2020: 4609317, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32832184

RESUMO

Pseudohypertriglyceridemia is an overestimation of serum triglyceride levels that may incorrectly lead to a diagnosis of hypertriglyceridemia. Glycerol kinase deficiency is a condition in which glycerol cannot be phosphorylated to glycerol-3-phosphate, resulting in elevated levels of serum glycerol. Laboratory assays that measure triglycerides indirectly may be affected by elevated glyerol levels and incorrectly report serum tryglyceride levels. We present a case of a novel missense mutation in the GK gene leading to isolated glycerol kinase deficiency and pseudohypertriglyceridemia in a male infant of a mother with gestational diabetes. This paper reviews glycerol kinase deficiency, describes the challenges in diagnosing pseudohypertriglyceridemia, and provides suggestions on improving diagnostic accuracy. Additionally, a potential maternal-fetal interaction between gestational diabetes and glycerol kinase deficiency is discussed.

12.
Cancer Metab ; 8: 8, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32699630

RESUMO

BACKGROUND: During breast cancer progression, the epithelial to mesenchymal transition has been associated with metastasis and endocrine therapy resistance; however, the underlying mechanisms remain elusive. To gain insight into this process, we studied the transition undergone by MCF7-derived cells, which is driven by the constitutive nuclear expression of a MKL1 variant devoid of the actin-binding domain (MKL1 ΔN200). We characterized the adaptive changes that occur during the MKL1-induced cellular model and focused on regulation of translation machinery and metabolic adaptation. METHODS: We performed a genome-wide analysis at the transcriptional and translational level using ribosome profiling complemented with RNA-Seq and analyzed the expression of components of the translation machinery and enzymes involved in energy metabolism. NGS data were correlated with metabolomic measurements and quantification of specific mRNAs extracted from polysomes and western blots. RESULTS: Our results reveal the expression profiles of a luminal to basal-like state in accordance with an epithelial to mesenchymal transition. During the transition, the synthesis of ribosomal proteins and that of many translational factors was upregulated. This overexpression of the translational machinery appears to be regulated at the translational level. Our results indicate an increase of ribosome biogenesis and translation activity. We detected an extensive metabolic rewiring occurring in an already "Warburg-like" context, in which enzyme isoform switches and metabolic shunts indicate a crucial role of HIF-1α along with other master regulatory factors. Furthermore, we detected a decrease in the expression of enzymes involved in ribonucleotide synthesis from the pentose phosphate pathway. During this transition, cells increase in size, downregulate genes associated with proliferation, and strongly upregulate expression of cytoskeletal and extracellular matrix genes. CONCLUSIONS: Our study reveals multiple regulatory events associated with metabolic and translational machinery adaptation during an epithelial mesenchymal-like transition process. During this major cellular transition, cells achieve a new homeostatic state ensuring their survival. This work shows that ribosome profiling complemented with RNA-Seq is a powerful approach to unveil in-depth global adaptive cellular responses and the interconnection among regulatory circuits, which will be helpful for identification of new therapeutic targets.

13.
PLoS One ; 15(3): e0221837, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126063

RESUMO

Despite being the subject of intensive research, tuberculosis, caused by Mycobacterium tuberculosis, remains at present the leading cause of death from an infectious agent. Secreted and cell wall proteins interact with the host and play important roles in pathogenicity. These proteins are explored as candidate diagnostic markers, potential drug targets or vaccine antigens, and more recently special attention is being given to the role of their post-translational modifications. With the purpose of contributing to the proteomic and glycoproteomic characterization of this important pathogen, we performed a shotgun analysis of culture filtrate proteins of M. tuberculosis based on a liquid nano-HPLC tandem mass spectrometry and a label-free spectral counting normalization approach for protein quantification. We identified 1314 M. tuberculosis proteins in culture filtrate and found that the most abundant proteins belong to the extracellular region or cell wall compartment, and that the functional categories with higher protein abundance factor were virulence, detoxification and adaptation, and cell wall and cell processes. We could identify a group of proteins consistently detected in previous studies, most of which were highly abundant proteins. In culture filtrate, 140 proteins were predicted to contain one of the three types of bacterial N-terminal signal peptides. Besides, various proteins belonging to the ESX secretion systems, and to the PE and PPE families, secreted by the type VII secretion system using nonclassical secretion signals, were also identified. O-glycosylation was identified in 46 proteins, many of them lipoproteins and cell wall associated proteins. Finally, we provide proteomic evidence for 33 novel O-glycosylated proteins, aiding to the glycoproteomic characterization of relevant antigenic membrane and exported proteins. These findings are expected to collaborate with the research on pathogen derived biomarkers, virulence factors and vaccine candidates, and to provide clues to the understanding of the pathogenesis and survival strategies adopted by M. tuberculosis.


Assuntos
Proteínas de Bactérias/metabolismo , Mycobacterium tuberculosis/metabolismo , Mycobacterium tuberculosis/patogenicidade , Proteoma , Proteômica/métodos , Antígenos de Bactérias/metabolismo , Sistemas de Secreção Bacterianos/metabolismo , Vacinas Bacterianas , Parede Celular , Cromatografia Líquida , Glicosilação , Interações Hospedeiro-Patógeno , Proteínas de Membrana/metabolismo , Espectrometria de Massas em Tandem , Tuberculose/microbiologia , Virulência , Fatores de Virulência/metabolismo
14.
Biochim Biophys Acta Gene Regul Mech ; 1863(5): 194507, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32113984

RESUMO

Estrogen receptor (ERα) is central in driving the development of hormone-dependent breast cancers. A major challenge in treating these cancers is to understand and overcome endocrine resistance. The Megakaryoblastic Leukemia 1 (MKL1, MRTFA) protein is a master regulator of actin dynamic and cellular motile functions, whose nuclear translocation favors epithelial-mesenchymal transition. We previously demonstrated that nuclear accumulation of MKL1 in estrogen-responsive breast cancer cell lines promotes hormonal escape. In the present study, we confirm through tissue microarray analysis that nuclear immunostaining of MKL1 is associated with endocrine resistance in a cohort of breast cancers and we decipher the underlining mechanisms using cell line models. We show through gene expression microarray analysis that the nuclear accumulation of MKL1 induces dedifferentiation leading to a mixed luminal/basal phenotype and suppresses estrogen-mediated control of gene expression. Chromatin immunoprecipitation of DNA coupled to high-throughput sequencing (ChIP-Seq) shows a profound reprogramming in ERα cistrome associated with a massive loss of ERα binding sites (ERBSs) generally associated with lower ERα-binding levels. Novel ERBSs appear to be associated with EGF and RAS signaling pathways. Collectively, these results highlight a major role of MKL1 in the loss of ERα transcriptional activity observed in certain cases of endocrine resistances, thereby contributing to breast tumor cells malignancy.


Assuntos
Neoplasias da Mama/metabolismo , Núcleo Celular/metabolismo , Receptor alfa de Estrogênio/metabolismo , Regulação Neoplásica da Expressão Gênica , Transativadores/metabolismo , Transporte Ativo do Núcleo Celular , Neoplasias da Mama/genética , Estrogênios/metabolismo , Feminino , Humanos , Células MCF-7 , Ligação Proteica
15.
Cancers (Basel) ; 12(2)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050651

RESUMO

The tumor suppressor protein p53 orchestrates cellular responses to a vast number of stresses, with DNA damage and oncogenic activation being some of the best described. The capacity of p53 to control cellular events such as cell cycle progression, DNA repair, and apoptosis, to mention some, has been mostly linked to its role as a transcription factor. However, how p53 integrates different signaling cascades to promote a particular pathway remains an open question. One way to broaden its capacity to respond to different stimuli is by the expression of isoforms that can modulate the activities of the full-length protein. One of these isoforms is p47 (p53/47, Δ40p53, p53ΔN40), an alternative translation initiation variant whose expression is specifically induced by the PERK kinase during the Unfolded Protein Response (UPR) following Endoplasmic Reticulum stress. Despite the increasing knowledge on the p53 pathway, its activity when the translation machinery is globally suppressed during the UPR remains poorly understood. Here, we focus on the expression of p47 and we propose that the alternative initiation of p53 mRNA translation offers a unique condition-dependent mechanism to differentiate p53 activity to control cell homeostasis during the UPR. We also discuss how the manipulation of these processes may influence cancer cell physiology in light of therapeutic approaches.

16.
Front Oncol ; 10: 572564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425723

RESUMO

PURPOSE: Single extracranial metastases from ovarian and uterine malignancies have historically been treated with surgery or conventional radiation. We report mature local control (LC), overall survival (OS), progression free survival (PFS), and toxicity for patients who completed 5-fraction stereotactic body radiation therapy (SBRT). METHODS: Patients with biopsy-proven, single extracranial metastases from primary ovarian and uterine malignancies treated with 5-fraction SBRT were included. Patients were stratified based on tumor volume (small < 50 cc or large ≥ 50 cc) and dose (low dose < 35 Gy or high ≥ 35 Gy). Kaplan-Meier method was used to estimate LC, OS, and PFS. RESULTS: Between July 2007 and July 2012, 20 patients underwent SBRT to a single extracranial metastasis. Primary site was divided evenly between ovarian and uterine (n = 10 each). Metastases involved the liver (30%), abdominal lymph nodes (25%), lung (20%), pelvic lymph nodes (10%), spine (10%), and extremity (5%). The median gross tumor volume (GTV) was 42.5 cc (range, 5-273 cc) and the median dose to the GTV was 35 Gy (range, 30-50 Gy). At a median follow-up of 56 months, the 5-year LC and OS estimates were 73 and 46%. When stratified by tumor volume, the 5-year LC and OS for small tumors were significantly better at 100% (p < 0.01) and 65% (p < 0.02). When stratified by dose, the 5-year LC was 87.5% with high dose and 53.6% with low dose (p = 0.035). The 5-year PFS for the entire cohort was 20%. Four patients with small metastases who had complete response remained disease free at study completion and were considered cured (median PFS > 10 years). Treatment was generally well tolerated, and only one patient experienced a late grade III musculoskeletal SBRT related toxicity. CONCLUSIONS: SBRT is a versatile, well-tolerated, and effective treatment option for single extracranial metastases from ovarian and uterine primary tumors. 35 Gy in five fractions appears to be a practical minimum effective dose. Four patients with small metastases were disease free at the study completion and considered cured. However, patients with larger metastases (≥50 cc) may require higher SBRT dosing or alternative treatments.

17.
R Soc Open Sci ; 6(11): 190773, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31827830

RESUMO

In both prokaryotic and eukaryotic genomes, synonymous codons are unevenly used. Such differential usage of optimal or non-optimal codons has been suggested to play a role in the control of translation initiation and elongation, as well as at the level of transcription and mRNA stability. In the case of membrane proteins, codon usage has been proposed to assist in the establishment of a pause necessary for the correct targeting of the nascent chains to the translocon. By using as a model UreA, the Aspergillus nidulans urea transporter, we revealed that a pair of non-optimal codons encoding amino acids situated at the boundary between the N-terminus and the first transmembrane segment are necessary for proper biogenesis of the protein at 37°C. These codons presumably regulate the translation rate in a previously undescribed fashion, possibly contributing to the correct interaction of ureA-translating ribosome-nascent chain complexes with the signal recognition particle and/or other factors, while the polypeptide has not yet emerged from the ribosomal tunnel. Our results suggest that the presence of the pair of non-optimal codons would not be functionally important in all cellular conditions. Whether this mechanism would affect other proteins remains to be determined.

18.
Rev. am. med. respir ; 19(4): 313-320, sept. 2019. tab, graf
Artigo em Espanhol | BINACIS, LILACS | ID: biblio-1119811

RESUMO

La estancia hospitalaria prolongada durante un episodio de exacerbación en Enfermedad Pulmonar Obstructiva Crónica representa una condición que aumenta el riesgo de complicaciones médicas asociadas. Objetivo: El objetivo de este estudio fue determinar los factores asociados a una estancia hospitalaria prolongada en exacerbaciones de Enfermedad Pulmonar Obstructiva Crónica, a través de un modelo de predicción. Materiales y métodos: En un estudio de tipo corte transversal recopilamos los datos de los registros médicos en un hospital localizado en la región oriente de Colombia, entre los años 2012-2014. Se realizó análisis descriptivo, bivariado y multivariado Resultados: Un total de 212 pacientes fueron incluidos en este estudio, 61.32% presentaron estancia hospitalaria prolongada. Encontramos asociación estadística significativa entre estancia hospitalaria prolongada y las variables independientes producto del análisis bivariado: disnea (OR: 2.87 p = 0.04), fiebre (OR: 2; p = 0.02), oxígeno hospitalario (OR: 2.34, p = 0.003), anticolinérgicos hospitalarios (OR: 2.91, p = 0.002), antibiótico hospitalario (OR: 2.25, p = 0.004), segmentados (OR: 1.02, p= 0.01) y linfocitos (OR: 0.95, p = 0.003). El modelo predictivo tenía un valor de p de 0.4950 en el análisis de bondad (prueba de Pearson) y un valor de p de 0.2689 en el test de bondad de ajuste (prueba de Hosmer-Lemeshow) indicando adecuado ajuste. Además, el modelo presentó un área bajo la curva de 0.6588. Conclusiones: Nuestro modelo de predicción incluyo las variables: edad, anticolinérgicos y segmentados, por su asociación significativa. Tiene adecuado ajuste y con un buen patrón de predicción.


Assuntos
Humanos , Doença Pulmonar Obstrutiva Crônica , Hospitais , Tempo de Internação
19.
Rev. am. med. respir ; 19(4): 321-328, sept. 2019. tab, graf
Artigo em Inglês | LILACS, BINACIS | ID: biblio-1119812

RESUMO

A prolonged hospital length of stay during an episode of exacerbation of chronic obstructive pulmonary disease is a condition that increases the risk of suffering associated medical complications. Objective: The objective of this study was to determine the factors associated with a prolonged hospital length of stay in exacerbations of chronic obstructive pulmonary disease through a prediction model. Materials and Methods: In a cross-sectional study we gathered the data of the medical records of a hospital located in the Eastern region of Colombia, between years 2012 and 2014. We carried out a descriptive, bivariate and multivariate analysis. Results: A total of 212 patients were included in this study. 61.32% showed a prolonged hospital length of stay. We found a significant statistical association between the prolonged hospital stay and the independent variables of the bivariate analysis: dyspnea (OR [Odds Ratio]: 2.87 p = 0.04), fever (OR: 2; p = 0.02), inpatient oxygen (OR: 2.34, p = 0.003), inpatient anticholinergics (OR: 2.91, p = 0.002), inpatient antibiotic (OR: 2.25, p= 0.004), segs (OR: 1.02, p= 0.01) and lymphocytes (OR: 0.95, p = 0.003). The predictive model had a p value of 0.4950 in the analysis of goodness (Pearson Test) and a p value of 0.2689 in the goodness of fit test (Hosmer-Lemeshow Test), indicating an adequate fit. Also, the model showed an area under the curve of 0.6588. Conclusions: Our prediction model included the following variables: age, anticholinergics and segs, for their significant association. It has an adequate fit and a good pattern of prediction.


Assuntos
Humanos , Doença Pulmonar Obstrutiva Crônica , Hospitais , Tempo de Internação
20.
Rev. cuba. enferm ; 34(2): e1570, abr.-jun. 2018. tab, graf
Artigo em Espanhol | LILACS, BDENF - Enfermagem, CUMED | ID: biblio-1099035

RESUMO

RESUMEN Introducción: La salud móvil es una forma económica de mejorar el control y seguimiento de los pacientes, y puede ayudar a optimizar la atención de un centro médico. Sin embargo, su potencial aún no ha sido completamente estudiado. Objetivo: Exponer los efectos de la utilización de la aplicación móvil VILLAHEALTH en el comportamiento y desempeño del personal de enfermería. Métodos: Observación sistemática de personal de salud en sus labores diarias. Se escogieron a ocho enfermeras que poseían un dispositivo móvil, y que estaban familiarizadas con la aplicación del sistema Android; la misma que logra almacenar estados, tratamientos e información básica del paciente, y también programa tareas con notificaciones que se muestran en el calendario del celular. Se midió y comparó los tiempos de respuesta con y sin la ayuda de la aplicación. Resultados: Con las notificaciones de la aplicación, el 77,08 por ciento de las veces, las tareas eran comenzadas antes de 5 minutos de su programación, frente al 25,00 por ciento sin su ayuda. La media de tiempo de respuesta con la aplicación fue de 105,18 (± 86,08) segundos, mientras que sin la aplicación fue de 616,72 (± 223,30) segundos. Conclusión: Con la aplicación VILLAHEALTH, los usuarios empezaron sus actividades en los cinco primeros minutos a partir del inicio establecido en comparación a los 10 minutos sin ella. Además, la aplicación ayudó al personal de enfermería a reducir sus tiempos de respuesta para tratar a los pacientes(AU)


ABSTRACT Introduction: Mobile health is an inexpensive way to improve the control and monitoring of patients, and may help improve the service a medical center has. However, Its full potential still hasn't been studied. Objective: To show the results of the infirmary personnel's behaviour when using the mobile application VILLAHEALTH in their professional performance. Methods: Systematic observation of health personnel in their daily work. Eight nurses were selected who owned a smartphone with Internet access and were familiarized with the Android application, which stores the states, treatments and basic patient information, and programs tasks with notifications which are displayed on the calendar. The response times with and without the help of the application were measured and compared. Results: With the application notifications, 77,08 percent of the time the tasks were started within 5 minutes of programming, compared to 25,00 percent without its help. The average response time with the application was 105,18 (± 86,08) seconds, while without it was 616,72 (± 223,30) seconds. Conclusion: Using the VILLAHEALTH app, users started their activities within the first five minutes, compared to the 10 minutes without using it. In addition, the app helped nurses reduce response times when treating patients(AU)


Assuntos
Humanos , Telemedicina/métodos , Aplicativos Móveis/tendências , Smartphone , Recursos Humanos de Enfermagem/ética
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