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1.
Int J Womens Health ; 16: 605-617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645983

RESUMO

Background: Cervical cancer is one of the leading causes of cancer death in women, even though it is a preventable disease. Most deaths occur in low- and middle-income countries. In addition to early detection and receipt of standard treatments, survivorship is an important component of high quality of care across the cancer continuum. Objective: To assess the survival status of advanced-stage cervical cancer patients after cancer treatment has started. Methods and Materials: A one-year prospective cohort study was employed to assess the survival status of women with advanced stages of cervical cancer. A total of 180 cervical cancer patients were recruited, and the study was conducted from January 10, 2022, to September 20, 2023. Data entry and analysis were done in the SPSS 29 version. Descriptive statistics were used to examine participant characteristics. The Kaplan-Meier procedure and log rank test were used to estimate the duration of survival. Bivariate and multivariate Cox regression analyses were computed for predictor variables with survival status. Results: Patients receiving cancer treatment at FIGO stages IVA and IVB had survived by 56% and 24%, respectively, whereas patients receiving treatment at stages IIB and IIIA had survived by 100%. The estimated mean survival time at one-year follow-up was 5.706 months (95% CI: 3.785-7.627) for patients with FIGO stage IVB, but 11.537 months (95% CI: 11.199-11.887) for those with stages II and III (P < 0.001). Women over 60 years old had a 1.5-fold higher risk of death than those under 60 (HR: 1.482, P = 0.040). Conclusion: The one-year cumulative survival rate among advanced-stage cervical cancer patients was 77%. Major factors associated with survival were age, cancer stage, the presence of anemia, and waiting time for treatment.

2.
Cancer Manag Res ; 16: 311-323, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646146

RESUMO

Background: The development of health concepts beyond traditional markers of illness and death has made the evaluation of quality of life (QoL) crucial to patient care. Yet, there is little research evaluating the pre- and post-treatment QoL of cervical cancer survivors in Ethiopia. Objective: This study aimed to assess the pre- and post-treatment QoL of women diagnosed with advanced-stage cervical cancer. Methods and Materials: A cohort design was conducted at the Tikur Anbessa Specialized Hospital Oncology Center. A total of 166 cervical cancer patients were recruited consecutively. Data was collected through interviews with standardized questionnaires before and after treatment. The Wilcoxon rank test was used to assess the significant differences in pre-treatment and post-treatment quality of life. Additionally, the Mann-Whitney U-test was also employed. Statistical significance was determined with p-values <0.05 and a 95% confidence interval. Results: Women who were in stages IVA and IVB were 24.7% and 10.2%, respectively. Both the global health scale (66.67 [47.92-75] to 83.33 [66.67-83.33]) and the functional domain QoL (66.67 [40-80] to 70 [46.67-86.66]) showed statistically significant improvements from pre-treatment to post-treatment QoL. Women under the age of 45 were found to have higher global health QOL (P < 0.001) and functional domain QOL (P = 0.029). Women presented in stages II and III had comparatively higher global health QoL (P = 0.008) and functional domain QoL (P = 0.021). Conclusion: Global health QOL and the majority of functional quality of life significantly improved following six months of cancer treatment. But there was no discernible change in terms of sexual enjoyment, sexual function, or activity. Age, marital status, the duration since diagnosis, the stage of the cancer, and the presence of comorbidities were the factors that affected the improvement of post-treatment quality of life.

3.
Proc Inst Mech Eng H ; 237(10): 1167-1176, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37776125

RESUMO

Mobile bearing dislocation occurs in 1- 6% of Oxford Domed Lateral replacements. Dislocations are predominantly medial, but can occur anteriorly or posteriorly. They tend to occur when the knee is flexed. It is not clear how dislocations can be prevented. A previously described mechanical rig for assessing mobile bearing dislocation was updated so as to study dislocation with the knee in flexion. Sub-categories for the description of each type of dislocation were introduced. Dislocation was only possible when the knee was distracted. As the amount of distraction possible in the knee is variable, the risk of dislocation is related to the amount of distraction in the rig necessary for a dislocation. The type of dislocation requiring the least distraction was medial `edge' dislocation in which the edge of the bearing dislocates onto the tibial wall, which is the most common type of dislocation. The amount of distraction necessary decreased the further the bearing was from the wall and with 50% posterior overhang. Rotation of the knee did not influence the amount of distraction. In conclusion dislocation can only occur if the lateral compartment is distracted. To reduce the dislocation risk, surgeons should aim to position the femoral and tibial components so that the bearing is as close as possible to the wall without jamming against it and the tibial component should be positioned flush with the posterior tibial cortex. If, during the surgery, the mobile bearing can easily be dislocated onto the wall the surgeon should consider changing to a fixed bearing. The tibial component should also be positioned flush with the posterior tibial cortex, as if it is too far forward this may contribute to dislocation.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Osteoartrite do Joelho , Humanos , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Fêmur/cirurgia , Desenho de Prótese
4.
Biol Res Nurs ; 25(3): 417-425, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36637872

RESUMO

Electronic cigarette use is highest among adults of child-bearing age. Many parents that use electronic cigarettes believe that secondhand exposure of electronic cigarette vapors for their children is not dangerous and is less harmful than secondhand exposure to traditional cigarette smoke. These beliefs may prompt excessive secondhand exposure to electronic cigarette vapors for their children. Little research has been done to document exposure in children. The traditional biological method of exposure detection is through a blood draw, which is difficult and undesirable in children. The purpose of this study was to assess the feasibility of using saliva and exhaled breath condensate as non-invasive biomatrices for detecting secondhand electronic cigarette vapor exposure in children. In this cross-sectionally designed study, we recruited 22 children exposed to electronic cigarette vapors and 26 non-exposed between the ages of 4-12 years. We compared metabolic features across three biomatrices, blood, saliva, and exhaled breath condensate. We noted moderate to strong pairwise, sample-specific, and feature-specific adjusted correlations. Annotated features associated with direct and secondhand electronic cigarette exposure were noted. These results demonstrate that less invasive biomatrices may be used to detect features associated with secondhand electronic cigarette vapor exposure in children.


Assuntos
Vapor do Cigarro Eletrônico , Sistemas Eletrônicos de Liberação de Nicotina , Poluição por Fumaça de Tabaco , Adulto , Criança , Pré-Escolar , Humanos , Vapor do Cigarro Eletrônico/efeitos adversos , Projetos Piloto , Saliva , Poluição por Fumaça de Tabaco/efeitos adversos , Metabolômica
5.
Oral Dis ; 29(4): 1875-1884, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35285123

RESUMO

OBJECTIVE: Electronic cigarettes have increased in popularity globally. Vaping may be associated with oral symptoms and pathologies including dental and periodontal damage, both of which have an underlying microbial etiology. The primary aim of this pilot study, therefore, was to compare the oral microbiome of vapers and non-vapers. SUBJECTS AND METHODS: This secondary data analysis had a cross-sectional comparative descriptive design and included data for 36 adults. Bacterial 16S rRNA genes were extracted and amplified from soft tissue oral swab specimens and taxonomically classified using the Human Oral Microbiome Database. RESULTS: Data for 18 vapers and 18 non-vapers were included in this study. Almost 56% of the vapers also smoked conventional cigarettes. Beta diversity differences were identified between vapers and non-vapers. Vapers had a significantly higher relative abundance of an unclassified species of Veillonella compared with non-vapers. Dual users had higher alpha diversity compared with exclusive vapers. Beta diversity was also associated with dual use. Multiple OTUs were identified to be associated with dual use of e-cigarettes and conventional cigarettes. CONCLUSIONS: Vapers exhibit an altered oral microbiome. Dual use of electronic cigarettes and conventional cigarettes is associated with the presence of several known pathogenic microbes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Adulto , Humanos , Estudos Transversais , Projetos Piloto , RNA Ribossômico 16S/genética , Fumantes
6.
Sci Rep ; 12(1): 2068, 2022 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35136092

RESUMO

Due to ligament laxity, bearing dislocation occurs in 1-6% of Oxford Domed Lateral (ODL) replacements with most dislocations occurring medially. Dislocations were studied using a previously built mechanical rig, however testing using the rig was inefficient. The aim of this study was to develop a better tool that was more reliable and efficient. An established robotics software package, the Open Motion Planning Library, was modified to accept the ODL components. Using a robotics path planning algorithm, the mobile bearing was allowed to find a way out from between the femoral and tibial components i.e. to dislocate. Testing assessed a range of clinically relevant positions of the femoral component relative to the tibial component. Dislocations were labelled as medial, lateral, anterior or posterior depending on the dislocation direction. The Distraction to Dislocation (DD) measured the minimum vertical distraction of the femoral component from the tibial component for a dislocation to occur. Results were validated against the mechanical rig. Statistical analysis of medial dislocation showed excellent agreement with an intraclass correlation value of 0.993 (95% CI 0.982-0.998). All DDs from the dislocation analysis tool were within 1 mm of the mechanical rig DDs with results sharing a remarkably similar trend. The robotics dislocation analysis tool output DDs which were marginally higher than the manual mechanical rig: 0.50 mm anteriorly, 0.25 mm posteriorly and 0.50 mm laterally. Medially, the computational DD differed on average by 0.09 mm (stand deviation: 0.2026 mm). Our study describes the development and validation of a novel robotics dislocation analysis tool, which allows mobile bearing dislocation risk quantification. The tool may also be used to improve surgical implantation parameters and to assess new implant designs that aim to reduce the medial dislocation risk to an acceptable level.


Assuntos
Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Luxação do Joelho/prevenção & controle , Prótese do Joelho , Procedimentos Cirúrgicos Robóticos/métodos , Algoritmos , Engenharia Biomédica/métodos , Humanos , Luxação do Joelho/diagnóstico , Articulação do Joelho/cirurgia , Osteoartrite do Joelho/cirurgia , Desenho de Prótese , Pesquisa Translacional Biomédica/métodos
7.
Knee ; 28: 214-228, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33422937

RESUMO

BACKGROUND: Bearing dislocation is a problem following mobile bearing Oxford lateral Unicompartmental Knee Replacement (UKR). Therefore, the design of the tibial component was changed from a flat tibial surface to a domed tibial surface with a biconcave bearing to increase bearing entrapment. This systematic review compared the dislocation and revision rates of the two designs. METHODS: Two authors independently searched MEDLINE, EMBASE and ISI Web of Science, reference lists of retrieved articles, and the internet. Randomised, cohort, case-control and case studies of adult patients with lateral knee osteoarthritis treated with flat or domed Oxford lateral UKR and their outcomes were included. The overall dislocation rate and the annual revision rate (per 100 component years) were determined. RESULTS: Nine studies (937 knees) met the inclusion criteria (3 flat, 6 domed). Four studies (all domed) had a low risk of bias and five had a high risk (3 flat, 2 domed), so data should be interpreted with caution. The bearing dislocation rate decreased from 17% (flat) to 3.7% (domed). Dislocations occurred on average at 16 months and medial dislocations were most common. The revision rate excluding dislocation decreased from 1.1%pa to 0.7%pa. PROSPERO registration: CRD42019139250. CONCLUSION: Modifying the tibial component from a flat to a domed shape decreased the bearing dislocation rate to 3.7% and increased the 10 year survival rate excluding dislocation to 93%. The dislocation rate is still relatively high so bearing stability should be assessed intra-operatively and if unacceptable, a fixed bearing version of the Oxford lateral tibial component can be inserted.


Assuntos
Artroplastia do Joelho/instrumentação , Luxação do Joelho/etiologia , Prótese do Joelho/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Humanos , Desenho de Prótese , Falha de Prótese , Reoperação
8.
Bone Joint J ; 102-B(8): 1033-1040, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32731833

RESUMO

AIMS: To report mid- to long-term results of Oxford mobile bearing domed lateral unicompartmental knee arthroplasty (UKA), and determine the effect of potential contraindications on outcome. METHODS: A total of 325 consecutive domed lateral UKAs undertaken for the recommended indications were included, and their functional and survival outcomes were assessed. The effects of age, weight, activity, and the presence of full-thickness erosions of cartilage in the patellofemoral joint on outcome were evaluated. RESULTS: Median follow-up was seven years (3 to 14), and mean age at surgery was 65 years (39 to 90). Median Oxford Knee Score (OKS) was 43 (interquartile range (IQR) 37 to 47), with 260 (80%) achieving a good or excellent score (OKS > 34). Revisions occurred in 34 (10%); 14 (4%) were for dislocation, of which 12 had no recurrence following insertion of a new bearing, and 12 (4%) were revised for medial osteoarthritis (OA). Ten-year survival was 85% (95% confidence interval (CI) 79 to 90, at risk 72). Age, weight, activity, and patellofemoral erosions did not have a significant effect on the clinical outcome or survival. CONCLUSION: Domed lateral UKA provides a good alternative to total knee arthroplasty (TKA) in the management of lateral compartment OA. Although dislocation is relatively easy to treat successfully, the dislocation rate of 4% is high. It is recommended that the stability of the bearing is assessed intraoperatively. If the bearing can easily be displaced, the fixed rather than the mobile bearing version of the Oxford lateral tibial component should be inserted instead. Younger age, heavier weight, high activity, and patellofemoral erosions did not detrimentally affect outcome, so should not be considered contraindications. Cite this article: Bone Joint J 2020;102-B(8):1033-1040.


Assuntos
Artroplastia do Joelho/métodos , Hemiartroplastia/métodos , Osteoartrite do Joelho/cirurgia , Desenho de Prótese/métodos , Reoperação/métodos , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/efeitos adversos , Bases de Dados Factuais , Feminino , Seguimentos , Hemiartroplastia/efeitos adversos , Humanos , Luxações Articulares/cirurgia , Prótese do Joelho , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Falha de Prótese , Recuperação de Função Fisiológica , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Resultado do Tratamento
9.
Cancer Prev Res (Phila) ; 13(6): 551-562, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32161072

RESUMO

Sulforaphane (SFN), a potent antioxidant and antiinflammatory agent, has been shown to protect against cancers especially at early stages. However, how SFN affects UVB-mediated epigenome/DNA methylome and transcriptome changes in skin photodamage has not been fully assessed. Herein, we investigated the transcriptomic and DNA methylomic changes during tumor initiation, promotion, and progression and its impact and reversal by SFN using next-generation sequencing (NGS) technology. The results show that SFN reduced tumor incidence and tumor number. SFN's protective effects were more dramatic in the early stages than with later stages. Bioinformatic analysis of RNA sequencing (RNA-seq) data shows differential expressed genes and identifies the top canonical pathways related to SFN treatment of UVB-induced different stages of epidermal carcinogenesis. These pathways include p53 signaling, cell cycle: G2-M DNA damage checkpoint regulation, Th1, and Th2 activation pathway, and PTEN signaling pathways. The top upstream regulators related to UVB and SFN treatment as time progressed include dextran sulfate, TP53, NFE2L2 (Nrf2), IFNB1, and IL10RA. Bioinformatic analysis of Methyl-seq data shows several differential methylation regions induced by UVB were attenuated by SFN. These include Notch1, Smad6, Gnai3, and Apc2 Integrative analysis of RNA-seq and DNA-seq/CpG methylome yields a subgroup of genes associated with ultraviolet B (UVB) and SFN treatment. The changes in gene expression were inversely correlated with promoter CpG methylation status. These genes include Pik3cd, Matk, and Adm2 In conclusion, our study provides novel insights on the impact of SFN on the transcriptomic and DNA methylomic of UVB-induced different stages of skin cancer in mice.


Assuntos
Anticarcinógenos/uso terapêutico , Metilação de DNA/efeitos dos fármacos , Epigenoma/efeitos dos fármacos , Isotiocianatos/uso terapêutico , Neoplasias Induzidas por Radiação/prevenção & controle , Neoplasias Cutâneas/prevenção & controle , Sulfóxidos/uso terapêutico , Transcriptoma/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Acetona/toxicidade , Animais , Ilhas de CpG/efeitos dos fármacos , DNA de Neoplasias/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Camundongos , Camundongos Pelados , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Induzidas por Radiação/etiologia , Neoplasias Induzidas por Radiação/genética , Regiões Promotoras Genéticas , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , RNA-Seq , Radiossensibilizantes/toxicidade , Distribuição Aleatória , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética
10.
Crit Rev Toxicol ; 50(2): 97-127, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32043402

RESUMO

Introduction: Electronic cigarette (e-cigarette) use is becoming more prevalent and is particularly popular among adolescents and conventional smokers. While the oral health sequelae of conventional smoking are well-established, the impact of e-cigarettes on oral health is still unknown. This study aims to systematically review the available research evidence on the oral health impact of e-cigarette use.Methods: This systematic review was conducted according to PRISMA guidelines and used the Effective Public Health Practice Project Quality Assessment Tool to evaluate the evidence. Three electronic databases (PubMed, Web of Science, and Embase) were systematically searched for studies including case reports. Two independent reviewers extracted data and synthesized the findings.Results: Ninety-nine articles were included in this systematic review. Analyses of the articles yielded seven categories based on symptom similarity and/or focus: mouth effects, throat effects, periodontal effects, dental effects, cytotoxic/genotoxic/oncologic effects, oral microbiome effects, and traumatic/accidental injury. The majority of mouth and throat symptoms experienced by e-cigarette users were relatively minor and temporary, with some evidence that conventional smokers who switched to e-cigarettes experienced mitigation of these symptoms. E-cigarette exposure increased the risk for deteriorating periodontal, dental and gingival health as well as changes to the oral microbiome. Extensive dental damage as a result of e-cigarette explosions were described in case reports. Components of e-cigarette vapor have known cytotoxic, genotoxic, and carcinogenic properties.Conclusions: Although switching to e-cigarettes may mitigate oral symptomatology for conventional smokers, findings from this review suggest that a wide range of oral health sequelae may be associated with e-cigarette use. Well-designed studies to investigate oral health outcomes of e-cigarette use are needed.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Saúde Bucal , Vaping/tendências , Humanos , Fumantes , Fumar
11.
Women Health ; 59(9): 1026-1074, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-30835645

RESUMO

Socioeconomically disadvantaged pregnant women are especially at risk for smoking. To understand better this health behavior disparity, this systematic, integrative, comprehensive review aimed to identify factors related to prenatal smoking among socioeconomically disadvantaged women in the United States. A comprehensive literature search yielded 67 articles published between 2008 and 2016. Associated factors included any study variable related to persistent prenatal smoking. The Social Ecological Model (SEM), a multidimensional ecological framework, was used to organize the findings. Thirty-eight factors were explored in the reviewed studies and categorized according to SEM dimensions: individual, interpersonal, organizational, community, public policies and laws. At the individual level, most studies identified the socioeconomically disadvantaged prenatal smoker as older, US-born, White, unmarried, and multiparous. Other individual-level factors included alcohol abuse, nicotine dependence, and psychosocial factors such as stress and depressive symptoms. For broader levels of the SEM, associated factors included abuse/trauma, secondhand smoke exposure, lack of prenatal care, smoking cessation interventions, neighborhood risk, and state level initiatives such as cigarette taxes. The results of this review suggested multiple directions for future research to move science toward effective, scalable, and sustainable approaches that effectively address prenatal smoking among socioeconomically disadvantaged women.


Assuntos
Comportamentos Relacionados com a Saúde , Conhecimentos, Atitudes e Prática em Saúde , Acessibilidade aos Serviços de Saúde , Gestantes/psicologia , Cuidado Pré-Natal , Características de Residência , Fumar/efeitos adversos , Populações Vulneráveis , Adulto , Feminino , Disparidades nos Níveis de Saúde , Humanos , Relações Interpessoais , Gravidez , Fumar/psicologia , Determinantes Sociais da Saúde , Fatores Socioeconômicos , Estados Unidos
12.
Cardiovasc Eng Technol ; 10(2): 205-215, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30767113

RESUMO

Despite advances in modern surgery, congenital heart disease remains a medical challenge and major cause of infant mortality. Valved conduits are routinely used to surgically correct blood flow in hearts with congenital malformations by connecting the right ventricle to the pulmonary artery (RV-PA). This review explores the current range of RV-PA conduits and describes their strengths and disadvantages. Homografts and xenografts are currently the primary treatment modalities, however both graft types have limited biocompatibility and durability, and present a disease transmission risk. Structural deterioration of a replaced valve can lead to pulmonary valve stenosis and/or regurgitation. Moreover, as current RV-PA conduits are of a fixed size, multiple subsequent operations are required to upsize a valved conduit over a patient's lifetime. We assess emerging biomaterials and tissue engineering techniques with a view to replicating the features of native tissues, including matching the durability and elasticity required for normal fluid flow dynamics. The benefits and limitations of incorporating cellular elements within the biomaterial are also discussed. Present review demonstrates that an alignment of medical and engineering disciplines will be ultimately required to produce a biocompatible and high-functioning artificial conduit.


Assuntos
Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Cardiopatias Congênitas/cirurgia , Implante de Prótese de Valva Cardíaca/instrumentação , Próteses Valvulares Cardíacas , Ventrículos do Coração/cirurgia , Artéria Pulmonar/cirurgia , Animais , Implante de Prótese Vascular/efeitos adversos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/fisiopatologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Humanos , Desenho de Prótese , Falha de Prótese , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do Tratamento
13.
Cancer Lett ; 449: 20-30, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30771437

RESUMO

Exposure to ultraviolet B (UVB) irradiation results in multitude of cellular responses including generation of reactive oxygen species and DNA damage and is responsible for non-melanoma skin cancers (NMSCs). Although genetic mutation is well documented, the epi-mutation, the alteration in epigenetics, remains elusive. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in UVB-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages. Methyl-seq and RNA-seq were performed to examine the methylation and corresponding transcriptome alterations. The methylation profiles in mouse epidermis were altered by UVB-irradiation as time progresses. Ingenuity Pathways Analysis (IPA) identified many cancer related pathways including PTEN, p53, Nrf2 and inflammatory signaling in UVB-irradiation induced carcinogenesis. Additionally, some novel genes involved in skin carcinogenesis that were not previously reported were differentially methylated, including Enf2, Mgst2, Vegfa, and Cdk4. Taken together, the current study provides novel profiles and insights of methylation and transcriptomic changes at different stages of carcinogenesis in UVB-irradiation induced NMSC and offers potential targets for prevention and treatment of NMSC at different stages of human skin cancer.


Assuntos
Metilação de DNA , Redes Reguladoras de Genes/efeitos da radiação , Análise de Sequência de DNA/métodos , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos , Animais , Ilhas de CpG , Progressão da Doença , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Camundongos , Estadiamento de Neoplasias , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética
14.
AAPS J ; 20(2): 32, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29603113

RESUMO

Nuclear factor erythroid-2-related factor-2 (Nrf2 or NFE2L2) is a master regulator of the anti-oxidative stress response, which is involved in the defense against many oxidative stress/inflammation-mediated diseases, including anticancer effects elicited by an increasing number of natural products. Our previous studies showed that the epigenetic modification of the Nrf2 gene plays a key role in restoring the expression of Nrf2. In this study, we aimed to investigate the epigenetic regulation of Nrf2 by astaxanthin (AST) and fucoxanthin (FX), carotenoids which are abundant in microalgae and seaweeds, in mouse skin epidermal JB6 P+ cells. FX induced the anti-oxidant response element (ARE)-luciferase and upregulated the mRNA and protein levels of Nrf2 and Nrf2 downstream genes in HepG2-C8 cells overexpressing the ARE-luciferase reporter. Both FX and AST decreased colony formation in 12-Otetradecanoylphorbol-13-acetate (TPA)-induced transformation of JB6 P+ cells. FX decreased the methylation of the Nrf2 promoter region in the JB6 P+ cells by the bisulfite conversion and pyrosequencing. Both FX and AST significantly reduced DNA methyltransferase (DNMT) activity but did not affect histone deacetylase (HDAC) activity in JB6 P+ cells. In summary, our results show that FX activates the Nrf2 signaling pathway, induces the epigenetic demethylation of CpG sites in Nrf2 and blocks the TPA-induced transformation of JB6 P+ cells, indicating the potential health-promoting effects of FX in skin cancer prevention.


Assuntos
Transformação Celular Neoplásica/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Xantofilas/farmacologia , Animais , Elementos de Resposta Antioxidante/genética , Ilhas de CpG/genética , Desmetilação do DNA/efeitos dos fármacos , Células Epidérmicas , Técnicas de Silenciamento de Genes , Células Hep G2 , Humanos , Camundongos , Fator 2 Relacionado a NF-E2/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/prevenção & controle , Acetato de Tetradecanoilforbol/farmacologia
15.
Clin Nurs Res ; 26(4): 419-450, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-26935345

RESUMO

This integrative review provides an overview of nicotine dependence measures used with perinatal women and an evaluation of their psychometric properties. Fifty-five articles that met inclusion and exclusion criteria were identified from five different databases. Most of the studies used the Fagerström Test for Nicotine Dependence (FTND). Other approaches included diagnostic tests, the Wisconsin Inventory of Smoking Dependence Motives (WISDM), the Tobacco Dependence Screener, and single-item measures. This review indicated that the FTND may not be the best option for measuring nicotine dependence in this population. The WISDM is a newer instrument that has excellent psychometric properties and captures nonnicotinic dimensions of nicotine dependence relevant to women. Future research is needed to assess its reliability in the perinatal population. Other recommendations from this review include the use of biomarker validation, thorough psychometric reporting on nicotine dependence instruments, and the use of multiple instruments to maximize comparability between nicotine dependence instruments.


Assuntos
Assistência Perinatal , Inquéritos e Questionários , Tabagismo/psicologia , Comportamento Aditivo/psicologia , Feminino , Humanos , Gravidez , Psicometria , Fumar/psicologia
16.
Nurs Res ; 66(1): 2-11, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27977563

RESUMO

BACKGROUND: Low-income, unemployed women with low levels of education are more likely to smoke during pregnancy compared to their higher-income, employed, and well-educated counterparts. The reserve capacity model (RCM) offers a theoretical framework to explain how psychosocial factors may serve as pathways connecting socioeconomic status (SES) to health behaviors. Research supports the link between prenatal smoking and several psychosocial variables such as chronic stressors, depressive symptoms, and social support. How these variables interrelate to explain the predominance of prenatal smoking in lower socioeconomic groups of pregnant women has not been fully elucidated. OBJECTIVE: The aim of this study was to test the RCM to evaluate the roles of early pregnancy levels of chronic stress, quality of the primary intimate relationship, and depressive symptoms in explaining the relationship between SES and persistent prenatal smoking. METHODS: A secondary analysis of data from 370 pregnant nonsmokers, spontaneous quitters, and persistent prenatal smokers was conducted. On the basis of the RCM, chronic stressors, depressive symptoms, and the quality of the primary intimate relationship were evaluated as potential mediating variables linking SES with persistent prenatal smoking using path analysis. RESULTS: Path analyses indicated that a simple model with all three psychosocial variables as mediators of the relationship between SES and persistent prenatal smoking provided the best fit. DISCUSSION: Findings indicated that chronic stressors, depressive symptoms, and the quality of the primary intimate relationship play important roles in the pathway from SES to prenatal smoking status. This knowledge can assist in the development of prevention and intervention strategies to target these variables and ultimately reduce prenatal smoking.


Assuntos
Comportamento Materno/psicologia , Modelos Psicológicos , Mães/psicologia , Complicações na Gravidez/psicologia , Cuidado Pré-Natal/métodos , Fumar/psicologia , Atitude Frente a Saúde , Feminino , Humanos , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Fatores de Risco , Fumar/epidemiologia , Prevenção do Hábito de Fumar , Fatores Socioeconômicos
17.
Muscle Nerve ; 54(1): 157-61, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27065302

RESUMO

INTRODUCTION: While anticancer immunotherapies have traditionally focused on activation of the immune system, there is recent interest in disinhibition of the natural antitumor immune response by targeting immune checkpoints such as cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). One humanized monoclonal antibody against PD-1, pembrolizumab, was recently approved for treatment of metastatic malignant melanoma. METHODS: We report exacerbation of myasthenia gravis (MG) after treatment with pembrolizumab and provide a brief literature review. RESULTS: We describe a 75-year-old man with stable MG who experienced myasthenic crisis in the setting of pembrolizumab treatment. A concurrent azathioprine taper was a possible although unlikely contributor given the short time interval between taper and exacerbation. CONCLUSIONS: As long-term data become available regarding the adverse immune effects of novel checkpoint inhibitors, clinicians should be mindful of their risks/benefits and of possible autoimmune disease exacerbation. Muscle Nerve 54: 157-161, 2016.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/efeitos adversos , Melanoma/complicações , Melanoma/tratamento farmacológico , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/complicações , Idoso , Humanos , Masculino
18.
MCN Am J Matern Child Nurs ; 39(6): 375-80, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25333805

RESUMO

PURPOSE: To compare inpatient postpartum current and former smokers on: need for smoking cessation assistance; cessation interventions received from healthcare providers; cessation methods used; perceived barriers of cessation; exposure to second hand smoke (SHS); interest in postdischarge interventions; and smoking abstinence self-efficacy (SASE). STUDY DESIGN AND METHODS: A descriptive comparative study was conducted using a cross-sectional survey of 24 postpartum women in the inpatient setting. Surveys were administered by face-to-face interview, with a paper-and-pencil option, and included questions from the Pregnancy Risk Assessment Monitoring System and the SASE Scale. RESULTS: Women were predominantly low-income, unemployed, and Medicaid insured. Two-thirds of current smokers indicated that they needed help with smoking cessation. Most women in both groups received advice to quit smoking. Fewer, however, received specific types of assistance to stop smoking. The predominant smoking cessation method attempted in both groups was the "cold turkey" method. More former smokers than current smokers maintained a nonsmoking home environment. More current smokers than former smokers were interested in postdischarge interventions. CLINICAL IMPLICATIONS: Current smokers need help quitting smoking and former smokers need postpartum relapse interventions. Providers should be intentional about offering existing interventions to help women quit smoking. Affordable and accessible interventions are needed that address unique stressors experienced by women, which include screening for depression and anxiety, and that incorporate smoking cessation interventions for spouses and partners who smoke. Cessation and relapse prevention interventions for postpartum women should start in the postpartum inpatient period and continue after discharge.


Assuntos
Promoção da Saúde , Período Pós-Parto/psicologia , Abandono do Hábito de Fumar/psicologia , Fumar/terapia , Estudos Transversais , Feminino , Humanos , Gravidez , Recidiva , Inquéritos e Questionários
19.
Nat Rev Rheumatol ; 8(10): 610-21, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22945592

RESUMO

Gout is a common and very painful inflammatory arthritis caused by hyperuricaemia. This review provides an update on the genetics of hyperuricaemia and gout, including findings from genome-wide association studies. Most of the genes that associated with serum uric acid levels or gout are involved in the renal urate-transport system. For example, the urate transporter genes SLC2A9, ABCG2 and SLC22A12 modulate serum uric acid levels and gout risk. The net balance between renal urate absorption and secretion is a major determinant of serum uric acid concentration and loss-of-function mutations in SLC2A9 and SLC22A12 cause hereditary hypouricaemia due to reduced urate absorption and unopposed urate secretion. However, the variance in serum uric acid explained by genetic variants is small and their clinical utility for gout risk prediction seems limited because serum uric acid levels effectively predict gout risk. Urate-associated genes and genetically determined serum uric acid levels were largely unassociated with cardiovascular-metabolic outcomes, challenging the hypothesis of a causal role of serum uric acid in the development of cardiovascular disease. Strong pharmacogenetic associations between HLA-B*5801 alleles and severe allopurinol-hypersensitivity reactions were shown in Asian and European populations. Genetic testing for HLA-B*5801 alleles could be used to predict these potentially fatal adverse effects.


Assuntos
Gota/genética , Hiperuricemia/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Alopurinol/efeitos adversos , Proteínas Facilitadoras de Transporte de Glucose/genética , Gota/tratamento farmacológico , Supressores da Gota/efeitos adversos , Humanos , Proteínas de Neoplasias/genética , Transportadores de Ânions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/genética , Ácido Úrico/sangue
20.
Front Biosci (Elite Ed) ; 4(7): 2525-35, 2012 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-22652658

RESUMO

This study investigated the effects of homocysteine (Hcy) on angiogenesis in cultured human umbilical vein endothelial cells (HUVEC) and zebrafish embryos. We found that Hcy (50 micromol/L) significantly decreased cell numbers, viability, and induced a G1/S arrest in HUVEC in the presence of adenosine (Ade, 50 micromol/L). Hcy, in combination with Ade, reduced migration and suppressed tube-like formation on Matrigel in HUVEC. Further, Hcy reduced subintestinal vessel formation in zebrafish embryos. Interestingly, Hcy-induced inhibitory effects on cell growth, migration, tube-like formation, and vessel formation in HUVEC and zebra fish embryos were abolished by the supplement of recombinant VEGF (10 ng/ml). Finally, Hcy in combination with Ade reduced the mRNA levels of VEGF, VEGFR-1, VEGFR-2, and attenuated protein levels of VEGF, ERK1/2 and Akt. The present study suggests that Hcy inhibits angiogenesis, and that the mechanism anti-angiogenic effects of Hcy may be through VEGF/VEGFR, Akt, and ERK1/2 inhibition.


Assuntos
Homocisteína/fisiologia , Neovascularização Fisiológica , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Sequência de Bases , Ciclo Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Primers do DNA , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Humanos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Peixe-Zebra
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