Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer.

Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.

Evaluation in design science: A framework to support project studies in the context of University Research Centres.

This paper proposes a discussion of the evaluation of an artefact developed under the Design Science paradigm using the Delphi method. It evaluates the Ecosystem framework of University Research Centres in Project Studies, considering a set of criteria pre-established in the literature. The Delphi method is an evaluation implemented in an electronic platform involving twenty-one participants, among whom were academics, practitioners, and PhD candidates in the field of project management. It reached consensus and stability in two rounds: the results indicate a consensus among the participants in the applicability, novelty, simplicity, completeness, fidelity to modelled phenomena, consistency and internal coherence, scalability, flexibility, interest, elegance, and reusability criteria. Usability was the only criterion that did not attain the predefined percentage of consensus among the participants (70%). Given the framework's characteristics, Delphi participants indicated the need to produce complementary guidelines for its implementation.

HPV testing for cervical cancer screening: Should reflex cytology be performed after a positive test for HPV 16 and 18?

At Portuguese-organized cervical cancer (CC) screening programs, all women testing positive for human papillomavirus (HPV) 16 and/or 18 are referred for immediate colposcopy. This study aimed to evaluate the utility of reflex cytology in women who test positive for HPV 16 and/or 18 to improve the efficiency of CC screening. A cross-sectional and retrospective study was performed based on data from the routine CC screening protocol in force at Cova da Beira University Hospital Center, Portugal between August 2012 and June 2021. The screening method was the Cobas 4800 HPV test using the liquid medium Surepath. In all the selected cases, the patient's HPV test results and the cytology and histology findings of the biopsies obtained using colposcopy were analyzed. This study included 339 women who first tested positive for HPV 16 and/or 18 and were referred for immediate colposcopy, in whom 40 (11.8%) cases of high-grade squamous intraepithelial lesion (HSIL+) were diagnosed. Of these, 12 (30%) had reflex cytology negative for intraepithelial lesion or malignancy (NILM) and 14 (35%) had HSIL+ cytology. After 3 years, 14 (9.3%) of the 150 women who were still undergoing follow-up were diagnosed with histologic HSIL+ lesions, of which 5 (35.7%) had baseline NILM cytology. Despite the small sample, the results of this study allow us to conclude that reflex cytology is not useful for discrimination to immediate referral for colposcopy in women who test positive for HPV 16 and/or 18, as most women with a histologic diagnosis of an HSIL+ lesion had

Steroid hormone levels and bone mineral density in women over 65 years of age.

Previous studies using immunoassays for steroid measurements have focused on the association between steroid hormone levels and bone mineral density (BMD) in postmenopausal women, obtaining contradictory results. This study aimed to assess this association using a highly sensitive bioanalytical method. A total of 68 postmenopausal women, aged 65-89 years, were enrolled in a cross-sectional study. Measurements of the BMD of the hip and lumbar spine were performed using dual energy X-ray absorptiometry, and serum hormone levels were quantified by gas chromatography and tandem mass spectrometry. Associations between estradiol (E2), testosterone, dehydroepiandrosterone (DHEA), androstenedione and T score levels of the hip and lumbar spine were evaluated, after adjustment for confounding variables. The analysis revealed a statistically significant association between testosterone and the T score of the hip (p = 0.035), but not that of the lumbar spine. No statistically significant associations were found between E2, DHEA, androstenedione and the T scores of the hip and the lumbar spine. Using a highly sensitive hormone assay method, our study identified a significant association between testosterone and BMD of the hip in women over 65 years of age, suggesting that lower testosterone increases the risk of osteoporosis.

[Consensus Guidelines for the Management of Abnormal Cervical Cancer Screening Tests by the SPCPTGI]. / Orientações de Consenso para a Abordagem dos Resultados Alterados nos Testes de Rastreio do Cancro do Colo do Útero pela SPCPTGI.

Cervical cancer is one of the most common types of cancer in women. Cervical cancer screening is needed for the detection and treatment of cervical neoplastic lesions that can evolve to neoplasia and to reduce the incidence of cervical cancer. Recently, changes were made to increase the efficiency of the screening process such as employing the human papilloma virus detection test as the gold standard for cervical cancer screening and acknowledging the importance of adapting clinical practice to consider the risk of developing this neoplasia. Considering this paradigm shift, new clinical practice guidelines are now needed. For this purpose, a group of experts analyzed and discussed the most recent literature, defining recommendations and proposing clinical practice guidelines that focus on risk stratification, diagnostic evaluation, and on the therapeutical approach and follow-up of women with altered screening results. The aim of this article is to guide clinical practice regarding actions to take in face of altered results of cervical cancer screening and, consequently, to improve the secondary prevention of this condition.

O cancro do colo do útero (CCU) é globalmente um dos tipos de cancro mais comum em mulheres. O rastreio do CCU é indispensável para a deteção e tratamento de lesões neoplásicas cervicais que possam evoluir para neoplasia, com o objectivo de reduzir a incidência deste cancro. Nos últimos anos, têm ocorrido alterações que visam o aumento da eficácia do rastreio. Nomeadamente, o uso de teste de deteção do vírus do papiloma humano como método de rastreio primário do CCU e a valorização da importância de adaptar a prática clínica em função do risco de desenvolvimento do CCU. Desta forma, são necessárias novas normas de atuação clínica, que contemplem esta mudança de paradigma. Assim, um grupo de especialistas analisou e discutiu a literatura mais recente, definindo recomendações e propondo normas de prática clínica que se focam na estratificação de risco, avaliação diagnóstica, e na conduta terapêutica e de seguimento de mulheres com resultados dos testes de rastreio alterados. Este trabalho tem como objetivo facilitar a prática clínica em resposta a resultados alterados nos testes e, consequentemente, melhorar a prevenção secundária do CCU.

Steroid hormone levels in postmenopausal hysterectomised women with and without ovarian conservation: the continuous endocrine function of the ovaries.

This study aims to clarify the effect of postmenopausal bilateral oophorectomy on plasma steroid hormone levels. Women who were submitted in the postmenopausal period to hysterectomy for uterine benign conditions were divided into two groups: 18 women had isolated hysterectomy and 11 had hysterectomy with bilateral salpingo-oophorectomy. In both groups serum hormone levels were quantified by solid phase extraction and gas chromatography and tandem mass spectrometry. Differences in dehydroepiandrosterone (DHEA), testosterone, androstenedione and oestradiol were determined in both groups. The analysis revealed lower steroid levels in the bilateral salpingo-oophorectomy group when compared to the isolated hysterectomy group with statistically significant differences found for DHEA (5.8 ± 3.2 vs. 9.4 ± 4.4 ng/mL; p = 0.019) and oestradiol (0.69 ± 0.4 vs. 1.48 ± 4.3 ng/mL; p = 0.007). The results are consistent with a significant endocrine activity of the postmenopausal ovary. The clinical consequences of these findings need to be clarified and postmenopausal prophylactic bilateral salpingo-oophorectomy re-evaluated.IMPACT STATEMENTWhat is already known on this subject? Although it is consensual that premenopausal prophylactic bilateral oophorectomy should not be performed because it has harmful effects on women's health, the evidence regarding the effects of postmenopausal prophylactic bilateral oophorectomy is scarce and this procedure continues to be a regular practice. Few studies have demonstrated that postmenopausal ovaries still have endocrine activity that may impact older women's health.What do the results of this study add? This is the first study to compare hormone levels of postmenopausal women based on their hysterectomy and oophorectomy status using GC-MS/MS, a highly sensitive bioanalytical assay for the measurement of steroid hormones. Previous studies relied on immunoassays and did not compare DHEA levels, which according to the intracrinology theory is a precursor for androgens and oestrogens. In this study, statistically significant lower levels of DHEA and oestradiol were found after postmenopausal bilateral salpingo-oophorectomy.What are the implications of these findings for clinical practice and/or further research? This is a pilot study that may lead to further investigation in this area to clarify the impact of the prophylactic removal of postmenopausal ovaries on older women's health and lead to changes in surgical procedures.

Aptamer-Functionalized Gold Nanoparticles for Drug Delivery to Gynecological Carcinoma Cells.

Cervical cancer is one of the most common cancers and is one of the major cause of deaths in women, especially in underdeveloped countries. The patients are usually treated with surgery, radiotherapy, and chemotherapy. However, these treatments can cause several side effects and may lead to infertility. Another concerning gynecologic cancer is endometrial cancer, in which a high number of patients present a poor prognosis with low survival rates. AS1411, a DNA aptamer, increases anticancer therapeutic selectivity, and through its conjugation with gold nanoparticles (AS1411-AuNPs) it is possible to improve the anticancer effects. Therefore, AS1411-AuNPs are potential drug carriers for selectively delivering therapeutic drugs to cervical cancer. In this work, we used AS1411-AuNPs as a carrier for an acridine orange derivative (C8) or Imiquimod (IQ). The AS1411 aptamer was covalently bound to AuNPs, and each drug was associated via supramolecular assembly. The final nanoparticles presented suitable properties for pharmaceutical applications, such as small size, negative charge, and favorable drug release properties. Cellular uptake was characterized by confocal microscopy and flow cytometry, and effects on cellular viability were determined by MTT assay. The nanoparticles were then incorporated into a gel formulation of polyethylene glycol, suitable for topical application in the female genital tract. This gel showed promising tissue retention properties in Franz cells studies in the porcine vaginal epithelia. These findings suggest that the tested nanoparticles are promising drug carriers for cervical cancer therapy.

The International Society for the Study of Vulvovaginal Disease Vaginal Wet Mount Microscopy Guidelines: How to Perform, Applications, and Interpretation.

OBJECTIVES: The aims of the study were to assess the available literature concerning the indications, performance, technique, and classification of wet mount microscopy (WMM) and to establish evidence-based recommendations. METHODS: Literature review from the main scientific databases was performed by the ad hoc "Vaginitis and Microbiome Committee" of the International Society for the Study of Vulvovaginal Disease. The document was approved by the executive council and membership of the International Society for the Study of Vulvovaginal Disease. RESULTS: Available data are limited and usually of low level of evidence. Nevertheless, it shows that WMM is capable of reducing misdiagnosis, overtreatment, and undertreatment of vaginal conditions. It has an excellent performance for the diagnosis of bacterial vaginosis and variable performance for trichomoniasis and candidiasis. It is the gold standard for aerobic vaginitis/desquamative inflammatory vaginitis. Currently, there is no recommendation to use WMM in the screening of asymptomatic women.The use of phase contrast is recommended to improve performance and reproducibility. Sampling location, devices, and technique have an impact on the results.Available scoring and classification scores have significant limitations. CONCLUSIONS: Wet mount microscopy is a point-of-care, inexpensive, and fast technique that, with practice, can be mastered by office clinicians. It should be considered a basic skill in the curricula of gynecology and obstetrics residencies. Recommendations are provided on sampling, reading, and scoring.

Influence of Estrogenic Metabolic Pathway Genes Polymorphisms on Postmenopausal Breast Cancer Risk.

Estrogen metabolism plays an important role in tumor initiation and development. Lifetime exposure to high estrogens levels and deregulation of enzymes involved in estrogen biosynthetic and metabolic pathway are considered risk factors for breast cancer. The present study aimed to evaluate the impact of mutations acquisition during the lifetime in low penetrance genes that codify enzymes responsible for estrogen detoxification. Genotype analysis of GSTM1 and GSTT1 null polymorphisms, CYP1B1 Val432Leu and MTHFR C677T polymorphisms was performed in 157 samples of women with hormone-dependent breast cancer and correlated with the age at diagnosis. The majority of patients with GSTT1 null genotype and with both GSTM1 and GSTT1 null genotypes were 50 years old or more at the diagnosis (p-value = 0.021 and 0.018, respectively). Older women with GSTM1 null genotype were also carriers of the CYP1B1Val allele (p-value = 0.012). As well, GSTT1 null and CYP1B1Val genotypes were correlated with diagnosis at later ages (p-value = 0.022). Similar results were found associating MTHFR C677T and GSTT1 null polymorphism (p-value = 0.034). Our results suggest that estrogen metabolic pathway polymorphisms constitute a factor to be considered simultaneously with models for breast cancer risk assessment.

Gestão de projetos no contexto público: mapeamento do campo de investigação / Gestión de proyectos en el contexto público: mapeo del campo de investigación / Project management in the public context: research field mapping

Resumo O advento da Nova Gestão Pública introduziu o conceito de gestão de projetos, até então exclusivo do setor privado, abrindo caminho para o aumento da eficiência do Estado. Nesse cenário, o objetivo deste artigo é localizar, sintetizar e identificar as proximidades teóricas entre os estudos de gestão de projetos no contexto público. Para alcançá-lo, definiu-se a abordagem metodológica bibliométrica recorrendo à análise relacional de citações, realizada pelos métodos de cocitação e de pareamento bibliográfico, a fim de descobrir relações de conectividade entre as obras publicadas. As análises fatoriais exploratórias da cocitação e do pareamento conduziram a 6 fatores, indicando a estrutura intelectual e possibilitando, também, a geração de um framework de integração dos fatores a partir das citações mais frequentes. Os resultados indicaram a prevalência de estudos sobre competências em gestão de projetos e governo eletrônico. Abre-se, ainda, o leque de discussões com a apresentação de uma agenda especificamente direcionada à gestão de projetos públicos.

Resumen El advenimiento de la Nueva Gestión Pública introdujo el concepto de gestión de proyectos, hasta entonces exclusivo del sector privado, allanando el camino para aumentar la eficiencia del Estado. En este escenario, el objetivo de este artículo es localizar, sintetizar e identificar la proximidad teórica entre los estudios de gestión de proyectos en el contexto público. Para lograr esto, se definió el enfoque metodológico bibliométrico mediante el análisis relacional de citas, realizado por los métodos de cocitación y emparejamiento bibliográfico para descubrir relaciones de conectividad entre los trabajos publicados. El análisis factorial exploratorio de la cocitación y del emparejamiento condujo a 6 factores, lo que indica la estructura intelectual, y también permite la generación de un framework para integrar factores a partir de las citas más frecuentes. Los resultados indicaron la prevalencia de estudios sobre habilidades en gestión de proyectos y gobierno electrónico. También se amplía la gama de discusiones con la presentación de una agenda específicamente dirigida a la gestión de proyectos públicos.

Abstract The advent of New Public Management introduced the concept of project management until then exclusive to the private sector, paving the way for increased state efficiency. In this scenario, this article aims to locate, synthesize, and identify the theoretical proximity among studies on project management in the public context. The bibliometric methodological approach used relational analysis of citations and the methods of cocitation and coupling to reveal the connections among the studies published. Exploratory factor analysis of cocitation and coupling led to six factors, indicating the intellectual structure, and enabling the generation of a factor integration framework from the most frequent citations. The results indicated the prevalence of studies on project management and e-government competencies. It also amplifies discussions with the presentation of an agenda directed explicitly to the management of public projects.

The prognostic value of NRF2 in breast cancer patients: a systematic review with meta-analysis.

PURPOSE: Nuclear factor E2-related factor 2 (NRF2) is a transcription factor that plays a major role in the regulation of intracellular antioxidant response. The effect of NRF2 overexpression in many malignancies is still unclear and recent meta-analysis correlated NRF2 overexpression with poor prognosis in a variety of human cancers. However, the effect of NRF2 overexpression in breast cancer is still unclear. Thus, the main goal of this work was to clarify the role of NRF2 expression in survival and relapse of breast cancer patients by performing a systematic review according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement, followed by a meta-analysis. METHODS: The electronic search was conducted in PubMed, Scopus, SciELO, Web of Science and Embase between November of 2017 and September of 2018. To be included, studies should evaluate NRF2 expression in breast cancer tissue, through immunohistochemistry and/or mRNA and had to report one or more of the following outcomes: overall survival (OS), disease-free survival (DFS), mean survival and median survival. RESULTS: For the meta-analysis, seven studies were included and NRF2 expression was correlated with OS and DFS. It was observed that compared to patients with low NRF2 expression, patients with NRF2 overexpression had poorer OS with a hazard ratio of 1.82 (95% CI 1.32-2.50; p value < 0.0001), and poorer DFS, with a hazard ratio of 1.79 (95% CI 1.07-3.01; p value = 0.03). CONCLUSIONS: These results suggest that tumours that overexpress NRF2 have a worse clinical outcome. Thus, NRF2 expression could be a marker for the prognostic of breast cancer patients and, in the future, it would be pertinent to focus on improving treatment efficacy for patients with NRF2 overexpression.

Effects of physical exercise on outcomes of cardiac (dys)function in women with breast cancer undergoing anthracycline or trastuzumab treatment: study protocol for a systematic review.

BACKGROUND: Cardiotoxicity is a known complication and one of the most adverse effects from the use of conventional treatments such as anthracyclines and trastuzumab in breast cancer (BC) care. This phenomenon has been associated with the restriction of therapeutic options and the increase of cardiovascular complications, which may compromise the survival of patients. Implementation of preventive strategies is an important approach for the management of this issue. Physical exercise has been proposed as a non-pharmacological strategy to counteracting cardiotoxicity. The aim of this protocol is to describe the rationale and methods for a systematic review of published randomized controlled trials (RCTs) that have analysed the effects of physical exercise on outcomes of cardiac (dys)function in women with BC undergoing neoadjuvant or adjuvant treatment containing anthracyclines and/or trastuzumab. METHODS AND ANALYSIS: This is a protocol for a systematic review reported according to the PRISMA-P 2015 checklist. Randomized controlled trials (RCTs) will be included. The literature will be screened on MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus. The risk of bias of the included RCTs will be assessed using the Cochrane Collaboration's tool. The primary outcomes will be systolic function (left ventricular ejection fraction), diastolic function (E/A' ratio, deceleration time of early left ventricular filling, isovolumetric relaxation time, E/E' septal and lateral ratio) and myocardial deformation imaging outcomes (strain and strain rate [measured in longitudinal, radial, or circumferential directions]). Secondary outcomes will be cardiac biomarkers (troponin I or T, high-sensitivity troponin I or T, brain natriuretic peptide, amino terminal of B-type natriuretic peptide). Data will be descriptively reported, and quantitative synthesis will also be considered if the included studies are sufficiently homogenous. DISCUSSION: This systematic review will help to understand the effectiveness of physical exercise on counteracting cardiotoxicity related to anticancer therapies in women with BC. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018096060.

Health-related quality of life and physical fitness in breast cancer patients: the impact of a supervised physical exercise program in women with no exercise experience.

After breast cancer diagnosis (BCD), localized breast cancer (BC) patients are treated with curative intent by several therapeutic modalities. Despite the benefit of those therapies, the induction of side effects is acommon consequence affecting psychosocial and physiological outcomes. This quasi-experimental study compared physical fitness in recent-term (14-30 months; n= 11) and later-term (74-92 months; n= 8) BCD patients. After inclusion, recent-term BCD patients were engaged in asupervised exercise program and was explored its impact on physical fitness, health-related quality of life (HR-QOL) and fatigue. At baseline (M1) and after 8 (M2) and 16 weeks (M3) of this period, HR-QOL and fatigue were evaluated by the EORTC QLQ-C30 questionnaire and physical fitness through the estimation of maximum oxygen consumption (VO2max,ml.kg.min-1), handgrip force (kg) and sit-stand test. At baseline, women with later-term BCD have revealed better VO2max (p < 0.05) than recent-term BCD patients. There was asignificant time*group interaction for physical fitness outcomes and only the patients who have participated in the exercise program reported significant changes between baseline and at 16 weeks. The observed results demonstrated that performing regular exercise is associated with effective psychosocial and physiological recovery after BCD.

Prognosis of hormone-dependent breast cancer seems to be influenced by KEAP1, NRF2 and GSTM1 genetic polymorphisms.

Influence of Glutathione S-transferase Mu1 (GSTM1) has long been studied in breast cancer and GSTM1 null genotype was correlated with breast cancer risk. Nuclear factor-erythroid 2-related factor-2 (NRF2) is a transcription factor that forms a complex with Kelch-like ECH-associated protein-1 (KEAP1). Recent studies have demonstrated that expression of these proteins is deregulated in several malignancies. Thus, in the present study we aim to distinguish GSTM1 heterozygous from wild type genotype in breast cancer patients and evaluate the presence and clinical significance of NRF2 and KEAP1 polymorphisms, alone or in association, with breast cancer prognosis, in cases confirmed to have GSTM1-present genotype. Study population consisted in 52 patients with breast cancer. Genomic DNA was extracted, GSTM1 was genotyped through multiplex PCR and gene dose was evaluated through real-time PCR. All cases were sequenced, through Sanger sequencing, for specific regions of NRF2 and KEAP1. Genotyping and clinicopathological data were correlated and statistical analysis was performed. GSTM1 wild type was identified in 1 case and 26 cases were identified as heterozygous, these data were correlated with Human Epidermal growth factor Receptor 2 (HER2) status (p value = 0.017). We also verified that most cancers diagnosed at younger ages had the presence of KEAP1 and/or NRF2 polymorphisms. The association of GSTM1 heterozygous genotype with rs1048290 and rs35652124 seems to be associated with HER2+ (p < 0.05). Our results suggest that GSTM1 * 1/0 genotype and the cumulative presence of at least one allele mutated in KEAP1 and/or NRF2 polymorphisms might be associated with worse prognosis for breast cancer patients.

Budget impact analysis of cervical cancer screening in Portugal: comparison of cytology and primary HPV screening strategies.

BACKGROUND: Primary Human Papilloma Virus (HPV) testing is the currently recommended cervical cancer (CxCa) screening strategy by the Portuguese Society of Gynecology (SPG) clinical consensus. However, primary HPV testing has not yet been adopted by the Portuguese organized screening programs. This modelling study compares clinical benefits and costs of replacing the current practice, namely cytology with ASCUS HPV triage, with 2 comparative strategies: 1) HPV (pooled) test with cytology triage, or 2) HPV test with 16/18 genotyping and cytology triage, in organized CxCa screenings in Portugal. METHODS: A budget impact model compares screening performance, clinical outcomes and budget impact of the 3 screening strategies. A hypothetical cohort of 2,078,039 Portuguese women aged 25-64 years old women is followed for two screening cycles. Screening intervals are 3 years for cytology and 5 years for the HPV strategies. Model inputs include epidemiological, test performance and medical cost data. Clinical impacts are assessed with the numbers of CIN2-3 and CxCa detected. Annual costs, budget impact and cost of detecting one CIN2+ were calculated from a public healthcare payer's perspective. RESULTS: HPV testing with HPV16/18 genotyping and cytology triage (comparator 2) shows the best clinical outcomes at the same cost as comparator 1 and is the most cost-effective CxCa screening strategy in the Portuguese context. Compared to screening with cytology, it would reduce annual CxCa incidence from 9.3 to 5.3 per 100,000, and CxCa mortality from 2.7 to 1.1 per 100,000. Further, it generates substantial cost savings by reducing the annual costs by €9.16 million (- 24%). The cost of detecting CIN2+ decreases from the current €15,845 to €12,795. On the other hand, HPV (pooled) test with cytology triage (comparator 1) reduces annual incidence of CxCa to 6.9 per 100,000 and CxCa mortality to 1.6 per 100,000, with a cost of €13,227 per CIN2+ detected with annual savings of €9.36 million (- 24%). The savings are mainly caused by increasing the length of routine screening intervals from three to five years. CONCLUSION: The results support current clinical recommendations to replace cytology with HPV with 16/18 genotyping with cytology triage as screening algorithm.

Survey on Aesthetic Vulvovaginal Procedures: What do Portuguese Doctors and Medical Students Think? / Inquérito sobre procedimentos estéticos vulvovaginais: qual a opinião dos médicos e estudantes de medicina portugueses?

Abstract Objective To assess themedical doctors andmedical students' opinion regarding the evidence and ethical background of the performance of vulvovaginal aesthetic procedures (VVAPs). Methods Cross-sectional online survey among 664 Portuguese medical doctors and students. Results Most participants considered that there is never or there rarely is amedical reason to perform: vulvar whitening (85.9% [502/584]); hymenoplasty (72.0% [437/607]); mons pubis liposuction (71.6% [426/595]); "G-spot" augmentation (71.0% [409/576]); labia majora augmentation (66.3% [390/588]); labia minora augmentation (58.3% [326/559]); or laser vaginal tightening (52.3%[313/599]).Gynecologists and specialistsweremore likely to consider that there are no medical reasons to performVVAPs; the opposite was true for plastic surgeons and students/residents. Hymenoplasty raised ethical doubts in 51.1% (283/554) of the participants. Plastic surgeons and students/residents were less likely to raise ethical objections, while the opposite was true for gynecologists and specialists. Most considered that VVAPs could contribute to an improvement in self-esteem(92.3% [613/664]); sexual function (78.5% [521/664]); vaginal atrophy (69.9% [464/664]); quality of life (66.3% [440/664]); and sexual pain (61.4% [408/664]). Conclusions While medical doctors and students acknowledge the lack of evidence and scientific support for the performance of VVAPs, most do not raise ethical objections about them, especially if they are students or plastic surgeons, or if they have had or have considered having plastic surgery.

Resumo Objetivos Avaliar a opinião de médicos e estudantes de medicina relativamente à evidência e contexto ético para a realização de procedimentos estéticos vulvovaginais (PEVVs). Métodos Estudo transversal, consistindo de inquérito online a 664 médicos e estudantes de medicina portugueses. Resultados A maioria dos participantes considerou que nunca ou raramente há uma razão médica para a realização de: branqueamento vulvar (85,9% [502/584]); himenoplastia (72,0% [437/607]); lipoaspiração do mons pubis (71,6% [426/595]); aumento do "ponto G" (71,0% [409/576]); aumento dos grandes lábios (66,3% [390/588]); aumento dos pequenos lábios (58,3% [326/559]) ou aperto vaginal com laser (52,3% [313/599]). Ser ginecologista e especialista associou-se a maior probabilidade de considerar não haver razões médicas para a realização de PEVV; o oposto foi verdade para os cirurgiões plásticos e estudantes/internos. A himenoplastia levantou dúvidas em termos éticos em 51,1% (283/554) dos participantes. Cirurgiões plásticos e estudantes/internos relatarammenos dúvidas emtermos éticos; o oposto foi verdade para os ginecologistas ou especialistas. Amaioria considerou que os PEVVs podemcontribuir para uma melhoria na autoestima (92,3% [613/664]); função sexual (78,5% [521/664]); atrofia vaginal (69,9% [464/664]); qualidade de vida (66,3% [440/664]); e dor sexual (61,4% [408/664]). Conclusões Ainda que os médicos e estudantes de medicina reconheçam a falta de evidência e bases científicas para a realização de PEVVs, a maioria não levanta objecções em termos éticos, especialmente se forem estudantes, cirurgiões plásticos, ou se eles próprios tiverem sido submetidos a cirurgia plástica ou considerem vir a sê-lo.

Survey on Aesthetic Vulvovaginal Procedures: What do Portuguese Doctors and Medical Students Think?

Objective To assess the medical doctors and medical students' opinion regarding the evidence and ethical background of the performance of vulvovaginal aesthetic procedures (VVAPs). Methods Cross-sectional online survey among 664 Portuguese medical doctors and students. Results Most participants considered that there is never or there rarely is a medical reason to perform: vulvar whitening (85.9% [502/584]); hymenoplasty (72.0% [437/607]); mons pubis liposuction (71.6% [426/595]); "G-spot" augmentation (71.0% [409/576]); labia majora augmentation (66.3% [390/588]); labia minora augmentation (58.3% [326/559]); or laser vaginal tightening (52.3% [313/599]). Gynecologists and specialists were more likely to consider that there are no medical reasons to perform VVAPs; the opposite was true for plastic surgeons and students/residents.Hymenoplasty raised ethical doubts in 51.1% (283/554) of the participants. Plastic surgeons and students/residents were less likely to raise ethical objections, while the opposite was true for gynecologists and specialists.Most considered that VVAPs could contribute to an improvement in self-esteem (92.3% [613/664]); sexual function (78.5% [521/664]); vaginal atrophy (69.9% [464/664]); quality of life (66.3% [440/664]); and sexual pain (61.4% [408/664]). Conclusions While medical doctors and students acknowledge the lack of evidence and scientific support for the performance of VVAPs, most do not raise ethical objections about them, especially if they are students or plastic surgeons, or if they have had or have considered having plastic surgery.

Objetivos Avaliar a opinião de médicos e estudantes de medicina relativamente à evidência e contexto ético para a realização de procedimentos estéticos vulvovaginais (PEVVs). Métodos Estudo transversal, consistindo de inquérito online a 664 médicos e estudantes de medicina portugueses. Resultados A maioria dos participantes considerou que nunca ou raramente há uma razão médica para a realização de: branqueamento vulvar (85,9% [502/584]); himenoplastia (72,0% [437/607]); lipoaspiração do mons pubis (71,6% [426/595]); aumento do "ponto G" (71,0% [409/576]); aumento dos grandes lábios (66,3% [390/588]); aumento dos pequenos lábios (58,3% [326/559]) ou aperto vaginal com laser (52,3% [313/599]). Ser ginecologista e especialista associou-se a maior probabilidade de considerar não haver razões médicas para a realização de PEVV; o oposto foi verdade para os cirurgiões plásticos e estudantes/internos.A himenoplastia levantou dúvidas em termos éticos em 51,1% (283/554) dos participantes. Cirurgiões plásticos e estudantes/internos relataram menos dúvidas em termos éticos; o oposto foi verdade para os ginecologistas ou especialistas.A maioria considerou que os PEVVs podem contribuir para uma melhoria na autoestima (92,3% [613/664]); função sexual (78,5% [521/664]); atrofia vaginal (69,9% [464/664]); qualidade de vida (66,3% [440/664]); e dor sexual (61,4% [408/664]). Conclusões Ainda que os médicos e estudantes de medicina reconheçam a falta de evidência e bases científicas para a realização de PEVVs, a maioria não levanta objecções em termos éticos, especialmente se forem estudantes, cirurgiões plásticos, ou se eles próprios tiverem sido submetidos a cirurgia plástica ou considerem vir a sê-lo.

A Two-Step Segmentation Method for Breast Ultrasound Masses Based on Multi-resolution Analysis.

Breast ultrasound images have several attractive properties that make them an interesting tool in breast cancer detection. However, their intrinsic high noise rate and low contrast turn mass detection and segmentation into a challenging task. In this article, a fully automated two-stage breast mass segmentation approach is proposed. In the initial stage, ultrasound images are segmented using support vector machine or discriminant analysis pixel classification with a multiresolution pixel descriptor. The features are extracted using non-linear diffusion, bandpass filtering and scale-variant mean curvature measures. A set of heuristic rules complement the initial segmentation stage, selecting the region of interest in a fully automated manner. In the second segmentation stage, refined segmentation of the area retrieved in the first stage is attempted, using two different techniques. The AdaBoost algorithm uses a descriptor based on scale-variant curvature measures and non-linear diffusion of the original image at lower scales, to improve the spatial accuracy of the ROI. Active contours use the segmentation results from the first stage as initial contours. Results for both proposed segmentation paths were promising, with normalized Dice similarity coefficients of 0.824 for AdaBoost and 0.813 for active contours. Recall rates were 79.6% for AdaBoost and 77.8% for active contours, whereas the precision rate was 89.3% for both methods.

Tumour necrosis factor alpha 308 G/A is a risk marker for the progression from high-grade lesions to invasive cervical cancer.

Tumour necrosis factor alpha (TNF-α) is a strong pro-inflammatory cytokine with important functions on immune response to viral infections. A single nucleotide polymorphism on the -308 position of the promoter region of TNFA gene characterised by a G > A transition has been associated with different TNF-α levels and therefore with differential susceptibility for the development several diseases. A cross-sectional case-control study was performed with 509 women with cancer from the northern region of Portugal, including 205 healthy women and 337 women with different cervical lesions including invasive cervical. The -308G > A polymorphism genotyping was performed with TaqMan® SNP Genotyping Assay and studied for its association with cervical cancer development. This study showed increased frequency of the -308A allele in women with any cervical lesions. Statistical analysis revealed that -308A carriers are associated with an almost 2-fold increased risk for invasive cervical cancer development (p = 0.005; odds ratio (OR) = 1.87). Similar results were found when comparing the risk of progression between preinvasive lesions and invasive cervical cancer development (p = 0.002; OR = 2.41). Our results reveal that -308 TNFA AA individuals are at increased risk of invasive cervical cancer development and more important, that the risk is significantly increased for the progression from premalignant lesion to invasive cancer. Considering previous data and this study, this polymorphism confirms to be a significant marker in our population.

Abnormal uterine bleeding as a presenting symptom is related to multiple uterine leiomyoma: an ultrasound-based study.

PURPOSE: To determine the prevalence of uterine leiomyomas, diagnosed by ultrasound, in a private health care setting located in the central eastern region of Portugal, and to explore the demographic and clinical factors related to diagnosis and symptomatology. PATIENTS AND METHODS: The files of 624 patients attending a private clinic in Covilhã, Portugal, from January 2 to December 31, 2010 were retrieved for evaluation. Pelvic ultrasound record, age, weight, height, age at menarche, number of pregnancies and deliveries, marital status, menstrual cycles characteristic, and contraceptive method at consultation were included in the analysis. RESULTS: Uterine leiomyoma (UL) was diagnosed by ultrasonography in 161 (25.8%) patients. A single UL was diagnosed in 80 (49.7%) patients. In 79 (49.1%) patients, the largest leiomyoma had a dimension <20 mm. Prevalence of UL was age dependent: at 11.0% for women 20-39 years old; 45.4% for those aged 40-59 years; and 19.5% for women 60 years or older. Metrorrhagia was the most distressing presenting symptom. When menorrhagia was the presenting symptom, the probability of having an ultrasound diagnosis of UL was 73.3%. Metrorrhagia or menorrhagia, as presenting symptom, was significantly related to the ultrasound diagnosis of multiple ULs. CONCLUSION: UL was especially prevalent in women aged between 40 and 59 years. Patients with multiple ULs had significantly more abnormal uterine bleeding. In patients with menorrhagia or metrorrhagia, special attention should be taken in searching for the presence of multiple ULs during ultrasound.