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1.
Cell ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39163861

RESUMO

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). FarE mediates OA resistance, while OhyA is robustly active in the vaginal microbiota and enhances bacterial fitness by biochemically sequestering OA in a derivative form only ohyA-harboring organisms can exploit. OA promotes L. crispatus dominance more effectively than antibiotics in an in vitro BV model, suggesting a metabolite-based treatment approach.

2.
Cell ; 185(10): 1619-1622, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35561661

RESUMO

Progress in studying sex as a biological variable (SABV) is slow, and the influence of gendered effects of the social environment on biology is largely unknown. Yet incorporating these concepts into basic science research will enhance our understanding of human health and disease. We provide steps to move this process forward.


Assuntos
Pesquisa Biomédica , Feminino , Humanos , Masculino , Medicina de Precisão , Caracteres Sexuais , Fatores Sexuais , Saúde da Mulher
3.
Annu Rev Physiol ; 84: 59-85, 2022 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-34780257

RESUMO

The role of central estrogen in cognitive, metabolic, and reproductive health has long fascinated the lay public and scientists alike. In the last two decades, insight into estrogen signaling in the brain and its impact on female physiology is beginning to catch up with the vast information already established for its actions on peripheral tissues. Using newer methods to manipulate estrogen signaling in hormone-sensitive brain regions, neuroscientists are now identifying the molecular pathways and neuronal subtypes required for controlling sex-dependent energy allocation. However, the immense cellular complexity of these hormone-sensitive brain regions makes it clear that more research is needed to fully appreciate how estrogen modulates neural circuits to regulate physiological and behavioral end points. Such insight is essential for understanding how natural or drug-induced hormone fluctuations across lifespan affect women's health.


Assuntos
Estrogênios , Longevidade , Encéfalo/metabolismo , Estrogênios/metabolismo , Feminino , Humanos , Hipotálamo/metabolismo , Neurônios/fisiologia , Transdução de Sinais
4.
Genet Epidemiol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940271

RESUMO

In most Proteome-Wide Association Studies (PWAS), variants near the protein-coding gene (±1 Mb), also known as cis single nucleotide polymorphisms (SNPs), are used to predict protein levels, which are then tested for association with phenotypes. However, proteins can be regulated through variants outside of the cis region. An intermediate GWAS step to identify protein quantitative trait loci (pQTL) allows for the inclusion of trans SNPs outside the cis region in protein-level prediction models. Here, we assess the prediction of 540 proteins in 1002 individuals from the Women's Health Initiative (WHI), split equally into a GWAS set, an elastic net training set, and a testing set. We compared the testing r2 between measured and predicted protein levels using this proposed approach, to the testing r2 using only cis SNPs. The two methods usually resulted in similar testing r2, but some proteins showed a significant increase in testing r2 with our method. For example, for cartilage acidic protein 1, the testing r2 increased from 0.101 to 0.351. We also demonstrate reproducible findings for predicted protein association with lipid and blood cell traits in WHI participants without proteomics data and in UK Biobank utilizing our PWAS weights.

5.
Circulation ; 149(19): e1143-e1163, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38567497

RESUMO

Guideline-directed medical therapies and guideline-directed nonpharmacological therapies improve quality of life and survival in patients with heart failure (HF), but eligible patients, particularly women and individuals from underrepresented racial and ethnic groups, are often not treated with these therapies. Implementation science uses evidence-based theories and frameworks to identify strategies that facilitate uptake of evidence to improve health. In this scientific statement, we provide an overview of implementation trials in HF, assess their use of conceptual frameworks and health equity principles, and provide pragmatic guidance for equity in HF. Overall, behavioral nudges, multidisciplinary care, and digital health strategies increased uptake of therapies in HF effectively but did not include equity goals. Few HF studies focused on achieving equity in HF by engaging stakeholders, quantifying barriers and facilitators to HF therapies, developing strategies for equity informed by theory or frameworks, evaluating implementation measures for equity, and titrating strategies for equity. Among these HF equity studies, feasibility was established in using various educational strategies to promote organizational change and equitable care. A couple include ongoing randomized controlled pragmatic trials for HF equity. There is great need for additional HF implementation trials designed to promote delivery of equitable guideline-directed therapy.


Assuntos
American Heart Association , Equidade em Saúde , Insuficiência Cardíaca , Ciência da Implementação , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/diagnóstico , Humanos , Estados Unidos , Disparidades em Assistência à Saúde
6.
Brain ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657115

RESUMO

Valproate is the most effective treatment for idiopathic generalised epilepsy. Current guidance precludes its use in women of childbearing potential, unless other treatments are ineffective or not tolerated, because of high teratogenicity. This risk was recently extended to men. New guidance will limit use both in men and women aged <55 years, resulting in withdrawal of valproate from men already taking it, as occurs for women. Whether there are risks of personal harm (including injury or death) associated with valproate withdrawal has not yet been quantified for men or women on valproate, meaning clinicians cannot reliably counsel either sex when discussing valproate withdrawal with them, despite that this concern may be at the forefront of patients' and clinicians' minds. We assessed whether there are any morbidity or mortality risks associated with valproate withdrawal in young men and women. We performed a retrospective cohort study of internationally derived electronic health data within the TriNetX Global Collaborative Network. Included were men and women aged 16-54 years with ≥1 epilepsy disease or symptom code between 01/12/2017-01/12/2018 and ≥2 valproate prescriptions over the preceding two years (01/01/2015-30/11/2017). 5-year propensity-matched risks of mortality and a range of morbidity outcomes were compared between those remaining on vs. withdrawn from valproate during the 01/12/2017-01/12/2018 recruitment period, regardless of whether switched to another antiseizure medication. Survival analysis was undertaken using Cox-proportional hazard models, generating hazard ratios (HRs) with 95% confidence intervals (CIs). 8,991 men and 5,243 women taking valproate were recruited. 28% of men and 36% of women were subsequently withdrawn from valproate. Valproate withdrawal was associated with significantly increased risks of emergency department attendance (HRs overall: 1.236 (CI 1.159-1.319), men: 1.181 (CI 1.083-1.288), women: 1.242 (CI 1.125-1.371)), hospital admission (HRs overall: 1.160 (CI 1.081-1.246), men: 1.132 (CI 1.027-1.249), women: 1.147 (CI 1.033-1.274)), falls (HRs overall: 1.179 (CI 1.041-1.336), men: 1.298 (CI 1.090-1.546)), injuries (HRs overall: 1.095 (CI 1.021-1.174), men: 1.129 (CI 1.029-1.239)), burns (HRs overall: 1.592 (CI 1.084-2.337)), and new-onset depression (HRs overall 1.323 (CI 1.119-1.565), women: 1.359 (CI 1.074-1.720)). The risk of these outcomes occurring was 1-7% higher in those withdrawn from valproate than in those remaining on valproate. Overall, valproate withdrawal was not associated with increased mortality. These results may help patients and clinicians have a more informed discussion about personal safety when considering valproate withdrawal.

7.
J Med Genet ; 61(4): 392-398, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38124001

RESUMO

BACKGROUND: In Japan, the public insurance policy was revised in 2020 to cover hereditary breast and ovarian cancer (HBOC), including genetic testing and surveillance, for patients with breast cancer (BC). Consequently, the demand for risk-reducing salpingo-oophorectomy (RRSO) has increased. This study aimed to clarify the changes in the demand and timing of genetic testing and RRSO associated with public insurance coverage for HBOC in Japan. METHODS: This retrospective analysis included 350 women with germline BRCA (gBRCA) pathogenic variants (PVs) who had visited gynaecologists; they received gBRCA genetic testing at 45.1±10.6 (20-74) years. The use of medical testing and preventive treatment was compared between the preinsurance and postinsurance groups using Mann-Whitney U and Fisher's exact tests. RESULTS: The findings indicate that RRSO rates doubled from 31.4% to 62.6% among patients with gBRCA-PV. The implementation rate was 32.4% among unaffected carriers and 70.3% among BC-affected patients. Younger patients received genetic testing with significantly shorter intervals between BC diagnosis and genetic testing and between genetic testing and RRSO. CONCLUSION: Overall, the insurance coverage for HBOC patients with BC has increased the frequency of RRSO in Japan. However, a comparison between the number of probands and family members indicated that the diagnosis among family members is inadequate. The inequality in the use of genetic services by socioeconomic groups is an issue of further concern.


Assuntos
Neoplasias da Mama , Neoplasias Ovarianas , Humanos , Feminino , Salpingo-Ooforectomia , Estudos Retrospectivos , Neoplasias Ovarianas/genética , Testes Genéticos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Células Germinativas/patologia , Mutação , Ovariectomia , Proteína BRCA1/genética , Predisposição Genética para Doença
8.
J Med Genet ; 61(8): 803-809, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38834293

RESUMO

BACKGROUND: No validation has been conducted for the BOADICEA multifactorial breast cancer risk prediction model specifically in BRCA1/2 pathogenic variant (PV) carriers to date. Here, we evaluated the performance of BOADICEA in predicting 5-year breast cancer risks in a prospective cohort of BRCA1/2 PV carriers ascertained through clinical genetic centres. METHODS: We evaluated the model calibration and discriminatory ability in the prospective TRANsIBCCS cohort study comprising 1614 BRCA1 and 1365 BRCA2 PV carriers (209 incident cases). Study participants had lifestyle, reproductive, hormonal, anthropometric risk factor information, a polygenic risk score based on 313 SNPs and family history information. RESULTS: The full multifactorial model considering family history together with all other risk factors was well calibrated overall (E/O=1.07, 95% CI: 0.92 to 1.24) and in quintiles of predicted risk. Discrimination was maximised when all risk factors were considered (Harrell's C-index=0.70, 95% CI: 0.67 to 0.74; area under the curve=0.79, 95% CI: 0.76 to 0.82). The model performance was similar when evaluated separately in BRCA1 or BRCA2 PV carriers. The full model identified 5.8%, 12.9% and 24.0% of BRCA1/2 PV carriers with 5-year breast cancer risks of <1.65%, <3% and <5%, respectively, risk thresholds commonly used for different management and risk-reduction options. CONCLUSION: BOADICEA may be used to aid personalised cancer risk management and decision-making for BRCA1 and BRCA2 PV carriers. It is implemented in the free-access CanRisk tool (https://www.canrisk.org/).


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Neoplasias da Mama , Predisposição Genética para Doença , Heterozigoto , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/epidemiologia , Proteína BRCA2/genética , Proteína BRCA1/genética , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Fatores de Risco , Medição de Risco , Polimorfismo de Nucleotídeo Único/genética
9.
J Med Genet ; 61(7): 716-725, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38575303

RESUMO

BACKGROUND: 1 in 40 UK Jewish individuals carry a pathogenic variant in BRCA1/BRCA2. Traditional testing criteria miss half of carriers, and so population genetic testing is being piloted for Jewish people in England. There has been no qualitative research into the factors influencing BRCA awareness and testing experience in this group. This study aimed to explore these and inform improvements for the implementation of population genetic testing. METHODS: Qualitative study of UK Jewish adults who have undergone BRCA testing. We conducted one-to-one semistructured interviews via telephone or video call using a predefined topic guide, until sufficient information power was reached. Interviews were audio-recorded, transcribed verbatim and interpreted using applied thematic analysis. RESULTS: 32 individuals were interviewed (28 carriers, 4 non-carriers). We interpreted five themes intersecting across six time points of the testing pathway: (1) individual differences regarding personal/family history of cancer, demographics and personal attitudes/approach; (2) healthcare professionals' support; (3) pathway access and integration; (4) nature of family/partner relationships; and (5) Jewish community factors. Testing was largely triggered by connecting information to a personal/family history of cancer. No participants reported decision regret, although there was huge variation in satisfaction. Suggestions were given around increasing UK Jewish community awareness, making information and support services personally relevant and proactive case management of carriers. CONCLUSIONS: There is a need to improve UK Jewish community BRCA awareness and to highlight personal relevance of testing for individuals without a personal/family history of cancer. Traditional testing criteria caused multiple issues regarding test access and experience. Carriers want information and support services tailored to their individual circumstances.


Assuntos
Proteína BRCA1 , Proteína BRCA2 , Testes Genéticos , Judeus , Humanos , Judeus/genética , Judeus/psicologia , Feminino , Adulto , Reino Unido/epidemiologia , Pessoa de Meia-Idade , Masculino , Proteína BRCA1/genética , Proteína BRCA2/genética , Predisposição Genética para Doença , Pesquisa Qualitativa , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/psicologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/diagnóstico , Genes BRCA1
10.
Semin Immunol ; 51: 101482, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-34120819

RESUMO

Women and girls represent a key population driving new HIV infections and persistence of the HIV pandemic. A key determinant of HIV susceptibility is the composition of the vaginal microbiome, which can influence the local immune cell population, inflammation status, and HIV prevention drug levels. While a low-diversity composition dominated by Lactobacillus crispatus is associated with a decreased risk of HIV acquisition, high diversity environments associated with bacterial vaginosis increase risk of HIV. Given the important role of the vaginal microbiome in determining HIV susceptibility, altering the microbiome towards a Lactobacillus-dominated state is an attractive complementary strategy to reduce HIV incidence rates. Here, we provide an overview of the mechanisms by which the vaginal microbiome may contribute to HIV acquisition risk. Furthermore, we address the advantages and limitations of historical treatments and emerging technologies under investigation to modify the vaginal microbiome, including: antibiotics, bacteriophages, probiotics, topicals, and engineered bacteria. By addressing the current state of vaginal microbiome knowledge and strategies for manipulation, we hope to amplify the growing calls for increased resources and research into vaginal microbial health, which will be essential to accelerating preventative efforts amongst the world's most vulnerable populations.


Assuntos
Infecções por HIV , Microbiota , Vaginose Bacteriana , Disbiose , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/terapia , Humanos , Vagina/microbiologia , Vaginose Bacteriana/epidemiologia , Vaginose Bacteriana/microbiologia , Vaginose Bacteriana/terapia
11.
Eur Heart J ; 45(17): 1505-1511, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38551446

RESUMO

The sex disparity in outcomes of patients with cardiovascular disease is well-described and has persisted across recent decades. While there have been several proposed mechanisms to explain this disparity, there are limited data on female patient-physician sex concordance and its association with outcomes. The authors review the existing literature on the relationship between patient-physician sex concordance and clinical outcomes in patients with cardiovascular disease, the evidence of a benefit in clinical outcomes with female patient-physician sex concordance, and the possible drivers of such a benefit and highlight directions for future study.


Assuntos
Doenças Cardiovasculares , Relações Médico-Paciente , Humanos , Feminino , Masculino , Fatores Sexuais , Resultado do Tratamento
12.
Clin Infect Dis ; 78(6): 1617-1628, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38180851

RESUMO

BACKGROUND: We evaluated associations between antepartum weight change and adverse pregnancy outcomes and between antiretroviral therapy (ART) regimens and week 50 postpartum body mass index in IMPAACT 2010. METHODS: Women with human immunodeficiency virus (HIV)-1 in 9 countries were randomized 1:1:1 at 14-28 weeks' gestational age (GA) to start dolutegravir (DTG) + emtricitabine (FTC)/tenofovir alafenamide fumarate (TAF) versus DTG + FTC/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF. Insufficient antepartum weight gain was defined using Institute of Medicine guidelines. Cox-proportional hazards regression models were used to evaluate the association between antepartum weight change and adverse pregnancy outcomes: stillbirth (≥20 weeks' GA), preterm delivery (<37 weeks' GA), small size for GA (<10th percentile), and a composite of these endpoints. RESULTS: A total of 643 participants were randomized: 217 to the DTG + FTC/TAF, 215 to the DTG + FTC/TDF, and 211 to the EFV/FTC/TDF arm. Baseline medians were as follows: GA, 21.9 weeks; HIV RNA, 903 copies/mL; and CD4 cell count, 466/µL. Insufficient weight gain was least frequent with DTG + FTC/TAF (15.0%) versus DTG + FTC/TDF (23.6%) and EFV/FTC/TDF (30.4%). Women in the DTG + FTC/TAF arm had the lowest rate of composite adverse pregnancy outcome. Low antepartum weight gain was associated with higher hazard of composite adverse pregnancy outcome (hazard ratio, 1.44 [95% confidence interval, 1.04-2.00]) and small size for GA (1.48 [.99-2.22]). More women in the DTG + FTC/TAF arm had a body mass index ≥25 (calculated as weight in kilograms divided by height in meters squared) at 50 weeks postpartum (54.7%) versus the DTG + FTC/TDF (45.2%) and EFV/FTC/TDF (34.2%) arms. CONCLUSIONS: Antepartum weight gain on DTG regimens was protective against adverse pregnancy outcomes typically associated with insufficient weight gain, supportive of guidelines recommending DTG-based ART for women starting ART during pregnancy. Interventions to mitigate postpartum weight gain are needed.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Período Pós-Parto , Complicações Infecciosas na Gravidez , Resultado da Gravidez , Piridonas , Tenofovir , Humanos , Feminino , Gravidez , Infecções por HIV/tratamento farmacológico , Tenofovir/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/análogos & derivados , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Adulto , Oxazinas/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/virologia , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/efeitos adversos , Alanina/uso terapêutico , Aumento de Peso/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/efeitos adversos , HIV-1/efeitos dos fármacos , Adulto Jovem
13.
Cancer Sci ; 115(2): 611-622, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38041484

RESUMO

This study aimed to investigate the association between daily sedentary time and the risk of breast cancer (BC) in a large Japanese population. The participants were 36,023 women aged 35-69 years from the Japan Multi-Institutional Collaborative Cohort Study. Cox proportional hazards analysis was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for BC incidence in relation to time spent sedentarily (categorical variables: <7 and ≥7 hours/day [h/d]). Additionally, the associations of BC incidence to the joint effect of sedentary time with each component of physical activity, such as leisure-time metabolic equivalents (METs), frequency of leisure-time physical activity, and daily walking time, were examined. During 315,189 person-years of follow-up, 554 incident cases of BC were identified. When compared to participants who spent <7 h/d sedentary, those who spent ≥7 h/d sedentary have a significantly higher risk of BC (HR, 1.36; 95% CI, 1.07-1.71). The corresponding HRs among participants who spent ≥7 h/d sedentary with more physical activity, such as ≥1 h/d for leisure-time METs, ≥3 days/week of leisure-time physical activity, and ≥1 h/d of daily walking were 1.58 (95% CI, 1.11-2.25), 1.77 (95% CI, 1.20-2.61), and 1.42 (95% CI, 1.10-1.83), respectively, compared with those who spent <7 h/d sedentary. This study found that spending ≥7 h/d of sedentary time is associated with the risk of BC. Neither leisure-time physical activity nor walking had a BC-preventive effect in those with ≥7 h/d of sedentary time.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Comportamento Sedentário , Japão/epidemiologia , Estudos de Coortes , Atividade Motora , Fatores de Risco
14.
Am J Epidemiol ; 193(1): 75-86, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-37489623

RESUMO

No randomized controlled trial has evaluated the effect of long-term alcohol interventions on mortality. Results reported in existing observational studies may be subject to selection bias and time-varying confounding. Using data from the Australian Longitudinal Study on Women's Health 1946-1951 birth cohort, collected regularly from 1996-2016, we estimated all-cause and cancer mortality had women been assigned various alcohol interventions (in categories ranging from 0 to >30 g/day ethanol, or reduced to ≤20 g/day if higher) at baseline, and had they maintained these levels of consumption. The cumulative risks for all-cause and cancer mortality were 5.6% (10,118 women followed for 20 years) and 2.9% (18 years), respectively. For all-cause and cancer mortality, baseline ethanol up to 30 g/day showed lower risk and >30 g/day showed higher risk relative to abstention. Had women sustainedly followed the interventions, a similar relationship was observed for all-cause mortality. However, the negative association observed for intakes ≤30 g/day and positive association for intakes >30 g/day was not evident for cancer mortality. Our findings suggest that all-cause mortality could have been lower than observed if this cohort of women had consumed some alcohol (no more than 30 g/day) rather than no consumption, but cancer mortality might not.


Assuntos
Neoplasias , Saúde da Mulher , Feminino , Humanos , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Austrália/epidemiologia , Etanol , Estudos Longitudinais , Pessoa de Meia-Idade
15.
Front Neuroendocrinol ; 68: 101042, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332783

RESUMO

Women's psychological and behavioral responses to hormonal contraceptive (HC) treatment can be highly variable. One of the great challenges to researchers seeking to improve the experiences of women who use HCs is to identify the sources of this variability to minimize unpleasant psychobehavioral side-effects. In the following, we provide recommendations for programs of research aimed at identifying sources of heterogeneity in women's experiences with HC. First, we review research demonstrating person- and prescription- based heterogeneity in women's psychobehavioral responses to HCs. Next, we identify several promising person- and prescription- based sources of this heterogeneity that warrant future research. We close with a discussion of research approaches that are particularly well-suited to address the research questions raised in article. Together, this review provides researchers with several promising research pathways to help support the development of a precision medicine approach to HC treatment.


Assuntos
Anticoncepção , Contracepção Hormonal , Humanos , Feminino , Anticoncepção/psicologia , Medicina de Precisão
16.
Cancer ; 130(18): 3147-3156, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38736319

RESUMO

BACKGROUND: In the Women's Health Initiative (WHI) randomized trial, dietary intervention significantly reduced breast cancer mortality, especially in women with more metabolic syndrome (MetS) components. Therefore, this study investigated the associations of MetS and obesity with postmenopausal breast cancer after long-term follow-up in the WHI clinical trials. METHODS: A total of 68,132 postmenopausal women, without prior breast cancer and with normal mammogram, were entered into WHI randomized clinical trials; 63,330 women with an entry MetS score comprised the study population. At entry, body mass index (BMI) was determined; MetS score (0, 1-2, and 3-4) included the following: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or hypertension history), (3) high-cholesterol history, and (4) diabetes history. Study outcomes included breast cancer incidence, breast cancer mortality, deaths after breast cancer, and results by hormone receptor status. RESULTS: After a >20-year mortality follow-up, a higher MetS score (3-4), adjusted for BMI, was significantly associated with more poor prognosis, estrogen receptor (ER)-positive, progesterone receptor (PR)-negative cancers (p = .03), 53% more deaths after breast cancer (p < .001), and 44% higher breast cancer mortality (p = .03). Obesity status, adjusted for MetS score, was significantly associated with more good prognosis, ER-positive, PR-positive cancers (p < .001), more total breast cancers (p < .001), and more deaths after breast cancer (p < .001), with higher breast cancer mortality only in women with severe obesity (BMI, ≥35 kg/m2; p < .001). CONCLUSIONS: MetS and obesity status have independent, but differential, adverse associations with breast cancer receptor subtypes and breast cancer mortality risk. Both represent separate targets for breast cancer prediction and prevention strategies.


Assuntos
Índice de Massa Corporal , Neoplasias da Mama , Síndrome Metabólica , Obesidade , Pós-Menopausa , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/epidemiologia , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/mortalidade , Obesidade/complicações , Obesidade/epidemiologia , Pessoa de Meia-Idade , Incidência , Idoso , Saúde da Mulher , Fatores de Risco
17.
Annu Rev Med ; 73: 339-354, 2022 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-35084994

RESUMO

Spontaneous coronary artery dissection (SCAD) is an uncommon but increasingly recognized cause of acute myocardial infarction (MI) among young and middle-aged women and is an important cause of pregnancy-associated MI. Over 90% of SCAD patients are women. Compared to patients with MI caused by atherosclerosis, SCAD patients have fewer cardiovascular risk factors but more often have systemic arteriopathy, most commonly fibromuscular dysplasia. Angiographically, SCAD is characterized by the presence of an intramural hematoma with or without an intimal tear. Accurate recognition of characteristic findings on coronary angiography is critical, as there are important differences in the acute and long-term management of MI caused by SCAD versus atherosclerosis. Acutely, most SCAD patients should be managed conservatively, since percutaneous revascularization is associated with more complications and SCAD-affected vessels usually heal without intervention. Randomized clinical trials and other prospective evaluations are needed, especially to clarify optimal treatment and prevention strategies.


Assuntos
Anomalias dos Vasos Coronários , Doenças Vasculares , Angiografia Coronária/efeitos adversos , Anomalias dos Vasos Coronários/diagnóstico por imagem , Anomalias dos Vasos Coronários/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Gravidez , Fatores de Risco , Doenças Vasculares/complicações , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/terapia
18.
Am J Physiol Heart Circ Physiol ; 326(3): H752-H759, 2024 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-38214902

RESUMO

Sleep disturbance, one of the most common menopausal symptoms, contributes to autonomic dysfunction and is linked to hypertension and cardiovascular risk. Longitudinal studies suggest that hyperreactivity of blood pressure (BP) to a stressor can predict the future development of hypertension. It remains unknown if postmenopausal females who experience sleep disturbance (SDG) demonstrate greater hemodynamic and sympathetic neural hyperreactivity to a stressor. We hypothesized that postmenopausal females with reported sleep disturbance would exhibit increased hemodynamic and sympathetic reactivity to a stressor compared with postmenopausal females without sleep disturbance (non-SDG). Fifty-five postmenopausal females (age, 62 ± 4 yr old; SDG, n = 36; non-SDG; n = 19) completed two study visits. The Menopause-Specific Quality of Life Questionnaire (MENQOL) was used to assess the presence of sleep disturbance (MENQOL sleep scale, ≥2 units). Beat-to-beat BP (finger plethysmography), heart rate (HR; electrocardiogram), and muscle sympathetic nerve activity (MSNA; microneurography; SDG, n = 25; non-SDG, n = 15) were continuously measured during a 10-min baseline and 2-min stressor (cold pressor test; CPT) in both groups. Menopause age and body mass index were similar between groups (P > 0.05). There were no differences between resting BP, HR, or MSNA (P > 0.05). HR and BP reactivity were not different between SDG and non-SDG (P > 0.05). In contrast, MSNA reactivity had a more rapid increase in the first 30 s of the CPT in the SDG (burst incidence, Δ10.2 ± 14.8 bursts/100 hb) compared with the non-SDG (burst incidence, Δ4.0 ± 14.8 bursts/100 hb, time × group, P = 0.011). Our results demonstrate a more rapid sympathetic neural reactivity to a CPT in postmenopausal females with perceived sleep disturbance, a finding that aligns with and advances recent evidence that sleep disturbance is associated with sympathetic neural hyperactivity in postmenopausal females.NEW & NOTEWORTHY This is the first study to demonstrate that muscle sympathetic nerve activity (MSNA) to a cold pressor test is augmented in postmenopausal females with perceived sleep disturbance. The more rapid increase in MSNA reactivity during the cold pressor test in the sleep disturbance group was present despite similar increases in the perceived pain levels between groups. Baseline MSNA burst incidence and burst frequency, as well as blood pressure and heart rate, were similar between the sleep disturbance and nonsleep disturbance groups.


Assuntos
Hipertensão , Transtornos do Sono-Vigília , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Pós-Menopausa , Qualidade de Vida , Músculo Esquelético/inervação , Pressão Sanguínea/fisiologia , Sistema Nervoso Simpático , Frequência Cardíaca/fisiologia , Sono , Transtornos do Sono-Vigília/diagnóstico
19.
Breast Cancer Res Treat ; 205(3): 487-495, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38453780

RESUMO

PURPOSE: Cancer screening is a public health intervention aiming to reduce cancer-caused deaths. This study aims to determine the factors affecting the mammography screening time among women aged 40-69. METHODS: The micro dataset obtained from the Türkiye Health Survey conducted by the Turkish Statistical Institute (TurkStat) in 2019 and 2022 was used in the present study. Stereotype logistic regression was used to determine the variables affecting mammography screening and period for breast cancer prevention in women in Türkiye. RESULTS: Given the results achieved from the analysis, it was found that factors such as age, marital status, general health condition, comorbidity, receiving psychosocial support, high blood lipid levels, and performing breast self-examinations affected women's adherence to cancer screening programs. CONCLUSION: Since adherence to mammography increases with age, it is recommended to pay importance to education for women approaching the age of mammography screening. Educated individuals are expected to have access to multiple sources of information as to cancer and to access this information more easily. In order to gain more insight into the recommended preventive measures and outcomes related to cancer, it is suggested to review policies, which will increase the educational level of women, and provide privileges in the field of education.


Assuntos
Neoplasias da Mama , Detecção Precoce de Câncer , Mamografia , Humanos , Feminino , Neoplasias da Mama/prevenção & controle , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/diagnóstico por imagem , Mamografia/estatística & dados numéricos , Pessoa de Meia-Idade , Turquia/epidemiologia , Adulto , Detecção Precoce de Câncer/psicologia , Detecção Precoce de Câncer/estatística & dados numéricos , Idoso , Fatores de Risco , Programas de Rastreamento/métodos , Autoexame de Mama/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde
20.
Breast Cancer Res Treat ; 207(1): 65-79, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38730133

RESUMO

BACKGROUND: Whether DCIS is associated with higher breast cancer-specific and all-cause mortality is unclear with few studies in older women. Therefore, we examined DCIS and breast cancer-specific, cardiovascular (CVD)-specific, and all-cause mortality among Women's Health Initiative (WHI) Clinical Trial participants overall and by age (< 70 versus ≥ 70 years). METHODS: Of 68,132 WHI participants, included were 781 postmenopausal women with incident DCIS and 781 matched controls. Serial screening mammography was mandated with high adherence. DCIS cases were confirmed by central medical record review. Adjusted multivariable Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Kaplan Meier (KM) plots were used to assess 10-year and 20-year mortality rates. RESULTS: After 20.3 years total, and 13.2 years median post-diagnosis follow-up, compared to controls, DCIS was associated with higher breast cancer-specific mortality (HR 3.29; CI = 1.32-8.22, P = 0.01). The absolute difference in 20-year breast cancer mortality was 1.2% without DCIS and 3.4% after DCIS, log-rank P = 0.026. Findings were similar by age (< 70 versus ≥ 70 years) with no interaction (P interaction = 0.80). Incident DCIS was not associated with CVD-specific mortality (HR 0.77; CI-0.54-1.09, P = 0.14) or with all-cause mortality (HR 0.96; CI = 0.80-1.16, P = 0.68) with similar findings by age. CONCLUSIONS: In postmenopausal women, incident DCIS was associated with over three-fold higher breast cancer-specific mortality, with similar findings in younger and older postmenopausal women. These finding suggest caution in using age to adjust DCIS clinical management or research strategies.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Pós-Menopausa , Humanos , Feminino , Neoplasias da Mama/mortalidade , Neoplasias da Mama/epidemiologia , Idoso , Pessoa de Meia-Idade , Carcinoma Intraductal não Infiltrante/mortalidade , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/patologia , Fatores Etários , Saúde da Mulher , Causas de Morte , Modelos de Riscos Proporcionais , Estudos de Casos e Controles , Mamografia , Estimativa de Kaplan-Meier , Fatores de Risco
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