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1.
Int J Hyg Environ Health ; 260: 114390, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38772087

RESUMO

OBJECTIVES: In the US, violations of drinking water regulations are highest in lower-income rural areas overall, and particularly in Central Appalachia. However, data on drinking water use, quality, and associated health outcomes in rural Appalachia are limited. We sought to assess public and private drinking water sources and associated risk factors for waterborne pathogen exposures for individuals living in rural regions of Appalachian Virginia. METHODS: We administered surveys and collected tap water, bottled water, and saliva samples in lower-income households in two adjacent rural counties in southwest Virginia (bordering Kentucky and Tennessee). Water samples were tested for pH, temperature, conductivity, total coliforms, E. coli, free chlorine, nitrate, fluoride, heavy metals, and specific pathogen targets. Saliva samples were analyzed for antibody responses to potentially waterborne infections. We also shared water analysis results with households. RESULTS: We enrolled 33 households (83 individuals), 82% (n = 27) with utility-supplied water and 18% with private wells (n = 3) or springs (n = 3). 58% (n = 19) reported household incomes of <$20,000/year. Total coliforms were detected in water samples from 33% (n = 11) of homes, E. coli in 12%, all with wells or springs (n = 4), and Aeromonas, Campylobacter, and Enterobacter in 9%, all spring water (n = 3). Diarrhea was reported for 10% of individuals (n = 8), but was not associated with E. coli detection. 34% (n = 15) of saliva samples had detectable antibody responses for Cryptosporidium spp., C. jejuni, and Hepatitis E. After controlling for covariates and clustering, individuals in households with septic systems and straight pipes had significantly higher likelihoods of antibody detection (risk ratios = 3.28, 95%CI = 1.01-10.65). CONCLUSIONS: To our knowledge, this is the first study to collect and analyze drinking water samples, saliva samples, and reported health outcome data from low-income households in Central Appalachia. Our findings indicate that utility-supplied water in this region was generally safe, and individuals in low-income households without utility-supplied water or sewerage have higher exposures to waterborne pathogens.

2.
Arch Gynecol Obstet ; 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787416

RESUMO

Transition from antepartum to postpartum care is important, but often fragmented, and attendance at postpartum visits can be poor. Access to care is especially important for individuals diagnosed antepartum with conditions associated with longer-term implications, including gestational diabetes (GDM) and hypertensive disorders in pregnancy (HDP). Strategies to link and strengthen this transition are essential to support people to attend recommended appointments and testing. This narrative review evaluates what is known about postpartum transition of care after higher-risk antepartum conditions, discusses barriers and facilitators to uptake of recommended testing, and outlines strategies trialled to increase both postpartum attendance and testing. Barriers to attendance frequently overlap with general barriers to accessing healthcare. Specific postpartum challenges include difficulties with transport, coordinating breastfeeding and childcare access. Systemic challenges include inadequate communication to women around implications of health conditions diagnosed in pregnancy, and the importance of postpartum follow up. Uptake of recommended testing after a diagnosis of GDM and HDP is variable but generally suboptimal. Strategies which demonstrate promise include the use of patient navigators, focused education and specialised clinics. Reminder systems have had variable impact. Telehealth and technology are under-utilised in this field but offer promising options particularly with the expansion of virtual healthcare into routine maternity care. Strategies to improve both attendance rates and uptake of testing must be designed to address disparities in healthcare access and tailored to the needs of the community. This review provides a starting point to develop such strategies from the community level to the population level.

3.
BJGP Open ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331467

RESUMO

BACKGROUND: Early cancer diagnosis is associated with improved mortality and morbidity; however, studies indicate that women and individuals from ethnic minorities experience longer times to diagnosis and worse prognosis compared to their counterparts for various cancers. In countries with a gatekeeper healthcare system, such as UK, most suspected cancer referrals are initiated in primary care. AIM: To understand the extent of evidence available on the relationship between primary care cancer referral pathways and cancer outcomes in relation to gender across different ethnic groups. This will identify research gaps and enable development of strategies to ease potential inequalities in cancer diagnosis. DESIGN & SETTING: A scoping review based on the Joanna Briggs Institute methodology. PRISMA-ScR will be used. METHOD: Electronic databases and private collections of the team members will be searched for studies. Two independent reviewers will carry out the study selection and data extraction. Based on participants, concept and context framework, this review will consider studies after year 2000 that explored the relationship between gender, across various ethnic groups, and cancer outcomes following primary care cancer referral in countries with gatekeeper healthcare systems (UK, New Zealand, Sweden, Australia, Canada, Denmark, Ireland and Norway). Results will be presented as a narrative analysis. CONCLUSION: The results are expected to provide an overview of the discrepancies in primary care cancer referrals based on gender across ethnic groups, which will be crucial to define an appropriate range of strategies to ease any inequalities in primary healthcare cancer diagnosis. OPEN SCIENCE FRAMEWORK PROTOCOL REGISTRATION: https://osf.io/jvtxb.

4.
Immunotherapy ; 16(6): 381-390, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38197144

RESUMO

Aim: Neurological adverse events (NAEs) are infrequent immune checkpoint inhibitor (ICI) outcomes poorly characterized in extant research, complicating their clinical management. Methods: This study characterized the frequency, severity, patterning and timing of NAEs using a large retrospective registry, including all patients who received at least one dose of an ICI from 2/1/2011-4/7/2022 within our health network. Results: Among 3137 patients, there were 54 NAEs (1.72% any grade; 0.8% grade 3-4). Most NAEs were peripheral (57.4%) versus central (42.6%). Melanoma and renal cell carcinoma were significantly associated with NAEs. Conclusion: The incidence of NAEs was rare though higher than many prior case estimates; the timing was consistent with other AEs. NAEs frequently occurred in tumor types known to favor brain metastases.


Immune checkpoint inhibitors are new drugs for cancer. They boost your body's defenses to fight cancer cells. These drugs can be used alone or with other cancer treatments. Most people are okay with these medicines, but some might have problems in different parts of the body. This can be tricky to figure out. Rarely, there can be issues in the brain or nerves. These side effects are rare, happening in about 2 in every 100 people who use the drugs. They are more common in certain cancers like melanoma and kidney cancer. As doctors learn more about these side effects, they can better predict, treat, and prevent them.


Assuntos
Neoplasias Encefálicas , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Estudos Retrospectivos , Carcinoma de Células Renais/tratamento farmacológico
5.
PLoS Pathog ; 20(1): e1011280, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38271464

RESUMO

Subverting the host immune response to inhibit inflammation is a key virulence strategy of Yersinia pestis. The inflammatory cascade is tightly controlled via the sequential action of lipid and protein mediators of inflammation. Because delayed inflammation is essential for Y. pestis to cause lethal infection, defining the Y. pestis mechanisms to manipulate the inflammatory cascade is necessary to understand this pathogen's virulence. While previous studies have established that Y. pestis actively inhibits the expression of host proteins that mediate inflammation, there is currently a gap in our understanding of the inflammatory lipid mediator response during plague. Here we used the murine model to define the kinetics of the synthesis of leukotriene B4 (LTB4), a pro-inflammatory lipid chemoattractant and immune cell activator, within the lungs during pneumonic plague. Furthermore, we demonstrated that exogenous administration of LTB4 prior to infection limited bacterial proliferation, suggesting that the absence of LTB4 synthesis during plague contributes to Y. pestis immune evasion. Using primary leukocytes from mice and humans further revealed that Y. pestis actively inhibits the synthesis of LTB4. Finally, using Y. pestis mutants in the Ysc type 3 secretion system (T3SS) and Yersinia outer protein (Yop) effectors, we demonstrate that leukocytes recognize the T3SS to initiate the rapid synthesis of LTB4. However, several Yop effectors secreted through the T3SS effectively inhibit this host response. Together, these data demonstrate that Y. pestis actively inhibits the synthesis of the inflammatory lipid LTB4 contributing to the delay in the inflammatory cascade required for rapid recruitment of leukocytes to sites of infection.


Assuntos
Peste , Yersinia pestis , Humanos , Animais , Camundongos , Yersinia pestis/metabolismo , Peste/microbiologia , Sistemas de Secreção Tipo III/metabolismo , Leucotrieno B4/metabolismo , Leucócitos/metabolismo , Inflamação , Proteínas de Bactérias/metabolismo
6.
BMC Cancer ; 24(1): 158, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297229

RESUMO

BACKGROUND: Guidelines recommend cardiovascular risk assessment and counseling for cancer survivors. For effective implementation, it is critical to understand survivor cardiovascular health (CVH) profiles and perspectives in community settings. We aimed to (1) Assess survivor CVH profiles, (2) compare self-reported and EHR-based categorization of CVH factors, and (3) describe perceptions regarding addressing CVH during oncology encounters. METHODS: This cross-sectional analysis utilized data from an ongoing NCI Community Oncology Research Program trial of an EHR heart health tool for cancer survivors (WF-1804CD). Survivors presenting for routine care after potentially curative treatment recruited from 8 oncology practices completed a pre-visit survey, including American Heart Association Simple 7 CVH factors (classified as ideal, intermediate, or poor). Medical record abstraction ascertained CVD risk factors and cancer characteristics. Likert-type questions assessed desired discussion during oncology care. RESULTS: Of 502 enrolled survivors (95.6% female; mean time since diagnosis = 4.2 years), most had breast cancer (79.7%). Many survivors had common cardiovascular comorbidities, including high cholesterol (48.3%), hypertension or high BP (47.8%) obesity (33.1%), and diabetes (20.5%); 30.5% of survivors received high cardiotoxicity potential cancer treatment. Less than half had ideal/non-missing levels for physical activity (48.0%), BMI (18.9%), cholesterol (17.9%), blood pressure (14.1%), healthy diet (11.0%), and glucose/ HbA1c (6.0%). While > 50% of survivors had concordant EHR-self-report categorization for smoking, BMI, and blood pressure; cholesterol, glucose, and A1C were unknown by survivors and/or missing in the EHR for most. Most survivors agreed oncology providers should talk about heart health (78.9%). CONCLUSIONS: Tools to promote CVH discussion can fill gaps in CVH knowledge and are likely to be well-received by survivors in community settings. TRIAL REGISTRATION: NCT03935282, Registered 10/01/2020.


Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Feminino , Humanos , Masculino , Pressão Sanguínea , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Colesterol , Estudos Transversais , Seguimentos , Glucose , Nível de Saúde , Medição de Risco , Fatores de Risco , Sobreviventes , Estados Unidos , Ensaios Clínicos como Assunto
7.
Artigo em Inglês | MEDLINE | ID: mdl-38265120

RESUMO

AIMS: To explore the incidence and complexity of women presenting for maternity care who require concurrent cancer care, and to report the birth outcomes of these women. MATERIALS AND METHODS: A retrospective audit of women attending a 'high risk' maternal medicine clinic at an Australian tertiary maternity hospital between 1 October 2021 and 30 April 2023 was conducted. The inclusion criteria were a diagnosis of cancer and a concurrent pregnancy, or a diagnosis of cancer prior to the current pregnancy. Clinic lists and coding data were screened via the electronic medical record to identify potential subjects. Data were collected from the individual maternity and neonatal records. RESULTS: Forty of 705 (5.7%) women attending the maternal medicine clinic met the inclusion criteria, of which ten had a new diagnosis of cancer in pregnancy and 30 presented for maternity care after a previous diagnosis of cancer. Cancer therapy during pregnancy included surgery and chemotherapy. Most pregnancies (92.5%) resulted in term deliveries (≥37 weeks gestation). Four neonates were preterm, and one was small-for-gestational-age. Caesarean section delivery and post-partum haemorrhage were more common than expected, but the rate of other adverse pregnancy outcomes was consistent with the background population. Over half of neonates required neonatal intensive care unit / special care nursery admission but the indications for admission were common, self-limiting conditions, and the length of stay was short (mean <5.0 days). CONCLUSIONS: Approximately 6% of women attending the maternal medicine clinic had a current or previous diagnosis of cancer. Most pregnancies resulted in term deliveries and neonatal outcomes were excellent.

8.
Vaccine ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38238113

RESUMO

During the COVID-19 vaccination rollout from March 2021- December 2022, the Centers for Disease Control and Prevention funded 110 primary and 1051 subrecipient partners at the national, state, local, and community-based level to improve COVID-19 vaccination access, confidence, demand, delivery, and equity in the United States. The partners implemented evidence-based strategies among racial and ethnic minority populations, rural populations, older adults, people with disabilities, people with chronic illness, people experiencing homelessness, and other groups disproportionately impacted by COVID-19. CDC also expanded existing partnerships with healthcare professional societies and other core public health partners, as well as developed innovative partnerships with organizations new to vaccination, including museums and libraries. Partners brought COVID-19 vaccine education into farm fields, local fairs, churches, community centers, barber and beauty shops, and, when possible, partnered with local healthcare providers to administer COVID-19 vaccines. Inclusive, hyper-localized outreach through partnerships with community-based organizations, faith-based organizations, vaccination providers, and local health departments was critical to increasing COVID-19 vaccine access and building a broad network of trusted messengers that promoted vaccine confidence. Data from monthly and quarterly REDCap reports and monthly partner calls showed that through these partnerships, more than 295,000 community-level spokespersons were trained as trusted messengers and more than 2.1 million COVID-19 vaccinations were administered at new or existing vaccination sites. More than 535,035 healthcare personnel were reached through outreach strategies. Quality improvement interventions were implemented in healthcare systems, long-term care settings, and community health centers resulting in changes to the clinical workflow to incorporate COVID-19 vaccine assessments, recommendations, and administration or referrals into routine office visits. Funded partners' activities improved COVID-19 vaccine access and addressed community concerns among racial and ethnic minority groups, as well as among people with barriers to vaccination due to chronic illness or disability, older age, lower income, or other factors.

9.
iScience ; 27(1): 108600, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38179062

RESUMO

Fleas transmit Yersinia pestis directly within the dermis of mammals to cause bubonic plague. Syringe-mediated inoculation is widely used to recapitulate bubonic plague and study Y. pestis pathogenesis. However, intradermal needle inoculation is tedious, error prone, and poses a significant safety risk for laboratorians. Microneedle arrays (MNAs) are micron-scale polymeric structures that deliver materials to the dermis, while minimizing the risk of needle sticks. We demonstrated that MNA inoculation is a viable strategy to recapitulate bubonic plague and study bacterial virulence by defining the parameters needed to establish a lethal infection in the mouse model and characterizing the course of infection using live-animal optical imaging. Using MNAs, we also demonstrated that Y. pestis must overcome calprotectin-mediated zinc restriction within the dermis and dermal delivery of an attenuated mutant has vaccine potential. Together, these data demonstrate that MNAs are a safe alternative to study Y. pestis pathogenesis in the laboratory.

10.
Clin Neuropsychol ; 38(1): 116-134, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37081825

RESUMO

Objective: Neuropsychological assessment (NP) feedback helps patients and caregivers understand assessment results to maximise their utility and impact in everyday life. Yet feedback practices are inconsistent and there are no evidence-based guidelines for how feedback should be most effectively delivered. The aim of our study was to develop a psychometrically sound feedback competency checklist, the Psychology Competency Assessment Tool - Feedback (PsyCET-F), for use in research, training, and clinical settings. Method: The Delphi method of expert consensus was used to establish checklist items that clearly described competencies important for NP feedback. To examine the inter-rater reliability of the checklist, two experienced neuropsychologists rated the competencies demonstrated by trainee neuropsychologists across four feedback sessions. Results: After two Delphi rounds, consensus was reached on the 20-item checklist. Consensus was defined as at least 80% agreement amongst the panel of 20 experts. Four item categories resulted from the Delphi: (a) Opening the Session; (b) Applying Specific Feedback Techniques; (c) Engagement, Collaboration, and Alliance; and (d) Structuring and Ending the Session. Inter-rater reliability was moderate (κW = 0.79, p <.001, 80.52% agreement) when using a simple coding system, coded as Beginner, Intermediate, Competent, and Skilful; and strong (κW = 0.82, p <.001) when competency level was coded using an 8-point, detailed coding method. Conclusions: The PsyCET-F is psychometrically sound and fit-for-purpose for measuring competencies in giving NP feedback. It can be used in the training of clinicians to develop effective feedback skills. International benchmarking and usability testing will be conducted in a future study.


Assuntos
Competência Clínica , Humanos , Retroalimentação , Reprodutibilidade dos Testes , Testes Neuropsicológicos , Consenso
11.
J Psychosoc Oncol ; 42(1): 90-112, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37345874

RESUMO

PURPOSE: A single-arm trial evaluated the feasibility, acceptability, and outcomes of COPE-D, a collaborative care intervention for underserved cancer patients with depression. METHODS: Bilingual (Spanish and English) care managers provided counseling and/or medication management in consultation with physicians. Outcomes were treatment improvement (≥ 5-point reduction in PHQ-9), treatment response (≥ 50% reduction in PHQ-9), suicidal ideation resolution, and changes in depression (PHQ-9), anxiety (GAD-2), sleep disturbance (PSQI), global mental and physical health (PROMIS), social isolation (PROMIS), and qualitative feedback. RESULTS: 193 patients consented to participate. 165 initiated and 141 completed treatment, with 65% and 56% achieving treatment improvement and response, respectively. Outcomes did not differ by ethnicity (31% Hispanic), cancer stage (71% stages III-IV), income, or education. Suicidal ideation, depression, anxiety, sleep disturbance, and social isolation also improved. Qualitative feedback was largely positive. CONCLUSION: COPE-D improved depression and quality of life among underserved patients, with acceptable retention rates.


Assuntos
Depressão , Neoplasias , Humanos , Depressão/terapia , Depressão/psicologia , Populações Vulneráveis , Qualidade de Vida , Estudos de Viabilidade , Neoplasias/terapia
12.
Implement Sci Commun ; 4(1): 139, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37974245

RESUMO

BACKGROUND: To address the evolving needs and context changes due to the COVID-19 pandemic, we adapted Connect for Health, an evidence-based, primary care, pediatric weight management intervention. The objective of this study is to describe the planned adaptation process to ensure continued and equitable program uptake during the pandemic. METHODS: Guided by adaptation frameworks, we identified the core functions and forms of Connect for Health and then adapted the intervention in response to a changing healthcare context. We engaged stakeholders and surveyed parents of children with a BMI ≥ 85th percentile and pediatric clinicians and examined their experiences using telehealth for pediatric weight management and needs and preferences. Using multivariable logistic regression, we examined the preferences of parents with limited English proficiency regarding key aspects of pediatric weight management. RESULTS: We surveyed 200 parents and 43% had a primary language of Spanish. Parents wanted care to be a combination of in-person and virtual visits (80%). We found that parents with limited English proficiency had a higher odds ratio of affirming in-person visits are better than virtual visits for ensuring their child's health concern can be taken care of (OR: 2.91; 95% CI: 1.36, 6.21), feeling comfortable when discussing personal information (OR: 3.91; 95% CI: 1.82, 8.43), talking about healthy behaviors and setting goals (OR: 3.09; 95% CI: 1.39, 6.90), and talking about mental health and overall well-being (OR: 4.02; 95% CI: 1.83, 8.87) than parents without limited English proficiency. We surveyed 75 clinicians and 60% felt telehealth was a useful tool to provide care for pediatric weight management. Clinicians felt virtual visits did not pose barriers to all aspects of care. Informed by the surveys and stakeholder input, we made clinician- and family-level adaptations while retaining the program's function. CONCLUSIONS: By engaging stakeholders and adapting the program for telehealth, we optimized the reach and fit of Connect for Health to ensure its continued uptake. We have provided a real-world example of how clinical innovations can evolve and how to systematically plan adaptations in response to changing healthcare contexts. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04042493), Registered on August 2, 2019.

13.
Med Phys ; 50(11): 7118-7129, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37800880

RESUMO

BACKGROUND: Microwave imaging has been proposed for medical applications, creating maps related to water content of tissues. Breast imaging has emerged as a key application because the signals can be coupled directly into the breast and experience limited attenuation in fatty tissues. While the literature contains reports of tumor detection with microwave approaches, there is limited exploration of treatment monitoring. PURPOSE: This study aims to detect treatment-related changes in breast tissue with a low-resolution microwave scanner. METHODS: Microwave scans of 15 patients undergoing treatment for early-stage breast cancer are collected at up to 4 time points: after surgery (baseline), 6 weeks after accelerated partial breast radiation, as well as 1 and 2 years post-treatment. Both the treated and untreated breast are scanned at each time point. The microwave scanner consists of planar transmit and receive arrays and uses signals from 0.1 to 10 GHz. The average microwave frequency properties (permittivity) are calculated for each scan to enable quantitative comparison. Baseline and 6-week results are analyzed with a two-way ANOVA with blocking. RESULTS: Consistent properties are observed for the untreated breast over time, similar to a previous study. Comparison of the scans of the treated and untreated breast suggests increased properties related to treatment, particularly at baseline and 6-weeks following radiotherapy. Analysis of the average properties of the scans with ANOVA indicates statistically significant differences ( p < 0.05 $p < 0.05$ ) in the treated and untreated breast at these time points. CONCLUSIONS: Microwave imaging has the potential to track treatment-related changes in breast tissues.


Assuntos
Neoplasias da Mama , Imageamento de Micro-Ondas , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Micro-Ondas/uso terapêutico , Projetos Piloto , Mama/diagnóstico por imagem , Mama/patologia
14.
Lancet Reg Health Eur ; 32: 100716, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37635923
15.
Cancers (Basel) ; 15(15)2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37568751

RESUMO

Diagnosing cancer may be expedited by decreasing referral risk threshold. Clinical Practice Research Datalink participants (≥40 years) had a positive predictive value (PPV) ≥3% feature for breast, lung, colorectal, oesophagogastric, pancreatic, renal, bladder, prostatic, ovarian, endometrial or laryngeal cancer in 2016. The numbers of participants with features representing a 1-1.99% or 2-2.99% PPV for same cancer in the previous year were reported, alongside the time difference between meeting the ≥3% criteria and the lower threshold criteria. A total of 8616 participants had a PPV ≥3% feature, of whom 365 (4.2%) and 1147 (13.3%), respectively, met 2-2.99% and 1-1.99% criteria in the preceding year. The median time difference was 131 days (Interquartile Range (IQR) 27 to 256) for the 2-2.99% band and 179 days (IQR 58 to 289) for the 1-1.99% band. Results were heterogeneous across cancer sites. For some cancers, participants may progress from presenting lower- to higher-risk features before meeting urgent referral criteria; however, this was not usually the case. The details of specific features across multiple cancer sites will allow for a tailored approach to future reductions in referral thresholds, potentially improving the efficiency of urgent cancer referrals for the benefit both of individuals and the National Health Service (NHS).

16.
J Clin Endocrinol Metab ; 109(1): e397-e405, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-37410931

RESUMO

CONTEXT: Body weight and composition may change over the natural menopause transition. Whether surgical menopause has similar effects, and the impact of hormone replacement therapy (HRT), are unknown. Understanding the metabolic effects of surgical menopause will inform clinical care. OBJECTIVE: To prospectively measure weight and body composition over 24 months following surgical menopause compared with a similar comparison group who retained their ovaries. METHODS: Prospective observational study of weight change from baseline to 24 months in 95 premenopausal women at elevated risk of ovarian cancer planning risk-reducing salpingo-oophorectomy (RRSO) and 99 comparators who retained their ovaries. Change in body composition from baseline to 24 months was also assessed by dual-energy x-ray absorptiometry in a subgroup of 54 women who underwent RRSO and 81 comparators who retained their ovaries. In the subgroup, weight, fat mass, lean mass, and abdominal fat measures were compared between groups. RESULTS: At 24 months both groups had gained weight (RRSO 2760 ± 4860 g vs comparators 1620 ± 4540 g) with no difference between groups (mean difference 730 g; 95% CI 920 g to 2380 g; P = .383). In the body composition subgroup, there was no difference in weight between groups at 24 months (mean difference 944 g; 95% CI -1120 g to 2614 g; P = .431). RRSO women may have gained slightly more abdominal visceral adipose tissue (mean difference 99.0 g; 95% CI 8.8 g to 189.2 g; P = .032) but there were no other differences in body composition. There were also no differences in weight or body composition between HRT users and nonusers at 24 months. CONCLUSION: 24 months after RRSO, there was no difference in body weight compared with women who retained their ovaries. RRSO women gained more abdominal visceral adipose tissue than comparators, but there were no other differences in body composition. Use of HRT following RRSO had no effect on these outcomes.


Assuntos
Neoplasias Ovarianas , Salpingo-Ooforectomia , Feminino , Humanos , Estudos Prospectivos , Menopausa , Terapia de Reposição Hormonal , Peso Corporal , Ovariectomia
17.
EMBO Rep ; 24(10): e57369, 2023 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-37501563

RESUMO

Nutritional immunity includes sequestration of transition metals from invading pathogens. Yersinia pestis overcomes nutritional immunity by secreting yersiniabactin to acquire iron and zinc during infection. While the mechanisms for yersiniabactin synthesis and import are well-defined, those responsible for yersiniabactin secretion are unknown. Identification of this mechanism has been difficult because conventional mutagenesis approaches are unable to inhibit trans-complementation by secreted factors between mutants. To overcome this obstacle, we utilized a technique called droplet Tn-seq (dTn-seq), which uses microfluidics to isolate individual transposon mutants in oil droplets, eliminating trans-complementation between bacteria. Using this approach, we first demonstrated the applicability of dTn-seq to identify genes with secreted functions. We then applied dTn-seq to identify an AcrAB efflux system as required for growth in metal-limited conditions. Finally, we showed this efflux system is the primary yersiniabactin secretion mechanism and required for virulence during bubonic and pneumonic plague. Together, these studies have revealed the yersiniabactin secretion mechanism that has eluded researchers for over 30 years and identified a potential therapeutic target for bacteria that use yersiniabactin for metal acquisition.


Assuntos
Peste , Yersinia pestis , Humanos , Yersinia pestis/genética , Peste/genética , Peste/microbiologia , Fenóis , Tiazóis/farmacologia , Metais , Proteínas de Bactérias/genética
18.
Ecol Evol ; 13(7): e10323, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37492456

RESUMO

Social interactions can drive distinct gene expression profiles which may vary by social context. Here we use female sailfin molly fish (Poecilia latipinna) to identify genomic profiles associated with preference behavior in distinct social contexts: male interactions (mate choice) versus female interactions (shoaling partner preference). We measured the behavior of 15 females interacting in a non-contact environment with either two males or two females for 30 min followed by whole-brain transcriptomic profiling by RNA sequencing. We profiled females that exhibited high levels of social affiliation and great variation in preference behavior to identify an order of magnitude more differentially expressed genes associated with behavioral variation than by differences in social context. Using a linear model (limma), we took advantage of the individual variation in preference behavior to identify unique gene sets that exhibited distinct correlational patterns of expression with preference behavior in each social context. By combining limma and weighted gene co-expression network analyses (WGCNA) approaches we identified a refined set of 401 genes robustly associated with mate preference that is independent of shoaling partner preference or general social affiliation. While our refined gene set confirmed neural plasticity pathways involvement in moderating female preference behavior, we also identified a significant proportion of discovered that our preference-associated genes were enriched for 'immune system' gene ontology categories. We hypothesize that the association between mate preference and transcriptomic immune function is driven by the less well-known role of these genes in neural plasticity which is likely involved in higher-order learning and processing during mate choice decisions.

19.
J Diabetes Metab Disord ; 22(1): 861-871, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37250371

RESUMO

Purpose: Open-source automated insulin delivery (AID) is used by thousands of people with type 1 diabetes (T1D), but has unknown generalisability to marginalised ethnic groups. This study explored experiences of Indigenous Maori participants in the CREATE trial with use of an open-source AID system to identify enablers/barriers to health equity. Methods: The CREATE randomised trial compared open-source AID (OpenAPS algorithm on an Android phone with a Bluetooth-connected pump) to sensor-augmented pump therapy. Kaupapa Maori Research methodology was used in this sub-study. Ten semi-structured interviews with Maori participants (5 children, 5 adults) and whanau (extended family) were completed. Interviews were recorded and transcribed, and data were analysed thematically. NVivo was used for descriptive and pattern coding. Results: Enablers/barriers to equity aligned with four themes: access (to diabetes technologies), training/support, operation (of open-source AID), and outcomes. Participants described a sense of empowerment, and improved quality of life, wellbeing, and glycaemia. Parents felt reassured by the system's ability to control glucose, and children were granted greater independence. Participants were able to use the open-source AID system with ease to suit whanau needs, and technical problems were manageable with healthcare professional support. All participants identified structures in the health system precluding equitable utilisation of diabetes technologies for Maori. Conclusion: Maori experienced open-source AID positively, and aspired to use this therapy; however, structural and socio-economic barriers to equity were identified. This research proposes strength-based solutions which should be considered in the redesign of diabetes services to improve health outcomes for Maori with T1D.Trial Registration: The CREATE trial, encompassing this qualitative sub-study, was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12620000034932p) on the 20th January 2020. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-023-01215-3.

20.
Cancer ; 129(15): 2385-2394, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37211959

RESUMO

BACKGROUND: Understanding the relationship between tobacco use and symptom burden may inform tobacco treatment interventions tailored to the needs of individuals with cancer. METHODS: The study included 1409 adult cancer survivors from Wave 5 of the US Food and Drug Administration Population Assessment of Tobacco and Health (PATH) Study. A multivariate analysis of variance controlling for age, sex, and race/ethnicity assessed the association of cigarette smoking and vaping on cancer-related symptom burden (fatigue, pain, emotional problems) and quality of life (QoL). Generalized linear mixed models controlling for the same factors were used to assess associations among symptom burden, QoL, and quit-smoking intentions, quit-smoking likelihood, and past 12-month smoking quit attempts. RESULTS: Weighted rates of current cigarette smoking and vaping were 14.21% and 2.88%, respectively. Current smoking was associated with greater fatigue (p < .0001; partial η 2  = .02), pain (p < .0001; partial η 2  = .08), emotional problems (p < .0001; partial η 2  = .02), and worse QoL (p < .0001; partial η 2  = .08). Current vaping was associated with greater fatigue (p = .001; partial η 2  = .008), pain (p = .009; partial η 2  = .005), and emotional problems (p = .04; partial η 2  = .003), but not worse QoL (p = .17). Higher cancer symptom burden was not associated with reduced interest in quitting, likelihood of quitting, or odds of past year quit attempts (p > .05 for each). CONCLUSIONS: Among adults with cancer, current smoking and vaping were associated with greater symptom burden. Survivors' interest in and intentions to quit smoking were not related to symptom burden. Future research should examine the role of tobacco cessation in improving symptom burden and QoL.


Assuntos
Fumar Cigarros , Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias , Abandono do Hábito de Fumar , Produtos do Tabaco , Vaping , Adulto , Humanos , Qualidade de Vida , Abandono do Hábito de Fumar/psicologia , Fumar Cigarros/epidemiologia , Dor/epidemiologia , Dor/etiologia , Vaping/epidemiologia , Fadiga/epidemiologia , Fadiga/etiologia , Produtos do Tabaco/efeitos adversos , Neoplasias/epidemiologia
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