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BACKGROUND: Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. METHODS: In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m2, methotrexate 50 mg/m2, and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. FINDINGS: Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43). INTERPRETATION: Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy. FUNDING: Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).
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BACKGROUND: Current processes collecting cancer stage data in population-based cancer registries (PBCRs) lack standardisation, resulting in difficulty utilising diverse data sources and incomplete, low-quality data. Implementing a cancer staging tiered framework aims to improve stage collection and facilitate inter-PBCR benchmarking. OBJECTIVE: Demonstrate the application of a cancer staging tiered framework in the Western Australian Cancer Staging Project to establish a standardised method for collecting cancer stage at diagnosis data in PBCRs. METHODS: The tiered framework, developed in collaboration with a Project Advisory Group and applied to breast, colorectal, and melanoma cancers, provides business rules - procedures for stage collection. Tier 1 represents the highest staging level, involving complete American Joint Committee on Cancer (AJCC) tumour-node-metastasis (TNM) data collection and other critical staging information. Tier 2 (registry-derived stage) relies on supplementary data, including hospital admission data, to make assumptions based on data availability. Tier 3 (pathology stage) solely uses pathology reports. FINDINGS: The tiered framework promotes flexible utilisation of staging data, recognising various levels of data completeness. Tier 1 is suitable for all purposes, including clinical and epidemiological applications. Tiers 2 and 3 are recommended for epidemiological analysis alone. Lower tiers provide valuable insights into disease patterns, risk factors, and overall disease burden for public health planning and policy decisions. Capture of staging at each tier depends on data availability, with potential shifts to higher tiers as new data sources are acquired. CONCLUSIONS: The tiered framework offers a dynamic approach for PBCRs to record stage at diagnosis, promoting consistency in population-level staging data and enabling practical use for benchmarking across jurisdictions, public health planning, policy development, epidemiological analyses, and assessing cancer outcomes. Evolution with staging classifications and data variable changes will futureproof the tiered framework. Its adaptability fosters continuous refinement of data collection processes and encourages improvements in data quality.
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Estadiamento de Neoplasias , Neoplasias , Sistema de Registros , Humanos , Austrália Ocidental/epidemiologia , Neoplasias/patologia , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Coleta de Dados/métodos , Coleta de Dados/normas , BenchmarkingRESUMO
Ultra-processed food consumption has increased worldwide, yet little is known about the potential links with taste preference and sensitivity. This exploratory study aimed to (i) compare sweet and salty taste detection thresholds and preferences following consumption of ultra-processed and unprocessed diets, (ii) investigate whether sweet and salty taste sensitivity and preference were associated with taste substrates (i.e. sodium and sugar) and ad libitum nutrient intake, and (iii) examine associations of taste detection thresholds and preferences with blood pressure (BP) and anthropometric measures following consumption of ultra-processed and unprocessed diets. In a randomized crossover study, participants (N = 20) received ultra-processed or unprocessed foods for 2 weeks, followed by the alternate diet. Baseline food intake data were collected prior to admission. Taste detection thresholds and preferences were measured at the end of each diet arm. Taste-substrate/nutrient intake, body mass index (BMI), and body weight (BW) were measured daily. No significant differences were observed in participant salt and sweet detection thresholds or preferences after 2 weeks on ultra-processed or unprocessed diets. There was no significant association between salt and sweet taste detection thresholds, preferences, and nutrient intakes on either diet arm. A positive correlation was observed between salt taste preference and systolic BP (r = 0.59; P = 0.01), BW (r = 0.47, P = 0.04), and BMI (r = 0.50; P = 0.03) following consumption of the ultra-processed diet. Thus, a 2-week consumption of an ultra-processed diet does not appear to acutely impact sweet or salty taste sensitivity or preference. Trial Registration: ClinicalTrials.gov Identifier NCT03407053.
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Preferências Alimentares , Paladar , Humanos , Estudos Cross-Over , Projetos Piloto , Dieta , Ingestão de Energia , Peso CorporalRESUMO
BACKGROUND: Cancer stage at diagnosis is essential for understanding cancer outcomes, guiding cancer control activities and healthcare services, and enabling benchmarking nationally and internationally. Yet, most cancer registries in Australia do not routinely collect this data. This study explored key stakeholders' perceptions of implementing cancer staging utilising Natural Language Processing and Machine Learning algorithms within the Western Australian Cancer Registry. METHODS: Perceptions of key breast and colorectal cancer stakeholders, including registry staff, clinicians, consumers, data scientists, biostatisticians, data management, healthcare staff, and health researchers, were collected. Prospective and retrospective qualitative proformas at two-time points of the Western Australian Cancer Staging Project were employed. The Consolidated Framework for Implementation Research was used to guide data collection, analysis and interpretation embedded in a Participatory Action Research approach. Data analysis also incorporated Framework Analysis and an adapted version of grading qualitative data using a visual traffic light labelling system to highlight the levels of positivity, negativity, and implementation concern. RESULTS: Twenty-nine pre-proformas and 18 post-proformas were completed online via REDCap. The grading and visual presentation of barriers and enablers aided interpretation and reviewing predicted intervention outcomes. Of the selected constructs, complexity (the perceived difficulty of the intervention) was the strongest barrier and tension for change (the situation needing change) was the strongest enabler. Implementing cancer staging into the Western Australian Cancer Registry was considered vital. Benefits included improved knowledge and understanding of various outcomes (e.g., treatment received as per Optimum Care Pathways) and benchmarking. Barriers included compatibility issues with current systems/workflows, departmental/higher managerial support, and future sustainment. CONCLUSIONS: The findings aid further review of data gaps, additional cancer streams, standardising cancer staging and future improvements. The study offers an adapted version of a rapid qualitative data collection and analytic approach for establishing barriers and enablers. The findings may also assist other population-based cancer registries considering collecting cancer stage at diagnosis.
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Gerenciamento de Dados , Neoplasias , Humanos , Austrália/epidemiologia , Estadiamento de Neoplasias , Estudos Prospectivos , Estudos Retrospectivos , Sistema de Registros , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapiaRESUMO
BACKGROUND: To maintain and improve the quality of the cancer nursing workforce, it is crucial to understand the factors that influence retention and job satisfaction. We aimed to investigate the characteristics of cancer nurses in Australia and identify predictors of job satisfaction. METHODS: We analysed data from an anonymous cross-sectional survey distributed through the Cancer Nurses Society Australia membership and social media platforms from October 2021 to February 2022. The survey was compared to national nursing registration data. Data were analysed with non-parametric tests, and a stepwise, linear regression model was developed to best predict job satisfaction. RESULTS: Responses were received from 930 cancer nurses. Most respondents (85%) described themselves as experienced nurses, and more than half had post-graduate qualifications. We identified individual, organizational, and systemic factors that contribute to job satisfaction and can impact in workforce shortages. The findings include strategies to address and prioritize workforce challenges. There were 89 different titles for advanced practice nursing roles. Managing high workload was a reported challenge by 88%. Intention to stay less than 10 years was reported by nearly 60%; this was significantly correlated with job satisfaction and age. Significantly higher scores for job satisfaction were associated with those who had career progression opportunities, career development opportunities, adequate peer support and a clearly defined scope of role. Conversely, job satisfaction scores decreased the more people agreed there was a lack of leadership and they had insufficient resources to provide quality care. CONCLUSION: Cancer nurses are critical to the delivery of cancer care however, the workforce faces multiple challenges. This study provides an understanding of the Australian cancer nursing workforce characteristics, their roles and activities, and highlights important considerations for retaining nurses in the profession.
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BACKGROUND: Multiple clinical trials demonstrate consistent but modest benefit of adjuvant extended endocrine therapy (EET) in HR + breast cancer patients. Predictive biomarkers to identify patients that benefit from EET are critical to balance modest reductions in risk against potential side effects of EET. This study compares the performance of the Breast Cancer Index, BCI (HOXB13/IL17BR, H/I), with expression of estrogen (ER), progesterone (PR), and androgen receptors (AR), and Ki67, for prediction of EET benefit. METHODS: Node-positive (N+) patients from the Trans-aTTom study with available tissue specimen and BCI results (N = 789) were included. Expression of ER, PR, AR, and Ki67 was assessed by quantitative immunohistochemistry. BCI (H/I) gene expression analysis was conducted by quantitative RT-PCR. Statistical significance of the treatment by biomarker interaction was evaluated by likelihood ratio tests based on multivariate Cox proportional models, adjusting for age, tumor size, grade, and HER2 status. Pearson's correlation coefficients were calculated to evaluate correlations between BCI (H/I) versus ER, PR, AR, Ki67 and AR/ER ratio. RESULTS: EET benefit, measured by the difference in risk of recurrence between patients treated with tamoxifen for 10 versus 5 years, is significantly associated with increasing values of BCI (H/I) (interaction P = 0.01). In contrast, expression of ER (P = 0.83), PR (P = 0.66), AR (P = 0.78), Ki67 (P = 0.87) and AR/ER ratio (P = 0.84) exhibited no significant relationship with EET benefit. BCI (H/I) showed a very weak negative correlation with ER (r = - 0.18), PR (r = - 0.25), and AR (r = - 0.14) expression, but no correlation with either Ki67 (r = 0.04) or AR/ER ratio (r = 0.02). CONCLUSION: These findings are consistent with the growing body of evidence that BCI (H/I) is significantly predictive of response to EET and outcome. Results from this direct comparison demonstrate that expression of ER, PR, AR, Ki67 or AR/ER ratio are not predictive of benefit from EET. BCI (H/I) is the only clinically validated biomarker that predicts EET benefit.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptores Androgênicos/genética , Progesterona , Receptores de Estrogênio/metabolismo , Antígeno Ki-67/genética , Prognóstico , Estrogênios , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Biomarcadores Tumorais/metabolismo , Receptor ErbB-2 , Proteínas de HomeodomínioRESUMO
The purpose of this Special Communication is to discuss the rationale and design of the Movement Matters Activity Program for Stroke (MMAP) and explore implementation successes and challenges in home health and outpatient therapy practices across the stroke belt state of North Carolina. MMAP is an interventional component of the Comprehensive Postacute Stroke Services Study, a randomized multicenter pragmatic trial of stroke transitional care. MMAP was designed to maximize survivor health, recovery, and functional independence in the community and to promote evidence-based rehabilitative care. MMAP provided training, tools, and resources to enable rehabilitation providers to (1) prescribe physical activity and exercise according to evidence-based guidelines and programs, (2) match service setting and parameters with survivor function and benefit coverage, and (3) align treatment with quality metric reporting to demonstrate value-based care. MMAP implementation strategies were aligned with the Expert Recommendations for Implementing Change project, and MMAP site champion and facilitator survey feedback were thematically organized into the Consolidated Framework for Implementation Research domains. MMAP implementation was challenging, required modification and was affected by provider- and system-level factors. Program and study participation were limited and affected by practice priorities, productivity standards, and stroke patient volume. Sites with successful implementation appeared to have empowered MMAP champions in vertically integrated systems that embraced innovation. Findings from this broad evaluation can serve as a road map for the design and implementation of other comprehensive, complex interventions that aim to bridge the currently disconnected realms of acute care, postacute care, and community resources.
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Exercício Físico , Promoção da Saúde , Avaliação de Programas e Projetos de Saúde , Reabilitação do Acidente Vascular Cerebral/métodos , Cuidados Semi-Intensivos , Cuidado Transicional , Humanos , North Carolina , Recuperação de Função FisiológicaRESUMO
OBJECTIVES: Psychosocial interventions that mitigate psychosocial distress in cancer patients are important. The primary aim of this study was to examine the feasibility and acceptability of an adaptation of the Mindful Self-Compassion (MSC) program among adult cancer patients. A secondary aim was to examine pre-post-program changes in psychosocial wellbeing. METHOD: The research design was a feasibility and acceptability study, with an examination of pre- to post-intervention changes in psychosocial measures. A study information pack was posted to 173 adult cancer patients 6 months-5 years post-diagnosis, with an invitation to attend an eight-week group-based adaptation of the MSC program. RESULTS: Thirty-two (19%) consented to the program, with 30 commencing. Twenty-seven completed the program (mean age: 62.93 years, SD 14.04; 17 [63%] female), attending a mean 6.93 (SD 1.11) group sessions. There were no significant differences in medico-demographic factors between program-completers and those who did not consent. However, there was a trend toward shorter time since diagnosis in the program-completers group. Program-completers rated the program highly regarding content, relevance to the concerns of cancer patients, and the likelihood of recommending the program to other cancer patients. Sixty-three percent perceived that their mental wellbeing had improved from pre- to post-program; none perceived a deterioration in mental wellbeing. Small-to-medium effects were observed for depressive symptoms, fear of cancer recurrence, stress, loneliness, body image satisfaction, mindfulness, and self-compassion. SIGNIFICANCE OF RESULTS: The MSC program appears feasible and acceptable to adults diagnosed with non-advanced cancer. The preliminary estimates of effect sizes in this sample suggest that participation in the program was associated with improvements in psychosocial wellbeing. Collectively, these findings suggest that there may be value in conducting an adequately powered randomized controlled trial to determine the efficacy of the MSC program in enhancing the psychosocial wellbeing of cancer patients.
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Empatia , Neoplasias/psicologia , Pacientes/psicologia , Autocuidado/métodos , Adaptação Psicológica , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Atenção Plena/métodos , Neoplasias/complicaçõesRESUMO
Many children fail to comprehend what they read because they do not monitor their understanding, which requires making accurate judgements of what they know and then employing repair strategies when comprehension fails. Relying on research from learning science and cognitive and developmental psychology, we developed the Word Knowledge e-Book (WKe-Book) to improve children's calibration of their word knowledge, strategy use, and word knowledge overall; skills which are associated with reading comprehension. The WKe-Book, which is read on a tablet computer, is a choose-your-own adventure book where choices require choosing between two rare words (e.g., cogitate vs. procrastinate). Depending on the word chosen, the story follows a different plot. There are also embedded comprehension questions where students receive immediate feedback with consequences for incorrect answers, such as being sent back to reread a few pages. In a randomized controlled trial, we tested whether students (N = 603 in 25 third through fifth grade classrooms in Arizona in the US) reading the WKe-Book would demonstrate improved word knowledge, strategy use, and word knowledge calibration. Classrooms were randomly assigned to read the WKe-Book immediately (treatment) or later (delayed-treatment control), and within classrooms, students were randomly assigned to either participate in a 15-minute weekly book club (book club treatment) or to read the WKe-Book independently with no book club (no book club control). Results revealed a significant treatment effect of the WKe-Book on students' word knowledge, word knowledge calibration, and strategy use, which predicted student performance on standardized reading comprehension and vocabulary measures. The effects were greater for students who participated in weekly book clubs compared to students in the no book club control. These findings suggest that the affordances offered by technology, which are unavailable in paper-based books, can support students' development of metacognition, including word knowledge calibration, strategy use, and word learning skills.
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To determine the prevalence, associated factors, and relationships between symptoms of depression, symptoms of posttraumatic stress (PTS), and relationship distress in mothers and fathers of very preterm (VPT) infants (< 32 weeks). Mothers (n = 323) and fathers (n = 237) completed self-report measures on demographic and outcome variables at 38 days (SD = 23.1, range 9-116) postpartum while their infants were still hospitalised. Of mothers, 46.7% had a moderate to high likelihood of depression, 38.1% had moderate to severe symptoms of PTS, and 25.1% were in higher than average relationship distress. The corresponding percentages in fathers were 16.9, 23.7, and 27%. Depression was positively associated with having previous children (p = 0.01), speaking little or no English at home (p = 0.01), financial stress (p = 0.03), and recently accessing mental health services (p = 0.003) for mothers, and financial stress (p = 0.005) and not being the primary income earner (p = 0.04) for fathers. Similar associations were found for symptoms of PTS and relationship distress. Being in higher relationship distress increased the risk of depression in both mothers (p < .001) and fathers (p = 0.03), and PTS symptoms in mothers (p = 0.001). For both mothers and fathers, depression was associated with more severe PTS symptoms (p < .001). Fathers of VPT infants should be screened for mental health problems alongside mothers, and postpartum parent support programs for VPT infants should include strategies to improve the couple relationship.
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Depressão/psicologia , Pai/psicologia , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso/psicologia , Relações Interpessoais , Mães/psicologia , Pais/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/psicologia , Adulto , Depressão/epidemiologia , Feminino , Humanos , Recém-Nascido , Masculino , Saúde Mental , Período Pós-Parto , Prevalência , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estresse Psicológico/epidemiologiaRESUMO
Cancer is the leading cause of death for Korean Americans (KAs). Breast cancer (BC) is the most commonly occurring cancer among KA women, and its rate has been rapidly increasing. Low BC screening rates for KAs puts them at greater risk for late-stage breast cancer. We conducted a systematic review of the published literature on cancer screening among KAs, and identified 38 eligible studies. Despite significant increases in mammogram utilization over the past two decades, KAs have consistently lower rates of mammogram screening than other American populations. KA women also report lower rates of clinical breast examination and breast self-examination. Screening rates are higher among adults with higher socioeconomic status, greater acculturation to the United States, more cancer knowledge, higher perceived susceptibility to BC, more social support, and better access to health services. However, fear of finding something wrong, fear of embarrassment or lack of modesty, not knowing where to go for screening, believing that mammography is only necessary when symptoms are present, and perceived time and cost difficulties in accessing mammography were reported as barriers to mammogram screening. Coordinated efforts from clinicians, public health workers, KA cultural and religious organizations, and the broader breast cancer advocacy and awareness community are necessary for improving BC screening among KAs.
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Asiático/estatística & dados numéricos , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer/estatística & dados numéricos , Mamografia/estatística & dados numéricos , Asiático/psicologia , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , República da Coreia/etnologia , Fatores Socioeconômicos , Estados UnidosRESUMO
BACKGROUND: Drug resistance in breast cancer is the major obstacle to effective treatment with chemotherapy. While upregulation of multidrug resistance genes is an important component of drug resistance mechanisms in vitro, their clinical relevance remains to be determined. Therefore, identifying pathways that could be targeted in the clinic to eliminate anthracycline-resistant breast cancer remains a major challenge. METHODS: We generated paired native and epirubicin-resistant MDA-MB-231, MCF7, SKBR3 and ZR-75-1 epirubicin-resistant breast cancer cell lines to identify pathways contributing to anthracycline resistance. Native cell lines were exposed to increasing concentrations of epirubicin until resistant cells were generated. To identify mechanisms driving epirubicin resistance, we used a complementary approach including gene expression analyses to identify molecular pathways involved in resistance, and small-molecule inhibitors to reverse resistance. In addition, we tested its clinical relevance in a BR9601 adjuvant clinical trial. RESULTS: Characterisation of epirubicin-resistant cells revealed that they were cross-resistant to doxorubicin and SN-38 and had alterations in apoptosis and cell-cycle profiles. Gene expression analysis identified deregulation of histone H2A and H2B genes in all four cell lines. Histone deacetylase small-molecule inhibitors reversed resistance and were cytotoxic for epirubicin-resistant cell lines, confirming that histone pathways are associated with epirubicin resistance. Gene expression of a novel 18-gene histone pathway module analysis of the BR9601 adjuvant clinical trial revealed that patients with low expression of the 18-gene histone module benefited from anthracycline treatment more than those with high expression (hazard ratio 0.35, 95 % confidence interval 0.13-0.96, p = 0.042). CONCLUSIONS: This study revealed a key pathway that contributes to anthracycline resistance and established model systems for investigating drug resistance in all four major breast cancer subtypes. As the histone modification can be targeted with small-molecule inhibitors, it represents a possible means of reversing clinical anthracycline resistance. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00003012 . Registered on 1 November 1999.
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Antraciclinas/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética , Histonas/biossíntese , Adulto , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inibidores de Histona Desacetilases/administração & dosagem , Histonas/genética , Humanos , Irinotecano , Células MCF-7 , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Adulto JovemRESUMO
Neuronal pentraxin receptor (NPR) is a synaptic protein implicated in AMPA receptor trafficking at excitatory synapses. Since glutamate neurotransmission is disrupted in Alzheimer's disease (AD), NPR levels measured from plasma represent a potential biomarker for synaptic dysfunction associated with AD. We sought to determine the relationship between AD pathology and brain and plasma NPR levels by examining age-associated NPR levels in these compartments in a transgenic APP/PS1 rat model of AD. NPR levels in cortical homogenate were similar in wild-type (Wt) and APP/PS1 rats at 3 months of age (prior to Aß plaque deposition), but significantly increased in APP/PS1 rats by 9 and 18-20 months of age (after the onset of plaque deposition). These age-dependent differences were driven by proportional increases in NPR in membrane-associated cortical fractions. Genotype-related differences in NPR expression were also seen in the hippocampus, which exhibits significant Aß pathology, but not in the cerebellum, which does not. Plasma analyses revealed increased levels of a 26 kDa NPR fragment in APP/PS1 rats relative to Wt rats by 18-20 months of age, which correlated with the levels of full-length NPR in cortex. Our findings indicate that cerebral accumulation of NPR and Aß occurs with similar temporal and regional patterns in the APP/PS1 model, and suggest that a 26 kDa plasma NPR fragment may represent a peripheral biomarker of this process.
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Envelhecimento/metabolismo , Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Receptores de Superfície Celular/metabolismo , Proteínas ADAM/metabolismo , Proteína ADAM17 , Envelhecimento/sangue , Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Western Blotting , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Humanos , Aprendizagem em Labirinto/fisiologia , Presenilina-1/genética , Presenilina-1/metabolismo , Ratos Sprague-Dawley , Ratos Transgênicos , Receptores de Superfície Celular/sangueRESUMO
Increased dietary consumption of docosahexaenoic acid (DHA) is associated with decreased risk for Alzheimer's disease (AD). These effects have been postulated to arise from DHA's pleiotropic effects on AD pathophysiology, including its effects on ß-amyloid (Aß) production, aggregation, and toxicity. While in vitro studies suggest that DHA may inhibit and reverse the formation of toxic Aß oligomers, it remains uncertain whether these mechanisms operate in vivo at the physiological concentrations of DHA attainable through dietary supplementation. We sought to clarify the effects of dietary DHA supplementation on Aß indices in a transgenic APP/PS1 rat model of AD. Animals maintained on a DHA-supplemented diet exhibited reductions in hippocampal Aß plaque density and modest improvements on behavioral testing relative to those maintained on a DHA-depleted diet. However, DHA supplementation also increased overall soluble Aß oligomer levels in the hippocampus. Further quantification of specific conformational populations of Aß oligomers indicated that DHA supplementation increased fibrillar (i.e. putatively less toxic) Aß oligomers and decreased prefibrillar (i.e. putatively more toxic) Aß oligomers. These results provide in vivo evidence suggesting that DHA can modulate Aß aggregation by stabilizing soluble fibrillar Aß oligomers and thus reduce the formation of both Aß plaques and prefibrillar Aß oligomers. However, since fibrillar Aß oligomers still retain inherent neurotoxicity, DHA may need to be combined with other interventions that can additionally reduce fibrillar Aß oligomer levels for more effective prevention of AD in clinical settings.
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Doença de Alzheimer/dietoterapia , Peptídeos beta-Amiloides/metabolismo , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos , Hipocampo/metabolismo , Fragmentos de Peptídeos/metabolismo , Placa Amiloide/dietoterapia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/psicologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Hipocampo/patologia , Humanos , Masculino , Aprendizagem em Labirinto , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Placa Amiloide/psicologia , Presenilina-1/genética , Presenilina-1/metabolismo , Multimerização Proteica , Ratos Sprague-Dawley , Ratos Transgênicos , Resultado do TratamentoRESUMO
PURPOSE: Increasing numbers of haematology cancer survivors warrants identification of the most effective model of survivorship care to survivors from a diverse range of haematological cancers with aggressive treatment regimens. This review aimed to identify models of survivorship care to support the needs of haematology cancer survivors. METHOD: An integrative literature review method utilised a search of electronic databases (CINAHL, Medline, PsycInfo, PubMed, EMBASE, PsycArticles, and Cochrane Library) for eligible articles (up to July 2014). Articles were included if they proposed or reported the use of a model of care for haematology cancer survivors. RESULTS: Fourteen articles were included in this review. Eight articles proposed and described models of care, and six reported the use of a range of survivorship models of care in haematology cancer survivors. No randomised controlled trials or literature reviews were found to have been undertaken specifically with this cohort of cancer survivors. There was variation in the models described and who provided the survivorship care. CONCLUSION: Due to the lack of studies evaluating the effectiveness of models of care, it is difficult to determine the best model of care for haematology cancer survivors. Many different models of care are being put into practice before robust research is conducted. Therefore, well-designed high-quality pragmatic randomised controlled trials are required to inform clinical practice.
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Leucemia/enfermagem , Linfoma/enfermagem , Mieloma Múltiplo/enfermagem , Enfermagem de Atenção Primária , Sobreviventes , Adulto , Necessidades e Demandas de Serviços de Saúde , Humanos , Leucemia/mortalidade , Linfoma/mortalidade , Modelos Teóricos , Mieloma Múltiplo/mortalidadeRESUMO
This letter was sent to the Honourable Helen Morton by Emma Campbell after the Occupational Therapy Australia National Conference. A number of members of First Australian and Australian OTs online were keen to show their support for Emma's letter and share this with other OT colleagues.
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Competência Cultural , Disparidades nos Níveis de Saúde , Havaiano Nativo ou Outro Ilhéu do Pacífico , Terapia Ocupacional , Política , Austrália , HumanosRESUMO
Technological advances have influenced practice patterns and innovation in many health disciplines, including respiratory therapy. Collaborative approaches and knowledge-sharing environments are vital in addressing problems and adopting emerging technology. This article illustrates how the emergence of low-cost three-dimensional printing technology to physically reproduce the results of computed tomography imaging data can provide ways to assess airway abnormalities and symptomology not explained by traditional diagnostic methods.
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BACKGROUND: Taxanes such as paclitaxel and docetaxel are used successfully to treat breast cancer, usually in combination with other agents. They interfere with microtubules causing cell cycle arrest; however, the mechanisms underlying the clinical effects of taxanes are yet to be fully elucidated. METHODS: Isogenic paclitaxel resistant (PACR) MDAâMBâ231, paclitaxel resistant ZR75â1 and docetaxel resistant (DOCR) ZR75â1 cell lines were generated by incrementally increasing taxane dose in native cell lines in vitro. We used aCGH analysis to identify mechanisms driving taxane resistance. RESULTS: Taxane resistant cell lines exhibited an 18-170 fold increased resistance to taxanes, with the ZR75-1 resistant cell lines also demonstrating cross resistance to anthracyclines. Paclitaxel treatment of native cells resulted in a G2/M block and a decrease in the G1 phase of the cell cycle. However, in the resistant cell lines, minimal changes were present. Functional network analysis revealed that the mitotic prometaphase was lost in the resistant cell lines. CONCLUSION: This study established a model system for examining taxane resistance and demonstrated that both MDR and mitosis represent common mechanism of taxane resistance.
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Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Paclitaxel/farmacologia , Taxoides/farmacologia , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Linhagem Celular Tumoral , Hibridização Genômica Comparativa , Docetaxel , Resistência a Múltiplos Medicamentos , Expressão Gênica , Humanos , Concentração Inibidora 50RESUMO
Enumerated threat agent lists have long driven biodefense priorities. The global SARS-CoV-2 pandemic demonstrated the limitations of searching for known threat agents as compared to a more agnostic approach. Recent technological advances are enabling agent-agnostic biodefense, especially through the integration of multi-modal observations of host-pathogen interactions directed by a human immunological model. Although well-developed technical assays exist for many aspects of human-pathogen interaction, the analytic methods and pipelines to combine and holistically interpret the results of such assays are immature and require further investments to exploit new technologies. In this manuscript, we discuss potential immunologically based bioagent-agnostic approaches and the computational tool gaps the community should prioritize filling.
RESUMO
OBJECTIVES: Amidst the fulfilment of making a positive impact on patients' lives, cancer nurses also contend with high workloads, limited resources, and barriers to career advancement. Understanding the perceptions of cancer nurses is essential in addressing these challenges and fostering an environment that promotes both professional satisfaction and optimal patient care. Our aim was to explore Australian cancer nurses' experiences and perspectives of workforce challenges and their proposed solutions to address them. METHODS: The Cancer Nurses Society Australia workforce cross-sectional survey was distributed online in 2022 through professional networks and social media. Free text responses to open-ended questions were analyzed using qualitative content analysis and inductive processes. RESULTS: Responses from 601 cancer nurses highlight the intricate interplay between rewards and obstacles experienced by the profession and identify key areas for improvement. Positive and negative quotes highlight the passion of cancer nurses which were summarized into themes and subthemes: 1) Finding fulfilment while struggling against the tide. While feeling undervalued and facing workload pressures, burnout and limited opportunities for career progression, nurses express love for their jobs, finding it rewarding yet emotionally challenging. 2) Grassroots solutions versus organizational inertia. Proposed solutions included addressing nurse-to-patient ratios, proactive succession planning, more specific education, dedicated time for learning, and mentorship and career development programs. Perceived barriers to initiatives included lethargic management and resistance to change. Networking opportunities, appropriate remuneration, and interdisciplinary teamwork with an appreciation of individual expertise are desired. CONCLUSIONS: Our findings give a voice to the cancer nurses of Australia. Nurses identified a range of solutions to address workforce challenges. IMPLICATIONS FOR NURSING PRACTICE: Addressing the systemic issues that contribute to high workload and impede nurses' well-being and their recognition, and promoting policies to support professional growth will increase satisfaction, enhance patient care outcomes, and contribute to a sustainable workforce.