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2.
J Am Chem Soc ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38961828

RESUMO

The solution-state fluxional behavior of bullvalene has fascinated physical organic and supramolecular chemists alike. Little effort, however, has been put into investigating bullvalene applications in bulk, partially due to difficulties in characterizing such dynamic systems. To address this knowledge gap, we herein probe whether bullvalene Hardy-Cope rearrangements can be mechanically perturbed in bulk polymer networks. We use dynamic mechanical analysis to demonstrate that the activation barrier to the glass transition process is significantly elevated for bullvalene-containing materials relative to "static" control networks. Furthermore, bullvalene rearrangements can be mechanically perturbed at low temperatures in the glassy region; such behavior facilitates energy dissipation (i.e., increased hysteresis energy) and polymer chain alignment to stiffen the material (i.e., increased Young's modulus) under load. Computational simulations corroborate our work that showcases bullvalene as a reversible "low-force" covalent mechanophore in the modulation of viscoelastic behavior.

3.
Mol Metab ; : 101980, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950777

RESUMO

OBJECTIVE: In this investigation, we addressed the contribution of the core circadian clock factor, BMAL1, in skeletal muscle to both acute transcriptional responses to exercise and transcriptional remodeling in response to exercise training. Additionally, we adopted a systems biology approach to investigate how loss of skeletal muscle BMAL1 altered peripheral tissue homeostasis as well as exercise training adaptations in iWAT, liver, heart, and lung of male mice. METHODS: Combining inducible skeletal muscle specific BMAL1 knockout mice, physiological testing and standardized exercise protocols, we performed a multi-omic analysis (transcriptomics, chromatin accessibility and metabolomics) to explore loss of muscle BMAL1 on muscle and peripheral tissue responses to exercise. RESULTS: Muscle-specific BMAL1 knockout mice demonstrated a blunted transcriptional response to acute exercise, characterized by the lack of upregulation of well-established exercise responsive transcription factors including Nr4a3 and Ppargc1a. Six weeks of exercise training in muscle-specific BMAL1 knockout mice induced significantly greater and divergent transcriptomic and metabolomic changes in muscle. Surprisingly, liver, lung, inguinal white adipose and heart showed divergent exercise training transcriptomes with less than 5% of 'exercise-training' responsive genes shared for each tissue between genotypes. CONCLUSIONS: Our investigation has uncovered the critical role that BMAL1 plays in skeletal muscle as a key regulator of gene expression programs for both acute exercise and training adaptations. In addition, our work has uncovered the significant impact that altered exercise response in muscle and its likely impact on the system plays in the peripheral tissue adaptations to exercise training. Our work also demonstrates that if the muscle adaptations diverge to a more maladaptive state this is linked to increased gene expression signatures of inflammation across many tissues. Understanding the molecular targets and pathways contributing to health vs. maladaptive exercise adaptations will be critical for the next stage of therapeutic design for exercise mimetics.

4.
Breast Cancer Res ; 26(1): 109, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956693

RESUMO

BACKGROUND: The effect of gender-affirming testosterone therapy (TT) on breast cancer risk is unclear. This study investigated the association between TT and breast tissue composition and breast tissue density in trans masculine individuals (TMIs). METHODS: Of the 444 TMIs who underwent chest-contouring surgeries between 2013 and 2019, breast tissue composition was assessed in 425 TMIs by the pathologists (categories of lobular atrophy and stromal composition) and using our automated deep-learning algorithm (% epithelium, % fibrous stroma, and % fat). Forty-two out of 444 TMIs had mammography prior to surgery and their breast tissue density was read by a radiologist. Mammography digital files, available for 25/42 TMIs, were analyzed using the LIBRA software to obtain percent density, absolute dense area, and absolute non-dense area. Linear regression was used to describe the associations between duration of TT use and breast tissue composition or breast tissue density measures, while adjusting for potential confounders. Analyses stratified by body mass index were also conducted. RESULTS: Longer duration of TT use was associated with increasing degrees of lobular atrophy (p < 0.001) but not fibrous content (p = 0.82). Every 6 months of TT was associated with decreasing amounts of epithelium (exp(ß) = 0.97, 95% CI 0.95,0.98, adj p = 0.005) and fibrous stroma (exp(ß) = 0.99, 95% CI 0.98,1.00, adj p = 0.05), but not fat (exp(ß) = 1.01, 95%CI 0.98,1.05, adj p = 0.39). The effect of TT on breast epithelium was attenuated in overweight/obese TMIs (exp(ß) = 0.98, 95% CI 0.95,1.01, adj p = 0.14). When comparing TT users versus non-users, TT users had 28% less epithelium (exp(ß) = 0.72, 95% CI 0.58,0.90, adj p = 0.003). There was no association between TT and radiologist's breast density assessment (p = 0.58) or LIBRA measurements (p > 0.05). CONCLUSIONS: TT decreases breast epithelium, but this effect is attenuated in overweight/obese TMIs. TT has the potential to affect the breast cancer risk of TMIs. Further studies are warranted to elucidate the effect of TT on breast density and breast cancer risk.


Assuntos
Densidade da Mama , Mama , Mamografia , Testosterona , Pessoas Transgênero , Humanos , Densidade da Mama/efeitos dos fármacos , Feminino , Adulto , Testosterona/uso terapêutico , Mamografia/métodos , Mama/diagnóstico por imagem , Mama/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Índice de Massa Corporal , Procedimentos de Readequação Sexual/efeitos adversos , Procedimentos de Readequação Sexual/métodos
6.
Diabetes Care ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38889071

RESUMO

OBJECTIVE: In this study we examine whether hospitalized coronavirus disease 2019 (COVID-19) pneumonia increases long-term cardiovascular mortality more than other hospitalized pneumonias in people with type 2 diabetes and aim to quantify the relative cardiovascular disease (CVD) mortality risks associated with COVID-19 versus non-COVID-19 pneumonia. RESEARCH DESIGN AND METHODS: With use of the SCI-Diabetes register, two cohorts were identified: individuals with type 2 diabetes in 2016 and at the 2020 pandemic onset. Hospital and death records were linked for determination of pneumonia exposure and CVD deaths. Poisson regression estimated rate ratios (RRs) for CVD death associated with both pneumonia types, with adjustment for confounders. Median follow-up durations were 1,461 days (2016 cohort) and 700 days (2020 cohort). RESULTS: The adjusted RR for CVD death following non-COVID-19 pneumonia was 5.51 (95% CI 5.31-5.71) prepandemic and 7.3 (6.86-7.76) during the pandemic. For COVID-19 pneumonia, the RR was 9.13 (8.55-9.75). Beyond 30 days post pneumonia, the RRs converged, to 4.24 (3.90-4.60) for non-COVID-19 and 3.35 (3.00-3.74) for COVID-19 pneumonia, consistent even with exclusion of prior CVD cases. CONCLUSIONS: Hospitalized pneumonia, irrespective of causal agent, marks an increased risk for CVD death immediately and over the long-term. COVID-19 pneumonia poses a higher CVD death risk than other pneumonias in the short-term, but this distinction diminishes over time. These insights underscore the need for including pneumonia in CVD risk assessments, with particular attention to the acute impact of COVID-19 pneumonia.

7.
Transl Cancer Res ; 13(5): 2535-2543, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38881922

RESUMO

Despite the promise of concurrent radiotherapy (RT) and immunotherapy in head and neck cancer (HNC), multiple randomized trials of this combination have had disappointing results. To evaluate potential immunologic mechanisms of RT resistance, we compared pre-treatment HNCs that developed RT resistance to a matched cohort that achieved curative status. Gene set enrichment analysis demonstrated that a pre-treatment pro-immunogenic tumor microenvironment (TME), including type II interferon [interferon gamma (IFNγ)] and tumor necrosis factor alpha (TNFα) signaling, predicted cure while type I interferon [interferon alpha (IFNα)] enrichment was associated with an immunosuppressive TME found in tumors that went on to recur. We then used immune deconvolution of RNA sequencing datasets to evaluate immunologic cell subset enrichment. This identified M2 macrophage signaling associated with type I IFN pathway expression in RT-recurrent disease. To further dissect mechanism, we then evaluated differential gene expression between pre-treatment and RT-resistant HNCs from sampled from the same patients at the same anatomical location in the oral cavity. Here, recurrent samples exhibited upregulation of type I IFN-stimulated genes (ISGs) including members of the IFN-induced protein with tetratricopeptide repeats (IFIT) and IFN-induced transmembrane (IFITM) gene families. While several ISGs were upregulated in each recurrent cancer, IFIT2 was significantly upregulated in all recurrent tumors when compared with the matched pre-RT specimens. Based on these observations, we hypothesized sustained type I IFN signaling through ISGs, such as IFIT2, may suppress the intra-tumoral immune response thereby promoting radiation resistance.

8.
J Sports Sci ; : 1-10, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899730

RESUMO

This study examined the criterion validity of an ecological momentary assessment (EMA)-reported physical activity and sedentary time compared with accelerometry in shift workers and non-shift workers. Australian workers (n = 102) received prompts through a mobile EMA app and wore the Actigraph accelerometer on the right hip for 7-10 days. Participants received five EMA prompts per day at 3-hour intervals on their mobile phones. EMA prompts sent to shift workers (SW-T) were tailored according to their work schedule. Non-shift workers (NSW-S) received prompts at standardised times. To assess criterion validity, the association of EMA-reported activities and the Actigraph accelerometer activity counts and number of steps were used. Participants were 36 ± 11 years and 58% were female. On occasions where participants reported physical activity, acceleration counts per minute (CPM) and steps were significantly higher (ß = 1184 CPM, CI 95%: 1034, 1334; ß = 20.9 steps, CI 95%: 18.2, 23.6) than each of the other EMA activities. Acceleration counts and steps were lower when sitting was reported than when no sitting was reported by EMA. Our study showed that EMA-reported physical activity and sedentary time was significantly associated with accelerometer-derived data. Therefore, EMA can be considered to assess shift workers' movement-related behaviours with accelerometers to provide rich contextual data.

9.
Br J Pharmacol ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840293

RESUMO

BACKGROUND AND PURPOSE: Thromboxane A2 (TXA2) is a prostanoid produced during platelet activaton, important in enhancing platelet reactivity by activation of TP receptors. However, due to the short half-life, studying TXA2 signalling is challenging. To enhance our understanding of TP receptor-mediated platelet biology, we therefore synthesised mono and difluorinated TXA2 analogues and explored their pharmacology on heterologous and endogenously expressed TP receptor function. EXPERIMENTAL APPROACH: Platelet functional and signalling responses were studied using aggregometry, Ca2+ mobilisation experiments and immunoblotting and compared with an analogue of the TXA2 precursor prostaglandin H2, U46619. Gαq/Gαs receptor signalling was determined using a bioluminescence resonance energy transfer (BRET) assay in a cell line overexpression system. KEY RESULTS: BRET studies revealed that F-TXA2 and F2-TXA2 promoted receptor-stimulated TP receptor G-protein activation similarly to U46619. Unexpectedly, F2-TXA2 caused reversible aggregation in platelets, whereas F-TXA2 and U46619 induced sustained aggregation. Blocking the IP receptor switched F2-TXA2-mediated reversible aggregation into sustained aggregation. Further BRET studies confirmed F2-TXA2-mediated IP receptor activation. F2-TXA2 rapidly and potently stimulated platelet TP receptor-mediated protein kinase C/P-pleckstrin, whereas IP-mediated protein kinase A/P-vasodilator-stimulated phosphoprotein was more delayed. CONCLUSION AND IMPLICATIONS: F-TXA2 is a close analogue to TXA2 used as a selective tool for TP receptor platelet activation. In contrast, F2-TXA2 acts on both TP and IP receptors differently over time, resulting in an initial wave of TP receptor-mediated platelet aggregation followed by IP receptor-induced reversibility of aggregation. This study reveals the potential difference in the temporal aspects of stimulatory and inhibitory pathways involved in platelet activation.

11.
JAMA Netw Open ; 7(6): e2415983, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38848061

RESUMO

Importance: Sport-related concussion (SRC), a form of mild traumatic brain injury, is a prevalent occurrence in collision sports. There are no well-established approaches for tracking neurobiologic recovery after SRC. Objective: To examine the levels of serum glial fibrillary acidic protein (GFAP) and neurofilament light (NfL) in Australian football athletes who experience SRC. Design, Setting, and Participants: A cohort study recruiting from April 10, 2021, to September 17, 2022, was conducted through the Victorian Amateur Football Association, Melbourne, Australia. Participants included adult Australian football players with or without SRC. Data analysis was performed from May 26, 2023, to March 27, 2024. Exposure: Sport-related concussion, defined as at least 1 observable sign and/or 2 or more symptoms. Main Outcomes and Measures: Primary outcomes were serum GFAP and NfL levels at 24 hours, and 1, 2, 4, 6, 8, 12, and 26 weeks. Secondary outcomes were symptoms, cognitive performance, and return to training times. Results: Eighty-one individuals with SRC (median age, 22.8 [IQR, 21.3-26.0] years; 89% male) and 56 control individuals (median age, 24.6 [IQR, 22.4-27.3] years; 96% male) completed a total of 945 of 1057 eligible testing sessions. Compared with control participants, those with SRC exhibited higher GFAP levels at 24 hours (mean difference [MD] in natural log, pg/mL, 0.66 [95% CI, 0.50-0.82]) and 4 weeks (MD, 0.17 [95% CI, 0.02-0.32]), and NfL from 1 to 12 weeks (1-week MD, 0.31 [95% CI, 0.12-0.51]; 2-week MD, 0.38 [95% CI, 0.19-0.58]; 4-week MD, 0.31 [95% CI, 0.12-0.51]; 6-week MD, 0.27 [95% CI, 0.07-0.47]; 8-week MD, 0.36 [95% CI, 0.15-0.56]; and 12-week MD, 0.25 [95% CI, 0.04-0.46]). Growth mixture modeling identified 2 GFAP subgroups: extreme prolonged (16%) and moderate transient (84%). For NfL, 3 subgroups were identified: extreme prolonged (7%), moderate prolonged (15%), and minimal or no change (78%). Individuals with SRC who reported loss of consciousness (LOC) (33% of SRC cases) had higher GFAP at 24 hours (MD, 1.01 [95% CI, 0.77-1.24]), 1 week (MD, 0.27 [95% CI, 0.06-0.49]), 2 weeks (MD, 0.21 [95% CI, 0.004-0.42]) and 4 weeks (MD, 0.34 [95% CI, 0.13-0.55]), and higher NfL from 1 week to 12 weeks (1-week MD, 0.73 [95% CI, 0.42-1.03]; 2-week MD, 0.91 [95% CI, 0.61-1.21]; 4-week MD, 0.90 [95% CI, 0.59-1.20]; 6-week MD, 0.81 [95% CI, 0.50-1.13]; 8-week MD, 0.73 [95% CI, 0.42-1.04]; and 12-week MD, 0.54 [95% CI, 0.22-0.85]) compared with SRC participants without LOC. Return to training times were longer in the GFAP extreme compared with moderate subgroup (incident rate ratio [IRR], 1.99 [95% CI, 1.69-2.34]; NfL extreme (IRR, 3.24 [95% CI, 2.63-3.97]) and moderate (IRR, 1.43 [95% CI, 1.18-1.72]) subgroups compared with the minimal subgroup, and for individuals with LOC compared with those without LOC (IRR, 1.65 [95% CI, 1.41-1.93]). Conclusions and Relevance: In this cohort study, a subset of SRC cases, particularly those with LOC, showed heightened and prolonged increases in GFAP and NfL levels, that persisted for at least 4 weeks. These findings suggest that serial biomarker measurement could identify such cases, guiding return to play decisions based on neurobiologic recovery. While further investigation is warranted, the association between prolonged biomarker elevations and LOC may support the use of more conservative return to play timelines for athletes with this clinical feature.


Assuntos
Traumatismos em Atletas , Biomarcadores , Concussão Encefálica , Proteína Glial Fibrilar Ácida , Humanos , Concussão Encefálica/sangue , Concussão Encefálica/fisiopatologia , Concussão Encefálica/complicações , Masculino , Feminino , Biomarcadores/sangue , Adulto , Proteína Glial Fibrilar Ácida/sangue , Traumatismos em Atletas/sangue , Traumatismos em Atletas/complicações , Traumatismos em Atletas/fisiopatologia , Adulto Jovem , Futebol Americano/lesões , Austrália , Proteínas de Neurofilamentos/sangue , Estudos de Coortes , Recuperação de Função Fisiológica/fisiologia , Atletas/estatística & dados numéricos
12.
PLoS One ; 19(6): e0303033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38861557

RESUMO

BACKGROUND: In response to the adverse impacts of the COVID-19 lockdown measures Move Well, Feel Good (MWFG) was developed as a school intervention using improvement of motor competence as a mechanism for promoting positive mental health. Study objectives were to evaluate the feasibility and acceptability of MWFG and to describe changes in child-level outcomes. METHODS: Five northwest England primary schools were recruited. MWFG was delivered over 10-weeks through physical education (PE) lessons, which were supplemented by optional class-time, break-time, and home activities. The intervention focused on development of 9-10 year-old children's motor competence in locomotor, object control, and stability skills, and psychosocial skills. Feasibility was evaluated against nine pre-defined criteria using surveys, interviews (teachers), and focus groups (children). Pre- and post-intervention assessments of motor competence, mental health, prosocial behaviour, wellbeing, and 24-hour movement behaviours were also completed. RESULTS: The five recruited schools represented 83% of the target number, 108 children consented (54% of target) with teachers recruited in all schools (100% of target). Intervention dose was reflected by 76% of the 45 scheduled PE lessons being delivered, and adherence was strong (>85% of children attending ≥75% of lessons). Positive indicators of acceptability were provided by 86% of children, 83% of PE teachers, and 90% of class teachers. Data collection methods were deemed acceptable by 91% of children and 80% of class teachers, and children spoke positively about participating in the data collection. Child-level outcome data collection was completed by 65%-97% of children, with a 3%-35% attrition rate at post-intervention, depending on measure. Favourable changes in motor competence (+13.7%), mental health difficulties (-8.8%), and prosocial behaviour (+7.6%) were observed. CONCLUSIONS: MWFG is an acceptable and feasible motor competence intervention to promote positive mental health. Content and delivery modifications could inform progression to a pilot trial with a more robust design.


Assuntos
COVID-19 , Estudos de Viabilidade , Saúde Mental , Instituições Acadêmicas , Humanos , Criança , Masculino , Feminino , COVID-19/prevenção & controle , COVID-19/epidemiologia , COVID-19/psicologia , Destreza Motora , Educação Física e Treinamento/métodos , Inglaterra , Promoção da Saúde/métodos , SARS-CoV-2
14.
Eur J Heart Fail ; 2024 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-38923253

RESUMO

AIMS: We hypothesized that the current gold standard for risk stratification of patients with acute heart failure (AHF), the Multiple Estimation of risk based on the Emergency department Spanish Score In patients with AHF (MEESSI-AHF) risk score, can be further improved by adding systemic inflammation as quantified by C-reactive protein (CRP). METHODS AND RESULTS: In a prospective multicentre diagnostic study (BASEL V), AHF was centrally adjudicated by two independent cardiologists. The MEESSI-AHF risk score was calculated using an established reduced and recalibrated model containing 12 independent risk factors. Model extension was performed by refitting and adding CRP in the logistic regression model with 30-day mortality as binary outcome. Discrimination, calibration and clinical usefulness were used to assess the performance of the extended Multiple Estimation of risk based on the Emergency department Spanish Score In patients (MEESSI) model. Validation was performed in an independent, retrospective and single-centre AHF cohort. Among 1208 AHF patients with complete data allowing calculation of the recalibrated MEESSI and the extended MEESSI models, the prognostic accuracy for 30-day mortality of the extended MEESSI model (c-statistic 0.83, 95% confidence interval [CI] 0.79-0.87) was significantly higher compared to the recalibrated model (c-statistic 0.79, 95% CI 0.75-0.83, p = 0.013). The extended model allowed to stratify a higher percentage of patients into the lowest risk group compared to the recalibrated model (33.1% vs. 20.3%). Demonstrating a calibration plot's slope of 1.00 (95% CI 0.81-1.19) and an intercept of 0.0 (95% CI -0.22 to 0.22), the extended MEESSI model achieved excellent and improved calibration. Results were confirmed in the independent validation cohort (n = 575). CONCLUSIONS: Quantifying inflammation using CRP concentration provided incremental value in AHF risk stratification using the established MEESSI model.

15.
JACS Au ; 4(6): 2300-2311, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38938799

RESUMO

Redox-active polymers serving as the active materials in solid-state electrodes offer a promising path toward realizing all-organic batteries. While both cathodic and anodic redox-active polymers are needed, the diversity of the available anodic materials is limited. Here, we predict solid-state structural, ionic, and electronic properties of anodic, phthalimide-containing polymers using a multiscale approach that combines atomistic molecular dynamics, electronic structure calculations, and machine learning surrogate models. Importantly, by combining information from each of these scales, we are able to bridge the gap between bottom-up molecular characteristics and macroscopic properties such as apparent diffusion coefficients of electron transport (D app). We investigate the impact of different polymer backbones and of two critical factors during battery operation: state of charge and polymer swelling. Our findings reveal that the state of charge significantly influences solid-state packing and the thermophysical properties of the polymers, which, in turn, affect ionic and electronic transport. A combination of molecular-level properties (such as the reorganization energy) and condensed-phase properties (such as effective electron hopping distances) determine the predicted ranking of electron transport capabilities of the polymers. We predict D app for the phthalimide-based polymers and for a reference nitroxide radical-based polymer, finding a 3 orders of magnitude increase in D app (≈10-6 cm2 s-1) with respect to the reference. This study underscores the promise of phthalimide-containing polymers as highly capable redox-active polymers for anodic materials in all-organic batteries, due to their exceptional predicted electron transport capabilities.

16.
Phys Med Rehabil Clin N Am ; 35(3): 665-678, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945658

RESUMO

Traumatic Brain Injury (TBI) cases often involve both medical and legal issues, litigation and prolonged recovery timelines. As TBI cases are often complex, and can have a significant impact on the lives of the patients and their families/caregivers, having a comprehensive understanding of the causes, diagnoses, treatments and long term outcomes will be valuable in understanding the medical and legal aspects of this type of injury. Patients, families, and health care professionals will all benefit from a deeper understanding of the medical and legal aspects of TBI, which should help improve rehabilitation and recovery outcomes.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Lesões Encefálicas Traumáticas/reabilitação
17.
Appl Health Econ Health Policy ; 22(4): 527-542, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38755403

RESUMO

BACKGROUND: Decision-makers require knowledge of the strengths and weaknesses of decision-analytic models used to evaluate healthcare interventions to be able to confidently use the results of such models to inform policy. A number of aspects of model validity have previously been described, but no systematic approach to assessing the validity of a model has been proposed. This study aimed to consolidate the different aspects of model validity into a step-by-step approach to assessing the strengths and weaknesses of a decision-analytic model. METHODS: A pre-defined set of steps were used to conduct the validation process of an exemplar early decision-analytic-model-based cost-effectiveness analysis of a risk-stratified national breast cancer screening programme [UK healthcare perspective; lifetime horizon; costs (£; 2021)]. Internal validation was assessed in terms of descriptive validity, technical validity and face validity. External validation was assessed in terms of operational validation, convergent validity (or corroboration) and predictive validity. RESULTS: The results outline the findings of each step of internal and external validation of the early decision-analytic-model and present the validated model (called 'MANC-RISK-SCREEN'). The positive aspects in terms of meeting internal validation requirements are shown together with the remaining limitations of MANC-RISK-SCREEN. CONCLUSION: Following a transparent and structured validation process, MANC-RISK-SCREEN has been shown to have satisfactory internal and external validity for use in informing resource allocation decision-making. We suggest that MANC-RISK-SCREEN can be used to assess the cost-effectiveness of exemplars of risk-stratified national breast cancer screening programmes (NBSP) from the UK perspective. IMPLICATIONS: A step-by-step process for conducting the validation of a decision-analytic model was developed for future use by health economists. Using this approach may help researchers to fully demonstrate the strengths and limitations of their model to decision-makers.


Assuntos
Neoplasias da Mama , Análise Custo-Benefício , Técnicas de Apoio para a Decisão , Detecção Precoce de Câncer , Humanos , Neoplasias da Mama/diagnóstico , Feminino , Detecção Precoce de Câncer/economia , Reino Unido , Medição de Risco , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Idoso
18.
Age Ageing ; 53(Suppl 2): ii80-ii89, 2024 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-38748910

RESUMO

BACKGROUND: Increasing fruit and vegetable (FV) consumption is associated with reduced cardiovascular disease risk in observational studies but with little evidence from randomised controlled trials (RCTs). The impact of concurrent pharmacological therapy is unknown. OBJECTIVE: To pool data from six RCTs to examine the effect of increasing FV intake on blood pressure (BP) and lipid profile, also exploring whether effects differed by medication use. DESIGN: Across trials, dietary intake was assessed by diet diaries or histories, lipids by routine biochemical methods and BP by automated monitors. Linear regression provided an estimate of the change in lipid profile or BP associated with a one portion increase in self-reported daily FV intake, with interaction terms fitted for medication use. RESULTS: The pooled sample included a total of 554 participants (308 males and 246 females). Meta-analysis of regression coefficients revealed no significant change in either systolic or diastolic BP per portion FV increase, although there was significant heterogeneity across trials for systolic BP (I2 = 73%). Neither adjusting for change in body mass index, nor analysis according to use of anti-hypertensive medication altered the relationship. There was no significant change in lipid profile per portion FV increase, although there was a significant reduction in total cholesterol among those not on lipid-lowering therapy (P < 0.05 after Bonferroni correction). CONCLUSION: Pooled analysis of six individual FV trials showed no impact of increasing intake on BP or lipids, but there was a total cholesterol-lowering effect in those not on lipid-lowering therapy.


Assuntos
Pressão Sanguínea , Frutas , Lipídeos , Ensaios Clínicos Controlados Aleatórios como Assunto , Verduras , Humanos , Pressão Sanguínea/efeitos dos fármacos , Masculino , Feminino , Pessoa de Meia-Idade , Lipídeos/sangue , Idoso , Dieta Saudável , Anti-Hipertensivos/uso terapêutico , Biomarcadores/sangue
19.
Ann Vasc Surg ; 106: 438-466, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38815914

RESUMO

BACKGROUND: Spinal cord ischemia is one of the complications that can occur after open and endovascular thoracoabdominal aortic repair. This occurs despite various perioperative approaches, including distal aortic perfusion, hybrid procedures with extra anatomical bypasses, motor-evoked potential, and cerebrospinal fluid drainage. The inability to recognize spinal ischemia in a timely manner remains a devastating complication after thoracoabdominal aortic repair.This review aims to look at novel technologies that are designed for continuous monitoring to detect early changes that signal the development of spinal cord ischemia and to discuss their benefits and limitations. METHODS: We conducted a systematic review of the technologies available for continuous monitoring in the intensive care unit for early detection of spinal cord ischemia. Studies were eligible for inclusion if they used different technologies for monitoring spinal ischemia during the postoperative period. All articles that were not available in English were excluded. To ensure that all relevant articles were included, no other significant restrictions were imposed. RESULTS: We identified 59 studies from the outset to December 2022 to be included in our study. New techniques have been studied as potentially useful monitoring tools that could provide simple and effective monitoring of the spinal cord. These include near-infrared spectroscopy, contrast-enhanced ultrasound, magnetic resonance imaging, fiber optic monitoring of the spinal cord, and cerebrospinal fluid biomarkers. CONCLUSIONS: Despite the development of new techniques to monitor for postoperative spinal cord ischemia, their use remains limited. We recommend more future research to ensure rapid intervention for our patients.

20.
J Affect Disord ; 360: 198-205, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38788855

RESUMO

BACKGROUND: Low social support has been identified as a risk factor for perinatal mental health problems. However, previous studies mainly focused on partner support or general social support and neglected the roles of grandparents. Here, we examine whether a lack of grandparental support is related to increased risk of a diagnosis of perinatal depression. In addition, we examine whether poor grandparental support is related to more depressive symptoms in mothers with and without previously diagnosed perinatal depression and whether perceived grandparental support buffers against parenting difficulties in mothers with perinatal depression. METHODS: The sample was drawn from an Australian pregnancy cohort study and consisted of 725 women, including 230 women who met criteria for Major Depression. At 12 months postpartum, women reported on grandparental geographical proximity and hours of grandparental childcare support. Perceived grandparental support was assessed with the Postpartum Social Support Questionnaire and parenting difficulties and depressive symptoms with the Parenting Stress Index and the Edinburgh Postnatal Depression Scale. RESULTS: Perceived grandparental support was related to fewer depressive symptoms among mothers with perinatal depression. In addition, higher levels of perceived grandparental support were related to lower parenting stress in mothers with and without perinatal depression. LIMITATIONS: Intergenerational conflicts and quality of grandparenting were not assessed. CONCLUSIONS: Our findings indicate that supportive grandparents may prevent the development of more severe perinatal depression in mothers experiencing perinatal mental health problems. Future studies should examine whether involving grandparents in treatment may add to the effectiveness of existing perinatal mental health interventions.


Assuntos
Depressão Pós-Parto , Avós , Poder Familiar , Apoio Social , Humanos , Feminino , Avós/psicologia , Adulto , Gravidez , Depressão Pós-Parto/psicologia , Poder Familiar/psicologia , Austrália , Transtorno Depressivo Maior/psicologia , Relação entre Gerações , Fatores de Risco , Estudos de Coortes , Mães/psicologia , Inquéritos e Questionários , Estresse Psicológico/psicologia
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