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1.
Front Nutr ; 10: 1111681, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36960205

RESUMO

Introduction: This research integrates literature on masculinity stress-the distress experienced as the result of a perceived discrepancy with male gender norms-with research on goal conflict to examine preferences for plant-based meat alternatives (PBMAs). Men experiencing masculinity stress are likely to hold salient a goal of being masculine, which should lead to less preference for PBMAs. However, many of these men simultaneously hold competing goals, such as making ethical food choices, which remain inhibited in favor of the focal masculinity goal. We argue that once men experiencing masculinity stress highlight their masculinity through the selection of a manly product, they satisfy that higher-order goal and are then free to pursue previously inhibited goals, such as making an ethical choice through the selection of PBMAs. Methods: We present the results of three studies supporting these expectations. Study 1 tests the link between masculinity stress and meat (alternative) consumption using consumer search behavior collected from Google Trends, showing that masculinity stress is positively (negatively) correlated with searches for red meat (PBMAs). Study 2 shows that men experiencing masculinity stress are more inclined to choose PBMAs, provided they are presented within a masculine product context. Study 3 presents a parallel mediation model, showing that ethical considerations (as opposed to masculine goals) shape the choice of PBMA preference. Results and discussion: We conclude with a discussion of theoretical implications for the impression management strategies utilized by men experiencing masculinity stress and practical implications for the growing PBMA industry.

2.
J Consum Aff ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35600325

RESUMO

In 2021, the United States government provided a third economic impact payment (EIP) for those designated as experiencing greater need due to the COVID-19 pandemic. With a particular focus on scarcity and ontological insecurity, we collected time-separated data prior to, and following, the third EIP to examine how these variables shape consumer allocation of stimulus funds. We find that scarcity is positively associated with feelings of ontological insecurity, which, interestingly, correlates to a greater allocation of stimulus funds toward charitable giving. We further find evidence that mutability moderates the relationship between ontological insecurity and allocations to charitable giving. In other words, it is those who feel most insecure, but perceive that their resource situation is within their control, who allocated more to charity giving. We discuss the implications of these findings for theory, policy-makers, and the transformative consumer research (TCR) movement.

3.
Appetite ; 171: 105729, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619245

RESUMO

This work explores the effects of masculinity stress-distress arising from a perceived discrepancy with male gender norms-on red meat consumption, which has potentially substantial individual, collective, and ecological consequences. Across three studies, we demonstrate a positive indirect effect of masculinity stress on red meat consumption. This occurs through beliefs that meat consumption can augment masculinity-an effect which is moderated by one's self-assessed traditional masculinity (study 1). We further demonstrate attenuation of the effect of masculinity stress on red meat preference when a red meat product is associated with an out-group (i.e., women; study 2) and show that this effect does not extend to women. In study 3, we show that the effect of masculinity stress on choice of red meat is attenuated following a masculinity affirmation. We finish with a detailed discussion of implications and directions for future research. Taken together, we provide convergent evidence that masculinity stress is associated with red meat preference, and that this preference can be discouraged by leveraging out-group reference information and masculinity affirmation. In so doing, this research provides a series of contributions to the literatures on meat eating and vegetarianism specifically, as well as gender identity maintenance more broadly.


Assuntos
Masculinidade , Carne Vermelha , Dieta Vegetariana , Feminino , Humanos , Masculino , Carne
4.
J Gambl Stud ; 37(2): 623-642, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32666374

RESUMO

The current research focuses on how the use of "skeuomorphs" in digital design interacts with an illusion of control to influence gambling behavior. Skeuomorphism is a design concept in which an aspect of a modern item is made to represent its outdated counterpart, even if this representation serves no functional purpose, such as hands "dealing" cards or horses "racing" on the screen of a digital machine. It is proposed that the inclusion of these non-essential links to physical objects in digital gambling games interacts with a player's illusion of control over the outcome to influence behavior. Shown across a pretest and three experiments, the inclusion of skeuomorphic elements in the design of gambling games, compared to a minimalistic "flat" design, increases amount gambled. Additionally, skeuomorphism and manipulated illusion of control interact to further increase the amount gambled. The manuscript concludes with a discussion on the practical, theoretical, and policy implications of this research.


Assuntos
Jogo de Azar/psicologia , Ilusões/psicologia , Controle Interno-Externo , Jogos de Vídeo/psicologia , Percepção Visual , Adulto , Animais , Cavalos , Humanos , Masculino , Fatores de Risco
5.
Injury ; 51(7): 1536-1542, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32434718

RESUMO

As our population ages and increasing numbers of older patients experience major trauma it is important to understand factors that influence outcomes in this patient cohort. The aim of this study is to assess the impact of frailty in older patients who experience major trauma (Injury Severity Score (ISS) greater than 15). A retrospective cohort review using the national trauma registry data (Trauma Audit and Research Network) and an institutional database was carried out on all patients aged 60 years or older with an ISS> 15 who were treated at the regional Major Trauma Centre from 2014 to 2017 following major trauma. Frailty was assessed using the modified frailty index (mFI). Outcomes assessed included mortality, complications, hospital stay, functional outcome and discharge destination. 819 patients were included in the study. The most common mechanism of injury was fall from a height less than 2m (57.4%). 412 (51.3%) patients had a low frailty score, 280 (35%) had an intermediate frailty score and 110 (14%) had high frailty score. Increased frailty was associated with increased mortality at discharge (18.7%, 14.6% and 26.4% for low, intermediate and high frailty groups) and at one year (26.2%, 35.2% and 51%, respectively). Other predictors of mortality included male sex, age >90 years and the occurrence of a serious complication. Increasing frailty was also associated with an increased risk of serious complications including unplanned intubation, infection and progressive renal failure, and discharge to a destination other than home. This is the first study that has delineated the impact of frailty in older patients who experience major trauma and provides important information for patients, their families and healthcare providers. Future studies should focus on identifying care pathways that counteract the impact of frailty in this setting.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Causas de Morte , Fragilidade/epidemiologia , Alta do Paciente/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Idoso Fragilizado , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Centros de Traumatologia , Reino Unido , Ferimentos e Lesões
6.
Diagn Progn Res ; 2: 15, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31093564

RESUMO

BACKGROUND: Influenza is an acute viral infection of the respiratory tract. A rapid confirmatory diagnosis of influenza is important, since it is highly transmissible and outbreaks of influenza within the hospital setting increase morbidity and mortality. The objective of this study was to evaluate the cost implications, from the perspective of the UK NHS, of using on-label nasal swabs with the Alere™ i Influenza A & B test in a near patient setting. METHODS: A cost consequence model was developed. The time horizon of the model was from hospital admission on suspicion of influenza until the end of treatment (following a diagnosis of influenza or discharge from hospital). Data on the prevalence of influenza and the sensitivity and specificity of the Alere™ i Influenza A & B test came from two prospective observational diagnostic accuracy studies. Costs were obtained from published resources. Uncertainties in the model data were investigated using deterministic, one-way sensitivity analyses. RESULTS: Using the Alere™ i Influenza A & B point of care test with nasal swabs (on label) in NHS medical assessment units and emergency departments could save approximately £242,730 per 1000 adults presenting with influenza-like symptoms. The main cause for this was reduced times to availability of the result compared with the laboratory RT-PCR test. Other key drivers of savings were the cost of isolation, the prevalence of influenza, the specificity of the test, and the availability of isolation resources. CONCLUSIONS: The Alere™ i Influenza A & B point of care test would have greatest impact in hospitals that have extensive delays in the time to receive a result. Sensitivity analyses identified the model parameters which would have greatest effect on the result and confirmed that assumptions were conservative, i.e. did not change key results.

7.
J Hosp Infect ; 98(4): 382-390, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29222034

RESUMO

OBJECTIVE: The global burden of invasive fungal disease is increasing. Candida albicans remains the leading cause of fungal bloodstream infections, although non-albicans candidal infections are emerging. Areas of controversy regarding diagnosis and management are hampering our ability to respond effectively to this evolving threat. The purpose of this narrative review is to address current controversies and provide recommendations to supplement guidelines. DIAGNOSIS OF INVASIVE CANDIDIASIS: Diagnosis of invasive candidiasis requires a combination of diagnostic tests and patient risk factors. Beta-D glucan and Candida albicans germ tube antibody are both used as biomarkers as adjuncts to diagnosis, although direct culture remains the gold standard. Scoring systems are available to help distinguish between colonization and invasive disease. TREATMENT OF INVASIVE CANDIDIASIS: Echinocandins are recommended as first-line therapy in candidaemia, with de-escalation to fluconazole when clinical stability is achieved. Empirical therapy is highly recommended in high-risk patients, but a more targeted pre-emptive approach is now being favoured. The evidence for prophylactic therapy remains weak. SUMMARY: Mortality attributable to invasive candidiasis may be as high as 70%. Prompt diagnosis and treatment, in conjunction with source control, are the key to improving outcomes.


Assuntos
Candidemia/diagnóstico , Candidemia/tratamento farmacológico , Cuidados Críticos/métodos , Estado Terminal , Gerenciamento Clínico , Adulto , Prova Pericial , Humanos , Sociedades
8.
Phys Rev Lett ; 119(16): 166101, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29099194

RESUMO

Electron tomography bears promise for widespread determination of the three-dimensional arrangement of atoms in solids. However, it remains unclear whether methods successful for crystals are optimal for amorphous solids. Here, we explore the relative difficulty encountered in atomic-resolution tomography of crystalline and amorphous nanoparticles. We define an informational entropy to reveal the inherent importance of low-entropy zone-axis projections in the reconstruction of crystals. In turn, we propose considerations for optimal sampling for tomography of ordered and disordered materials.

9.
J Hosp Infect ; 97(3): 301-309, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28558954

RESUMO

BACKGROUND: Clinical diagnostic sensitivity alone is inadequate in the diagnosis of influenza. Polymerase chain reaction (PCR) testing is sensitive but the inherent delays in result availability potentially prolong time to isolation and treatment. Until recently no near-patient test (NPT) has demonstrated adequate sensitivity for routine clinical use. AIM: To evaluate diagnostic accuracy, time to result availability, clinical impact, and cost consequences of Alere™ i Influenza A&B NPT (Alere Inc., Waltham, MA, USA) using off-label throat swabs. METHODS: Prospective, multi-centre [four UK National Health Service (NHS) hospitals], diagnostic accuracy cohort study with cost modelling. Throat swab samples from suspected influenza patients were tested for influenza using the reference standard of PCR; a second throat swab was tested using NPT. FINDINGS: A total of 827 participants were recruited; 589 were suitable for analysis: sensitivity was 75.8% [95% confidence interval (CI): 67.0-84.6]; specificity was 96.8% (95% CI: 95.2-98.3). Sensitivity varied between Sheffield (Northern General Hospital: 82.1%; Royal Hallamshire Hospital: 83.3%) and other sites (Doncaster Royal Infirmary: 71.4%; Newcastle's Royal Victoria Infirmary: 50.0%) whereas specificity was high (92-100%). Positive predictive value (PPV) was 81.2% (95% CI: 72.9-89.5) with negative predictive value 95.6% (95% CI: 93.9-97.4) with observed prevalence of 15.4%. Median time to result for PCR was 1.1 days (on-site laboratories) and 5.2 days (remote laboratories). Isolation findings: 75% influenza positive not isolated; 69% of isolated participants did not have influenza. For a cohort of 1000 participants, annual estimated non-diagnostic cost savings with NPT are £215,040. CONCLUSION: This first prospective study of the Alere i NPT using throat swabs demonstrates high specificity, high PPV during seasonal epidemics, and rapid result availability which could lead to substantial cost savings.


Assuntos
Custos e Análise de Custo , Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/métodos , Influenza Humana/diagnóstico , Faringe/virologia , Testes Imediatos/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Fatores de Tempo , Reino Unido , Adulto Jovem
10.
Clin Pharmacol Ther ; 101(5): 589-592, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28187516

RESUMO

The cancer community understands the value of blood profiling measurements in assessing and monitoring cancer. We describe an effort among academic, government, biotechnology, diagnostic, and pharmaceutical companies called the Blood Profiling Atlas in Cancer (BloodPAC) Project. BloodPAC will aggregate, make freely available, and harmonize for further analyses, raw datasets, relevant associated clinical data (e.g., clinical diagnosis, treatment history, and outcomes), and sample preparation and handling protocols to accelerate the development of blood profiling assays.


Assuntos
Atlas como Assunto , Neoplasias/sangue , Bases de Dados Factuais , Humanos
11.
Ir J Med Sci ; 186(4): 815-820, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27822907

RESUMO

OBJECTIVE: Intra-hospital transport (IHT) of critically ill patients is associated with morbidity and mortality. Mass transfer of patients, as happens with unit relocation, is poorly described. We outline the process and adverse events associated with the relocation of a critical care unit. DESIGN: Extensive planning of the relocation targeted patient and equipment transfer, reduction in clinical pressure prior to the event and patient care during the relocation phase. SETTING: The setting was a 30-bed, tertiary referral, combined medical and surgical critical care unit, located in a 570-bed hospital that serves as the national referral centre for cardiothoracic surgery and spinal injuries. PARTICIPANTS: All stakeholders relevant to the critical care unit relocation were involved, including nursing and medical staff, porters, information technology services, laboratory staff, project development managers, pharmacy staff and building contractors. MAIN OUTCOME MEASURES: Mortality at discharge from critical care unit and discharge from hospital were the main outcome measures. A wide range of adverse events were prospectively recorded, as were transfer times. RESULTS: Twenty-one patients underwent IHT, with a median transfer time of 10 min. Two transfers were complicated by equipment failure and three patients experienced an episode of hypotension requiring intervention. There were no cases of central venous or arterial catheter or endotracheal tube dislodgement, and hospital mortality at 30 days was 14%. CONCLUSION: Although IHT is associated with morbidity and mortality, careful logistical planning allows for efficient transfer with low complication rates.


Assuntos
Unidades de Terapia Intensiva/normas , Transferência de Pacientes/métodos , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Br J Anaesth ; 109(5): 762-8, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22923635

RESUMO

BACKGROUND: Ultrasound (US) guidance reduces complications and increases accuracy during internal jugular vein (IJV) cannulation. The subclavian vein (SCV) is popular but is less amenable to US guidance. The axillary vein (AxV), a direct continuation of the SCV, is an alternative, but to date, experience with US is limited to small case series. METHODS: Retrospective procedural data were collected on 2586 sequential patients referred for insertion of tunnelled central venous access at a UK tertiary centre from 2004 to 2011. RESULTS: A total of 99.8% of patients tolerated the procedure with local anaesthesia ± sedation; six patients had general anaesthesia. Twenty-six (1%) patients had uncorrected coagulopathy or thrombocytopenia. A total of 2572 (99.5%) of patients were cannulated successfully: right AxV 1644 cases, left AxV 279, right IJV 547, left IJV 89, other techniques 13, and 14 (0.5%) cases failed. The initial site chosen was successful in 96%. In patients who previously underwent long-term cannulation, 93.3% of lines were sited easily. Forty-eight (1.9%) procedural complications occurred. CONCLUSIONS: In this large analysis of US-guided central venous access in a complex patient group, the majority of patients were cannulated successfully and safely. The subset of patients undergoing AxV cannulation demonstrated a low rate of complications. The AxV route of access appears to be a safe and effective alternative to the IJV.


Assuntos
Veia Axilar/diagnóstico por imagem , Cateterismo Venoso Central/métodos , Veias Jugulares , Ultrassonografia de Intervenção/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Reino Unido , Adulto Jovem
13.
J Clin Dent ; 22(3): 62-7, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21905399

RESUMO

OBJECTIVE: The aim of this study was to characterize, in vitro, the mode of action of calcium sodium phosphosilicate (NovaMin) in occluding dentin tubules for the purpose of treating dentin hypersensitivity. METHODS: Calcium sodium phosphosilicate (CSPS) was combined with artificial saliva on surfaces of prepared dentin discs. The layer formed was initially examined by a scanning electron microscope (SEM). Focused ion beam (FIB) milling was used to make bulk cross-sections and thin film lamellae. Low kV scanning transmission electron microscopy (STEM), energy dispersive x-ray spectroscopy (EDS), and selected area electron diffraction were then used to characterize, chemically and structurally, the layer formed and the material occluding the tubules. Experiments were also performed to assess the suitability of using an environmental scanning electron microscope (ESEM) in wet mode to follow the transition from CSPS to hydroxyapatite. RESULTS: SEM imaging showed that a layer was formed on the treated dentin samples, and that this layer occluded tubules. Chemical and structural analysis of this material showed that it was hydroxyapatite-like. The wet mode ESEM experiments demonstrated that this technique has the potential to follow the transition from CSPS to the crystalline hydroxyapatite material. CONCLUSION: The use of modern imaging and analysis techniques has demonstrated, in vitro, the reaction of CSPS from an amorphous material to a crystalline hydroxyapatite-like material. These experiments confirmed an occlusion mode of action for CSPS for the treatment of dentin hypersensitivity.


Assuntos
Dessensibilizantes Dentinários/farmacologia , Sensibilidade da Dentina/tratamento farmacológico , Dentina/efeitos dos fármacos , Vidro , Condicionamento Ácido do Dente/métodos , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Ácido Cítrico/química , Cristalografia , Dentina/química , Dentina/ultraestrutura , Dessensibilizantes Dentinários/química , Durapatita/química , Vidro/química , Humanos , Teste de Materiais , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão e Varredura , Tamanho da Partícula , Saliva Artificial/química , Silicatos/química , Silicatos/farmacologia , Espectrometria por Raios X , Fatores de Tempo
14.
J Microsc ; 240(1): 1-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21050207

RESUMO

All biological tissues are three dimensional and contain structures that span a range of length scales from nanometres through to hundreds of millimetres. These are not ideally suited to current three-dimensional characterization techniques such as X-ray or transmission electron tomography. Such detailed morphological analysis is critical to understanding the structural features relevant to tissue function and designing therapeutic strategies intended to address structural deficiencies encountered in pathological states. We show that use of focused ion beam milling combined with scanning electron microscopy can provide three-dimensional information at nanometre resolution from biologically relevant volumes of material, in this case dentine.


Assuntos
Dentina/ultraestrutura , Tomografia com Microscopia Eletrônica/métodos , Imageamento Tridimensional , Microscopia Eletrônica de Varredura/métodos , Dente Serotino/ultraestrutura , Dentina/anatomia & histologia , Humanos , Hidroxiapatitas , Dente Serotino/anatomia & histologia
16.
Nanotechnology ; 21(15): 155102, 2010 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-20332564

RESUMO

p-aminobenzoic acid (PABA), a structural moiety of many commercial drugs, is self-assembled with linker alkyl side chains to form tubular nanostructures. The tubes exhibited fluorescence either intrinsic or from fluorescent molecules embedded in the wall during self-assembly. Uptake and inter-cellular delivery of the conjugated nanotubes in human cancer cells and in mouse embryonic stem cells were demonstrated by fluorescence imaging and flow cytometry. Biocompatibility, cytotoxicity and clearance were monitored both ex vivo in mouse multipotent embryonic stem cells and in vivo in adult Drosophila. Accumulation of nanotubes had no adverse effects and abnormalities on stem cell morphology and proliferation rate. A distinct distribution of two separate nanotubes in various internal organs of Drosophila interprets that accumulation of nanomaterials might be interdependent on the side chain modifications and physiological settings of cell or tissue types. Unlike carbon nanomaterials, exposure of PABA nanotubes does not produce any hazards including locomotion defects and mortality of adult flies. Despite differential uptake and clearance from multiple live tissues, the use of self-assembled nanotubes can add new dimensions and scope to the development of dual-purpose oral carriers for the fulfilment of many biological promises.


Assuntos
Aminopiridinas/farmacologia , Benzamidas/farmacologia , Materiais Biocompatíveis/farmacologia , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/metabolismo , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/efeitos dos fármacos , Nanotubos/química , Administração Oral , Aminopiridinas/química , Animais , Benzamidas/química , Materiais Biocompatíveis/química , Drosophila melanogaster/citologia , Células-Tronco Embrionárias/metabolismo , Larva/citologia , Larva/efeitos dos fármacos , Larva/metabolismo , Camundongos , Nanotubos/ultraestrutura , Especificidade de Órgãos/efeitos dos fármacos
17.
J Infect Dis ; 195(12): 1818-27, 2007 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-17492598

RESUMO

We have shown previously in animal model and in vitro systems that antimicrobial therapy intensity has a profound influence on subpopulations of resistant organisms. Little attention has been paid to the effect of therapy duration on resistant subpopulations. We examined the influence of therapy intensity (area under the concentration/time curve for 24 h:minimum inhibitory concentration [AUC24:MIC] ratio) and therapy duration on resistance emergence using an in vitro model of Staphylococcus aureus infection. AUC24:MIC ratios of>or=100 were necessary to kill a substantial portion of the total population. Importantly, we demonstrated that therapy duration is a critical parameter. As the duration increased beyond 5 days, the intensity needed to suppress the antibiotic-resistant subpopulations increased, even when the initial bacterial kill was>4 log10 (cfu/mL). These findings were prospectively validated in an independent experiment in which exposures were calculated from the results of fitting a large mathematical model to all data simultaneously. All of the prospectively determined predictions were fulfilled in this validation experiment.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/fisiologia , Fluoroquinolonas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Contagem de Colônia Microbiana , DNA Girase/genética , DNA Topoisomerase IV/genética , Fluoroquinolonas/metabolismo , Fluoroquinolonas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana , Modelos Teóricos , Reação em Cadeia da Polimerase , Ligação Proteica , Reprodutibilidade dos Testes , Fatores de Tempo
18.
Br J Cancer ; 90(7): 1437-42, 2004 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-15054468

RESUMO

Gastrointestinal carcinomas frequently disseminate within the abdominal cavity to form secondary peritoneal metastases. Invasion of the peritoneal mesothelium is fundamental to this process, yet the underlying invasive mechanisms remain unclear. Preliminary in vitro work suggested that tumour cells can induce mesothelial apoptosis, representing a novel mechanism of peritoneal invasion. We examined the role of tumour cell-induced mesothelial apoptosis and explored the role of the death ligand/receptor system, Fas Ligand/Fas, as mediators of the apoptotic process. Cultured human mesothelial cells were used to establish in vitro co-culture models with the SW480 colonic cancer cell line. Tumour-induced mesothelial apoptosis was confirmed by phase-contrast microscopy and apoptotic detection assays. Human mesothelial cells and SW480 tumour cells constitutively expressed Fas and Fas Ligand mRNA and protein as determined by RT-PCR and confocal fluorescent microscopy. Stimulation of human mesothelial cells with anti-Fas monoclonal antibody or crosslinked soluble Fas Ligand-induced apoptosis, confirming the functional status of the Fas receptor. Pretreatment of SW480 cells with a blocking recombinant anti-Fas Ligand monoclonal antibody significantly reduced mesothelial apoptosis, indicating that tumour-induced mesothelial apoptosis may, in part, be mediated via a Fas-dependent mechanism. This represents a novel mechanism of mesothelial invasion and offers several new targets for therapeutic intervention.


Assuntos
Apoptose , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Neoplasias Gastrointestinais/patologia , Receptor fas/fisiologia , Técnicas de Cocultura , Imunofluorescência , Neoplasias Gastrointestinais/metabolismo , Humanos , Invasividade Neoplásica , Cavidade Peritoneal/citologia , Células Tumorais Cultivadas
19.
J Clin Pathol ; 57(2): 193-5, 2004 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14747449

RESUMO

AIMS: To establish the relation between the amount of breast core needle biopsy (CNB) material examined and agreement between preoperative and postoperative histopathology parameters in invasive breast cancer. METHODS: The CNB and surgical specimen histopathology reports of 113 patients with invasive breast carcinoma were reviewed and the total amount of CNB material examined for each case was determined. Agreement was calculated for tumour type, grade, mitoses, nuclear pleomorphism, and tubule formation. Associations between the amount of CNB material and histopathology agreement before and after surgery were explored using binary logistic regression. RESULTS: Tumour type and grade agreed in 65.4% and 61.6% of cases, respectively. The components used to calculate grade--nuclear pleomorphism (57.4%), mitoses (59.4%), and tubule formation (55.6%)--agreed slightly less frequently. The proportion of cases with preoperative and postoperative assessments that agreed did not depend on the number of cores collected or the total amount of material examined. CONCLUSION: Neither tumour type and grade, nor the individual components used to calculate grade agreed consistently between the CNB and surgical specimen. The number of cores collected and the total amount of material reviewed by the pathologist does not influence the likelihood of agreement between preoperative and postoperative histopathology reports.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Biópsia por Agulha/métodos , Feminino , Humanos , Modelos Logísticos , Mitose , Invasividade Neoplásica , Cuidados Pós-Operatórios , Cuidados Pré-Operatórios/métodos , Prognóstico , Reprodutibilidade dos Testes
20.
Biophys J ; 86(1 Pt 1): 411-9, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14695283

RESUMO

Identifying the fold class of a protein sequence of unknown structure is a fundamental problem in modern biology. We apply a supervised learning algorithm to the classification of protein sequences with low sequence identity from a library of 174 structural classes created with the Combinatorial Extension structural alignment methodology. A class of rules is considered that assigns test sequences to structural classes based on the closest match of an amino acid index profile of the test sequence to a profile centroid for each class. A mathematical optimization procedure is applied to determine an amino acid index of maximal structural discriminatory power by maximizing the ratio of between-class to within-class profile variation. The optimal index is computed as the solution to a generalized eigenvalue problem, and its performance for fold classification is compared to that of other published indices. The optimal index has significantly more structural discriminatory power than all currently known indices, including average surrounding hydrophobicity, which it most closely resembles. It demonstrates >70% classification accuracy over all folds and nearly 100% accuracy on several folds with distinctive conserved structural features. Finally, there is a compelling universality to the optimal index in that it does not appear to depend strongly on the specific structural classes used in its computation.


Assuntos
Algoritmos , Aminoácidos/química , Inteligência Artificial , Proteínas/química , Proteínas/classificação , Análise de Sequência de Proteína/métodos , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular , Reconhecimento Automatizado de Padrão , Dobramento de Proteína , Proteínas/análise
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