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1.
Int J Tuberc Lung Dis ; 26(5): 399-405, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35505484

RESUMO

BACKGROUND: Australia has a low incidence of TB and has committed to eliminating the disease. Identification of risk factors associated with TB is critical to achieving this goal.METHODS: We undertook a prospective cohort study involving persons receiving TB treatment in four Australian jurisdictions. Risk factors and their association with delayed treatment completion (treatment delayed by at least 1 month) were analysed using univariate analyses and multivariate logistic regression.RESULTS: Baseline surveys were completed for 402 persons with TB. Most (86.1%) were born overseas. Exposure to a person with TB was reported by 19.4%. Diabetes mellitus (10.2%), homelessness (9.2%), cigarette smoking (8.7%), excess alcohol consumption (6.0%) and mental illness (6.2%) were other common risk factors. At follow-up, 24.8% of patients had delayed treatment completion, which was associated with adverse events (34.1%, aOR 6.67, 95% CI 3.36-13.27), excess alcohol consumption (6.0%, aOR 21.94, 95% CI 6.03-79.85) and HIV co-infection (2.7%, aOR 8.10, 95% CI 1.16-56.60).CONCLUSIONS: We identified risk factors for TB and their association with delayed treatment completion, not all of which are routinely collected for surveillance purposes. Recognition of these risk factors should facilitate patient-centred care and assist Australia in reaching TB elimination.


Assuntos
Infecções por HIV , Tuberculose , Austrália/epidemiologia , Infecções por HIV/epidemiologia , Humanos , Estudos Prospectivos , Fatores de Risco , Tempo para o Tratamento , Tuberculose/complicações , Tuberculose/epidemiologia
2.
Perspect Public Health ; 142(3): 167-174, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-33472547

RESUMO

AIMS: The outbreak of severe acute respiratory syndrome coronavirus 2 (COVID-19) is a global pandemic that has had substantial impact across societies. An attempt to reduce infection and spread of the disease, for most nations, has led to a lockdown period, where people's movement has been restricted resulting in a consequential impact on employment, lifestyle behaviours and wellbeing. As such, this study aimed to explore adults' thoughts and behaviours in response to the outbreak and resulting lockdown measures. METHODS: Using an online survey, 1126 adults responded to invitations to participate in the study. Participants, all aged 18 years or older, were recruited using social media, email distribution lists, website advertisement and word of mouth. Sentiment and personality features extracted from free-text responses using Artificial Intelligence methods were used to cluster participants. RESULTS: Findings demonstrated that there was varied knowledge of the symptoms of COVID-19 and high concern about infection, severe illness and death, spread to others, the impact on the health service and on the economy. Higher concerns about infection, illness and death were reported by people identified at high risk of severe illness from COVID-19. Behavioural clusters, identified using Artificial Intelligence methods, differed significantly in sentiment and personality traits, as well as concerns about COVID-19, actions, lifestyle behaviours and wellbeing during the COVID-19 lockdown. CONCLUSIONS: This time-sensitive study provides important insights into adults' perceptions and behaviours in response to the COVID-19 pandemic and associated lockdown. The use of Artificial Intelligence has identified that there are two behavioural clusters that can predict people's responses during the COVID-19 pandemic, which goes beyond simple demographic groupings. Considering these insights may improve the effectiveness of communication, actions to reduce the direct and indirect impact of the COVID-19 pandemic and to support community recovery.


Assuntos
COVID-19 , Adulto , Inteligência Artificial , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Pandemias , SARS-CoV-2
4.
BJOG ; 127(12): 1528-1535, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32340075

RESUMO

OBJECTIVE: To compare electrodiathermy with helium thermal coagulation in laparoscopic treatment of mild-to-moderate endometriosis. DESIGN: Parallel-group randomised controlled trial. SETTING: A UK endometriosis centre. POPULATION: Non-pregnant women aged 16-50 years with a clinical diagnosis of mild-to-moderate endometriosis. METHODS: If mild or moderate endometriosis was confirmed at laparoscopy, women were randomised to laparoscopic treatment with electrodiathermy or helium thermal coagulator. MAIN OUTCOME MEASURES: Cyclical pain and dyspareunia (rated on a 100-mm visual analogue scale, VAS), quality of life at baseline and at 6, 12 and 36 weeks following surgery, operative blood loss and surgical complications. RESULTS: A total of 192 women were randomised. Of these, 155 (81%) completed the primary outcome point at 12 weeks. In an intention-to-treat analysis, VAS scores for cyclical pain were significantly lower in the electrodiathermy group compared with the helium group at 12 weeks (mean difference, 9.43 mm; 95% CI 0.46, 18.40 mm; P = 0.039) and across all time points (mean difference, 10.13 mm; 95% CI 3.48, 16.78 mm; P = 0.003). A significant difference in dyspareunia also favoured electrodiathermy at 12 weeks (mean difference, 11.66 mm; 95% CI 1.39, 21.93 mm; P = 0.026). These effects were smaller than the proposed minimum important difference of 18.00 mm, however. Differences in some aspects of quality of life favoured electrodiathermy. There was no significant difference in operative blood loss (fold-change with helium as reference, 1.43; 95% CI 0.96, 2.15; P = 0.081). CONCLUSIONS: Although electrodiathermy was statistically superior to helium ablation in reducing cyclical pain and dyspareunia, these effects may be too small to be clinically significant. TWEETABLE ABSTRACT: Helium coagulation is not superior to electrodiathermy in laparoscopic treatment of mild-to-moderate endometriosis.


Assuntos
Técnicas de Ablação/métodos , Eletrocoagulação , Endometriose/cirurgia , Laparoscopia , Adolescente , Adulto , Método Duplo-Cego , Eletrocoagulação/métodos , Feminino , Hélio , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
6.
Eur J Cancer Care (Engl) ; 27(2): e12758, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28892208

RESUMO

This study aimed to ascertain the systemic barriers encountered by oncology health professionals (HPs) working with patients from ethnic minorities to guide the development of a communication skills training programme. Twelve medical and five radiation oncologists and 21 oncology nurses were invited to participate in this qualitative study. Participants were interviewed individually or in a focus group about their experiences working with people from minority backgrounds. All interviews were transcribed verbatim and analysed thematically. HPs encountered language and communication barriers in their interactions with patients and their families, which were perceived to impact negatively on the quality and amount of information and support provided. There was a shortage of, and poor processes for engaging, interpreters and some HPs were concerned about the accuracy of interpretation. HPs expressed a need for training in cultural awareness and communication skills with a preference for face-to-face delivery. A lack of funding, a culture of "learning on the job", and time constraints were systemic barriers to training. Oncologists and oncology nurses encounter complex challenges in clinical interactions with minority patients and their families, including difficulties working with interpreters. Formal training programmes targeted to the development of culturally competent communication skills are required.


Assuntos
Atitude do Pessoal de Saúde , Barreiras de Comunicação , Competência Cultural , Oncologistas/psicologia , Enfermagem Oncológica , Adulto , Etnicidade , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Grupos Minoritários , Neoplasias/terapia , Serviço Hospitalar de Oncologia/normas , Relações Profissional-Paciente , Pesquisa Qualitativa , Tradução
7.
Eur J Hum Genet ; 24(11): 1517-1523, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27329735

RESUMO

Selection of women for treatment-focused genetic testing (TFGT) following a new diagnosis of breast cancer is changing. Increasingly a patient's age and tumour characteristics rather than only their family history are driving access to TFGT, but little is known about the impact of receiving carrier-positive results in individuals with no family history of cancer. This study assesses the role of knowledge of a family history of cancer on psychosocial adjustment to TFGT in both women with and without mutation carrier-positive results. In-depth semistructured interviews were conducted with 20 women who had undergone TFGT, and who had been purposively sampled to represent women both family history and carrier status, and subjected to a rigorous qualitative analysis. It was found that mutation carriers without a family history reported difficulties in making surgical decisions quickly, while in carriers with a family history, a decision regarding surgery, electing for bilateral mastectomy (BM), had often already been made before receipt of their result. Long-term adjustment to a mutation-positive result was hindered by a sense of isolation not only by those without a family history but also those with a family history who lacked an affected relative with whom they could identify. Women with a family history who had no mutation identified and who had not elected BM reported a lack of closure following TFGT. These findings indicate support deficits hindering adjustment to positive TFGT results for women with and without a family history, particularly in regard to immediate decision-making about risk-reducing surgery.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/psicologia , Testes Genéticos , Mutação , Revelação da Verdade , Adulto , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Heterozigoto , Humanos , Pessoa de Meia-Idade , Inquéritos e Questionários
8.
J Chem Inf Model ; 54(10): 2680-96, 2014 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-25233464

RESUMO

Sampling low energy conformations of macrocycles is challenging due to the large size of many of these molecules and the constraints imposed by the macrocycle. We present a new conformational search method (implemented in MacroModel) that uses brief MD simulations followed by minimization and normal-mode search steps. The method was parametrized using a set of 100 macrocycles from the PDB and CSD. It was then tested on a publicly available data set for which there are published results using alternative methods; we found that when the same force field is used (in this case MMFFs in vacuum), our method tended to identify conformations with lower energies than what the other methods identified. The performance on a new set of 50 macrocycles from the PDB and CSD was also quite good; the mean and median RMSD values for just the ring atoms were 0.60 and 0.33 Å, respectively. However, the RMSD values for macrocycles with more than 30 ring-atoms were quite a bit larger compared to the smaller macrocycles. Possible origins for this and ideas for improving the performance on very large macrocycles are discussed.


Assuntos
Ciclodextrinas/química , Peptídeos Cíclicos/química , Peptídeos/química , Software , Algoritmos , Conformação Molecular , Simulação de Dinâmica Molecular , Proteínas/química , Termodinâmica
9.
Psychooncology ; 22(9): 1994-2000, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23382138

RESUMO

BACKGROUND: Providing ongoing clinical care that adequately addresses patients' medical, psychosocial and information needs is challenging, particularly for patient groups at increased risk of developing life-threatening disease such as malignant melanoma. This study examined a model of clinical care developed by the High Risk Clinic (HRC) of the Sydney Melanoma Diagnostic Centre in relation to patient satisfaction. METHODS: Semi-structured telephone interviews were conducted and analyzed using the framework of Miles and Huberman, and themes were organized using the qualitative software package, QSR NVivo8. RESULTS: Twenty HRC patients participated in the study (nine men, 11 women; mean age 57.6 years, age range 34-74 years; response rate 91%). Satisfaction with clinical care at the HRC was high. Factors contributing to patient satisfaction included: rapid and regular access to physicians who were perceived by participants as experts, the development of confidence and trust in one's treating doctor, and a sense of being cared about and understood by one's healthcare team. Although one-third of the participants reported some inconveniences in attending the clinic, these were viewed as minor difficulties and not significant barriers to care. Formal psychological support was not sought or expected by participants, although many expressed long-standing melanoma-related fears and concerns. CONCLUSIONS: Accessible, expert medical attention, delivered in a patient-centered manner was integral to melanoma survivors' satisfaction with clinical management. Appropriate referrals to psychological support may further increase satisfaction with clinical care.


Assuntos
Melanoma/psicologia , Satisfação do Paciente , Neoplasias Cutâneas/psicologia , Sobreviventes/psicologia , Adulto , Idoso , Austrália , Feminino , Humanos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Avaliação das Necessidades , Risco , Neoplasias Cutâneas/terapia , Inquéritos e Questionários
10.
Support Care Cancer ; 20(11): 2949-58, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22441502

RESUMO

PURPOSE: Women with breast cancer, who are found to be BRCA1/2 mutation carriers, have a high risk of ovarian cancer and metachronous breast cancer. Treatment-focused genetic testing (TFGT), offered around the time of diagnosis, allows genetic test results to inform surgical treatment decisions. However, concern has been raised that offering TFGT at this time may overly increase psychological burden. This study aimed to qualitatively explore women's attitudes and experiences of TFGT. METHODS: Women who had been diagnosed with breast cancer at age 50 years or less undertook a semi-structured telephone interview (n = 26). The sample included women who had been offered TFGT, based on family history and/or other risk criteria (n = 14), and women who had been diagnosed within the past 6-12 months and had not been offered TFGT (n = 12). Interviews explored women's attitudes towards TFGT, perceived benefits and disadvantages, implications of TFGT and impact on surgical decision making. Interviews were transcribed verbatim and thematically analysed. RESULTS: Women expressed positive attitudes towards TFGT and felt it was highly relevant to their surgical decision making. They did not feel that an offer of TFGT shortly after, or at the time of diagnosis, added undue psychological burden. The majority of women interviewed felt that TFGT should be incorporated into standard clinical care. CONCLUSIONS: TFGT is viewed favourably by women newly diagnosed with breast cancer. Future randomized controlled trials are needed to examine the long-term impact of TFGT. We conclude that an offer of TFGT is not perceived as 'too much, too soon' by relevant patients.


Assuntos
Atitude Frente a Saúde , Neoplasias da Mama/psicologia , Tomada de Decisões , Testes Genéticos/métodos , Adulto , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Coleta de Dados , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Fatores de Tempo
11.
Gynecol Oncol ; 124(1): 153-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22032838

RESUMO

OBJECTIVE: There is growing evidence that the BRCA mutation status of women newly diagnosed with ovarian cancer may be used to make treatment recommendations in the future. This qualitative study aimed to assess women's attitudes and experiences toward treatment-focused genetic testing (TFGT). METHODS: Women (N=22) with ovarian cancer who had either (i) advanced disease and had previously had TFGT (n=12) or (ii) had a recent ovarian cancer diagnosis and were asked about their hypothetical views of TFGT (n=10), were interviewed in-depth. RESULTS: This study demonstrates that patients diagnosed with ovarian cancer found the concept of TFGT acceptable with the primary motivation for genetic testing being to increase their treatment options. Women reported that there was no decision to make about TFGT, and the advantages of TFGT were perceived to outweigh the disadvantages. Many women described elements of resilience and active coping, in the context of hypothetical and actual TFGT. CONCLUSIONS: Resilience and active coping strategies are important factors that warrant investigation as potential moderators of psychological distress in future prospective studies exploring the optimal way of offering BRCA genetic testing to women newly diagnosed with ovarian cancer, and to assess the impact of TFGT upon patients' survival, psychological distress, and quality of life.


Assuntos
Testes Genéticos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/psicologia , Aceitação pelo Paciente de Cuidados de Saúde , Tomada de Decisões , Feminino , Genes BRCA1 , Genes BRCA2 , Predisposição Genética para Doença , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Neoplasias Ovarianas/parasitologia , Medicina de Precisão/métodos , Medicina de Precisão/psicologia
12.
ACS Chem Biol ; 6(10): 1069-77, 2011 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-21793507

RESUMO

Tyrosine sulfate-mediated interactions play an important role in HIV-1 entry. After engaging the CD4 receptor at the cell surface, the HIV-1 gp120 glycoprotein binds to the CCR5 co-receptor via an interaction that requires two tyrosine sulfates, at positions 10 and 14 in the CCR5-N terminus. Building on previous structure determinations of this interaction, here we report the targeting of these tyrosine sulfate binding sites for drug design through in silico screening of small molecule libraries, identification of lead compounds, and characterization of biological activity. A class of tyrosine sulfate-mimicking small molecules containing a "phenyl sulfonate-linker-aromatic" motif was identified that specifically inhibited binding of gp120 to the CCR5-N terminus as well as to sulfated antibodies that recognize the co-receptor binding region on gp120. The most potent of these compounds bound gp120 with low micromolar affinity and its CD4-induced conformation with K(D)'s as tight as ∼50 nM. Neutralization experiments suggested the targeted site to be conformationally inaccessible prior to CD4 engagement. Primary HIV-1 isolates were weakly neutralized, preincubation with soluble CD4 enhanced neutralization, and engineered isolates with increased dependence on the N terminus of CCR5 or with reduced conformational barriers were neutralized with IC(50) values as low as ∼1 µM. These results reveal the potential of targeting the tyrosine sulfate interactions of HIV-1 and provide insight into how mechanistic barriers, evolved by HIV-1 to evade antibody recognition, also restrict small-molecule-mediated neutralization.


Assuntos
Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , Tirosina/análogos & derivados , Internalização do Vírus/efeitos dos fármacos , Antígenos CD4/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/tratamento farmacológico , HIV-1/fisiologia , Humanos , Modelos Moleculares , Tirosina/química , Tirosina/farmacologia
13.
J Anim Physiol Anim Nutr (Berl) ; 95(6): 798-807, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21198966

RESUMO

The aim of this study was to determine whether the glycaemic/insulinaemic responses to hay with non-structural carbohydrate (NSC, soluble carbohydrate) of 17% (HC), 10% (MC) or 4% (LC) differs in control horses and whether these responses differ between control and horses with polysaccharide storage myopathy (PSSM). Five clinically normal control horses and seven PSSM horses, all unfit and of Quarter Horse breeding (age 9.4 ± 3.4 years, body condition score range: 4.5-6). A crossover design compared the HC and LC hay, with horses randomly assigned to hay type for 5 days, and all horses fed the MC hay during washout, after which the diets were switched. Horses were fed 1.5% BW (as fed) divided into 2 feeding per day, no grain. On morning of the fifth day of each block (seventh day for washout), horses were given 0.5% BW in hay, blood was drawn before and every 30 min for 5 h after feeding, and the rate of intake was measured. Whole blood glucose and plasma insulin were measured. The intake rate was significantly higher for HC. In control horses, the insulin area under the curve (6891.7 ± 3524.2 HC vs. 1185.4 ± 530.2 LC) was significantly higher than LC. Polysaccharide storage myopathy horses had significantly higher glycaemic and insulinaemic responses to HC vs. LC, however; the magnitude of insulin response was lower and glucose response higher in PSSM vs. control horses. Results suggest that insulin responses can differ significantly with the NSC content of hay. Feeding hay with 17% NSC produces elevations in insulin that could be detrimental for PSSM horses.


Assuntos
Ração Animal/análise , Glicemia , Carboidratos da Dieta/análise , Doença de Depósito de Glicogênio/veterinária , Doenças dos Cavalos/metabolismo , Insulina/sangue , Fenômenos Fisiológicos da Nutrição Animal , Animais , Estudos Cross-Over , Dieta/veterinária , Doença de Depósito de Glicogênio/metabolismo , Cavalos
14.
J Chem Inf Model ; 50(4): 534-46, 2010 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-20373803

RESUMO

We describe the methodology, parametrization, and application of a conformational search method, called ConfGen, designed to efficiently generate bioactive conformers. We define efficiency as the ability to generate a bioactive conformation within a small total number of conformations using a reasonable amount of computer time. The method combines physics-based force field calculations with empirically derived heuristics designed to achieve efficient searching and prioritization of the ligand's conformational space. While many parameter settings are supported, four modes spanning a range of speed and quality trades-offs are defined and characterized. The validation set used to test the method is composed of ligands from 667 crystal structures covering a broad array of target and ligand classes. With the fastest mode, ConfGen uses an average of 0.5 s per ligand and generates only 14.3 conformers per ligand, at least one of which lies within 2.0 A root-mean-squared deviation of the crystal structure for 96% of the ligands. The most computationally intensive mode raises this recovery rate to 99%, while taking 8 s per ligand. Combining multiple search modes to "fill-in" holes in the conformation space or energy minimizing using an all-atom force field each lead to improvements in the recovery rates at higher resolutions. Overall, ConfGen is at least as good as competing programs at high resolution and demonstrates higher efficiency at resolutions sufficient for many downstream applications, such as pharmacophore modeling.


Assuntos
Biologia Computacional , Conformação Molecular , Avaliação Pré-Clínica de Medicamentos , Ligantes , Modelos Moleculares , Software , Fatores de Tempo
15.
J Med Primatol ; 38(6): 425-32, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19638102

RESUMO

PURPOSE: We used total body irradiation (TBI) as conditioning for cord blood transplantation studies in pigtailed macaques. In these studies, different doses of TBI were explored to obtain optimal myelosuppression with acceptable radiation-related side effects. METHODS: Four macaques received TBI ranging from 800 to 1320 cGy, followed by standard post-transplant care. Hematopoietic recovery was monitored by CBC and donor contribution by variable number of tandem repeats analysis. RESULTS: Animals receiving 800 or 1020 cGy TBI tolerated the irradiation well with autologous recovery of neutrophils within 24 days. At a dose of 1200 cGy, neither autologous recovery nor extramedullary toxicity was observed. A fourth animal received 1320 cGy of TBI and suffered significant toxicity necessitating termination of the study. CONCLUSIONS: We conclude that previously considered myeloablative doses of TBI allowed for autologous recovery in the pigtailed macaque, and that a dose of 1200 cGy may be most appropriate, providing both myeloablation and acceptable non-hematopoietic toxicities.


Assuntos
Medula Óssea/efeitos da radiação , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Irradiação Corporal Total , Animais , Plaquetas/efeitos da radiação , Medula Óssea/patologia , Relação Dose-Resposta à Radiação , Feminino , Hematopoese , Macaca nemestrina , Neutrófilos/efeitos da radiação , Contagem de Plaquetas , Doses de Radiação , Lesões por Radiação/patologia
16.
J Environ Manage ; 90(1): 251-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18082310

RESUMO

Habitat fragmentation is the focus of much conservation concern and associated research. In some countries, such as Britain, the main phase of fragmentation occurred centuries ago and the focus of conservation management is now on restoration and recovery. Scenario studies have suggested that spatial targeting is preferable if landscape scale restoration is to be achieved, and that this should bring greater benefits than site-focussed activities but this has rarely been tested in practice. In Britain, woodland expansion has been encouraged through a number of financial incentives, which have evolved from instruments that encouraged almost any addition to the potential woodland resource, to grant schemes that have set out to restore connectivity to remnant ancient woodland. This study assessed the degree of de-fragmentation achieved by woodland expansion on the Isle of Wight and in particular the success of spatial targeting of new woodland planting implemented through grant aid in the JIGSAW (Joining and Increasing Grant Scheme for Ancient Woodland) scheme. Five steps in the re-development of broad-leaved woodland were tested using eight indicators - six commonly used landscape metrics, and two ecologically scaled indicators derived from application of least-cost network evaluation. Only half of the measures indicated de-fragmentation over the whole sequence of five steps. However, the spatial targeting did appear successful, when compared to equivalent untargeted grant-aided woodland expansion, and resulted in positive change to six of the eight indicators. We discuss the utility of the indicators and ways in which future targeting could be supported by their application.


Assuntos
Agricultura/tendências , Conservação dos Recursos Naturais , Ecossistema , Árvores , Ilhas Anglo-Normandas , Geografia , Reino Unido
17.
Int J Mol Sci ; 9(2): 169-180, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19325741

RESUMO

Due to the concern on the availability of recoverable fossil fuel reserves and the environmental problems caused by the use those fossil fuels, considerable attention has been given to biodiesel production as an alternative to petrodiesel. However, as the biodiesel is produced from vegetable oils and animal fats, there are concerns that biodiesel feedstock may compete with food supply in the long-term. Hence, the recent focus is to find oil bearing plants that produce non-edible oils as the feedstock for biodiesel production. In this paper, two plant species, soapnut (Sapindus mukorossi) and jatropha (jatropha curcas, L.) are discussed as newer sources of oil for biodiesel production. Experimental analysis showed that both oils have great potential to be used as feedstock for biodiesel production. Fatty acid methyl ester (FAME) from cold pressed soapnut seed oil was envisaged as biodiesel source for the first time. Soapnut oil was found to have average of 9.1% free FA, 84.43% triglycerides, 4.88% sterol and 1.59% others. Jatropha oil contains approximately 14% free FA, approximately 5% higher than soapnut oil. Soapnut oil biodiesel contains approximately 85% unsaturated FA while jatropha oil biodiesel was found to have approximately 80% unsaturated FA. Oleic acid was found to be the dominant FA in both soapnut and jatropha biodiesel. Over 97% conversion to FAME was achieved for both soapnut and jatropha oil.

18.
Respir Res ; 7: 88, 2006 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16776827

RESUMO

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a debilitating disease characterized by exaggerated extracellular matrix deposition and aggressive lung structural remodeling. Disease pathogenesis is driven by fibroblastic foci formation, consequent on growth factor overexpression and myofibroblast proliferation. We have previously shown that both CTGF overexpression and myofibroblast formation in IPF cell lines are dependent on RhoA signaling. As RhoA-mediated regulation is also involved in cell cycle progression, we hypothesise that this pathway is key to lung fibroblast turnover through modulation of cyclin D1 kinetic expression. METHODS: Cyclin D1 expression was compared in primary IPF patient-derived fibroblasts and equivalent normal control cells. Quantitative real time PCR was employed to examine relative expression levels of cyclin D1 mRNA; protein expression was confirmed by western blotting. Effects of Rho signaling were investigated using transient transfection of constitutively active and dominant negative RhoA constructs as well as pharmacological inhibitors. Cellular proliferation of lung fibroblasts was determined by BrdU incorporation ELISA. To further explore RhoA regulation of cyclin D1 in lung fibroblasts and associated cell cycle progression, an established Rho inhibitor, Simvastatin, was incorporated in our studies. RESULTS: Cyclin D1 expression was upregulated in IPF compared to normal lung fibroblasts under exponential growth conditions (p < 0.05). Serum deprivation inhibited cyclin D1 expression, which was restored following treatment with fibrogenic growth factors (TGF-beta1 and CTGF). RhoA inhibition, using a dominant negative mutant and a pharmacological inhibitor (C3 exotoxin), suppressed levels of cyclin D1 mRNA and protein in IPF fibroblasts, with significant abrogation of cell turnover (p < 0.05). Furthermore, Simvastatin dose-dependently inhibited fibroblast cyclin D1 gene and protein expression, inducing G1 cell cycle arrest. Similar trends were observed in control experiments using normal lung fibroblasts, though exhibited responses were lower in magnitude. CONCLUSION: These findings report for the first time that cyclin D1 expression is deregulated in IPF through a RhoA dependent mechanism that influences lung fibroblast proliferation. This potentially unravels new molecular targets for future anti-IPF strategies; accordingly, Simvastatin inhibition of Rho-mediated cyclin D1 expression in IPF fibroblasts merits further exploitation.


Assuntos
Ciclina D1/genética , Fibroblastos/metabolismo , Fibrose Pulmonar/metabolismo , Transdução de Sinais/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismo , ADP Ribose Transferases/farmacologia , Toxinas Botulínicas/farmacologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Linhagem Celular , Fator de Crescimento do Tecido Conjuntivo , Ciclina D1/metabolismo , Fibroblastos/patologia , Fase G1/efeitos dos fármacos , Fase G1/fisiologia , Expressão Gênica/fisiologia , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Proteínas Imediatamente Precoces/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Pulmão/citologia , Fibrose Pulmonar/patologia , Transdução de Sinais/efeitos dos fármacos , Sinvastatina/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta1 , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologia , Proteína rhoA de Ligação ao GTP/antagonistas & inibidores
19.
Inj Prev ; 10(2): 83-7, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15066971

RESUMO

OBJECTIVE: To evaluate the effectiveness of injury prevention training. DESIGN: Cluster randomised controlled trial. SETTING: Primary care facilities in the East Midlands area of the United Kingdom. SUBJECTS: Midwives and health visitors. INTERVENTION: Evidence based training session on the risks associated with baby walkers. MAIN OUTCOME MEASURES: The primary outcome measures were knowledge of baby walker use and walker related injury, attitudes towards walkers and towards walker education, and practices relating to walker health education. RESULTS: Trained midwives and health visitors had greater knowledge of the risks associated with baby walkers than untrained midwives and health visitors (difference between the means 0.22; 95% confidence interval (CI) 0.12 to 0.33). Trained health visitors had more negative attitudes to baby walkers (difference between the means 0.35; 95% CI 0.10 to 0.59) and more positive attitudes towards baby walker health education (difference between the means 0.31; 95% CI 0.00 to 0.62) than untrained health visitors. Midwives who had been trained were more likely to discuss baby walkers in the antenatal period than those who were not trained (odds ratio 9.92; 95% CI 2.02 to 48.83). CONCLUSIONS: Injury prevention training was associated with increased knowledge, more negative attitudes towards walkers, and more positive attitudes towards walker education. Trained midwives were more likely to give advice antenatally. Training did not impact on other practices. Larger trials are required to assess the impact of training on parental safety behaviours, the adoption of safety practices, and injury reduction.


Assuntos
Enfermagem em Saúde Comunitária/educação , Conhecimentos, Atitudes e Prática em Saúde , Equipamentos para Lactente , Tocologia/educação , Ferimentos e Lesões/prevenção & controle , Atitude do Pessoal de Saúde , Análise por Conglomerados , Educação em Saúde , Humanos , Inquéritos e Questionários , Reino Unido
20.
J Sci Med Sport ; 4(3): 292-300, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11702916

RESUMO

This study investigated the use of an incremental, externally-paced 10 m shuttle walk test (SWT) as an objective, reliable and predictive test of functional capacity in patients with heart failure (CHF). The SWT was compared to a 6 minute walk test (6WT) and a maximal symptom-limited treadmill peak oxygen consumption (VO2peak) test. Experiment 1 examined the reproducibility of the SWT. Two SWF trials were performed and distance ambulated (DA), heart rate (HR) and rate of perceived exertion (RPE) results compared. In experiment 2, SWT, 6WT, and VO2 peak tests were performed and HR. RPE and ambulatory VO2 compared. The SWT demonstrated strong test/retest reliability for DA (r = 0.98). HR (r = 0.96) and RPE (r = 0.89). Treadmill VO2 peak was significantly correlated with DA during the SWT (r = 0.83, P < 0.05), but not the 6WT. SWT peak VO2 (18.5 +/- 1.8 ml.kg(-1) x min(-1)) and treadmill VO2 peak (18.3 +/-2.0 ml.kg(-1) x min(-1)) were also highly correlated (r = 0.78, P < 0.05). Conversely, 6WT peak VO2 and treadmill VO2 peak were not significantly correlated. This study suggests the SWT is a reliable, objective test, highly predictive of VO2 peak which may be a more optimal field exercise test than the self paced 6WT.


Assuntos
Teste de Esforço/métodos , Insuficiência Cardíaca/fisiopatologia , Consumo de Oxigênio , Aptidão Física/fisiologia , Caminhada/fisiologia , Teste de Esforço/normas , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Esforço Físico/fisiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
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