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1.
Int J Mol Sci ; 25(5)2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38474321

RESUMO

The appropriate expression and localization of cell surface cell adhesion molecules must be tightly regulated for optimal synaptic growth and function. How neuronal plasma membrane proteins, including cell adhesion molecules, cycle between early endosomes and the plasma membrane is poorly understood. Here we show that the Drosophila homolog of the chromatin remodeling enzymes CHD7 and CHD8, Kismet, represses the synaptic levels of several cell adhesion molecules. Neuroligins 1 and 3 and the integrins αPS2 and ßPS are increased at kismet mutant synapses but Kismet only directly regulates transcription of neuroligin 2. Kismet may therefore regulate synaptic CAMs indirectly by activating transcription of gene products that promote intracellular vesicle trafficking including endophilin B (endoB) and/or rab11. Knock down of EndoB in all tissues or neurons increases synaptic FasII while knock down of EndoB in kis mutants does not produce an additive increase in FasII. In contrast, neuronal expression of Rab11, which is deficient in kis mutants, leads to a further increase in synaptic FasII in kis mutants. These data support the hypothesis that Kis influences the synaptic localization of FasII by promoting intracellular vesicle trafficking through the early endosome.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/metabolismo , Proteínas de Drosophila/metabolismo , Junção Neuromuscular/metabolismo , Sinapses/metabolismo , Moléculas de Adesão Celular Neuronais/metabolismo , Neurônios/metabolismo
2.
Photochem Photobiol Sci ; 22(5): 1011-1047, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36856971

RESUMO

This assessment by the Environmental Effects Assessment Panel (EEAP) of the Montreal Protocol under the United Nations Environment Programme (UNEP) evaluates the effects of ultraviolet (UV) radiation on human health within the context of the Montreal Protocol and its Amendments. We assess work published since our last comprehensive assessment in 2018. Over the last four years gains have been made in knowledge of the links between sun exposure and health outcomes, mechanisms, and estimates of disease burden, including economic impacts. Of particular note, there is new information about the way in which exposure to UV radiation modulates the immune system, causing both harms and benefits for health. The burden of skin cancer remains high, with many lives lost to melanoma and many more people treated for keratinocyte cancer, but it has been estimated that the Montreal Protocol will prevent 11 million cases of melanoma and 432 million cases of keratinocyte cancer that would otherwise have occurred in the United States in people born between 1890 and 2100. While the incidence of skin cancer continues to rise, rates have stabilised in younger populations in some countries. Mortality has also plateaued, partly due to the use of systemic therapies for advanced disease. However, these therapies are very expensive, contributing to the extremely high economic burden of skin cancer, and emphasising the importance and comparative cost-effectiveness of prevention. Photodermatoses, inflammatory skin conditions induced by exposure to UV radiation, can have a marked detrimental impact on the quality of life of sufferers. More information is emerging about their potential link with commonly used drugs, particularly anti-hypertensives. The eyes are also harmed by over-exposure to UV radiation. The incidence of cataract and pterygium is continuing to rise, and there is now evidence of a link between intraocular melanoma and sun exposure. It has been estimated that the Montreal Protocol will prevent 63 million cases of cataract that would otherwise have occurred in the United States in people born between 1890 and 2100. Despite the clearly established harms, exposure to UV radiation also has benefits for human health. While the best recognised benefit is production of vitamin D, beneficial effects mediated by factors other than vitamin D are emerging. For both sun exposure and vitamin D, there is increasingly convincing evidence of a positive role in diseases related to immune function, including both autoimmune diseases and infection. With its influence on the intensity of UV radiation and global warming, the Montreal Protocol has, and will have, both direct and indirect effects on human health, potentially changing the balance of the risks and benefits of spending time outdoors.


Assuntos
Catarata , Melanoma , Neoplasias Cutâneas , Humanos , Estados Unidos , Qualidade de Vida , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Melanoma/epidemiologia , Melanoma/etiologia , Melanoma/prevenção & controle , Raios Ultravioleta/efeitos adversos , Vitamina D
3.
Front Cell Neurosci ; 16: 957232, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072568

RESUMO

The Tetraspanin (Tsp), CD63, is a transmembrane component of late endosomes and facilitates vesicular trafficking through endosomal pathways. Despite being widely expressed in the human brain and localized to late endosomes, CD63's role in regulating endo- and exocytic cycling at the synapse has not been investigated. Synaptic vesicle pools are highly dynamic and disruptions in the mobilization and replenishment of these vesicle pools have adverse neuronal effects. We find that the CD63 homologs, Tsp42Ee and Tsp42Eg, are expressed at the Drosophila neuromuscular junction to regulate synaptic vesicle pools through both shared and unique mechanisms. Tsp42Ee and Tsp42Eg negatively regulate endocytosis and positively regulate neurotransmitter release. Both tsp mutants show impaired locomotion, reduced miniature endplate junctional current frequencies, and increased endocytosis. Expression of human CD63 in Drosophila neurons leads to impaired endocytosis suggesting the role of Tsps in endocytosis is conserved. We further show that Tsps influence the synaptic cytoskeleton and membrane composition by regulating Futsch loop formation and synaptic levels of SCAR and PI(4,5)P2. Finally, Tsp42Ee and Tsp42Eg influence the synaptic localization of several vesicle-associated proteins including Synapsin, Synaptotagmin, and Cysteine String Protein. Together, our results present a novel function for Tsps in the regulation of vesicle pools and provide insight into the molecular mechanisms of Tsp-related synaptic dysfunction.

4.
Br J Cancer ; 126(1): 134-143, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34611308

RESUMO

BACKGROUND: We wished to examine treatment and outcome patterns in older diffuse large B-cell lymphoma (DLBCL) patients, with a focus on the effect of route-to-diagnosis to outcome. METHODS: Data were extracted from Public Health England's National Cancer Registration and Analysis Service between 2013 and 2015 included route-to-diagnosis, disease characteristics and survival for 9186 patients ≥65 years. Systemic Anti-Cancer Therapy data identified front-line regimens, cycles and doses. RESULTS: Route-to-diagnosis were emergency (34%), NHS urgent cancer pathway (rapid haemato-oncologist review <2 weeks), (29%) and standard GP referral (25%). The most common regimen was R-CHOP (n = 4392). 313 patients received R-miniCHOP (7% of R-CHOP). For all patients, 3-year overall survival (OS) for 65-79 years was 57% and for ≥80 years was 32%. Three-year OS for R-CHOP-treated patients diagnosed via emergency presentation was 54% (adjusted hazard ratio (HR) 1.63, p < 0.01) and 75% (adjusted HR 0.81, p < 0.01) on the NHS urgent cancer pathway (reference HR:1.00: GP referrals). 3-year OS was 54% for both R-miniCHOP and R-CHOP in ≥80 years. CONCLUSIONS: Our comprehensive population analysis is the first to show that the NHS urgent cancer pathway is associated with a superior survival after adjusting for multiple confounders. Equivalent survival for R-CHOP and R-mini-CHOP was demonstrated in those ≥80 years.


Assuntos
Assistência Ambulatorial/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bases de Dados Factuais/estatística & dados numéricos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Inglaterra/epidemiologia , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Linfoma Difuso de Grandes Células B/patologia , Prednisona/uso terapêutico , Estudos Retrospectivos , Rituximab/uso terapêutico , Taxa de Sobrevida , Vincristina/uso terapêutico
5.
J Dairy Sci ; 104(10): 10540-10549, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34275634

RESUMO

Gas production by obligatory heterofermentative lactic acid bacteria such as Paucilactobacillus wasatchensis is a sporadic problem in Cheddar cheese and results in undesired slits and cracks in the cheese. Growth of Pa. wasatchensis is not rapid, which makes investigations of gas production difficult to consistently execute. A primary objective of this study was to develop a model gas production test that could be used to investigate the effect of galactose and ribose utilization on gas production by Pa. wasatchensis and determine whether galactose-fermenting adjunct cultures could prevent gas formation. Paucilactobacillus wasatchensis WDC04 was inoculated at 101 to 106 cfu/mL into carbohydrate-restricted MRS broth containing different ribose and galactose levels and incubated for up to 21 d at 23°C. Gas production in the broth was detected using a Durham tube inverted on a 6-cm-long capillary tube; cells were enumerated at 4, 8, and 12 d; and residual galactose was also measured. Gas production was sporadic except for when 105 cfu/mL of Pa. wasatchensis WDC04 was inoculated into broth containing 0.3% ribose and 0.7% galactose. In those tubes, gas production was consistently observed after 8-d incubation, by which time galactose levels had decreased to 0.15%. Co-inoculation of Pa. wasatchensis WDC04 with as few as 103 cfu/mL of a lactose-negative galactose-positive adjunct culture (Pediococcus acidilactici 23F, Lacticaseibacillus paracasei UW4, or Lactobacillus helveticus 7995) resulted in galactose depletion by d 4 and no observable gas production by d 12. With less galactose available to the slower-growing Pa. wasatchensis WDC04, its growth was limited to 108 cfu/mL when any of the adjunct cultures was co-inoculated, compared with 109 cfu/mL when grown on its own. We concluded that galactose-fermenting adjunct cultures have potential for preventing unwanted gas production in cheese by competition for resources and especially by removing the 6-carbon galactose before it can be utilized for energy by an obligatory heterofermentative lactobacilli such as Pa. wasatchensis and produce carbon dioxide.


Assuntos
Queijo , Lactobacillus helveticus , Animais , Queijo/análise , Microbiologia de Alimentos , Galactose , Lactose
6.
Br Dent J ; 221(11): 701-704, 2016 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-27932844

RESUMO

Background The importance of supportive periodontal therapy following active treatment has been well documented but numerous studies have shown patient compliance to be poor. The aim of this study was to ascertain which factors affect patient compliance and whether this included routinely recorded periodontal indices.Methodology This was a five-year retrospective service evaluation study set within a private general dental practice. It utilised demographic and periodontal data from patients who attended the practice for chronic periodontal treatment in 2009 and ascertained whether there were links between this data and compliance with the supportive phase of periodontal treatment.Results Three hundred and ten patients satisfied the inclusion criteria of which 32.3% were categorised as compliant, 45.5% non-compliant and 22.3% erratic attenders. Patients who were statistically significantly more compliant were males (p = 0.03) and non-smokers (p = 0.01). There was a trend for older people to be more compliant; however this was not statistically significant. Plaque and bleeding scores were lower in the compliant group but only the bleeding scores were statistically significant (p = 0.03). The pocket probing depths were used as an indicator of disease severity and showed no significant relationship with compliance.Conclusion Although some of the periodontal parameters showed a statistically significant relationship with compliance, the difference between the parameters was clinically minimal suggesting that there is no definitive physical characteristic which is an indicator of patient compliance.


Assuntos
Cooperação do Paciente , Doenças Periodontais/terapia , Índice Periodontal , Seguimentos , Medicina Geral , Humanos , Masculino , Estudos Retrospectivos
7.
Clin Oncol (R Coll Radiol) ; 28(11): 695-707, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27637724

RESUMO

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Órgãos em Risco/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Humanos , Neoplasias Pulmonares/patologia , Imageamento por Ressonância Magnética/métodos , Tomografia por Emissão de Pósitrons/métodos , Tomografia Computadorizada por Raios X/métodos
8.
Epidemiol Psychiatr Sci ; 25(4): 393-402, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26074123

RESUMO

AIMS: Understanding the time-course of post-traumatic stress disorder (PTSD), and the underlying events, may help to identify those most at risk, and anticipate the number of individuals likely to be diagnosed after exposure to traumatic events. METHOD: Data from two health surveys were combined to create a cohort of 1119 Australian military personnel who deployed to the Middle East between 2000 and 2009. Changes in PTSD Checklist Civilian Version (PCL-C) scores and the reporting of stressful events between the two self-reported surveys were assessed. Logistic regression was used to examine the association between the number of stressful events reported and PTSD symptoms, and assess whether those who reported new stressful events between the two surveys, were also more likely to report older events. We also assessed, using linear regression, whether higher scores on the Kessler Psychological Distress Scale or the Alcohol Use Disorder Identification Test were associated with subsequent increases in the PCL-C in those who had experienced a stressful event, but who initially had few PTSD symptoms. RESULTS: Overall, the mean PCL-C scores in the two surveys were similar, and 78% of responders stayed in the same PCL-C category. Only a small percentage moved from having few symptoms of PTSD (PCL-C < 30) in Survey 1 to meeting the criteria for PTSD (PCL-C ≥ 50) at Survey 2 (1% of all responders, 16% of those with PCL-C ≥ 50 at Survey 2). Personnel who reported more stressful lifetime events were more likely to score higher on the PCL-C. Only 51% reported the same stressful event on both surveys. People who reported events occurring between the two surveys were more likely to record events from before the first survey which they had not previously mentioned (OR 1.48, 95% CI (1.17, 1.88), p < 0.001), than those who did not. In people who initially had few PTSD symptoms, a higher level of psychological distress, was significantly associated with higher PCL-C scores a few years later. CONCLUSIONS: The reporting of stressful events varied over time indicating that while the impact of some stressors endure, others may increase or decline in importance. When screening for PTSD, it is important to consider both traumatic experiences on deployment and other stressful life events, as well as other mental health problems among military personnel, even if individuals do not exhibit symptoms of PTSD on an initial assessment.


Assuntos
Militares/psicologia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico , Humanos , Oriente Médio , Estudos Retrospectivos , Transtornos de Estresse Pós-Traumáticos/diagnóstico
9.
Leukemia ; 29(9): 1928-38, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25943179

RESUMO

Bone marrow (BM) genetic abnormalities in myelodysplastic syndrome (MDS) have provided important biological and prognostic information; however, frequent BM sampling in older patients has been associated with significant morbidity. Utilizing single-nucleotide polymorphism array (SNP-A) and targeted gene sequencing (TGS) of 24 frequently mutated genes in MDS, we assessed the concordance of genetic abnormalities in BM and peripheral blood (PB) samples concurrently from 201 MDS patients. SNP-A karyotype in BM was abnormal in 108 (54%) and normal in 93 (46%) patients, with 95% (190/201) having an identical PB karyotype. The median copy number (CN) for deletions was significantly lower in BM (CN:1.4 (1-1.9)) than in PB (CN:1.5 (1-1.95), P<0.001). Using TGS, 71% (130/183) patients had BM somatic mutations with 95% (124/130) having identical mutations in PB. The mutant allele burden was lower in PB (median 27% (1-96%)) compared with BM (median 29% (1-100%); P=0.14) with no significant difference in the number, types of mutations or World Health Organization subtype. In all patients with discordant SNP (n=11) and mutation (n=6) profiles between BM and PB, shared abnormalities were always present irrespective of treatment status. Overall, 86% of patients had a clonal aberration with 95% having identical SNP-A karyotype and mutations in PB, thus enabling frequent assessment of response to treatment and disease evolution especially in patients with fibrotic or hypocellular marrows.


Assuntos
Células Sanguíneas/metabolismo , Células da Medula Óssea/metabolismo , Aberrações Cromossômicas , Genômica , Síndromes Mielodisplásicas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Células Sanguíneas/patologia , Medula Óssea/patologia , Células da Medula Óssea/patologia , Estudos de Coortes , Variações do Número de Cópias de DNA , Análise Mutacional de DNA , Feminino , Estudos de Associação Genética , Humanos , Cariótipo , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/patologia , Polimorfismo de Nucleotídeo Único , Adulto Jovem
10.
Health Promot Int ; 30(4): 881-90, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24770581

RESUMO

Healthy Stadia (HS) is a European public health pilot-program started in 2007 to support sports stadia in promoting the health of people who work and visit sports stadia, as well as inhabitants of the surrounding communities. The aim of this study is to describe the process evaluation of the program, from its beginning in July 2007 to December 2009, in order to assess the feasibility and sustainability of an HS network across Europe. The program involved nine associate partners involved in the coordination of activities at a local level, in the recruitment of stadia, in the development of specific program tasks and in the dissemination of the program at a national level. The activities of associate partners were evaluated through structured questionnaires administered every 6 months. The questionnaire response rate from associate partners was 77.8% for the first and third evaluations and 88.9% for the second and fourth evaluations. According to the evaluation's results, several good practices such as alcohol prevention policies and those supporting people with disabilities were implemented in stadia over the course of the program. Conversely, practices supporting mental health and green transport were generally not achieved. The implemented activities mainly involved staff and visitors. Lack of human and economic resources, especially toward the end of the program, was considered the principal challenge for program development. In conclusion, the process evaluation presented the feasibility of the HS program and the development of health promoting practices in sport stadia over time.


Assuntos
Promoção da Saúde/métodos , Esportes , Europa (Continente) , Humanos , Masculino , Desenvolvimento de Programas/métodos , Avaliação de Programas e Projetos de Saúde , Saúde Pública , Inquéritos e Questionários
11.
NMR Biomed ; 27(12): 1461-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25208220

RESUMO

The purpose of this work was to assess the reproducibility of percentage of ventilated lung volume (PV) measured from hyperpolarized (HP) (3)He and (1)H anatomical images acquired in the same breath-hold when compared with PV measured from (3)He and (1)H images from separate breath-holds. Volumetric (3)He ventilation and (1)H anatomical images of the same resolution were acquired during the same breath-hold. To assess reproducibility, this procedure was performed twice with a short gap between acquisitions. In addition, (1)H images were also acquired in a separate breath for comparison. PV ((3)He ventilated volume divided by (1)H total lung volume) was calculated using the single-breath-hold images (PV(single)) and the separate-breath-hold images (PV(separate)). Short-term reproducibility of PV measurement was assessed for both single- and separate-breath acquisitions. Dice similarity coefficients (DSCs) were calculated to quantify spatial overlap between (3)He and (1)H segmentations for the single- and separate-breath-hold acquisitions. The efficacy of using the separate-breath method combined with image registration was also assessed. The mean magnitude difference between the two sets of PV values (±standard deviation) was 1.49 ± 1.32% for PV(single) and 4.19 ± 4.10% for PV(separate), with a significant difference (p < 0.01). The mean magnitude difference between the two PV values for the registered separate-breath technique (PV(sep-registered)) was 2.27 ± 2.23%. Bland-Altman analysis showed that PV measured with single-breath acquisitions was more repeatable than PV measured with separate-breath acquisitions, regardless of image registration. DSC values were significantly greater (p < 0.01) for single-breath acquisition than for separate-breath acquisition. Acquisition of HP gas ventilation and (1)H anatomical images in a single breath-hold provides a more reproducible means of percentage lung ventilation volume measurement than the previously used separate-breath-hold scan approach, and reduces errors.


Assuntos
Hélio , Medidas de Volume Pulmonar/métodos , Imageamento por Ressonância Magnética , Prótons , Ventilação Pulmonar/fisiologia , Respiração , Adulto , Idoso , Humanos , Processamento de Imagem Assistida por Computador , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
12.
Br Dent J ; 217(3): 133-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25104693

RESUMO

Dental photography is essential in record keeping and it is important for all members of the dental team to be appropriately trained and for each practice to have the appropriate equipment. This article provides an overview of the applications of dental photography and equipment, and highlights issues of consent and duty of care.


Assuntos
Fotografia Dentária , Relações Dentista-Paciente , Humanos , Educação de Pacientes como Assunto
13.
Leukemia ; 28(9): 1793-8, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24919805

RESUMO

Definite progress has been made in the exploration of myelodysplastic syndromes (MDS) by flow cytometry (FCM) since the publication of the World Health Organization 2008 classification of myeloid neoplasms. An international working party initiated within the European LeukemiaNet and extended to include members from Australia, Canada, Japan, Taiwan and the United States has, through several workshops, developed and subsequently published consensus recommendations. The latter deal with preanalytical precautions, and propose small and large panels, which allow evaluating immunophenotypic anomalies and calculating myelodysplasia scores. The current paper provides guidelines that strongly recommend the integration of FCM data with other diagnostic tools in the diagnostic work-up of MDS.


Assuntos
Citometria de Fluxo/métodos , Síndromes Mielodisplásicas/classificação , Europa (Continente) , Guias como Assunto , Humanos , Síndromes Mielodisplásicas/diagnóstico , Organização Mundial da Saúde
14.
Biomed Chromatogr ; 27(3): 335-42, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22886846

RESUMO

A simple HPLC method has been developed to measure imatinib and N-desmethylimatinib (norimatinib) in plasma or serum at concentrations attained during therapy. Adaptation of this method to LC-MS/MS also allows dasatinib assay. A small sample volume (100 µL HPLC-UV, 50 µL LC-MS/MS) is required and analysis time is <5 min in each case. Detection was by UV (270 nm) or selective reaction monitoring (two transitions per analyte) tandem mass spectrometry. Assay calibration was linear (0.05-10 mg/L imatinib, 0.01-2.0 mg/L norimatinib and 1-200 µg/L dasatinib), with acceptable accuracy (86-114%) and precision (<14% RSD) for both methods. A comparison between whole blood and plasma confirmed that plasma is the preferred sample for imatinib and norimatinib assay. For dasatinib, although whole blood concentrations were slightly higher, plasma is still the preferred sample. Despite considerable variation in the (median, range) plasma imatinib and norimatinib concentrations in patient samples [1.66 (0.02-4.96) and 0.32 (0.01-0.99) mg/L, respectively, N = 104], plasma imatinib was >1 mg/L (suggested target for response) in all but one sample from patients achieving complete molecular response. As to dasatinib, the median (range) plasma dasatinib concentration was 13 (2-143) µg/L (N = 33). More observations are needed to properly assess the potential role of therapeutic drug monitoring in guiding treatment with dasatinib.


Assuntos
Benzamidas/sangue , Monitoramento de Medicamentos/métodos , Piperazinas/sangue , Inibidores de Proteínas Quinases/sangue , Pirimidinas/sangue , Tiazóis/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas/química , Cromatografia Líquida de Alta Pressão/métodos , Dasatinibe , Feminino , Hematócrito , Humanos , Mesilato de Imatinib , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Piperazinas/química , Inibidores de Proteínas Quinases/química , Pirimidinas/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem/métodos , Tiazóis/química
15.
Br Dent J ; 213(8): E14, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23099724

RESUMO

BACKGROUND: There is increasing evidence of the inappropriate use of antimicrobials in dentistry and this may contribute to the problem of antimicrobial resistance. The research to date with regard to efficacy of antimicrobial prophylaxis in reducing failure of integration and postoperative complications when placing dental implants remains equivocal. The aim of this study was to investigate how dentists in the UK use antimicrobials prophylactically in implant practice. METHOD: An e-mail link was provided in 2011 to an anonymous online (Smart-Survey) questionnaire using three databases of dentists who, by being on them, had registered an interest in placing dental implants. Absolute frequencies were used to describe the study sample demographics and examine the distribution of responses for all the variables investigated. RESULTS: One hundred and nine completed questionnaires were received. Seventy-two percent (n = 76) routinely prescribed prophylactic antibiotics for all procedures. There was a wide variation in the pre-operative and postoperative prescription regimens with the majority (84%) stating that it was to prevent infection at the site of surgery or to reduce a bacteraemia. CONCLUSIONS: Although this was a small study with a low response rate, wide variations in antibiotic prescribing regimens with respect to drug, dose and duration were found. Further research is needed and guidelines developed to prevent antibiotic overprescribing and misuse.


Assuntos
Antibioticoprofilaxia , Implantes Dentários , Amoxicilina/efeitos adversos , Atitude do Pessoal de Saúde , Bacteriemia/prevenção & controle , Implantação Dentária Endóssea/métodos , Odontólogos , Hipersensibilidade a Drogas/etiologia , Odontologia Baseada em Evidências , Feminino , Humanos , Prescrição Inadequada , Masculino , Osseointegração/efeitos dos fármacos , Infecção da Ferida Cirúrgica/prevenção & controle , Reino Unido
16.
Br Dent J ; 212(8): E12, 2012 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-22538925

RESUMO

BACKGROUND: The dental team could have an important role to play in general health risk assessment within primary and community healthcare.Aims To describe medical and dental attendance patterns, demographics and health profiles of patients routinely attending general dental practices in Warwickshire. To identify whether a subgroup attend dental practices regularly but attend medical practices infrequently and discuss whether preventive healthcare interventions delivered in general dental practice would be appropriate. METHODS: A self-completion questionnaire was administered to patients attending 16 dental practices in Warwickshire. RESULTS: Eight hundred and eleven completed questionnaires were returned (74% response). Seven hundred and eighty-nine (98%) respondents visited their dentist every one to two years or more frequently and of these a subgroup of 121 (15.3%) visited their general medical practice surgery or health centre less often than every two years. In the subgroup 9.5% reported high blood pressure, 17.6% currently smoked, 22% drank above recommended guidelines, 32.1% were overweight and 7.3% obese. DISCUSSION: The data suggest there may be a role for dental practitioners in identifying patients at risk of having undiagnosed or future general health problems and providing appropriate general health advice, screening or signposting the patient to relevant general healthcare facilities either within or external to the dental practice.


Assuntos
Odontologia Geral/estatística & dados numéricos , Medicina Geral/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Visita a Consultório Médico/estatística & dados numéricos , Encaminhamento e Consulta , Adulto , Inglaterra , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Medicina Estatal , Inquéritos e Questionários
17.
Anal Bioanal Chem ; 403(6): 1685-95, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22526649

RESUMO

Tyrosine kinase inhibitors (TKIs) are used to treat a number of cancers, including chronic myeloid leukaemia and hepatocellular carcinoma. Therapeutic drug monitoring (TDM) may be indicated to (1) monitor adherence, (2) guide dosage, and (3) minimise the risk of drug-drug interactions and dose-related toxicity. On-line, automated sample preparation provided by TurboFlow technology (ThermoFisher Scientific) in conjunction with the sensitivity and selectivity of tandem mass spectrometry (MS/MS) detection may be applied to the analysis of single drugs and metabolites. We report the use of TurboFlow LC-MS/MS for the analysis of nine TKIs and metabolites (imatinib, N-desmethylimatinib, dasatinib, nilotinib, erlotinib, gefitinib, lapatinib, sorafenib, sunitinib) in human plasma or serum for TDM purposes. An Aria Transcend TLX-II system coupled with a TSQ Vantage was used. Samples (50 µL) were vortex mixed with internal standard solution (150 µL imatinib-D(8), gefitinib-D(8), sunitinib-D(10), and nilotinib-(13)C (2) (15) N(2) in acetonitrile) and, after centrifugation 100 µL supernatant were injected directly onto a 50 × 0.5-mm Cyclone TurboFlow column. Analytes were focussed onto a 50 × 2.1-mm (3 µm) Hypersil GOLD analytical column and eluted with an acetonitrile/water gradient. Analytes were monitored in selected reaction monitoring mode (positive APCI). Total analysis time was 7 min without multiplexing. Calibration was linear (R(2) > 0.99) for all analytes. Inter- and intra-assay precision (in percent relative standard deviation, RSD) was <11 % and accuracy 89-117 % for all analytes. No matrix effects were observed. This method is suitable for high-throughput TDM in patients undergoing chronic therapy with TKIs and has been utilised in the analysis of clinical samples.


Assuntos
Automação , Cromatografia Líquida/métodos , Inibidores de Proteínas Quinases/sangue , Proteínas Tirosina Quinases/antagonistas & inibidores , Espectrometria de Massas em Tandem/métodos , Calibragem , Humanos , Inibidores de Proteínas Quinases/farmacologia , Padrões de Referência
18.
Leukemia ; 26(7): 1730-41, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22307178

RESUMO

Flow cytometry (FC) is increasingly recognized as an important tool in the diagnosis and prognosis of myelodysplastic syndromes (MDS). However, validation of current assays and agreement upon the techniques are prerequisites for its widespread acceptance and application in clinical practice. Therefore, a working group was initiated (Amsterdam, 2008) to discuss and propose standards for FC in MDS. In 2009 and 2010, representatives from 23, mainly European, institutes participated in the second and third European LeukemiaNet (ELN) MDS workshops. In the present report, minimal requirements to analyze dysplasia are refined. The proposed core markers should enable a categorization of FC results in cytopenic patients as 'normal', 'suggestive of', or 'diagnostic of' MDS. An FC report should include a description of validated FC abnormalities such as aberrant marker expression on myeloid progenitors and, furthermore, dysgranulopoiesis and/or dysmonocytopoiesis, if at least two abnormalities are evidenced. The working group is dedicated to initiate further studies to establish robust diagnostic and prognostic FC panels in MDS. An ultimate goal is to refine and improve diagnosis and prognostic scoring systems. Finally, the working group stresses that FC should be part of an integrated diagnosis rather than a separate technique.


Assuntos
Biomarcadores Tumorais/metabolismo , Citometria de Fluxo/normas , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/metabolismo , Guias de Prática Clínica como Assunto/normas , Medula Óssea/metabolismo , Medula Óssea/patologia , Citometria de Fluxo/métodos , Humanos , Imunofenotipagem , Agências Internacionais , Síndromes Mielodisplásicas/imunologia , Prognóstico , Padrões de Referência , Sociedades Científicas
19.
Br Dent J ; 211(6): E12, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21941301

RESUMO

OBJECTIVE: To investigate oral health awareness, oral hygiene and attitudes towards general dental practitioners' (GDP) involvement in diabetes screening in adults with diabetes. DESIGN: Self-completion questionnaire. SETTING: General medical practices in Warwickshire. SUBJECTS AND METHODS: Adults with diabetes attending clinics run by practice or diabetes nurses in general medical practices. RESULTS: Two hundred and twenty-nine of 615 (37.2%) questionnaires were completed in 14 general medical practices. The majority of respondents (79.8%, 178/223) visited a dentist once or twice a year, but oral care varied; 67.2% (133/198) reported brushing at least twice a day, whereas only 15.3% (29/190) flossed daily. Awareness of oral health risks was limited: 69.1% (150/217) had never received any oral health advice related to their diabetes. Over half of respondents supported the idea of dentists offering screening for diabetes (121/226, 53.5%). CONCLUSIONS: Many adults with diabetes have poor awareness of oral care and health complications associated with diabetes, and are receiving limited advice from healthcare professionals. Training and advice for both healthcare professionals and patients concerning the importance of good oral health in patients with diabetes is needed. The role of dentists in diabetes screening and support requires further investigation.


Assuntos
Complicações do Diabetes/prevenção & controle , Diabetes Mellitus/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Doenças da Boca/prevenção & controle , Saúde Bucal , Adulto , Idoso , Inquéritos de Saúde Bucal , Feminino , Odontologia Geral , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Doenças da Boca/complicações , Higiene Bucal/psicologia , Padrões de Prática Odontológica , Autocuidado/psicologia , Autocuidado/estatística & dados numéricos
20.
Br Dent J ; 210(7): 314-5, 2011 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-21475280
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