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1.
Oral Dis ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891012

RESUMO

OBJECTIVE: The objective of this paper was to provide an understanding of cachexia in relation to oral squamous cell carcinoma relevant to oral health care. The paper is a scoping review of aspects of the clinical presentation, aetiology and management of cachexia in relation to oral health and oral health care. METHODS: A combined search of MEDLINE and EMBASE databases (via OVID) was conducted using the terms ([Head and Neck] OR [Oral Squamous Cell Carcinoma]) AND (Cachexia). Duplicates were removed and results were subsequently limited to studies published between 2000 and 2023, humans and English language. After screening and full-text assessment a total number of 87 studies were included in the review. RESULTS: It is evident that cachexia is a not uncommon feature of patients with advanced malignancy of the head and neck driven by a multitude of mechanisms, induced by the tumour itself, that lead to reduced nutritional intake, increased metabolism and loss of adipose and skeletal tissue. CONCLUSION: While a variety of nutritional, physical, psychological and pharmacological interventions may improve quality and duration of life, ultimately the diagnosis of cachexia in relation to head and neck cancer remains an indicator of poor life expectancy.

2.
Nature ; 539(7627): 65-68, 2016 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-27626378

RESUMO

A unique feature of Pluto's large satellite Charon is its dark red northern polar cap. Similar colours on Pluto's surface have been attributed to tholin-like organic macromolecules produced by energetic radiation processing of hydrocarbons. The polar location on Charon implicates the temperature extremes that result from Charon's high obliquity and long seasons in the production of this material. The escape of Pluto's atmosphere provides a potential feedstock for a complex chemistry. Gas from Pluto that is transiently cold-trapped and processed at Charon's winter pole was proposed as an explanation for the dark coloration on the basis of an image of Charon's northern hemisphere, but not modelled quantitatively. Here we report images of the southern hemisphere illuminated by Pluto-shine and also images taken during the approach phase that show the northern polar cap over a range of longitudes. We model the surface thermal environment on Charon and the supply and temporary cold-trapping of material escaping from Pluto, as well as the photolytic processing of this material into more complex and less volatile molecules while cold-trapped. The model results are consistent with the proposed mechanism for producing the observed colour pattern on Charon.

3.
Respir Res ; 19(1): 213, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400950

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is chronic fibrosing pneumonia with an unpredictable natural disease history. Functional respiratory imaging (FRI) has potential to better characterize this disease. The aim of this study was to identify FRI parameters, which predict FVC decline in patients with IPF. METHODS: An IPF-cohort (treated with pamrevlumab for 48 weeks) was retrospectively studied using FRI. Serial CT's were compared from 66 subjects. Post-hoc analysis was performed using FRI, FVC and mixed effects models. RESULTS: Lung volumes, determined by FRI, correlated with FVC (lower lung volumes with lower FVC) (R2 = 0.61, p < 0.001). A negative correlation was observed between specific image based airway radius (siRADaw) at total lung capacity (TLC) and FVC (R2 = 0.18, p < 0.001). Changes in FVC correlated significantly with changes in lung volumes (R2 = 0.18, p < 0.001) and siRADaw (R2 = 0.15, p = 0.002) at week 24 and 48, with siRADaw being more sensitive to change than FVC. Loss in lobe volumes (R2 = 0.33, p < 0.001), increasing fibrotic tissue (R2 = 0.33, p < 0.001) and airway radius (R2 = 0.28, p < 0.001) at TLC correlated with changes in FVC but these changes already occur in the lower lobes when FVC is still considered normal. CONCLUSION: This study indicates that FRI is a superior tool than FVC in capturing of early and clinically relevant, disease progression in a regional manner.


Assuntos
Progressão da Doença , Fibrose Pulmonar Idiopática/diagnóstico por imagem , Fibrose Pulmonar Idiopática/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Capacidade Vital/fisiologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Volume de Ventilação Pulmonar/fisiologia , Tomografia Computadorizada por Raios X/normas
4.
Oral Dis ; 24(1-2): 233-237, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29480628

RESUMO

Chikungunya virus (CHIKV) was first isolated in humans in 1952, following an epidemic in Tanzania. The origin of the name means "to bend forward or become contorted," in reference to the posture adopted by patients due to the joint pain that occurs during the infection. Epidemiology data suggest that by the end of 2015, about 1.6 million people had been infected with CHIKV. The acute period of the disease is characterized by high fever, myalgia, joint pain, and severe and disabling polyarthritis, sometimes accompanied by headache, backache, and maculopapular rash, predominantly on the thorax. Around half of the patients will progress to the subacute and chronic phases, that is manifested by persistent polyarthritis/polyarthralgia, accompanied by morning stiffness and fatigue, which could remain for years. Oral features may include gingivitis possibly as a consequence of arthralgia of the hands leading to limited oral health measures as well as burning sensation and oral mucosal ulceration. Treatment in the acute phase includes acetaminophen, and weak opioids (tramadol or codeine) should be used in cases of severe or refractory pain. For patients who have progressed to the subacute stage and who have not had notable benefit from common analgesics or opioids, NSAIDs, or adjunctive pain medications (anticonvulsants or antidepressants) may be of benefit. In patients with moderate-to-severe musculoskeletal pain or in those who cannot be given or tolerate NSIADs or opiates, prednisolone should be prescribed.


Assuntos
Artralgia/tratamento farmacológico , Reação de Arthus/tratamento farmacológico , Febre de Chikungunya/complicações , Febre de Chikungunya/diagnóstico , Mialgia/tratamento farmacológico , Artralgia/virologia , Reação de Arthus/virologia , Terapia por Exercício , Gengivite/virologia , Humanos , Mialgia/virologia
5.
BMC Nephrol ; 19(1): 38, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29439674

RESUMO

BACKGROUND: Surveys using traditional measures of nutritional status indicate that muscle wasting is common among persons with end-stage kidney disease (ESKD). Up to 75% of adults undergoing maintenance dialysis show some evidence of muscle wasting. ESKD is associated with an increase in inflammatory cytokines and can result in cachexia, with the loss of muscle and fat stores. At present, only limited data are available on the classification of wasting experienced by persons with ESKD. Individuals with ESKD often exhibit symptoms of anorexia, loss of lean muscle mass and altered energy expenditure. These symptoms are consistent with the syndrome of cachexia observed in other chronic diseases, such as cancer, heart failure, and acquired immune deficiency syndrome. While definitions of cachexia have been developed for some diseases, such as cardiac failure and cancer, no specific cachexia definition has been established for chronic kidney disease. The importance of developing a definition of cachexia in a population with ESKD is underscored by the negative impact that symptoms of cachexia have on quality of life and the association of cachexia with a substantially increased risk of premature mortality. The aim of this study is to determine the clinical phenotype of cachexia specific to individuals with ESKD. METHODS: A longitudinal study which will recruit adult patients with ESKD receiving haemodialysis attending a Regional Nephrology Unit within the United Kingdom. Patients will be followed 2 monthly over 12 months and measurements of weight; lean muscle mass (bioelectrical impedance, mid upper arm muscle circumference and tricep skin fold thickness); muscle strength (hand held dynamometer), fatigue, anorexia and quality of life collected. We will determine if they experience (and to what degree) the known characteristics associated with cachexia. DISCUSSION: Cachexia is a debilitating condition associated with an extremely poor outcome. Definitions of cachexia in chronic illnesses are required to reflect specific nuances associated with each disease. These discrete cachexia definitions help with the precision of research and the subsequent clinical interventions to improve outcomes for patients suffering from cachexia. The absence of a definition for cachexia in an ESKD population makes it particularly difficult to study the incidence of cachexia or potential treatments, as there are no standardised inclusion criteria for patients with ESKD who have cachexia. Outcomes from this study will provide much needed data to inform development and testing of potential treatment modalities, aimed at enhancing current clinical practice, policy and education.


Assuntos
Caquexia/diagnóstico , Caquexia/fisiopatologia , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/fisiopatologia , Seleção de Pacientes , Fenótipo , Caquexia/epidemiologia , Humanos , Falência Renal Crônica/epidemiologia , Estudos Longitudinais , Diálise Renal/tendências , Reino Unido/epidemiologia
6.
Oral Dis ; 23(8): 1168-1179, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28779517

RESUMO

OBJECTIVES: To analyse the range of existing patient-reported outcome measures (PROMs) used in studies of recurrent aphthous stomatitis (RAS) and to evaluate their quality properties via the assessment of psychometric properties and interpretability. MATERIALS AND METHODS: Electronic databases were searched to identify relevant publications related to PROMs used in RAS. Publications were selected based on predefined criteria. All identified PROMs were then classified by measuring concepts and assessed for instrument characteristics and evidence for quality properties for RAS patients. RESULTS: Twenty-eight PROMs were used in studies of RAS patients. Instruments focused upon oral symptoms (n = 4), psychosocial status (n = 15) and quality of life (n = 9). Five PROMs (Oral Health-related Quality of Life-UK, Chronic Oral Mucosal Disease Questionnaire, Oral Health Impact Profile-14, Medical Outcome Study Short Form-36 and Mumcu's composite index) were found to have some evidence of psychometric performance. No PROMs showed evidence for interpretability of their scores in RAS patients. CONCLUSION: There was a wide range of PROMs used in clinical studies of RAS. The majority of these PROMs lack evidence of measurement properties and interpretability for RAS patients. Further studies are required to confirm whether these instruments are suitable and useful for this patient group.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Estomatite Aftosa , Humanos , Saúde Mental , Psicometria , Qualidade de Vida , Recidiva , Estomatite Aftosa/psicologia , Avaliação de Sintomas
7.
Oral Dis ; 23(4): 477-483, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28039941

RESUMO

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/efeitos adversos , Estudos Transversais , Difosfonatos/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
8.
J Evol Biol ; 29(5): 1045-58, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26864797

RESUMO

Community assembly is the result of multiple ecological and evolutionary forces that influence species coexistence. For flowering plants, pollinators are often essential for plant reproduction and establishment, and pollinator-mediated interactions may influence plant community composition. Here, we use null models and community phylogenetic analyses of co-occurrence patterns to determine the role of pollinator-mediated processes in structuring plant communities dominated by congeners. We surveyed three species-rich genera (Limnanthes, Mimulus and Clarkia) with centres of diversity in the Sierra Nevada of California. Each genus contains species that co-flower and share pollinators, and each has a robust phylogeny. Within each genus, we surveyed 44-48 communities at three spatial scales, measured floral and vegetative traits and tested for segregation or aggregation of: (i) species, (ii) floral traits (which are likely to be influenced by pollinators), and (iii) vegetative traits (which are likely affected by other environmental factors). We detected both aggregation and segregation of floral traits that were uncorrelated with vegetative trait patterns; we infer that pollinators have shaped the community assembly although the mechanisms may be varied (competition, facilitation, or filtering). We also found that mating system differences may play an important role in allowing species co-occurrence. Together, it appears that pollinators influence community assemblage in these three clades.


Assuntos
Evolução Biológica , Filogenia , Polinização , California , Clarkia , Flores
9.
Int Nurs Rev ; 63(2): 292-9, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26868263

RESUMO

BACKGROUND: The recent Fukushima Nuclear Power Plant accident was one of more than 200 serious nuclear/radiation incidents (accidents and disasters) that occurred worldwide since 1945. The current Fukushima disaster is in the recovery phase with the decreasing levels of radiation in the environment. However, fears and stigma related to the perceived risk of radiation exposure persist among the general population. INTRODUCTION: To improve on students' preparedness for social and public health challenges after a radiation incidence, radiation education was provided for undergraduate public health nursing students. AIM: This case study reports the development and implementation of the first class of radiation education in public health nursing, as well as students' reflections on their class experience. METHODS: We included a 90-min radiation class in an undergraduate public health nursing course in Tokyo, Japan. Lectures/discussion on technical and environmental aspects provided the minimally essential content for basic radiation knowledge. After class, all the 65 students were invited to freely write their reflections on the class. With their consent, 61 students' anonymous written accounts were qualitatively analysed. RESULTS: Five themes emerged: awareness of ignorance about radiation, problems produced by the mass media, becoming knowledgeable about radiation, public health nurses' role, and trustful and enjoyable lecture. DISCUSSION: The class inspired students to consider social, psychological and relational aspects of knowing and not knowing about radiation and their future professional role. CONCLUSION AND IMPLICATIONS FOR NURSING: Once radiation is taught at school, nursing students will emerge as professionals with the belief that radiation is within their professional purview. Education is key to disaster prevention, preparation, response and recovery. Given the ubiquitous nature of health challenges after a radiation incident, radiation education is indispensable for nursing students worldwide.


Assuntos
Educação em Enfermagem , Acidente Nuclear de Fukushima , Enfermagem em Saúde Pública , Desastres , Humanos , Japão , Estudantes de Enfermagem
10.
Analyst ; 140(15): 5198-204, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26086875

RESUMO

Despite the accessibility of the oral cavity to clinical examination, delays in diagnosis of oral and oropharyngeal carcinoma (OOPC) are observed in a large majority of patients, with negative impact on prognosis. Diagnostic aids might help detection and improve early diagnosis, but there remains little robust evidence supporting the use of any particular diagnostic technology at the moment. The aim of the present feasibility first-in-human study was to evaluate the preliminary diagnostic validity of a novel technology platform based on dielectrophoresis (DEP). DEP does not require labeling with antibodies or stains and it is an ideal tool for rapid analysis of cell properties. Cells from OOPC/dysplasia tissue and healthy oral mucosa were collected from 57 study participants via minimally-invasive brush biopsies and tested with a prototype DEP platform using median membrane midpoint frequency as main analysis parameter. Results indicate that the current DEP platform can discriminate between brush biopsy samples from cancerous and healthy oral tissue with a diagnostic sensitivity of 81.6% and a specificity of 81.0%. The present ex vivo results support the potential application of DEP testing for identification of OOPC. This result indicates that DEP has the potential to be developed into a low-cost, rapid platform as an assistive tool for the early identification of oral cancer in primary care; given the rapid, minimally-invasive and non-expensive nature of the test, dielectric characterization represents a promising platform for cost-effective early cancer detection.


Assuntos
Neoplasias Bucais/diagnóstico , Boca/patologia , Neoplasias Orofaríngeas/diagnóstico , Orofaringe/patologia , Biópsia , Detecção Precoce de Câncer/métodos , Eletroforese/métodos , Humanos , Mucosa Bucal/patologia , Neoplasias Bucais/patologia , Neoplasias Orofaríngeas/patologia
11.
J Environ Qual ; 44(3): 768-79, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26024257

RESUMO

A watershed's riparian corridor presents opportunities to stabilize streambanks, intercept runoff, and influence shallow groundwater with riparian buffers. This paper presents a system to classify these riparian opportunities and apply them toward riparian management planning in hydrologic unit code 12 watersheds. In two headwater watersheds from each of three landform regions found in Iowa and Illinois, high-resolution (3-m grid) digital elevation models were analyzed to identify spatial distributions of surface runoff contributions and zones with shallow water tables (SWTs) (within 1.5 m of the channel elevation) along the riparian corridors. Results were tabulated, and a cross classification was applied. Classes of buffers include those primarily placed to (i) trap runoff and sediment, (ii) influence shallow groundwater, (iii) address both runoff and shallow groundwater, and (iv) maintain/improve stream bank stability. Riparian buffers occupying about 2.5% of these six watersheds could effectively intercept runoff contributions from 81 to 94% of the watersheds' contributing areas. However, extents of riparian zones where a narrow buffer (<10 m wide) would adequately intercept runoff but where >25 m width of buffer vegetation could root to a SWT varied according to landform region ( < 0.10). Yet, these wide-SWT riparian zones were widespread and occupied 23 to 53% of the lengths of stream banks among the six watersheds. The wide-SWT setting provides opportunities to reduce dissolved nutrients (particularly NO-N) carried via groundwater. This riparian classification and mapping system is part of a ArcGIS toolbox and could provide a consistent basis to identify riparian management opportunities in Midwestern headwater catchments wherever high-resolution elevation data are available.

12.
J Environ Qual ; 44(3): 754-67, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-26024256

RESUMO

Spatial data on soils, land use, and topography, combined with knowledge of conservation effectiveness, can be used to identify alternatives to reduce nutrient discharge from small (hydrologic unit code [HUC]12) watersheds. Databases comprising soil attributes, agricultural land use, and light detection and ranging-derived elevation models were developed for two glaciated midwestern HUC12 watersheds: Iowa's Beaver Creek watershed has an older dissected landscape, and Lime Creek in Illinois is young and less dissected. Subsurface drainage is common in both watersheds. We identified locations for conservation practices, including in-field practices (grassed waterways), edge-of-field practices (nutrient-removal wetlands, saturated buffers), and drainage-water management, by applying terrain analyses, geographic criteria, and cross-classifications to field- and watershed-scale geographic data. Cover crops were randomly distributed to fields without geographic prioritization. A set of alternative planning scenarios was developed to represent a variety of extents of implementation among these practices. The scenarios were assessed for nutrient reduction potential using a spreadsheet approach to calculate the average nutrient-removal efficiency required among the practices included in each scenario to achieve a 40% NO-N reduction. Results were evaluated in the context of the Iowa Nutrient Reduction Strategy, which reviewed nutrient-removal efficiencies of practices and established the 40% NO-N reduction as Iowa's target for Gulf of Mexico hypoxia mitigation by agriculture. In both test watersheds, planning scenarios that could potentially achieve the targeted NO-N reduction but remove <5% of cropland from production were identified. Cover crops and nutrient removal wetlands were common to these scenarios. This approach provides an interim technology to assist local watershed planning and could provide planning scenarios to evaluate using watershed simulation models. A set of ArcGIS tools is being released to enable transfer of this mapping technology.

13.
Br J Dermatol ; 170(4): 794-801, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24088036

RESUMO

BACKGROUND: It has been suggested that intralesional triamcinolone injections represent a safe and effective therapeutic strategy in controlling the permanent disfiguring swelling of orofacial granulomatosis (OFG). However, robust supporting evidence is lacking, due to the variable and inconsistent design of available studies. OBJECTIVES: To investigate whether a standardized regimen of intralesional triamcinolone has beneficial long-term effects on orofacial swelling of OFG. We also studied potential associations with a number of prognostic factors. METHODS: We designed a retrospective observational study of a homogeneous cohort of 22 well-phenotyped patients with OFG. The primary outcome was defined as a statistically significant decrease in post-treatment disease severity. Statistically significant association with prognostic factors was the secondary outcome. Statistical analysis included Wilcoxon signed-rank tests and logistic regression. RESULTS: Compared with pretreatment, there were statistically significant decreases in disease severity scores at all time points until 48 months post-treatment (P < 0·01). Logistic regression analysis showed there was no independent prognostic variable of statistical significance (P > 0·05). The majority of patients (14/22, 63·6%) received one course of intralesional triamcinolone and did not experience disease recurrence. The mean disease-free period after the first course of intralesional therapy was 28·9 ± 18 months (95% confidence interval 28·7-29·1). No adverse effects were reported. CONCLUSIONS: This is the first study to have employed robust cohort methodology and sound statistics to demonstrate long-term effectiveness of intralesional triamcinolone in controlling the disfiguring swelling of OFG. Because of limitations inherent in observational studies, further research in the form of randomized case-control trials is needed to confirm the present findings.


Assuntos
Glucocorticoides/administração & dosagem , Granulomatose Orofacial/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Adolescente , Adulto , Idoso , Fatores de Confusão Epidemiológicos , Feminino , Glucocorticoides/efeitos adversos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Triancinolona Acetonida/efeitos adversos , Adulto Jovem
14.
Front Oral Health ; 5: 1359132, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813461

RESUMO

Introduction: Patient and Public Involvement (PPI) can have a positive impact on research. PPI can make research more meaningful and appropriate as well as preventing research waste. For decades, patient advocates with HIV have played a key part in public health and research. This article presents the PPI activity undertaken during a doctoral study. The aim of this article is to demonstrate how PPI was embedded into a doctoral study that explored the feasibility of HIV testing in dental settings. Methods: Patients and the public were invited to be involved with the feasibility study through various organisations and charities. A comprehensive PPI activity strategy was devised, and appropriate funding was obtained. Patients and the public were predominantly consulted or collaboratively involved with several aspects of the study. Findings: Patients and the public positively contributed to the intervention development and the resources supporting its implementation. As a result, the study resources (i.e., questionnaire and information leaflets) were easier to read, and the intervention was more appropriate to the needs of patients. Furthermore, the training and focus groups conducted with dental patients and people with HIV benefitted from input of people with lived experience. Conclusions: PPI can be embedded within doctoral studies provided there is sufficient funding, flexibility, and supervisory support. However, PPI activity may be impacted by limited resource and a priori research protocol and funding agreements.

15.
Gene Ther ; 20(1): 35-42, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22257934

RESUMO

An emerging strategy for the treatment of monogenic diseases uses genetic engineering to precisely correct the mutation(s) at the genome level. Recent advancements in this technology have demonstrated therapeutic levels of gene correction using a zinc-finger nuclease (ZFN)-induced DNA double-strand break in conjunction with an exogenous DNA donor substrate. This strategy requires efficient nucleic acid delivery and among viral vectors, recombinant adeno-associated virus (rAAV) has demonstrated clinical success without pathology. However, a major limitation of rAAV is the small DNA packaging capacity and to date, the use of rAAV for ZFN gene delivery has yet to be reported. Theoretically, an ideal situation is to deliver both ZFNs and the repair substrate in a single vector to avoid inefficient gene targeting and unwanted mutagenesis, both complications of a rAAV co-transduction strategy. Therefore, a rAAV format was generated in which a single polypeptide encodes the ZFN monomers connected by a ribosome skipping 2A peptide and furin cleavage sequence. On the basis of this arrangement, a DNA repair substrate of 750 nucleotides was also included in this vector. Efficient polypeptide processing to discrete ZFNs is demonstrated, as well as the ability of this single vector format to stimulate efficient gene targeting in a human cell line and mouse model derived fibroblasts. Additionally, we increased rAAV-mediated gene correction up to sixfold using a combination of Food and Drug Administration-approved drugs, which act at the level of AAV vector transduction. Collectively, these experiments demonstrate the ability to deliver ZFNs and a repair substrate by a single AAV vector and offer insights for the optimization of rAAV-mediated gene correction using drug therapy.


Assuntos
Antineoplásicos/farmacologia , Dependovirus/genética , Endonucleases/genética , Vetores Genéticos , Transdução Genética , Dedos de Zinco , Células 3T3 , Animais , Reparo do DNA , Células HEK293 , Humanos , Camundongos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Transformação Genética/efeitos dos fármacos , Estados Unidos , United States Food and Drug Administration
16.
Eur J Cancer Care (Engl) ; 22(3): 326-33, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23279159

RESUMO

The purpose of this paper is to examine the consequences that medical practitioners' decisions about whether or not to be candid about terminal prognosis have for those suffering from refractory cachexia and their families. It presents the findings of a qualitative study that used focus groups and semi-structured interviews of a volunteer sample of doctors, nurses and dieticians in a cancer centre of a large teaching hospital in Northern Ireland. Respondents reported that some physicians tended to avoid discussing terminal prognosis in a direct manner with their patients. Nurses and dieticians tended to be reluctant to engage in conversations about weight loss with patients with cachexia. One of the reasons they reported for their lack of acknowledgement of weight loss concerned the close association between refractory cachexia and terminal prognosis. Because they viewed the telling of bad news as an exclusive prerogative of medical practitioners, they did not feel in a position to discuss cachexia because they were concerned that this had the potential to raise end-of-life issues that lay outside the boundaries of their professional role. This meant patients and their families were provided with little information about how to cope with the distressing consequences of cachexia.


Assuntos
Atitude do Pessoal de Saúde , Caquexia/etiologia , Neoplasias/complicações , Assistência Terminal/psicologia , Revelação da Verdade , Adulto , Feminino , Grupos Focais , Humanos , Masculino , Irlanda do Norte , Pesquisa Qualitativa , Inquéritos e Questionários
17.
Br J Sports Med ; 47(16): 1054-8, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24068332

RESUMO

BACKGROUND: Oral health is important both for well-being and successful elite sporting performance. Reports from Olympic Games have found significant treatment needs; however, few studies have examined oral health directly. The aim of this study was to evaluate oral health, the determinants of oral health and the effect of oral health on well-being, training and performance of athletes participating in the London 2012 Games. METHODS: Cross-sectional study at the dental clinic within the Polyclinic in the athletes' village. Following informed consent, a standardised history, clinical examination and brief questionnaire were conducted. RESULTS: 302 athletes from 25 sports were recruited with data available for 278. The majority of athletes were from Africa, the Americas and Europe. Overall, the results demonstrated high levels of poor oral health including dental caries (55% athletes), dental erosion (45% athletes) and periodontal disease (gingivitis 76% athletes, periodontitis 15% athletes). More than 40% of athletes were 'bothered' by their oral health with 28% reporting an impact on quality of life and 18% on training and performance. Nearly half of the participants had not undergone a dental examination or hygiene care in the previous year. CONCLUSIONS: The oral health of athletes attending the dental clinic of the London 2012 Games was poor with a resulting substantial negative impact on well-being, training and performance. As oral health is an important element of overall health and well-being, health promotion and disease prevention interventions are urgently required to optimise athletic performance.


Assuntos
Desempenho Atlético/fisiologia , Saúde Bucal , Adolescente , Adulto , Bebidas/efeitos adversos , Estudos Transversais , Traumatismos Faciais/epidemiologia , Traumatismos Faciais/fisiopatologia , Feminino , Nível de Saúde , Humanos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Pericoronite/epidemiologia , Pericoronite/fisiopatologia , Qualidade de Vida , Doenças Dentárias/epidemiologia , Doenças Dentárias/fisiopatologia , Traumatismos Dentários/epidemiologia , Traumatismos Dentários/fisiopatologia , Adulto Jovem
18.
Geobiology ; 21(6): 708-724, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37724627

RESUMO

Precambrian organic-walled microfossils (OWMs) are primarily preserved in mudstones and shales that are low in total organic carbon (TOC). Recent work suggests that high TOC may hinder OWM preservation, perhaps because it interferes with chemical interactions involving certain clay minerals that inhibit the decay of microorganisms. To test if clay mineralogy controls OWM preservation, and if TOC moderates the effect of clay minerals, we compared OWM preservational quality (measured by pitting on fossil surfaces and the deterioration of wall margins) to TOC, total clay, and specific clay mineral concentrations in 78 shale samples from 11 lithologic units ranging in age from ca. 1650 to 650 million years ago. We found that the probability of finding well-preserved microfossils positively correlates with total clay concentrations and confirmed that it negatively correlates with TOC concentrations. However, we found no evidence that TOC influences the effect of clay mineral concentrations on OWM preservation, supporting an independent role of both factors on preservation. Within the total clay fraction, well-preserved microfossils are more likely to occur in shales with high illite concentrations and low berthierine/chamosite concentrations; however, the magnitude of their effect on preservation is small. Therefore, there is little evidence that bulk clay chemistry is important in OWM preservation. Instead, we propose that OWM preservation is largely regulated by physical properties that isolate organic remains from microbial degradation such as food scarcity (low TOC) and low sediment permeability (high total clay content): low TOC increases the diffusive distances between potential carbon sources and heterotrophic microbes (or their degradative enzymes), while high clay concentrations reduce sediment pore space, thereby limiting the diffusion of oxidants and degradative enzymes to the sites of decay.

19.
Plant Dis ; 96(3): 459, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30727117

RESUMO

Spruce needle drop (also known as sudden needle drop of spruce, both referred to as SNEED) is a condition consistently associated with the fungus Setomelanomma holmii. While the pathogenicity of this fungus is still under investigation, it has been reported to cause the discoloration and needle drop of older needles on white spruce (Picea glauca) and Colorado blue spruce (P. pungens) (1). In the spring and summer of 2011, the University of Illinois Plant Clinic received several samples of Norway spruce (P. abies) and Colorado blue spruce branches that all exhibited the same symptoms: browning of older needles followed by needle drop. Solitary, black, globose, 105 to 230 µm diameter pseudothecia were observed on the upper surface of the branches and bud scales with a dissecting microscope. Many of the fruiting structures contained setae. When examined under a compound microscope, asci were bitunicate, 60 to 100 × 10.5 to 15 µm (mean 71.9 × 12.7 µm), and contained eight pale brown, three-septate, 15.5 to 22.5 × 5.5 to 9 µm (mean 19.4 × 5 µm) ascospores. On the basis of the asci and ascospores, the fungus was tentatively identified as S. holmii. To confirm the identification, single-ascospore colonies were cultured on acid potato dextrose agar. DNA was extracted from the mycelia of a single colony and amplified with PCR using universal fungal primers (2). The amplified DNA was sequenced and assembled using the primers NS1, NS3, NS5, and NS7 in the forward direction and NS2, NS4, NS6, and NS8 in the reverse direction (2). When the consensus sequence was compared with all accessions in the National Center for Biotechnology Information GenBank nucleotide collection, it had 100% homology to the S. holmii 18S ribosomal gene (Accession No. AY161121, isolated from a sample of P. pungens collected in France). S. holmii was first observed in the United States in 1998 (1). Although it has been tentatively identified on the basis of morphological characteristics in many states in the Midwest, this is the first time it has been conclusively identified in Illinois to our knowledge. Additionally, this is the first time Norway spruce has been confirmed as a host of S. holmii based on genetic sequencing in Illinois. Sporulation has been observed from mid-May through early August. Currently, the presence of S. holmii has been confirmed in 14 counties in central and northern Illinois. References: (1) A. Rossman et al. Can. J. Bot. 80:1209, 2002. (2) T. J. White et al. Page 315 in: PCR Protocols: A Guide to Methods and Applications. M. A. Innis et al. eds. Academic Press, San Diego, CA, 1990.

20.
Br J Cancer ; 104(12): 1836-9, 2011 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-21610709

RESUMO

BACKGROUND: Poor cancer survival rates in the United Kingdom are often blamed on delayed medical care. A local audit of endometrial cancer revealed a variety of preventable delays. We surveyed practice in the South West of England to see if this was an isolated or widespread problem. METHODS: All 15 hospitals in the South West of England collected information prospectively from all women with endometrial cancer over 3 months in the spring of 2009. RESULTS: There were delays in all stages of the uterine cancer pathway. Excluding extraneous cases, 52% of women waited more than a month and 12% waited more than 6 months to see their GP from the onset of symptoms. Almost half the cases said they were unaware that abnormal bleeding was a symptom of cancer. Only a quarter of women had treatment within 31 days from the outpatient visit to first definitive treatment and 18% waited more than the target of 62 days for their treatment. CONCLUSIONS: Significant treatment delays occur because women do not report bleeding. If this is replicated throughout Britain, approximately 1000 women per year will delay presentation for at least 3 months and 600 will wait for more than 6 months.


Assuntos
Diagnóstico Tardio , Neoplasias do Endométrio/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Endométrio/diagnóstico , Inglaterra , Feminino , Clínicos Gerais , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Encaminhamento e Consulta , Fatores de Tempo
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