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1.
J Eur Acad Dermatol Venereol ; 36(3): 365-372, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34679239

RESUMO

S1P is a pleotropic sphingolipid signalling molecule that acts through binding to five high-affinity G-protein coupled receptors. S1P-signaling affects cell fate in a multitude of ways, e.g. influencing cell differentiation, proliferation, and apoptosis, as well as playing an important role in immune cell trafficking. Though many effects of S1P-signaling in the human body have been discovered, the full range of functions is yet to be understood. For inflammatory skin diseases such as atopic dermatitis and psoriasis, evidence is emerging that dysfunction and imbalance of the S1P-axis is a contributing factor. Multiple studies investigating the efficacy of S1PR modulators in alleviating the severity and symptoms of skin conditions in various animal models and human clinical trials have shown promising results and validated the interest in the S1P-axis as a potential therapeutic target. Even though the involvement of S1P-signalling in inflammatory skin diseases still requires further clarification, the implications of the recent findings may prompt expansion of research to additional skin conditions and more S1P-axis modulatory pharmaceuticals.


Assuntos
Dermatite , Dermatopatias , Animais , Humanos , Lisofosfolipídeos/metabolismo , Transdução de Sinais , Esfingosina/metabolismo
2.
J Eur Acad Dermatol Venereol ; 36(3): 380-390, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34779023

RESUMO

The plethora of pharmacologic treatments used for periorificial dermatitis (POD) makes clinical decision-making challenging. The objectives of this review were to assess the efficacy and safety of pharmacological interventions for POD in children and adults. The search was performed on 2 February 2021 and included seven databases and trial registries, with no date or language restrictions Study selection, data extraction and risk of bias assessments were performed independently and in duplicate by two authors, in accordance with a prespecified protocol. Meta-analyses were performed and reported in accordance with PRISMA guidelines. Where meta-analysis was not possible, a narrative synthesis was performed and reported in accordance with SWiM guidelines. The certainty of evidence was assessed using the Grading of Recommendation, Assessment, Development and Evaluation approach. Eleven studies representing 733 participants were included. Oral tetracycline may improve physician-reported severity of POD from day 20 onwards (low certainty evidence). Adverse effects may include abdominal discomfort, facial dryness and pruritus. Pimecrolimus cream may improve physician-reported severity slightly after 4 weeks of treatment (MD -0.49, 95% CI -1.02 to 0.04, n = 164, low certainty evidence). Adverse effects may include erythema, herpes simplex virus infection, burning and pruritus. Azelaic acid gel may result in no change in either physician- or patient-reported severity after 6 weeks of treatment. The evidence is very uncertain about the effect of praziquantel ointment on physician-reported severity and skin-related quality of life after 4 weeks of treatment. The evidence is also very uncertain about the effect of topical clindamycin/benzoyl peroxide on physician-reported severity. The body of evidence to inform treatment of POD currently consists of low and very low certainty evidence for important outcomes. Well-designed trials are needed to further investigate treatment options. Data are required for children and from low-middle income countries to improve external validity. Future trials should also include adequate post-treatment follow-up and standardized outcome measures.


Assuntos
Dermatite Perioral , Qualidade de Vida , Adulto , Criança , Emolientes/uso terapêutico , Humanos , Prurido/tratamento farmacológico
3.
Int J Obes (Lond) ; 44(9): 1958-1969, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32678325

RESUMO

Diet has important effects on normal physiology and the potential deleterious effects of high fat diets and obesity on male reproductive health are being increasingly described. We conducted a histological review of the effects of chronic high fat (HF) diet (using a mouse model fed a 45% fat diet for 21 weeks) with a discovery proteomic study to assess for changes in the abundance of proteins in the testis. Mice on a HF diet became obese and developed glucose intolerance. Using mass spectrometry, we identify 102 proteins affected in the testis of obese mice. These included structural proteins important for the blood testis barrier (filamin A, FLNA), proteins involved in oxidative stress responses (spermatogenesis associated 20, SPATA-20) and lipid homoeostasis (sterol regulatory element-binding protein 2, SREBP2 and apolipoprotein A1, APOA1). In addition, an important regulator protein paraspeckle component 1, PSPC-1, which interacts with the androgen receptor was significantly downregulated. Proteomic data was validated using both Western blotting and immunostaining which confirmed and localised protein expression in both mouse and human testis using biopsy specimens. This study focused mainly on the abnormalities that occurred at the protein level and as a result, we have identified several candidate proteins and conducted pathway analysis around the effects of HF diet on the testis providing novel insights not previously described. Some of the identified targets could be targeted therapeutically and future work is directed in this area.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/farmacologia , Obesidade/metabolismo , Proteoma/efeitos dos fármacos , Testículo , Animais , Humanos , Masculino , Camundongos , Testículo/efeitos dos fármacos , Testículo/patologia
4.
J Eur Acad Dermatol Venereol ; 33(6): 1042-1050, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30801794

RESUMO

Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21-1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non-significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71-3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High-quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.


Assuntos
Deficiências Nutricionais/metabolismo , Dermatite Atópica/metabolismo , Zinco/metabolismo , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/prevenção & controle , Suplementos Nutricionais , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Zinco/administração & dosagem , Zinco/deficiência
5.
J Neuroeng Rehabil ; 16(1): 128, 2019 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-31666096

RESUMO

BACKGROUND: Central Neuropathic Pain (CNP) is a frequent chronic condition in people with spinal cord injury (SCI). Previously, we showed that using laboratory brain-computer interface (BCI) technology for neurofeedback (NFB) training, it was possible to reduce CNP in people with SCI. In this study, we show results of patient self-managed treatment in their homes with a BCI-NFB using a consumer EEG device. METHODS: Users: People with chronic SCI (17 M, 3 F, 50.6 ± 14.1 years old), and CNP ≥4 on a Visual Numerical Scale. LOCATION: Laboratory training (up to 4 sessions) followed by home self-managed NFB. User Activity: Upregulating the EEG alpha band power by 10% above a threshold and at the same time downregulating the theta and upper beta (20-30 Hz) band power by 10% at electrode location C4. Technology: A consumer grade multichannel EEG headset (Epoch, Emotiv, USA), a tablet computer and custom made NFB software. EVALUATION: EEG analysis, before and after NFB assessment, interviews and questionnaires. RESULTS: Effectiveness: Out of 20 initially assessed participants, 15 took part in the study. Participants used the system for 6.9 ± 5.5 (median 4) weeks. Twelve participants regulated their brainwaves in a frequency specific manner and were most successful upregulating the alpha band power. However they typically upregulated power around their individual alpha peak (7.6 ± 0.8 Hz) that was lower than in people without CNP. The reduction in pain experienced was statistically significant in 12 and clinically significant (greater than 30%) in 8 participants. Efficiency: The donning was between 5 and 15 min, and approximately 10-20% of EEG data recorded in the home environment was noise. Participants were mildly stressed when self-administering NFB at home (2.4 on a scale 1-10). User satisfaction: Nine participants who completed the final assessment reported a high level of satisfaction (QUESQ, 4.5 ± 0.8), naming effectiveness, ease of use and comfort as main priorities. The main factors influencing frequency of NFB training were: health related issues, free time and pain intensity. CONCLUSION: Portable NFB is a feasible solution for home-based self-managed treatment of CNP. Compared to pharmacological treatments, NFB has less side effects and provides users with active control over pain. TRIAL REGISTRATION: GN15NE124 , Registered 9th June 2016.


Assuntos
Interfaces Cérebro-Computador , Neuralgia/etiologia , Neuralgia/terapia , Autocuidado/métodos , Traumatismos da Medula Espinal/complicações , Adolescente , Adulto , Idoso , Ritmo alfa , Ritmo beta , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurorretroalimentação/métodos , Medição da Dor , Satisfação do Paciente , Ritmo Teta , Adulto Jovem
6.
Clin Exp Allergy ; 48(9): 1238-1241, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29777628

RESUMO

The UK population is ageing and we can expect more referrals to allergy clinics for this age group. 16% of patients to our clinic are aged >60. Compared to younger patients, 3 times as many referrals were for angioedema. Overall, allergy was excluded in 79% of cases. 15% were diagnosed with previously unrecognised allergies, while allergic disease was confirmed in 6%, enabling optimised management. While the differential diagnosis of allergic conditions is wider in older people, assessment in the allergy clinic is helpful and adds value.


Assuntos
Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Adulto , Fatores Etários , Assistência Ambulatorial , Anafilaxia/diagnóstico , Anafilaxia/epidemiologia , Anafilaxia/imunologia , Humanos , Hipersensibilidade/diagnóstico , Vigilância em Saúde Pública , Encaminhamento e Consulta
7.
Psychooncology ; 26(4): 476-483, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27297097

RESUMO

OBJECTIVE: To compare psychosocial outcomes (follow-up related worries and satisfaction with follow-up related information and support) over 30 months of two alternative management policies for women with low-grade abnormal cervical cytology. METHODS: Women aged 20-59 years with low-grade cytological abnormalities detected in the National Health Service Cervical Screening Programme were randomised to cytological surveillance or initial colposcopy. A total of 3399 women who completed psychosocial questionnaires at recruitment were invited to complete questionnaires at 12, 18, 24 and 30 months. Linear mixed models were used to investigate differences between arms in the two psychosocial outcomes. Each outcome had a maximum score of 100, and higher scores represented higher psychosocial morbidity. RESULTS: On average, over 30 months, women randomised to colposcopy scored 2.5 points (95%CI -3.6 to -1.3) lower for follow-up related worries than women randomised to cytological surveillance. Women in the colposcopy arm also scored significantly lower for follow-up related satisfaction with information and support (-2.4; -3.3 to -1.4) over 30 months. For both outcomes, the average difference between arms was greatest at 12th- and 18th-month time points. These differences remained when the analysis was stratified by post-school education. CONCLUSIONS: Women with low-grade cytology, irrespective of their management, have substantial initial psychosocial morbidity that reduces over time. Implementation of newer screening strategies, which include surveillance, such as primary HPV screening, need to consider the information and support provided to women. © 2016 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.


Assuntos
Ansiedade/psicologia , Colposcopia/psicologia , Citodiagnóstico/psicologia , Displasia do Colo do Útero/psicologia , Neoplasias do Colo do Útero/psicologia , Adulto , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Morbidade , Inquéritos e Questionários , Neoplasias do Colo do Útero/patologia , Adulto Jovem , Displasia do Colo do Útero/patologia
8.
Dermatol Ther ; 30(4)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28598005

RESUMO

Alopecia areata (AA) is the commonest autoimmune cause of non-scarring alopecia. Topical treatments including corticosteroids and irritants maybe beneficial. Studies report variable hair regrowth with dithranol (anthralin) but all used low concentrations (0.1-1.25%) and inconsistent measurements of AA severity. We report retrospective data (2005-2014) of 102 patients who had failed ultra-potent topical steroids and were referred to a specialist hair clinic for treatment with dithranol up to 3%. The severity of alopecia areata tool was used and participants graded as mild (<25%), moderate (>25 to 75%), and severe (>75%) hair loss. Compared with baseline any and at-least 50% hair regrowth [72%, 68%, 50% and 61.5%, 48.4%, 37.5%, in mild, moderate and severe AA respectively] occurred in all groups (median treatment duration 12 months). Twenty-nine patients (28.4%) were discharged with complete regrowth; with no difference in proportions in severity groups (33.3%, 29%, and 21.9%) but in the period to discharge [7.9, 6.3, and 29.4 months (p-values <.05)] for mild, moderate, and severe AA. Treatment trials of 12 months with dithranol at higher concentrations may be an option in patients who failed potent topical or intra-lesional steroids) regardless of AA severity. Randomized trials (of less staining formulations) of dithranol are warranted.


Assuntos
Alopecia em Áreas/tratamento farmacológico , Antralina/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Administração Tópica , Relação Dose-Resposta a Droga , Feminino , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Humanos , Masculino , Estudos Retrospectivos
9.
Cytopathology ; 26(3): 178-87, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25099940

RESUMO

OBJECTIVE: Worldwide, each year, large numbers of women are referred for colposcopy following low-grade abnormal cervical cytology. Many have no visible abnormality on examination. The risk of cervical intra-epithelial neoplasia grade 2/3 (CIN2/3) in these women is low. It is unknown whether, for women, a normal colposcopy resolves the anxiety which often follows the receipt of an abnormal cytology result. We investigated the prevalence of adverse psychological outcomes over 30 months following a normal colposcopy. METHODS: This cohort study was nested within the UK TOMBOLA randomized controlled trial. Women aged 20-59 years, with recent low-grade cytology, who had a satisfactory colposcopy examination and normal transformation zone, completed the Hospital Anxiety and Depression Scale (HADS) and Process Outcome Specific Measure (POSM) at recruitment and during follow-up (12, 18, 24 and 30 months post-recruitment). Outcomes included percentages reporting significant anxiety (HADS anxiety subscale score ≥11), significant depression (HADS depression subscale score ≥8) or worries about the result of the next cytology test, cervical cancer, having sex, future fertility and general health at each time point (point prevalence) and during follow-up (cumulative prevalence). RESULTS: The study included 727 women. All psychological measures (except depression) had high prevalence at recruitment, falling substantially by 12 months. During follow-up, the cumulative prevalence of significant anxiety was 27% and significant depression was 21%. The most frequently reported worry was that the next cytology test would be abnormal (cumulative prevalence of 71%; point prevalence of ≥50% at 12 and 18 months). The cumulative prevalence values of worries about cervical cancer, having sex and future fertility were 33%, 20% and 16%, respectively. CONCLUSIONS: For some women who have low-grade cytology, a normal colposcopy does not appear to provide psychological reassurance.


Assuntos
Colposcopia/psicologia , Detecção Precoce de Câncer/psicologia , Displasia do Colo do Útero/psicologia , Adulto , Estudos de Coortes , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Uterinas/diagnóstico , Adulto Jovem
10.
Br J Cancer ; 111(3): 461-9, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-24992583

RESUMO

BACKGROUND: British 5-year survival from colorectal cancer (CRC) is below the European average, but the reasons are unclear. This study explored if longer provider delays (time from presentation to treatment) were associated with more advanced stage disease at diagnosis and poorer survival. METHODS: Data on 958 people with CRC were linked with the Scottish Cancer Registry, the Scottish Death Registry and the acute hospital discharge (SMR01) dataset. Time from first presentation in primary care to first treatment, disease stage at diagnosis and survival time from date of first presentation in primary care were determined. Logistic regression and Cox survival analyses, both with a restricted cubic spline, were used to model stage and survival, respectively, following sequential adjustment of patient and tumour factors. RESULTS: On univariate analysis, those with <4 weeks from first presentation in primary care to treatment had more advanced disease at diagnosis and the poorest prognosis. Treatment delays between 4 and 34 weeks were associated with earlier stage (with the lowest odds ratio occurring at 20 weeks) and better survival (with the lowest hazard ratio occurring at 16 weeks). Provider delays beyond 34 weeks were associated with more advanced disease at diagnosis, but not increased mortality. Following adjustment for patient, tumour factors, emergency admissions and symptoms and signs, no significant relationship between provider delay and stage at diagnosis or survival from CRC was found. CONCLUSIONS: Although allowing for a nonlinear relationship and important confounders, moderately long provider delays did not impact adversely on cancer outcomes. Delays are undesirable because they cause anxiety; this may be fuelled by government targets and health campaigns stressing the importance of very prompt cancer diagnosis. Our findings should reassure patients. They suggest that a health service's primary emphasis should be on quality and outcomes rather than on time to treatment.


Assuntos
Neoplasias Colorretais/patologia , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/terapia , Diagnóstico Tardio , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
11.
Nature ; 451(7175): 176-80, 2008 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-18075503

RESUMO

Biodegradation of crude oil in subsurface petroleum reservoirs has adversely affected the majority of the world's oil, making recovery and refining of that oil more costly. The prevalent occurrence of biodegradation in shallow subsurface petroleum reservoirs has been attributed to aerobic bacterial hydrocarbon degradation stimulated by surface recharge of oxygen-bearing meteoric waters. This hypothesis is empirically supported by the likelihood of encountering biodegraded oils at higher levels of degradation in reservoirs near the surface. More recent findings, however, suggest that anaerobic degradation processes dominate subsurface sedimentary environments, despite slow reaction kinetics and uncertainty as to the actual degradation pathways occurring in oil reservoirs. Here we use laboratory experiments in microcosms monitoring the hydrocarbon composition of degraded oils and generated gases, together with the carbon isotopic compositions of gas and oil samples taken at wellheads and a Rayleigh isotope fractionation box model, to elucidate the probable mechanisms of hydrocarbon degradation in reservoirs. We find that crude-oil hydrocarbon degradation under methanogenic conditions in the laboratory mimics the characteristic sequential removal of compound classes seen in reservoir-degraded petroleum. The initial preferential removal of n-alkanes generates close to stoichiometric amounts of methane, principally by hydrogenotrophic methanogenesis. Our data imply a common methanogenic biodegradation mechanism in subsurface degraded oil reservoirs, resulting in consistent patterns of hydrocarbon alteration, and the common association of dry gas with severely degraded oils observed worldwide. Energy recovery from oilfields in the form of methane, based on accelerating natural methanogenic biodegradation, may offer a route to economic production of difficult-to-recover energy from oilfields.


Assuntos
Metano/biossíntese , Petróleo/metabolismo , Alcanos/química , Alcanos/metabolismo , Anaerobiose , Archaea/genética , Archaea/metabolismo , Bactérias/genética , Bactérias/metabolismo , Biodegradação Ambiental , Canadá , Dióxido de Carbono/química , Dióxido de Carbono/metabolismo , Isótopos de Carbono/análise , Gases/análise , Gases/química , Gases/metabolismo , Metano/química
12.
Intern Med J ; 44(11): 1080-6, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24989694

RESUMO

BACKGROUND: Knowledge about kidney disease among the general population is poor but has not been assessed in the population selected for referral to nephrology care. AIM: This study aimed to determine patients' understanding of chronic kidney disease (CKD) when first presenting to a nephrology clinic. METHODS: Newly referred patients to a nephrology clinic were surveyed with open-ended questions about their understanding of CKD causes, symptoms and management. RESULTS: Two hundred and ten patients were surveyed. Median age was 66.5 years (interquartile range 52-77), 50.5% female and mean body mass index 29.7 ± 6.8 kg/m(2) . Prevalence of risk factors for CKD included 31% diabetic, 62% hypertension, 19% family history of CKD and 2% Aboriginal or Torres Strait Islander. CKD stage prevalence was 0 (8%), 1 (24%), 2 (11%), 3 (38.5%), 4 (18%) and 5 (0.5%). Eighty-two per cent were referred by their primary care physician and 29% had seen a nephrologist previously. Kidney Health Australia was mentioned by 2.4%. Sixteen per cent were unsure why they had been referred. CKD causes identified by patients were unsure (40%), alcohol (29%), hypertension (16%) and diabetes (14%). Symptoms identified included asymptomatic (16%), kidney pain (17%) and other (42%). Management suggested by patients was uncertain (51%), dialysis (32%) and anti-hypertensive medication (16%). Eighty-two per cent reported unsatisfactory education from their primary care physician. CONCLUSIONS: New patients referred to a renal outpatient department had poor knowledge about kidney disease. Education of patients should begin in primary care prior to referral. For most patients, education programmes need to be targeted at a simplistic level.


Assuntos
Instituições de Assistência Ambulatorial , Letramento em Saúde/métodos , Nefrologia/métodos , Encaminhamento e Consulta , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Idoso , Austrália/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto/métodos , Insuficiência Renal Crônica/terapia
13.
Diabetologia ; 56(6): 1350-5, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23475368

RESUMO

AIMS/HYPOTHESIS: Type 2 diabetes is characterised by impaired glucose-stimulated insulin secretion (GSIS) from pancreatic islets. Since erythropoietin-producing hepatoma (Eph)-ephrin bidirectional signalling fine-tunes GSIS from pancreatic beta cells, we investigated Eph receptor tyrosine kinases (RTK) as potential drug targets for selectively increasing GSIS. METHODS: Insulin secretion assays were carried out using mouse and human pancreatic islets as well as mouse insulinoma (MIN6) cells in the presence or absence of two Eph RTK inhibitors. Furthermore, the most potent inhibitor was injected into mice to evaluate its effects on glucose tolerance and plasma insulin levels. RESULTS: We showed that the Eph RTK inhibitors selectively increased GSIS from MIN6 cells as well as mouse and human islets. Our results also showed that the insulin secretory effects of these compounds required Eph-ephrin signalling. Finally, pharmacological inhibition of Eph receptor signalling improved glucose tolerance in mice. CONCLUSIONS/INTERPRETATION: We showed for the first time that Eph RTKs represent targets for small molecules to selectively increase GSIS and improve glucose tolerance.


Assuntos
Glucose/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Receptores da Família Eph/metabolismo , Animais , Benzamidas/farmacologia , Linhagem Celular , Sobrevivência Celular , Diabetes Mellitus Tipo 2/metabolismo , Eritropoetina/metabolismo , Humanos , Mesilato de Imatinib , Insulina/sangue , Secreção de Insulina , Insulinoma/metabolismo , Espectroscopia de Ressonância Magnética , Camundongos , Camundongos Transgênicos , Fosforilação , Piperazinas/farmacologia , Pirimidinas/farmacologia , Receptor EphA5/metabolismo , Receptores da Família Eph/antagonistas & inibidores
14.
Br J Cancer ; 109(6): 1618-24, 2013 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-23963148

RESUMO

BACKGROUND: Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC. METHODS: Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells. RESULTS: Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET-) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET- samples. CONCLUSION: By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques.


Assuntos
Neoplasias Colorretais/imunologia , Interpretação de Imagem Assistida por Computador/métodos , Linfócitos do Interstício Tumoral/imunologia , Reconhecimento Automatizado de Padrão/métodos , Algoritmos , Neoplasias Colorretais/patologia , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/patologia , Metástase Neoplásica , Fenótipo
15.
BJOG ; 120(9): 1133-42, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23573981

RESUMO

OBJECTIVE: To develop and evaluate a questionnaire to assess the burden of vulval intraepithelial neoplasia (VIN) in women. DESIGN: A questionnaire development study. SETTING: Vulval Disorders Clinic serving a regional population. SAMPLE: Fifty-eight women with a histological diagnosis of VIN registered with the Vulval Disorders Clinic. METHODS: A 37-item questionnaire was developed through a comprehensive literature review, consultation with specialist clinicians and pretesting to assess the burden experienced by women. The questionnaire was assessed for validity and reliability against existing questionnaires used in related disease areas. MAIN OUTCOME MEASURES: Spearman correlations were calculated between items in the VIN questionnaire with the scores of the Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS), Sabbatsberg Sexual Self-Rating Scale (SSRS) and the Process Outcome Specific Measure (POSM) to assess the new questionnaire's validity. Internal consistency was measured using Cronbach's alpha. Test-retest reliability was calculated using quadratic weighted kappa. RESULTS: The VIN questionnaire had a high degree of internal consistency (Cronbach's alpha, 0.89). Test-retest reliability was assessed, with most questions showing a quadratic weighted kappa value of 0.5 or above. Most questions showed a stronger correlation with the corrected total VIN score than with HADS anxiety and depression subscales and the SSRS, indicating discriminant validity. Most questions correlated significantly with the DLQI and POSM scores, indicating convergent validity. CONCLUSIONS: Initial assessment of the VIN questionnaire demonstrated that it is a valid and reliable measure of the burden of disease for women. The questionnaire could be used to compare new and existing treatments for VIN or to assess or monitor the impact of care.


Assuntos
Imagem Corporal/psicologia , Carcinoma in Situ/psicologia , Depressão/epidemiologia , Qualidade de Vida , Comportamento Sexual/psicologia , Inquéritos e Questionários , Neoplasias Vulvares/psicologia , Adulto , Idoso , Carcinoma in Situ/epidemiologia , Emoções , Feminino , Humanos , Pessoa de Meia-Idade , Psicometria , Reprodutibilidade dos Testes , Escócia/epidemiologia , Neoplasias Vulvares/epidemiologia
17.
Nat Food ; 4(1): 96-108, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37118582

RESUMO

Organizations are increasingly committing to biodiversity protection targets with focus on 'nature-positive' outcomes, yet examples of how to feasibly achieve these targets are needed. Here we propose an approach to achieve nature-positive targets with respect to the embodied biodiversity impacts of an organization's food consumption. We quantify these impacts using a comprehensive database of life-cycle environmental impacts from food, and map exploratory strategies to meet defined targets structured according to a mitigation and conservation hierarchy. By considering the varying needs and values across the organization's internal community, we identify a range of targeted approaches towards mitigating impacts, which balance top-down and bottom-up actions to different degrees. Delivering ambitious nature-positive targets within current constraints will be challenging, particularly given the need to mitigate cumulative impacts. Our results evidence that however committed an organization is to being nature positive in its food provision, this is unachievable in the absence of systems change.


Assuntos
Biodiversidade , Objetivos
18.
Perspect Public Health ; 143(6): 313-323, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37572038

RESUMO

AIMS: To explore existing regulatory mechanisms to restrict hot food takeaway (HFT) outlets through further understanding processes at local and national levels. METHODS: The Planning Appeals Portal was utilised to identify recent HFT appeal cases across England between December 2016 and March 2020. Eight case study sites were identified using a purposive sampling technique and interviews carried out with 12 professionals involved in planning and health to explore perceptions of and including factors that may impact on the HFT appeal process. Additionally, documents applicable to each case were analysed and a survey completed by seven Local Authority (LA) health professionals. To confirm findings, interpretation meetings were conducted with participants and a wider group of planning and public health professionals, including a representative from the Planning Inspectorate. RESULTS: Eight case study sites were identified, and 12 interviews conducted. Participants perceived that LAs would be better able to work on HFT appeal cases if professionals had a good understanding of the planning process/the application of local planning policy and supplementary planning documents; adequate time and capacity to deal with appeals cases; access to accurate, robust, and up to date information; support and commitment from elected members and senior management; good lines of communication with local groups/communities interested in the appeal; information and resources that are accessible and easy to interpret across professional groups. CONCLUSIONS: Communication across professional groups appeared to be a key factor in successfully defending decisions. Understanding the impact of takeaway outlets on health and communities in the long term was also important. To create a more robust appeals case and facilitate responsiveness, professionals involved in an appeal should know where to locate current records and statistical data. The enthusiasm of staff and support from senior management/elected officials will play a significant role in driving these agendas forward.


Assuntos
Políticas , Saúde Pública , Humanos , Inglaterra , Manipulação de Alimentos
19.
Intern Med J ; 42(8): 887-93, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22472068

RESUMO

BACKGROUND: Clinical outcomes for patients treated in public and private hospitals may be different. AIM: The aim of the study was to compare the characteristics and outcomes of patients receiving dialysis at public and private hospitals in Queensland. METHODS: Incident adult dialysis patients in Queensland registered with the Australia and New Zealand Dialysis and Transplant Registry between 1999 and 2009 were classified by dialysis modality at either a public or private hospital. Outcomes were dialysis patient characteristics and survival. RESULTS: Three thousand, three hundred and ten patients commenced dialysis in public hospitals, 1939 haemodialysis (HD) and 1371 peritoneal dialysis (PD). Seven hundred and ninety-three patients commenced dialysis in private hospitals, 757 HD and 36 PD. Compared with public HD, private HD patients were older, had more coronary artery disease and less diabetes, and were more likely to live in an urban area. Public HD patients were more likely to be obese and referred late to a nephrologist. Nearly all indigenous patients were managed in public hospitals. Private patients were more likely to have an arteriovenous fistula or graft at first HD (P < 0.001) but not after excluding late referrals (P = 0.09). Public hospitals provided longer HD sessions and more HD hours per week for all age groups except 75+ years. Compared with public hospital HD, patient survival adjusted for multiple variables was comparable for private hospital HD (hazard ratio 1.20 (95% confidence interval 0.98-1.46, P = 0.07)) but worse for public PD (hazard ratio 1.14 (95% confidence interval 1.05-1.24, P = 0.002)). CONCLUSION: Private HD patients are older and less likely to be diabetic than public patients. Patient survival is worse for public PD than public HD.


Assuntos
Hospitais Privados/tendências , Hospitais Públicos/tendências , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia , Diálise Renal/mortalidade , Diálise Renal/tendências , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Queensland/epidemiologia , Sistema de Registros , Taxa de Sobrevida/tendências
20.
Cytopathology ; 23(3): 150-60, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21366734

RESUMO

OBJECTIVE: To identify factors associated with default from follow-up cervical cytology tests. METHODS: A cohort study was conducted involving 2166 women, aged 20-59, with recent low-grade cervical cytology taken within the NHS Cervical Screening Programmes in Scotland and England, and managed by 6-monthly cytology in primary care. For the first (6-month) and second (12-month) surveillance cytology tests separately, women were categorized as 'on-time attendees' (attended ≤6 months of test being due), 'late attendees' (attended greater than 6 months after test was due) or 'non-attendees' (failed to attend). Multivariate odds ratios (ORs) were computed for factors associated with late and non-attendance. RESULTS: For the first surveillance test, risk of non-attendance was significantly higher in younger women, those without post-secondary education, and non-users of prescribed contraception. Factors significantly associated with late attendance for the first test were the same as for non-attendance, plus current smoking and having children. The most important predictor of non-attendance for the second surveillance test was late attendance for the first test (OR = 9.65; 95% CI, 6.60-16.62). Non-attendance for the second test was also significantly higher among women who were younger, smokers and had negative cytology on the first surveillance test. Late attendance for the second surveillance test was higher in women who were younger, smokers, had children and attended late for the first test. CONCLUSIONS: Women at highest risk of default from follow-up cytology tend to be young, smoke, lack post-secondary education, and have defaulted from a previous surveillance appointment. Tackling default will require development of targeted strategies to encourage attendance and research to better understand the reasons underpinning default.


Assuntos
Colo do Útero/patologia , Perda de Seguimento , Vigilância da População/métodos , Neoplasias do Colo do Útero/diagnóstico , Adulto , Fatores Etários , Atitude Frente a Saúde , Estudos de Coortes , Biologia Computacional , Detecção Precoce de Câncer/métodos , Inglaterra , Feminino , Seguimentos , Humanos , Estilo de Vida , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Escócia , Fumar/psicologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle , Adulto Jovem
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