Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 518
Filtrar
Mais filtros

Tipo de documento
Intervalo de ano de publicação
1.
BMC Public Health ; 22(1): 1453, 2022 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-35908051

RESUMO

BACKGROUND: One in three women experience sexual violence during their lifetime; however, little is known about this phenomenon with respect to justice-involved Latina mothers. Using the reproductive justice framework as a theoretical lens, we examined sexual violence in Latina mothers who had experienced incarceration and were thus involved in the justice system. METHODS: This was a secondary analysis of a qualitative data set. The reproductive justice framework provided a theoretical lens for examining the women's rights to bodily autonomy, to have or not have children, and to live in safe, sustainable environments given the intersection of incarceration and sexual violence. RESULTS: Women (N = 12) recounted their experiences of sexual violence after having been incarcerated. Incarceration and resulting sexual violence led to discrimination, limited bodily autonomy, sexual exploitation, substance use, depression, anxiety, re-traumatization, recidivism, underreporting of violence, underutilization of healthcare resources, strained relationships, family separation, and unsafe environments. CONCLUSIONS: More research is needed to understand the social, economic, and political contexts that perpetuate sexual violence among justice-involved women. Universal healthcare, participatory research, changing cultural mindsets, decriminalization of sex work, and more comprehensive tracking and prosecution of sexual predators may be key to ending sexual violence in justice-involved mothers.


Assuntos
Delitos Sexuais , Criança , Feminino , Hispânico ou Latino , Humanos , Mães , Violência , Direitos da Mulher
2.
J Eur Acad Dermatol Venereol ; 35(7): 1519-1527, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33630379

RESUMO

BACKGROUND: Pathologists sometimes disagree over the histopathologic diagnosis of melanoma. 'Over-calling' and 'under-calling' of melanoma may harm individuals and healthcare systems. OBJECTIVES: To estimate the extent of 'over-calling' and 'under-calling' of melanoma for a population undergoing one excision per person and to model the impact of potential solutions. METHODS: In this epidemiological modelling study, we undertook simulations using published data on the prevalence and diagnostic accuracy of melanocytic histopathology in the U.S. POPULATION: We simulated results for 10 000 patients each undergoing excision of one melanocytic lesion, interpreted by one community pathologist. We repeated the simulation using a hypothetical intervention that improves diagnostic agreement between community pathologist and a specialist dermatopathologist. We then evaluated four scenarios for how melanocytic lesions judged to be neither clearly benign (post-test probability of melanoma < 5%), nor clearly malignant (post-test probability of melanoma > 90%) might be handled, before sending for expert dermatopathologist review to decide the final diagnosis. These were (1) no intervention before expert review, (2) formal second community pathologist review, (3) intervention to increase diagnostic agreement and (4) both the intervention and formal second community pathologist review. The main outcomes were the probability of 'over-calling' and 'under-calling' melanoma, and number of lesions requiring expert referral for each scenario. RESULTS: For 10 000 individuals undergoing excision of one melanocytic lesion, interpreted by a community pathologist, a hypothetical intervention to improve histopathology agreement reduced the number of benign lesions 'over-called' as melanoma from 308 to 164 and the number of melanomas 'under-called' from 289 to 240. If all uncertain diagnoses were sent for expert review, the number of referrals would decrease from 1500 to 737 cases if formal second community pathologist review was used, and to 701 cases if the hypothetical intervention was additionally used. CONCLUSIONS: Interventions to improve histopathology agreement may reduce melanoma 'over-calling' and 'under-calling'.


Assuntos
Melanoma , Neoplasias Cutâneas , Diagnóstico Diferencial , Humanos , Melanócitos , Melanoma/diagnóstico , Melanoma/epidemiologia , Encaminhamento e Consulta , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/epidemiologia
3.
Cardiol Young ; 29(9): 1127-1136, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31414980

RESUMO

INTRODUCTION: Although chylothorax is an uncommon complication following paediatric cardiothoracic surgery, it has significant associated morbidities and increased in-hospital mortality, as well as results in higher costs. A lack of prospective evidence or consensus guidelines for management of chylothorax further hinders optimal management. The aim of this survey was to characterise variations in practice in the management of chylothorax and to identify areas for future research. MATERIALS AND METHODS: A descriptive, observational survey investigating conservative management practices of chylothorax was distributed internationally to health-care professionals in paediatric intensive care and cardiology units. The survey investigated five domains: the first providing general information about health-care professionals and four domains focusing on clinical practice including diet composition and duration. RESULTS: In total, sixty-four health-care professionals completed the survey, representing 38 organisations from 16 countries. The respondents were dietitians (80%), physicians (19%), and nurses (1%). In Australia and New Zealand, management was most commonly directed by physicians' preference (67%) as compared to unit protocols in Europe (67%), United States of America (67%), and Other regions (55%). Dietitians in Australia/New Zealand, United Kingdom, and Ireland followed the most restrictive diet therapy recommending <5 g long chain triglyceride fat per day (p < 0.00001). The duration of diet therapy significantly varied between regions: Australia/New Zealand: 4 weeks (36%) and 6 weeks (43%); Europe: 4 weeks (25%) and 6 weeks (57%); and North America: 4 weeks (18%) and 6 weeks (75%) (p < 0.00001). CONCLUSIONS: This survey highlights international variations in practice in the management of chylothorax, particularly with respect to treatment duration and dietary fat restriction. Future research should include a multi-centre randomised controlled trial to inform evidence-based practice and reduce morbidity, particularly poor growth.


Assuntos
Quilotórax/terapia , Tratamento Conservador/métodos , Dieta com Restrição de Gorduras/métodos , Gerenciamento Clínico , Inquéritos Nutricionais/métodos , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Pré-Escolar , Quilotórax/epidemiologia , Estudos Transversais , Saúde Global , Humanos , Lactente , Morbidade/tendências , Guias de Prática Clínica como Assunto , Estudos Prospectivos
4.
Diabet Med ; 35(10): 1440-1447, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29873107

RESUMO

AIM: To compare systematically the impact of two novel insulin-dosing algorithms (the Pankowska Equation and the Food Insulin Index) with carbohydrate counting on postprandial glucose excursions following a high fat and a high protein meal. METHODS: A randomized, crossover trial at two Paediatric Diabetes centres was conducted. On each day, participants consumed a high protein or high fat meal with similar carbohydrate amounts. Insulin was delivered according to carbohydrate counting, the Pankowska Equation or the Food Insulin Index. Subjects fasted for 5 h following the test meal and physical activity was standardized. Postprandial glycaemia was measured for 300 min using continuous glucose monitoring. RESULTS: 33 children participated in the study. When compared to carbohydrate counting, the Pankowska Equation resulted in lower glycaemic excursion for 90-240 min after the high protein meal (p < 0.05) and lower peak glycaemic excursion (p < 0.05). The risk of hypoglycaemia was significantly lower for carbohydrate counting and the Food Insulin Index compared to the Pankowska Equation (OR 0.76 carbohydrate counting vs. the Pankowska Equation and 0.81 the Food Insulin Index vs. the Pankowska Equation). There was no significant difference in glycaemic excursions when carbohydrate counting was compared to the Food Insulin Index. CONCLUSION: The Pankowska Equation resulted in reduced postprandial hyperglycaemia at the expense of an increase in hypoglycaemia. There were no significant differences when carbohydrate counting was compared to the Food Insulin Index. Further research is required to optimize prandial insulin dosing.


Assuntos
Algoritmos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Insulina/administração & dosagem , Refeições , Adolescente , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hiperglicemia/sangue , Hiperglicemia/prevenção & controle , Sistemas de Infusão de Insulina , Masculino
5.
Osteoarthritis Cartilage ; 25(3): 426-434, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27621213

RESUMO

OBJECTIVE: The purpose of this study was to determine if serum microRNA (miRNA) signatures were biomarkers of early cartilage degeneration in preclinical mouse models of post-traumatic osteoarthritis (OA) and inflammatory arthritis. METHODS: Cartilage degeneration was induced in 10-12 week old male C57BL6 mice by destabilization of the medial meniscus (DMM) or intra-articular injection of methylated-bovine-serum-albumin (AIA), with sham-operated or saline-injected control animals (n = 6/treatment/time). Total serum RNA and knee joints were isolated at 1, 4 and 16 weeks post-induction. Cartilage degeneration was scored histologically. Serum miRNA expression profiling was performed using Agilent microarrays and validated by qPCR. RESULTS: DMM-operated and AIA mice had characteristic cartilage degeneration (proteoglycan loss, chondrocyte hypertrophy, structural damage), that increased significantly with time compared with controls, and with distinct temporal differences between arthritis models. However, expression profiling revealed no statistically significant dysregulation of serum miRNAs between AIA vs saline-injected or DMM vs sham-operated control mice at the critical early disease stages. The inability to detect DMM or AIA serum miRNA signatures compared with controls was not due to the insensitivity of the expression profiling approach since significant changes were observed in miRNA expression between the arthritis models and between time points. CONCLUSION: While distinct patterns of progressive cartilage degradation were induced in the arthritis models, we were unable to identify any serum miRNAs that were significantly dysregulated in early stages of disease compared with controls. This suggests circulating serum miRNAs may not be useful as cartilage biomarkers in distinguishing the early or progressive stages of arthritis cartilage degeneration.


Assuntos
Cartilagem/patologia , Modelos Animais de Doenças , MicroRNAs/sangue , Osteoartrite/sangue , Animais , Biomarcadores/sangue , Masculino , Camundongos Endogâmicos C57BL , Osteoartrite/etiologia , Osteoartrite/patologia , Reação em Cadeia da Polimerase
6.
Br J Dermatol ; 177(5): 1285-1292, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28653324

RESUMO

BACKGROUND: Verrucae are a common foot skin pathology, which can in some cases persist for many years. Plantar verrucae can be unsightly and painful. There are a range of treatment options including needling. OBJECTIVES: The EVerT2 (Effective Verruca Treatments 2) trial aimed to evaluate the clinical and cost-effectiveness of the needling procedure for the treatment of plantar verrucae, relative to callus debridement. METHODS: This single-centre randomized controlled trial recruited 60 participants (aged ≥ 18 years with a plantar verruca). Participants were randomized 1 : 1 to the intervention group (needling) or the control group (debridement of the overlying callus). The primary outcome was clearance of the index verruca at 12 weeks after randomization. Secondary outcomes included recurrence of the verruca, clearance of all verrucae, number of verrucae, size of the index verruca, pain and participant satisfaction at 12 and 24 weeks. A cost-effectiveness analysis was carried out from the National Health Service perspective over 12 weeks. RESULTS: Sixty eligible patients were randomized (needling group n = 29, 48%; debridement group n = 31, 52%) and 53 were included in the primary analysis (needling n = 28, 97%; debridement n = 25, 81%). Clearance of the index verruca occurred in eight (15%) participants (needling n = 4, 14%; debridement n = 4, 16%; P = 0·86). The needling intervention costs were on average £14·33 (95% confidence interval 5·32-23·35) more per patient than for debridement. CONCLUSIONS: There is no evidence that the needling technique is more clinically or cost-effective than callus debridement. The results show a significant improvement in pain outcomes after needling compared with the debridement treatment alone.


Assuntos
Desbridamento/métodos , Dermatoses do Pé/terapia , Verrugas/terapia , Adulto , Idoso , Análise Custo-Benefício , Desbridamento/economia , Desbridamento/psicologia , Feminino , Dermatoses do Pé/economia , Dermatoses do Pé/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/etiologia , Agulhas , Satisfação do Paciente , Resultado do Tratamento , Verrugas/economia , Verrugas/psicologia , Adulto Jovem
7.
Eur Spine J ; 26(1): 189-199, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26321003

RESUMO

BACKGROUND CONTEXT: Various modifications to standard "rigid" anterior cervical plate designs (constrained plate) have been developed that allow for some degree of axial translation and/or rotation of the plate (semi-constrained plate)-theoretically promoting proper load sharing with the graft and improved fusion rates. However, previous studies about rigid and dynamic plates have not examined the influence of simulated muscle loading. PURPOSE: The objective of this study was to compare rigid, translating, and rotating plates for single-level corpectomy procedures using a robot testing system with follower load. STUDY DESIGN: In-vitro biomechanical test. METHODS: N = 15 fresh-frozen human (C3-7) cervical specimens were biomechanically tested. The follower load was applied to the specimens at the neutral position from 0 to 100 N. Specimens were randomized into a rigid plate group, a translating plate group and a rotating plate group and then tested in flexion, extension, lateral bending and axial rotation to a pure moment target of 2.0 Nm under 100N of follower load. Range of motion, load sharing, and adjacent level effects were analyzed using a repeated measures analysis of variance (ANOVA). RESULTS: No significant differences were observed between the translating plate and the rigid plate on load sharing at neutral position and C4-6 ROM, but the translating plate was able to maintain load through the graft at a desired level during flexion. The rotating plate shared less load than rigid and translating plates in the neutral position, but cannot maintain the graft load during flexion. CONCLUSIONS: This study demonstrated that, in the presence of simulated muscle loading (follower load), the translating plate demonstrated superior performance for load sharing compared to the rigid and rotating plates.


Assuntos
Placas Ósseas , Vértebras Cervicais/fisiologia , Vértebras Cervicais/cirurgia , Teste de Materiais , Suporte de Carga/fisiologia , Humanos , Pessoa de Meia-Idade , Amplitude de Movimento Articular/fisiologia , Robótica , Rotação
8.
J Fish Dis ; 40(9): 1141-1153, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28026008

RESUMO

Carp (Cyprinus carpio L.) is a pest species in Australian waterways, and cyprinid herpesvirus 3 (CyHV-3) is being considered as a potential biological control (biocontrol) agent. An important consideration for any such agent is its target specificity. In this study, the susceptibility to CyHV-3 of a range of non-target species (NTS) was tested. The NTS were as follows: 13 native Australian, and one introduced, fish species; a lamprey species; a crustacean; two native amphibian species (tadpole and mature stages); two native reptilian species; chickens; and laboratory mice. Animals were exposed to 100-1000 times the approximate minimum amount of CyHV-3 required to cause disease in carp by intraperitoneal and/or bath challenge, and then examined clinically each day over the course of 28 days post-challenge. There were no clinical signs, mortalities or histological evidence consistent with a viral infection in a wide taxonomic range of NTS. Furthermore, there was no molecular evidence of infection with CyHV-3, and, in particular, all RT-PCRs for viral mRNA were negative. As a consequence, the results encourage further investigation of CyHV-3 as a potential biocontrol agent that is specific for carp.


Assuntos
Agentes de Controle Biológico/toxicidade , Carpas , Doenças dos Peixes/virologia , Infecções por Herpesviridae/veterinária , Controle Biológico de Vetores/métodos , Animais , Austrália , Crustáceos/virologia , Suscetibilidade a Doenças/veterinária , Relação Dose-Resposta a Droga , Peixes/virologia , Herpesviridae/fisiologia , Infecções por Herpesviridae/virologia , Injeções Intraperitoneais , Espécies Introduzidas , RNA Viral/análise , Reação em Cadeia da Polimerase em Tempo Real/veterinária , Vertebrados/virologia
9.
Public Health ; 148: 13-18, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28404528

RESUMO

OBJECTIVES: This paper presents findings of a qualitative study of older people's use of alcohol during retirement and identifies ways that an improved understanding of older people's drinking can inform policy approaches to alcohol and active and healthy ageing. STUDY DESIGN: Qualitative semi-structured interviews conducted with a self-selecting sample of retired people. METHODS: Participants were recruited from three geographical locations in the West of Scotland. A quota sampling design was used to ensure a broad spread of participants in terms of socio-economic position, age and gender. In total 40 participants were interviewed and the data analysed thematically using Braun and Clarke's (2006) approach. RESULTS: Amongst those who used alcohol, it was most often framed in terms of pleasure, relaxation, socialising and as a way to mark the passage of time. Alcohol was often associated with social occasions and interactions both in private and in public spaces. There were also many examples of the use of imposed routines to limit alcohol use and of a decreasing volume of alcohol being consumed as participants aged. This suggests that older people are often active in constructing what they regard as 'healthier' routines around alcohol use. However, processes and circumstances associated with ageing can lead to risk of social isolation and/or increased alcohol consumption. Such processes include retirement from paid work and other 'biographical disruptions' such as caring for a partner, bereavement and/or loss of social networks. CONCLUSIONS: These findings highlight processes that can result in changes in drinking habits and routines. Whilst these processes can be associated with a reduction or cessation of alcohol use as people age, they can also be associated with increased risk of harmful alcohol consumption. Fractured or disrupted routines, particularly those associated with bereavement or the burden of caring responsibilities, through increasing the risk of loneliness and isolation, can construct increased risk of harmful alcohol consumption. These findings reframe the pathway of risk between ageing and alcohol-related harm by highlighting the vulnerability to harmful drinking practices brought by fracture or sudden change of routine. The findings point to a role for public health in supporting the reconstruction of routines that provide structure and meaning and can be used to actively manage the benefits and harms associated with drinking.


Assuntos
Envelhecimento/psicologia , Consumo de Bebidas Alcoólicas/psicologia , Política de Saúde , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Aposentadoria , Escócia
10.
Parasite Immunol ; 38(6): 340-51, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27059010

RESUMO

ES-62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)-induced airway hyper-responsiveness in mice by virtue of covalently attached anti-inflammatory phosphorylcholine (PC) residues. We have recently generated a library of small molecule analogues (SMAs) of ES-62 based around its active PC moiety as a starting point in novel drug development for asthma and identified two compounds - termed 11a and 12b - that mirror ES-62's protective effects. In this study, we have moved away from OVA, a model allergen, to test the SMAs against two clinically relevant allergens - house dust mite (HDM) and cockroach allergen (CR) extract. We show that both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, whereas only SMA 12b is effective in protecting against eosinophil-dependent HDM-induced allergy. These data therefore suggest that helminth molecule-induced protection against model allergens may not necessarily translate to clinically relevant allergens. Nevertheless, in this study, we have managed to demonstrate that it is possible to produce synthetic drug-like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans.


Assuntos
Acanthocheilonema/química , Alérgenos/imunologia , Proteínas de Helminto/imunologia , Fatores Imunológicos/imunologia , Hipersensibilidade Respiratória/prevenção & controle , Acanthocheilonema/imunologia , Animais , Baratas/química , Baratas/imunologia , Feminino , Proteínas de Helminto/administração & dosagem , Proteínas de Helminto/genética , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/genética , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pyroglyphidae/química , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/imunologia
11.
J Head Trauma Rehabil ; 31(2): 147-57, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26959668

RESUMO

OBJECTIVE: Evaluate sleep quality, its correlates, and the effect of telephone-based problem-solving treatment (PST) in active duty postdeployment service members with mild traumatic brain injury (mTBI) SETTING:: Randomized clinical trial. PARTICIPANTS: Active duty service members with combat-related mTBI. STUDY DESIGN: Education-only (EO) and PST groups (N = 178 each) received printed study materials and 12 educational brochures. The PST group additionally received up to 12 PST telephone calls addressing participant-selected issues. Outcomes were evaluated postintervention (6 months) and at 12 months. MAIN MEASURE: Pittsburgh Sleep Quality Index. RESULTS: Sleep quality was manifestly poor in both groups at baseline (Pittsburgh Sleep Quality Index = 12.5 ± 4). Overall sleep quality was significantly different between the PST and EO groups at 6 months (P = .003) but not at 12 months. Longitudinally, PST significantly improved sleep quality at 6 months (P = .001) but not over the follow-up. Low sleep quality was associated with concussion symptoms, pain, depression, and posttraumatic stress disorder at all time points (P < .0001). CONCLUSIONS: Sleep disorders, common in postdeployment service members with mTBI, are strongly associated with the presence of pain, posttraumatic stress disorder, and depression. Telephone-based PST may be an effective therapeutic approach for reducing sleep disorders in this population. Research should focus on maintenance of treatment gains.


Assuntos
Concussão Encefálica/psicologia , Concussão Encefálica/reabilitação , Militares , Resolução de Problemas , Transtornos do Sono-Vigília/terapia , Telemedicina , Adulto , Concussão Encefálica/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Sono-Vigília/etiologia , Transtornos de Estresse Pós-Traumáticos/etiologia , Transtornos de Estresse Pós-Traumáticos/terapia , Telefone , Adulto Jovem
13.
Osteoarthritis Cartilage ; 23(4): 661-70, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25600960

RESUMO

OBJECTIVE: To investigate the in vivo role of the IRE1/XBP1 unfolded protein response (UPR) signaling pathway in cartilage. DESIGN: Xbp1(flox/flox).Col2a1-Cre mice (Xbp1(CartΔEx2)), in which XBP1 activity is ablated specifically from cartilage, were analyzed histomorphometrically by Alizarin red/Alcian blue skeletal preparations and X-rays to examine overall bone growth, histological stains to measure growth plate zone length, chondrocyte organization, and mineralization, and immunofluorescence for collagen II, collagen X, and IHH. Bromodeoxyuridine (BrdU) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were used to measure chondrocyte proliferation and cell death, respectively. Chondrocyte cultures and microdissected growth plate zones were analyzed for expression profiling of chondrocyte proliferation or endoplasmic reticulum (ER) stress markers by Quantitative PCR (qPCR), and of Xbp1 mRNA splicing by RT-PCR to monitor IRE1 activation. RESULTS: Xbp1(CartΔEx2) displayed a chondrodysplasia involving dysregulated chondrocyte proliferation, growth plate hypertrophic zone shortening, and IRE1 hyperactivation in chondrocytes. Deposition of collagens II and X in the Xbp1(CartΔEx2) growth plate cartilage indicated that XBP1 is not required for matrix protein deposition or chondrocyte hypertrophy. Analyses of mid-gestation long bones revealed delayed ossification in Xbp1(CartΔEx2) embryos. The rate of chondrocyte cell death was not significantly altered, and only minimal alterations in the expression of key markers of chondrocyte proliferation were observed in the Xbp1(CartΔEx2) growth plate. IRE1 hyperactivation occurred in Xbp1(CartΔEx2) chondrocytes but was not sufficient to induce regulated IRE1-dependent decay (RIDD) or a classical UPR. CONCLUSION: Our work suggests roles for XBP1 in regulating chondrocyte proliferation and the timing of mineralization during endochondral ossification, findings which have implications for both skeletal development and disease.


Assuntos
Calcificação Fisiológica/fisiologia , Cartilagem Articular/patologia , Condrócitos/patologia , Proteínas de Ligação a DNA/genética , Deleção de Genes , Osteocondrodisplasias/patologia , Transdução de Sinais/fisiologia , Fatores de Transcrição/genética , Animais , Apoptose/fisiologia , Cartilagem Articular/fisiopatologia , Proliferação de Células/fisiologia , Proteínas de Ligação a DNA/fisiologia , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/fisiologia , Lâmina de Crescimento/patologia , Lâmina de Crescimento/fisiopatologia , Proteínas de Membrana/genética , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Transgênicos , Osteocondrodisplasias/fisiopatologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/fisiologia , Fatores de Transcrição de Fator Regulador X , Transdução de Sinais/genética , Fatores de Transcrição/fisiologia , Proteína 1 de Ligação a X-Box
15.
J Pharmacol Sci ; 127(3): 298-304, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25837926

RESUMO

The pathogenesis of glaucoma, a common neurodegenerative disease, involves an immunologic component. Changes in the natural autoantibody profile of glaucoma patients were detected, showing not only up-regulated but also down-regulated immunoreactivities. In recent studies we were able to demonstrate that the antibody changes have a large influence on protein profiles of neuroretinal cells. Furthermore we could demonstrate neuroprotective potential of one of the down-regulated antibodies (γ-synuclein antibody). Anti-GFAP antibody is another antibody found down-regulated in glaucoma patients. Since GFAP expression is intensified in glaucomatous retina, the aim of this study was to detect the effect of GFAP antibodies on neuroretinal cells. This is realized with a viability-test as well as proteomic analysis of cells incubated with GFAP antibodies. Furthermore, possible interaction partners of the GFAP antibody in neuroretinal cells were identified by western blot, mass spectrometry and indirect immunofluorescence staining. We found that the GFAP antibody is able to protect cells from oxidative stress, which is due to changed protein expressions of the actin cytoskeleton. Furthermore we detected a cross-reaction of the antibody to endoplasmic reticulum resident protein 57 on the cell membrane, which seems to lead to a changed signaling in the cells triggering the protective effects.


Assuntos
Autoanticorpos/fisiologia , Glaucoma/genética , Glaucoma/imunologia , Proteína Glial Fibrilar Ácida/imunologia , Estresse Oxidativo , Isomerases de Dissulfetos de Proteínas/imunologia , Células Ganglionares da Retina/imunologia , Citoesqueleto de Actina/genética , Citoesqueleto de Actina/metabolismo , Autoimunidade , Células Cultivadas , Reações Cruzadas , Regulação para Baixo , Proteínas do Olho/metabolismo , Humanos , Isomerases de Dissulfetos de Proteínas/genética
16.
Breast Cancer Res Treat ; 146(2): 447-50, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24916180

RESUMO

To report on a highly unusual case of a 20-year-old woman who presented with multifocal metaplastic breast cancer and was subsequently found to carry deleterious germline mutations in both BRCA1 and p53. Genetic testing was requested on an expedited basis to assist in surgical decision-making and BRCA1/2 and p53 genetic analysis was ordered concurrently. BRCA1/2 and p53 analyses were completed using a combination of direct DNA sequencing and multiplex ligation probe amplification (MLPA). The patient was found to carry a deletion of exon 3 of the BRCA1 gene and a splice site mutation at the exon4/intron4 boundary of the p53 gene. To our knowledge, this is the first report of double heterozygosity in BRCA1 and p53. The patient's clinical presentation is highly reminiscent of that predicted by preclinical mouse models. In patients with early onset breast cancer, the possibility of germline mutations in more than one cancer susceptibility gene should be considered. This could have important clinical implications for patients and their at-risk family members.


Assuntos
Neoplasias da Mama/genética , Genes BRCA1 , Genes BRCA2 , Genes p53 , Mutação em Linhagem Germinativa , Heterozigoto , Adulto , Idade de Início , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Aconselhamento Genético , Testes Genéticos , Humanos , Resultado do Tratamento , Adulto Jovem
17.
Heredity (Edinb) ; 113(3): 185-94, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24781803

RESUMO

Increasing data have supported the importance of divergence with gene flow (DGF) in the generation of biological diversity. In such cases, lineage divergence occurs on a shorter timescale than does the completion of reproductive isolation. Although it is critical to explore the mechanisms driving divergence and preventing homogenization by hybridization, it is equally important to document cases of DGF in nature. Here we synthesize data that have accumulated over the last dozen or so years on DGF in the chipmunk (Tamias) radiation with new data that quantify very high rates of mitochondrial DNA (mtDNA) introgression among para- and sympatric species in the T. quadrivittatus group in the central and southern Rocky Mountains. These new data (188 cytochrome b sequences) bring the total number of sequences up to 1871; roughly 16% (298) of the chipmunks we have sequenced exhibit introgressed mtDNA. This includes ongoing introgression between subspecies and between both closely related and distantly related taxa. In addition, we have identified several taxa that are apparently fixed for ancient introgressions and in which there is no evidence of ongoing introgression. A recurrent observation is that these introgressions occur between ecologically and morphologically diverged, sometimes non-sister taxa that engage in well-documented niche partitioning. Thus, the chipmunk radiation in western North America represents an excellent mammalian example of speciation in the face of recurrent gene flow among lineages and where biogeography, habitat differentiation and mating systems suggest important roles for both ecological and sexual selection.


Assuntos
Fluxo Gênico/genética , Sciuridae/genética , Animais , DNA Mitocondrial/genética , Ecologia/métodos , Ecossistema , Especiação Genética , América do Norte , Filogenia , Isolamento Reprodutivo
19.
J Hum Nutr Diet ; 26(2): 182-90, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23336961

RESUMO

BACKGROUND: The present study describes the development of evidence-based practice guidelines for the nutritional management of adult patients with head and neck cancer using a wiki platform to enable wide international stakeholder consultation and maintain currency. METHODS: A dietitian steering committee and a multidisciplinary steering committee were established for consultation. Traditional methods of evidence-based guideline development were utilised to perform the literature review, assess the evidence and produce a draft document. This was transferred to a wiki platform for stakeholder consultation and international endorsement processes in Australia, New Zealand and the UK. Data were collected on website traffic utilising Google Analytics. RESULTS: In addition to broad stakeholder consultation through the steering committees, an additional twenty comments were received via the wiki by twelve individuals covering six different professions from three different countries, compared to four comments by e-mail. The guidelines were subsequently endorsed by the dietetic associations of Australia, New Zealand and the UK. During a 4-month period monitoring the use of the guidelines, there were 2303 page views to the landing page from 33 countries. The average number of pages accessed per visit was five and the duration of time spent on the website was approximately 6 min. CONCLUSIONS: Using a wiki platform for guideline development and dissemination is a successful method for producing high-quality resources that can undergo wide international stakeholder review and include open public consultation. This can replace conventional methods whereby guidelines can quickly become outdated.


Assuntos
Medicina Baseada em Evidências , Neoplasias de Cabeça e Pescoço/terapia , Promoção da Saúde , Desnutrição/prevenção & controle , Política Nutricional , Apoio Nutricional/normas , Guias de Prática Clínica como Assunto , Adulto , Austrália , Pesquisa Biomédica/tendências , Consenso , Dietética/tendências , Neoplasias de Cabeça e Pescoço/complicações , Humanos , Disseminação de Informação , Cooperação Internacional , Internet , Desnutrição/complicações , Nova Zelândia , Apoio Nutricional/tendências , Sociedades Científicas , Fatores de Tempo , Reino Unido
20.
Knee Surg Sports Traumatol Arthrosc ; 21(4): 839-45, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22527415

RESUMO

PURPOSE: This study examined the change in femoral stress caused by graft tunnels drilled for anterior cruciate ligament (ACL) reconstruction. Using a computational model, the number, geometry and position of the graft tunnels exits were varied to determine the effect on bone stress. METHODS: A finite element model of the distal femur was developed from a CT scan of a cadaveric knee. To assess the model, the strain calculated computationally was compared to experimentally measured strains in eleven unpaired human cadaver femurs. Using the computational model, the number, geometry and position of the graft tunnel exits were varied to determine the effect on bone stress based on the stress concentration factor: the ratio of bone stress with tunnels to intact bone stress. RESULTS: The results indicated that the second tunnel in double-bundle ACL reconstruction results in approximately a 20 % increase in the maximum femoral stress as compared to single-bundle reconstruction. The highest stresses occur at the tunnel exits. The position of the tunnel exits effects femoral stress with the stress increasing slightly (AM SCR from 0.7 to 1 and PL SCR from 1.2 to 1.3) when the AM tunnel exit is moved anteriorly and having greater increases as the posterior lateral (PL) tunnel exit is moved laterally (PL SCR from 1.2 to 1.7) or posteriorly (PL SCR from 1.2 to 2). CONCLUSION: In anatomical ACL reconstruction, the tunnel entrances are dictated by anatomy; however, there can be variations in tunnel exit positions. Consideration should be given when positioning tunnel exits on the effect on stress in the femur. Moving the PL tunnel exit laterally or posteriorly increases in the stress at the PL tunnel exit.


Assuntos
Reconstrução do Ligamento Cruzado Anterior/métodos , Fêmur/fisiologia , Fêmur/cirurgia , Estresse Mecânico , Adulto , Ligamento Cruzado Anterior/cirurgia , Cadáver , Feminino , Fêmur/diagnóstico por imagem , Análise de Elementos Finitos , Humanos , Modelos Lineares , Modelos Biológicos , Tomografia Computadorizada por Raios X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA