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1.
Cell Tissue Res ; 386(1): 79-98, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34236518

RESUMO

The study of a desmoglein 2 murine model of arrhythmogenic cardiomyopathy revealed cardiac inflammation as a key early event leading to fibrosis. Arrhythmogenic cardiomyopathy (AC) is an inherited heart muscle disorder leading to ventricular arrhythmias and heart failure due to abnormalities in the cardiac desmosome. We examined how loss of desmoglein 2 (Dsg2) in the young murine heart leads to development of AC. Apoptosis was an early cellular phenotype, and RNA sequencing analysis revealed early activation of inflammatory-associated pathways in Dsg2-null (Dsg2-/-) hearts at postnatal day 14 (2 weeks) that were absent in the fibrotic heart of adult mice (10 weeks). This included upregulation of iRhom2/ADAM17 and its associated pro-inflammatory cytokines and receptors such as TNFα, IL6R and IL-6. Furthermore, genes linked to specific macrophage populations were also upregulated. This suggests cardiomyocyte stress triggers an early immune response to clear apoptotic cells allowing tissue remodelling later on in the fibrotic heart. Our analysis at the early disease stage suggests cardiac inflammation is an important response and may be one of the mechanisms responsible for AC disease progression.

2.
Clin Exp Dermatol ; 46(7): 1335-1336, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33964034
4.
BJA Educ ; 21(1): 40, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465177

RESUMO

[This corrects the article DOI: 10.1016/j.bjae.2020.07.004.].

5.
Br J Dermatol ; 183(5): 808-820, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32034956

RESUMO

BACKGROUND: Scabies is a common parasitic skin condition that causes considerable morbidity globally. Clinical and epidemiological research for scabies has been limited by a lack of standardization of diagnostic methods. OBJECTIVES: To develop consensus criteria for the diagnosis of common scabies that could be implemented in a variety of settings. METHODS: Consensus diagnostic criteria were developed through a Delphi study with international experts. Detailed recommendations were collected from the expert panel to define the criteria features and guide their implementation. These comments were then combined with a comprehensive review of the available literature and the opinion of an expanded group of international experts to develop detailed, evidence-based definitions and diagnostic methods. RESULTS: The 2020 International Alliance for the Control of Scabies (IACS) Consensus Criteria for the Diagnosis of Scabies include three levels of diagnostic certainty and eight subcategories. Confirmed scabies (level A) requires direct visualization of the mite or its products. Clinical scabies (level B) and suspected scabies (level C) rely on clinical assessment of signs and symptoms. Evidence-based, consensus methods for microscopy, visualization and clinical symptoms and signs were developed, along with a media library. CONCLUSIONS: The 2020 IACS Criteria represent a pragmatic yet robust set of diagnostic features and methods. The criteria may be implemented in a range of research, public health and clinical settings by selecting the appropriate diagnostic levels and subcategories. These criteria may provide greater consistency and standardization for scabies diagnosis. Validation studies, development of training materials and development of survey methods are now required. What is already known about this topic? The diagnosis of scabies is limited by the lack of accurate, objective tests. Microscopy of skin scrapings can confirm the diagnosis, but it is insensitive, invasive and often impractical. Diagnosis usually relies on clinical assessment, although visualization using dermoscopy is becoming increasingly common. These diagnostic methods have not been standardized, hampering the interpretation of findings from clinical research and epidemiological surveys, and the development of scabies control strategies. What does this study add? International consensus diagnostic criteria for common scabies were developed through a Delphi study with global experts. The 2020 International Alliance for the Control of Scabies (IACS) Criteria categorize diagnosis at three levels of diagnostic certainty (confirmed, clinical and suspected scabies) and eight subcategories, and can be adapted to a range of research and public health settings. Detailed definitions and figures are included to aid training and implementation. The 2020 IACS Criteria may facilitate the standardization of scabies diagnosis.


Assuntos
Escabiose , Administração Tópica , Consenso , Humanos , Escabiose/diagnóstico , Escabiose/epidemiologia , Pele
6.
Br J Dermatol ; 182(4): 837-838, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31621065
7.
Horm Behav ; 117: 104610, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31669457

RESUMO

Early-life stress exposure can confer vulnerability for development of psychiatric illnesses and impaired cognition in adulthood. It is well-known that early-life stress can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis in a sex-dependent manner. Specifically, uniparental rodent models of prolonged disrupted mother-offspring relationships (e.g., maternal separation) have demonstrated greater alterations in stress responsivity in adult males, compared to females. Also, chronic early-life stressors (e.g., limited bedding model) impair cognitive function in males more than females. However, the sex-dependent effects of early-life stress and later-life chronic HPA axis activation on cognition have not been well-characterized. Here, we utilized the biparental California mouse (Peromyscus californicus) to model the early-life adversity of paternal deprivation (PD). Fathers either remained in the nest (biparental care) or were permanently removed (PD) on postnatal day (PND) 1. Adult offspring were exposed to daily handling (control) or chronic variable stress (CVS; three stressors for seven days). Twenty-four hours after the final stressor, the novel object recognition (NOR) task commenced, followed by serum collection for corticosterone (CORT) analysis. Independent of sex or rearing, CVS increased CORT. Exploration during acquisition for the NOR task was increased as a result of CVS and PD. During NOR testing, non-stressed females exhibited greater difference scores (i.e., increased recognition memory), compared to non-stressed males. However, the addition of CVS diminished difference scores in females - an effect not observed in CVS-exposed males. Overall, these data suggest that neonatal paternal experience, sex, and chronic stress contribute to exploratory behavior, cognition, and stress hormone concentrations in a biparental species.


Assuntos
Privação Paterna , Peromyscus/fisiologia , Reconhecimento Psicológico/fisiologia , Estresse Psicológico , Animais , Cognição/fisiologia , Corticosterona/sangue , Comportamento Exploratório/fisiologia , Pai/psicologia , Feminino , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Comportamento Paterno/fisiologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Caracteres Sexuais , Estresse Psicológico/etiologia , Estresse Psicológico/fisiopatologia , Estresse Psicológico/psicologia , Fatores de Tempo
8.
9.
Epidemiol Infect ; 147: e250, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31496448

RESUMO

Currently no national guidelines exist for the management of scabies outbreaks in residential or nursing care homes for the elderly in the United Kingdom. In this setting, diagnosis and treatment of scabies outbreaks is often delayed and optimal drug treatment, environmental control measures and even outcome measures are unclear. We undertook a systematic review to establish the efficacy of outbreak management interventions and determine evidence-based recommendations. Four electronic databases were searched for relevant studies, which were assessed using a quality assessment tool drawing on STROBE guidelines to describe the quality of observational data. Nineteen outbreak reports were identified, describing both drug treatment and environmental management measures. The quality of data was poor; none reported all outcome measures and only four described symptom relief measures. We were unable to make definitive evidence-based recommendations. We draw on the results to propose a framework for data collection in future observational studies of scabies outbreaks. While high-quality randomised controlled trials are needed to determine optimal drug treatment, evidence on environmental measures will need augmentation through other literature studies. The quality assessment tool designed is a useful resource for reporting of outcome measures including patient-reported measures in future outbreaks.


Assuntos
Surtos de Doenças/prevenção & controle , Transmissão de Doença Infecciosa/prevenção & controle , Controle de Infecções/métodos , Escabiose/epidemiologia , Escabiose/prevenção & controle , Idoso , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/prevenção & controle , Infecções Comunitárias Adquiridas/terapia , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/terapia , Humanos , Casas de Saúde , Escabiose/diagnóstico , Escabiose/terapia , Reino Unido/epidemiologia
10.
BMC Dermatol ; 18(1): 11, 2018 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-30509232

RESUMO

BACKGROUND: Skin diseases are common and often have an impact on an individual's health-related quality of life. In rural communities where access to healthcare may be limited and individuals rely on farming for food and income, the impact of skin diseases may be greater. The objectives for this study were to perform an assessment of skin disease prevalence in a rural village in Laos and assess the associated impact of any skin disease found using the Dermatology Life Quality Index (DLQI). METHODS: A rural village was purposively selected and 340 participants examined by dermatologists over a four day period. Brief questionnaires were performed, followed by full body skin examinations and DLQI questionnaires completed were relevant. The data were analysed using chi square and Wilcoxon signed rank tests. RESULTS: One hundred and eighty-one participants were found to have a skin disease (53%). The six most common skin diseases were: eczema (22%), dermatophyte infections (19%), acne (10%), scabies infestation (9%), melasma (8%) and pityriasis versicolor (4%). Just over half of those with skin disease (51%) completed the DLQI, with scores ranging from 0 to 24. Those with skin problems on examination were significantly more likely to be farmers, have had a previous skin problem, be older or live in a smaller family. Conclusions This study represents the first formal documentation of skin disease prevalence in Laos and establishes the high rate of skin disease in the rural community and the associated impact these diseases have on health-related quality of life.


Assuntos
Nível de Saúde , Qualidade de Vida , População Rural/estatística & dados numéricos , Dermatopatias/epidemiologia , Acne Vulgar/epidemiologia , Acne Vulgar/psicologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bullying , Criança , Pré-Escolar , Dermatomicoses/epidemiologia , Dermatomicoses/psicologia , Eczema/epidemiologia , Eczema/psicologia , Feminino , Acesso aos Serviços de Saúde , Humanos , Lactente , Laos , Masculino , Melanose/epidemiologia , Melanose/psicologia , Pessoa de Meia-Idade , Neurodermatite/epidemiologia , Neurodermatite/psicologia , Dor , Prevalência , Prurido , Escabiose/epidemiologia , Escabiose/psicologia , Dermatopatias/psicologia , Participação Social , Inquéritos e Questionários , Tinha Versicolor/epidemiologia , Tinha Versicolor/psicologia , Adulto Jovem
11.
Equine Vet J ; 50(2): 270-272, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28727902

RESUMO

BACKGROUND: Assessment of faecal glucocorticoid metabolites (FGM) offers a noninvasive method of monitoring adrenal activity in domestic horses. Samples are collected on an opportunistic basis and, if they are not fresh or have been exposed to the elements before they are identified, may not accurately reflect FGM concentrations. OBJECTIVES: To explore the impact of a range of environmental conditions upon the integrity of FGM levels in equine faeces. STUDY DESIGN: In vitro experiment. METHOD: Equine faeces were exposed to six controlled environmental conditions intended to simulate a range of weather and seasonal patterns (temperate climate, high heat, high heat and rainfall, temperate climate and rainfall, high heat/temperate climate, freeze/thaw) over a period of 5 days. FGM were quantified using an enzyme-linked immunoassay. RESULTS: Faecal samples exposed to room temperature and high heat demonstrated significant increases in FGM levels over time. No changes in FGM levels were observed in the remaining treatments. MAIN LIMITATIONS: The study should be repeated in field conditions and with known high and low levels of FGM to further inform sampling regimes. CONCLUSIONS: Adrenal monitoring in the domestic horse should be performed with consideration of the impact of climate on the integrity of faecal samples in order to further inform sampling schedules and improve the reliability of results.


Assuntos
Fezes/química , Glucocorticoides/química , Cavalos/fisiologia , Temperatura , Animais , Glucocorticoides/metabolismo , Chuva , Fatores de Tempo
13.
Sci Rep ; 6: 25686, 2016 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-27157062

RESUMO

The residual hydrothermalism associated with submarine volcanoes, following an eruption event, plays an important role in the supply of CO2 to the ocean. The emitted CO2 increases the acidity of seawater. The submarine volcano of El Hierro, in its degasification stage, provided an excellent opportunity to study the effect of volcanic CO2 on the seawater carbonate system, the global carbon flux, and local ocean acidification. A detailed survey of the volcanic edifice was carried out using seven CTD-pH-ORP tow-yo studies, localizing the redox and acidic changes, which were used to obtain surface maps of anomalies. In order to investigate the temporal variability of the system, two CTD-pH-ORP yo-yo studies were conducted that included discrete sampling for carbonate system parameters. Meridional tow-yos were used to calculate the amount of volcanic CO2 added to the water column for each surveyed section. The inputs of CO2 along multiple sections combined with measurements of oceanic currents produced an estimated volcanic CO2 flux = 6.0 10(5) ± 1.1 10(5 )kg d(-1) which is ~0.1% of global volcanic CO2 flux. Finally, the CO2 emitted by El Hierro increases the acidity above the volcano by ~20%.

14.
Biol Lett ; 11(10)2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26510673

RESUMO

Dominant females in social species have been hypothesized to reduce the reproductive success of their subordinates by inducing elevated circulating glucocorticoid (GC) concentrations. However, this 'stress-related suppression' hypothesis has received little support in cooperatively breeding species, despite evident reproductive skews among females. We tested this hypothesis in the banded mongoose (Mungos mungo), a cooperative mammal in which multiple females conceive and carry to term in each communal breeding attempt. As predicted, lower ranked females had lower reproductive success, even among females that carried to term. While there were no rank-related differences in faecal glucocorticoid (fGC) concentrations prior to gestation or in the first trimester, lower ranked females had significantly higher fGC concentrations than higher ranked females in the second and third trimesters. Finally, females with higher fGC concentrations during the third trimester lost a greater proportion of their gestated young prior to their emergence from the burrow. Together, our results are consistent with a role for rank-related maternal stress in generating reproductive skew among females in this cooperative breeder. While studies of reproductive skew frequently consider the possibility that rank-related stress reduces the conception rates of subordinates, our findings highlight the possibility of detrimental effects on reproductive outcomes even after pregnancies have become established.


Assuntos
Glucocorticoides/análise , Herpestidae/fisiologia , Prenhez/metabolismo , Animais , Dominação-Subordinação , Fezes/química , Feminino , Gravidez , Estresse Fisiológico , Uganda
18.
Intern Med J ; 43(7): 778-83, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23611064

RESUMO

BACKGROUND: Plasma concentrations of the anticoagulant dabigatran are correlated with clinical outcomes, and are affected by renal function, intestinal P-glycoprotein (P-gp) activity and stomach acidity. AIMS: To determine the adherence to dabigatran etexilate renal dosing guidelines, the frequency of co-prescription of potentially interacting drugs in patients on dabigatran, and how these related to dabigatran dosing. METHODS: A retrospective chart review of 204 patients discharged from a tertiary hospital on dabigatran etexilate over a 12-month period. Creatinine clearance, using the Cockcroft-Gault equation, was used as the surrogate of renal function in the 86 patients where this was calculable. RESULTS: Prescribed dabigatran etexilate dose rates in relation to creatinine clearance and the manufacturer's guidelines were classified as 'standard', 'low' and 'high' in 47% (40/86), 49% (42/86) and 5% (4/86) of patients respectively. Co-prescribed drugs that potentially interact with dabigatran etexilate were present in 75% (154/204) of patients and included strong P-gp inhibitors (16%, 32/204), proton-pump inhibitors (46%, 94/204) and anti-platelet drugs (47%, 95/204). Co-prescription of strong P-gp inhibitors was associated with the prescription of 'low' dose rates relative to renal function (P = 0.025). CONCLUSIONS: Few patients were dosed excessively in relation to creatinine clearance. Around 50% was prescribed with 'low' dose rates in relation to creatinine clearance, which because of the association with co-prescription of strong P-gp inhibitors may be clinically appropriate. Most patients were co-prescribed with drugs that potentially interact with dabigatran etexilate.


Assuntos
Benzimidazóis/administração & dosagem , Rim/fisiologia , Pró-Fármacos/administração & dosagem , Piridinas/administração & dosagem , Centros de Atenção Terciária , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzimidazóis/metabolismo , Dabigatrana , Interações Medicamentosas/fisiologia , Feminino , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Pró-Fármacos/metabolismo , Piridinas/metabolismo , Estudos Retrospectivos
19.
Br J Dermatol ; 167(1): 29-35, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22348338

RESUMO

BACKGROUND: Leprosy is complicated by immunological reactions which can occur before, during and after successful completion of multidrug therapy. Genetic studies have suggested that polymorphisms in toll-like receptors (TLRs) may affect the susceptibility of an individual with leprosy to developing Type 1 reactions. OBJECTIVES: To examine the gene and protein expression of TLRs in the cutaneous lesions of leprosy Type 1 reactions at the onset of reaction and during systemic corticosteroid therapy. METHODS: Patients who were being treated for leprosy type 1 reactions with corticosteroids as part of a randomized controlled trial of corticosteroid treatment had skin biopsies performed before, during and at the end of treatment. The gene and protein expression of TLR2 and TLR4 were measured. RESULTS: We have demonstrated that the gene hARP-P0 is a suitable control gene for TLR gene expression studies in this population. The gene and protein expression of TLR2 and TLR4 were both reduced significantly during corticosteroid treatment. CONCLUSIONS: This is the first study to examine the expression of TLR2 and TLR4 in vivo in individuals experiencing leprosy Type 1 reactions. The data support the possibility of an important role for TLR2 and TLR4 in the pathogenesis of this important complication of leprosy.


Assuntos
Glucocorticoides/uso terapêutico , Hanseníase/tratamento farmacológico , Receptor 2 Toll-Like/fisiologia , Receptor 4 Toll-Like/fisiologia , Adolescente , Adulto , Análise de Variância , Antibióticos Antituberculose/uso terapêutico , DNA Complementar/biossíntese , Quimioterapia Combinada , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Hanseníase/genética , Hanseníase/mortalidade , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Prednisolona/uso terapêutico , Receptor 2 Toll-Like/efeitos dos fármacos , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 4 Toll-Like/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Adulto Jovem
20.
Clin Exp Dermatol ; 37(3): 219-26, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22277060

RESUMO

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.


Assuntos
Dermatopatias/radioterapia , Terapia Ultravioleta/métodos , Acesso aos Serviços de Saúde , Humanos , Terapia Ultravioleta/efeitos adversos , Reino Unido
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