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1.
Am J Med Genet A ; 194(7): e63603, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38511620

RESUMO

There is an emerging body of evidence showing that young patients, post haematopoietic stem cell transplantation (HSCT), can develop skeletal changes that mimic an osteochondrodysplasia process. The key discriminator is that these children have had otherwise normal growth and skeletal development before the therapeutic intervention (HSCT), typically for a haematological malignancy. Herein we present that case of a boy who underwent HSCT for Haemophagocytic Lymphohistiocytosis (HLH) aged 2 years. Following Intervention with HSCT this boy's growth has severely decelerated (stature less than 1st centile matched for age) and he has developed a spondyloepiphyseal dysplasia.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfo-Histiocitose Hemofagocítica , Osteocondrodisplasias , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Masculino , Osteocondrodisplasias/genética , Osteocondrodisplasias/patologia , Pré-Escolar , Linfo-Histiocitose Hemofagocítica/genética , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/etiologia , Transtornos do Crescimento/patologia , Transtornos do Crescimento/etiologia , Transtornos do Crescimento/genética
2.
Am J Physiol Regul Integr Comp Physiol ; 313(3): R290-R297, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28701320

RESUMO

Radiation exposure accelerates the onset of age-related diseases such as diabetes, cardiovascular disease, and neoplasia and, thus, lends insight into in vivo mechanisms common to these disorders. Fibrosis and extracellular matrix (ECM) remodeling, which occur with aging and overnutrition and following irradiation, are risk factors for development of type 2 diabetes mellitus. We previously demonstrated an increased incidence of skeletal muscle insulin resistance and type 2 diabetes mellitus in monkeys that had been exposed to whole body irradiation 5-9 yr prior. We hypothesized that irradiation-induced fibrosis alters muscle architecture, predisposing irradiated animals to insulin resistance and overt diabetes. Rhesus macaques (Macaca mulatta, n = 7-8/group) grouped as nonirradiated age-matched controls (Non-Rad-CTL), irradiated nondiabetic monkeys (Rad-CTL), and irradiated monkeys that subsequently developed diabetes (Rad-DM) were compared. Prior radiation exposure resulted in persistent skeletal muscle ECM changes, including a relative overabundance of collagen IV and a trend toward increased transforming growth factor-ß1. Preservation of microvascular markers differentiated the irradiated diabetic and nondiabetic groups. Microvascular density and plasma nitrate and heat shock protein 90 levels were lower in Rad-DM than Rad-CTL. These results are consistent with a protective effect of abundant microvasculature in maintaining glycemic control within radiation-induced fibrotic muscle.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Matriz Extracelular/patologia , Resistência à Insulina/efeitos da radiação , Microvasos/patologia , Microvasos/efeitos da radiação , Músculo Esquelético/patologia , Exposição à Radiação/efeitos adversos , Animais , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Relação Dose-Resposta à Radiação , Matriz Extracelular/efeitos da radiação , Feminino , Macaca mulatta , Masculino , Músculo Esquelético/efeitos da radiação , Doses de Radiação , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Lesões por Radiação/fisiopatologia , Espécies Reativas de Oxigênio
3.
BJOG ; 124(9): 1386-1393, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28102928

RESUMO

OBJECTIVE: To measure patterns of clinical activity at colposcopy before and after vaccinated women entered the Scottish Cervical Screening Programme (SCSP). DESIGN: Population-based observational study using nationally collected data. SETTING: Scottish colposcopy clinics. SAMPLE: All women with a date of birth on or after 1 January 1985 who attended colposcopy in Scotland between 2008 and 2014. METHODS: Routinely collected data from the Scottish National Colposcopy Clinical Information Audit System (NCCIAS) were extracted, including: referral criteria, referral cervical cytology, colposcopic findings, clinical procedures, and histology results. Analysis was restricted to those referred to colposcopy at age 20 or 21 years. MAIN OUTCOME MEASURES: Referral criteria, positive predictive value of colposcopy, default rates, and rates of cervical biopsies and treatments. RESULTS: A total of 7372 women referred for colposcopy at age 20 or 21 years were identified. There was a downward trend in the proportion of those referred with abnormal cytology (2008/9, 91.0%; 2013/14, 90.3%; linear trend P = 0.03). Women were less likely to have diagnostic or therapeutic interventions. The proportion with no biopsy (2008/9, 19.5%; 2013/14, 26.9%; linear trend P < 0.0001) and no treatment (2008/9, 74.9%; 2013/14, 91.8%; linear trend P < 0.0001) increased over the period of observation. CONCLUSIONS: A reduction in clinical activity related to abnormal screening referrals is likely to be associated with the human papillomavirus (HPV) catch-up immunisation programme. Referral criteria and the service provision of colposcopy needs to be planned carefully, taking account of the increasing number of women who have been immunised against HPV that will be entering cervical screening programmes worldwide. TWEETABLE ABSTRACT: Colposcopy referral criteria and service planning need attention following HPV immunisation programme.


Assuntos
Colposcopia/tendências , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus , Utilização de Procedimentos e Técnicas/tendências , Displasia do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Carga de Trabalho/estatística & dados numéricos , Adulto , Feminino , Humanos , Modelos Logísticos , Infecções por Papillomavirus/complicações , Encaminhamento e Consulta/tendências , Escócia , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia
4.
BJOG ; 124(9): 1394-1401, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28102931

RESUMO

OBJECTIVE: To determine whether human papillomavirus (HPV) immunisation has affected the prevalence of HPV genotypes and colposcopic features of cervical intraepithelial neoplasia (CIN) in young women referred for colposcopy. DESIGN: A two-centre observational study including vaccinated and unvaccinated women. SETTING: Colposcopy clinics serving two health regions in Scotland, UK. POPULATION: A total of 361 women aged 20-25 years attending colposcopy following an abnormal cervical cytology result at routine cervical screening. METHODS: Cervical samples were obtained from women for HPV DNA genotyping and mRNA E6/E7 expression of HPV 16, 18, 31, 33, and 45. Demographic data, cytology, and histology results and colposcopic features were recorded. Chi-square analysis was conducted to identify associations between vaccine status, HPV genotypes, and colposcopic features. MAIN OUTCOME MEASURES: Colposcopic features, HPV genotypes, mRNA expression, and cervical histology. RESULTS: The prevalence of HPV 16 was significantly lower in the vaccinated group (8.6%) compared with the unvaccinated group (46.7%) (P = 0.001). The number of cases of CIN2+ was significantly lower in women who had been vaccinated (P = 0.006). The HPV vaccine did not have a statistically significant effect on commonly recognised colposcopic features, but there was a slight reduction in the positive predictive value (PPV) of colposcopy for CIN2+, from 74% (unvaccinated) to 66.7% (vaccinated). CONCLUSIONS: In this group of young women with abnormal cytology referred to colposcopy, HPV vaccination via a catch-up programme reduced the prevalence of CIN2+ and HPV 16 infection. The reduced PPV of colposcopy for the detection of CIN2+ in women who have been vaccinated is at the lower acceptable level of the UK national cervical screening programme guidelines. TWEETABLE ABSTRACT: Reduction of hrHPV positivity and CIN in immunised women consistent with lower PPV of colposcopy for CIN2+.


Assuntos
Colposcopia , Papillomaviridae/genética , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus , Displasia do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/diagnóstico por imagem , Adulto , Estudos Transversais , Feminino , Genótipo , Humanos , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/prevenção & controle , Escócia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/prevenção & controle , Displasia do Colo do Útero/virologia
5.
Br J Cancer ; 114(11): 1261-4, 2016 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-27115467

RESUMO

BACKGROUND: Data on the effectiveness of one dose of HPV vaccine are lacking, particularly in population-based settings. Data from a national HPV immunisation catch-up programme of 14-18-year-old girls were used to assess the effectiveness of<3 doses of the bivalent vaccine on vaccine-type and cross-reactive-type HPV infection. METHODS: Cervical samples from women attending for their first cervical smear, which had been genotyped for HPV as part of a longitudinal HPV surveillance programme were linked to immunisation records to establish the number of vaccine doses (0, 1, 2 and 3) administered. Vaccine effectiveness (VE) adjusted for deprivation and age at first dose, was assessed for prevalent HPV 16/18 and HPV 31/33/45 infection. RESULTS: VE for prevalent HPV 16/18 infection associated with 1, 2 and 3 doses was 48.2% (95% CI 16.8, 68.9), 54.8% (95% CI 30.7, 70.8) and 72.8% (95% CI 62.8, 80.3). Equivalent VE for prevalent HPV 31/33/45 infection was -1.62% (95% CI -85.1, 45.3), 48.3% (95% CI 7.6, 71.8) and 55.2% (95% CI 32.6, 70.2). CONCLUSIONS: Consistent with recent aggregated trial data, we demonstrate the potential effectiveness of even one dose of HPV vaccine on vaccine-type infection. Given that these women were immunised as part of a catch-up campaign, the VE observed in this study is likely to be an underestimate of what will occur in girls vaccinated at younger ages. Further population-based studies which look at the clinical efficacy of one-dose schedules are warranted.


Assuntos
Papillomavirus Humano 16/isolamento & purificação , Papillomavirus Humano 18/isolamento & purificação , Papillomavirus Humano 31/isolamento & purificação , Imunização Secundária , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/imunologia , Vacinação , Adolescente , Fatores Etários , Colo do Útero/virologia , Reações Cruzadas , Relação Dose-Resposta Imunológica , Feminino , Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Papillomavirus Humano 31/imunologia , Humanos , Programas de Imunização , Esquemas de Imunização , Imunogenicidade da Vacina , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/virologia , Vacinas contra Papillomavirus/administração & dosagem , Vigilância da População , Prevalência , Escócia/epidemiologia , Esfregaço Vaginal
6.
Br J Cancer ; 114(5): 576-81, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26794278

RESUMO

BACKGROUND: To measure the uptake of first invitation to cervical screening by vaccine status in a population-based cohort offered HPV immunisation in a national catch-up campaign. METHODS: A retrospective observational study of routinely collected data from the Scottish Cervical Screening Programme. Data were extracted and linked from the Scottish Cervical Call Recall System, the Scottish Population Register and the Scottish Index of Multiple Deprivation. Records from 201 023 women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. Attendance for screening was within 12 months of the first invitation at age 20 years. RESULTS: There was a significant decline in overall attendance from the 1988 cohort to the 1993 cohort with the adjusted attendance ratio of the 1988 cohort being 1.49 times (95% CI 1.46-1.52) that of the 1993 cohort. Immunisation compensated for this decrease in uptake with unvaccinated individuals having a reduced ratio of attendance compared with those fully vaccinated (RR=0.65, 95% CI 0.64-0.65). Not taking up the opportunity for HPV immunisation was associated with an attendance for screening below the trend line for all women before the availability of HPV immunisation. CONCLUSIONS: HPV immunisation is not associated with the reduced attendance for screening that had been feared. Immunised women in the catch-up cohorts appear to be more motivated to attend than unimmunised women, but this may be a result of a greater awareness of health issues. These results, while reassuring, may not be reproduced in routinely immunised women. Continued monitoring of attendance for the first smear and subsequent routine smears is needed.


Assuntos
Detecção Precoce de Câncer/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Estudos de Casos e Controles , Feminino , Humanos , Estudos Retrospectivos , Escócia , Neoplasias do Colo do Útero/diagnóstico , Adulto Jovem
7.
Br J Cancer ; 114(5): 582-9, 2016 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-26931370

RESUMO

BACKGROUND: To document the effect of bivalent HPV immunisation on cervical cytology as a screening test and assess the implications of any change, using a retrospective analysis of routinely collected data from the Scottish Cervical Screening Programme (SCSP). METHODS: Data were extracted from the Scottish Cervical Call Recall System (SCCRS), the Scottish Population Register and the Scottish Index of Multiple Deprivation. A total of 95 876 cytology records with 2226 linked histology records from women born between 1 January 1988 and 30 September 1993 were assessed. Women born in or after 1990 were eligible for the national catch-up programme of HPV immunisation. The performance of cervical cytology as a screening test was evaluated using the key performance indicators used routinely in the English and Scottish Cervical Screening Programmes (NHSCSP and SCSP), and related to vaccination status. RESULTS: Significant reductions in positive predictive value (16%) and abnormal predictive value (63%) for CIN2+ and the mean colposcopy score (18%) were observed. A significant increase (38%) in the number of women who had to be referred to colposcopy to detect one case of CIN2+ was shown. The negative predictive value of negative- or low-grade cytology for CIN2+ increased significantly (12%). Sensitivity and specificity, as used by the UK cervical screening programmes, were maintained. CONCLUSIONS: The lower incidence of disease in vaccinated women alters the key performance indicators of cervical cytology used to monitor the quality of the screening programme. These findings have implications for screening, colposcopy referral criteria, colposcopy practice and histology reporting.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Lesões Intraepiteliais Escamosas Cervicais/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Estudos de Coortes , Colposcopia , Citodiagnóstico , Detecção Precoce de Câncer , Feminino , Humanos , Teste de Papanicolaou , Valor Preditivo dos Testes , Estudos Retrospectivos , Escócia , Sensibilidade e Especificidade , Lesões Intraepiteliais Escamosas Cervicais/diagnóstico , Lesões Intraepiteliais Escamosas Cervicais/prevenção & controle , Reino Unido , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/prevenção & controle , Esfregaço Vaginal , Adulto Jovem , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/prevenção & controle
8.
Nano Lett ; 15(8): 5408-13, 2015 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-26189994

RESUMO

GaAs core-shell p-n junction tunnel diodes were demonstrated by combining vapor-liquid-solid growth with gallium oxide deposition by atomic layer deposition for electrical isolation. The characterization of an ensemble of core-shell structures was enabled by the use of a tungsten probe in a scanning electron microscope without the need for lithographic processing. Radial tunneling transport was observed, exhibiting negative differential resistance behavior with peak-to-valley current ratios of up to 3.1. Peak current densities of up to 2.1 kA/cm(2) point the way to applications in core-shell photovoltaics and tunnel field effect transistors.

9.
Euro Surveill ; 20(8)2015 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-25742433

RESUMO

To evaluate seasonal trivalent inactivated influenza vaccine effectiveness (VE) in Scotland, we performed a Scotland-wide linkage of patient-level primary care, hospital and virological swab data from 3,323 swabs (pooling data over nine influenza seasons: 2000/01 to 2008/09). We estimated the VE for reducing realtime RT-PCR-confirmed influenza using a test-negative study design. Vaccination was associated with a 57% (95% confidence interval (CI): 31­73) reduction in the risk of PCR-confirmed influenza. VE was 60% (95% CI:22­79) for patients younger than 65 years and clinically at risk of serious complications from influenza, and 19% (95% CI: −104 to 68) for any individual 65 years and older. Vaccination was associated with substantial, sustained reductions in laboratory-confirmed influenza in the general population and younger patients in clinical at-risk groups.


Assuntos
Surtos de Doenças/prevenção & controle , Vírus da Influenza A/isolamento & purificação , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/imunologia , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A/genética , Vírus da Influenza A/imunologia , Influenza Humana/diagnóstico , Influenza Humana/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Atenção Primária à Saúde , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Escócia/epidemiologia , Estações do Ano , Vigilância de Evento Sentinela , Análise de Sequência de DNA , Fatores de Tempo , Resultado do Tratamento , Vacinação/estatística & dados numéricos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/imunologia , Adulto Jovem
10.
Br J Cancer ; 111(9): 1824-30, 2014 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-25180766

RESUMO

BACKGROUND: In Scotland, a national HPV immunisation programme began in 2008 for 12- to 13-year olds, with a catch-up campaign from 2008 to 2011 for those under the age of 18. To monitor the impact of HPV immunisation on cervical disease at the population level, a programme of national surveillance was established. METHODS: We analysed colposcopy data from a cohort of women born between 1988 and 1992 who entered the Scottish Cervical Screening Programme (SCSP) and were aged 20-21 in 2008-2012. RESULTS: By linking datasets from the SCSP and colposcopy services, we observed a significant reduction in diagnoses of cervical intraepithelial neoplasia 1 (CIN 1; RR 0.71, 95% CI 0.58 to 0.87; P=0.0008), CIN 2 (RR 0.5, 95% CI 0.4 to 0.63; P<0.0001) and CIN 3 (RR 0.45, 95% CI 0.35 to 0.58; P<0.0001) for women who received three doses of vaccine compared with unvaccinated women. CONCLUSIONS: To our knowledge, this is one of the first studies to show a reduction of low- and high-grade CIN associated with high uptake of the HPV bivalent vaccine at the population level. These data are very encouraging for countries that have achieved high HPV vaccine uptake.


Assuntos
Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Displasia do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/prevenção & controle , Adulto , Estudos de Coortes , Colposcopia , Feminino , Seguimentos , Humanos , Programas de Rastreamento , Programas Nacionais de Saúde , Gradação de Tumores , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Prevalência , Prognóstico , Escócia/epidemiologia , Displasia do Colo do Útero/epidemiologia , Displasia do Colo do Útero/patologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Vacinação , Potência de Vacina , Esfregaço Vaginal , Adulto Jovem
11.
Br J Cancer ; 110(11): 2804-11, 2014 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-24736582

RESUMO

BACKGROUND: In 2008, a national human papillomavirus (HPV) immunisation programme began in Scotland for 12-13 year old females with a three-year catch-up campaign for those under the age of 18. Since 2008, three-dose uptake of bivalent vaccine in the routine cohort aged 12-13 has exceeded 90% annually, while in the catch-up cohort overall uptake is 66%. METHODS: To monitor the impact of HPV immunisation, a programme of national surveillance was established (pre and post introduction) which included yearly sampling and HPV genotyping of women attending for cervical screening at age 20. By linking individual vaccination, screening and HPV testing records, we aim to determine the impact of the immunisation programme on circulating type-specific HPV infection particularly for four outcomes: (i) the vaccine types HPV 16 or 18 (ii) types considered to be associated with cross-protection: HPV 31, 33 or 45; (iii) all other high-risk types and (iv) any HPV. RESULTS: From a total of 4679 samples tested, we demonstrate that three doses (n=1100) of bivalent vaccine are associated with a significant reduction in prevalence of HPV 16 and 18 from 29.8% (95% confidence interval 28.3, 31.3%) to 13.6% (95% confidence interval 11.7, 15.8%). The data also suggest cross-protection against HPV 31, 33 and 45. HPV 51 and 56 emerged as the most prevalent (10.5% and 9.6%, respectively) non-vaccine high-risk types in those vaccinated, but at lower rates than HPV 16 (25.9%) in those unvaccinated. CONCLUSIONS: This data demonstrate the positive impact of bivalent vaccination on the prevalence of HPV 16, 18, 31, 33 and 45 in the target population and is encouraging for countries which have achieved high-vaccine uptake.


Assuntos
Papillomavirus Humano 16/imunologia , Papillomavirus Humano 18/imunologia , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Neoplasias do Colo do Útero/prevenção & controle , Vacinação , Estudos Transversais , Relação Dose-Resposta Imunológica , Feminino , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 18/genética , Humanos , Infecções por Papillomavirus/epidemiologia , Prevalência , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Potência de Vacina , Adulto Jovem
12.
J Inorg Biochem ; 259: 112663, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39024775

RESUMO

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.


Assuntos
Antibacterianos , Complexos de Coordenação , Gálio , Testes de Sensibilidade Microbiana , Gálio/química , Gálio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ligantes
13.
Br J Dermatol ; 167(5): 1032-6, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22709541

RESUMO

BACKGROUND: Rosacea is a chronic inflammatory condition that affects the skin of the face and the eyes. Erythematotelangiectatic rosacea is characterized by flushing, oedema and telangiectasia. Patients with rosacea demonstrate elevated densities of Demodex mites in their skin compared with controls. A bacterium (Bacillus oleronius) isolated from Demodex mites from a patient with papulopustular rosacea has been demonstrated to produce antigenic proteins that may play a role in papulopustular and ocular rosacea. OBJECTIVES: To establish whether there was a correlation between the reactivity of sera from patients with erythematotelangiectatic rosacea to Bacillus antigens, and to characterize the proteins to which these patients showed reactivity. METHODS: Serum samples from patients with erythematotelangiectatic rosacea and controls were examined for reactivity to Bacillus proteins by Western blot analysis. Proteins to which the sera reacted were excised from gels, trypsin digested, and putative identities were assigned following liquid chromatography-mass spectrometry (LC-MS) analysis. RESULTS: Eighty per cent (21/26) of patients with erythematotelangiectatic rosacea showed serum reactivity to the 62- and 83-kDa proteins of B. oleronius, compared with 40% (9/22) of controls (P = 0·004). The 62-kDa protein was characterized by LC-MS and showed homology to groEL chaperonin, which provokes a strong immune response in mammals. The 83-kDa protein showed homology to aconitate hydratase, of which expression is increased in bacteria under oxidative stress, and which is highly immunogenic. CONCLUSIONS: The majority of patients with erythematotelangiectatic rosacea show serum reactivity to two proteins from B. oleronius, suggesting that this bacterium may play a role in the induction of this condition. The two proteins to which patient sera reacted were found to be similar to a heat shock protein and an enzyme involved in regulating the stress response of the bacterium.


Assuntos
Antígenos de Bactérias/imunologia , Bacillus/imunologia , Proteínas de Bactérias/imunologia , Infestações por Ácaros/imunologia , Ácaros/microbiologia , Rosácea/imunologia , Aconitato Hidratase/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Bacillus/isolamento & purificação , Western Blotting , Chaperonina 60/imunologia , Cromatografia Líquida de Alta Pressão/métodos , Reações Cruzadas , Feminino , Humanos , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Rosácea/microbiologia , Adulto Jovem
14.
Br J Dermatol ; 166(4): 753-60, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22098186

RESUMO

BACKGROUND: Patients with rosacea demonstrate a higher density of Demodex mites in their skin than do controls. A bacterium isolated from a Demodex mite from a patient with papulopustular rosacea (PPR) was previously shown to provoke an immune response in patients with PPR or ocular rosacea, thus suggesting a possible role for bacterial proteins in the aetiology of this condition. OBJECTIVES: To examine the response of neutrophils to proteins derived from a bacterium isolated from a Demodex mite. METHODS: Bacterial cells were lysed and proteins were partially purified by ÄKTA fast protein liquid chromatography. Isolated neutrophils were exposed to bacterial proteins and monitored for alterations in migration, degranulation and cytokine production. RESULTS: Neutrophils exposed to proteins from Bacillus cells demonstrated increased levels of migration and elevated release of matrix metalloprotease 9, an enzyme known to degrade collagen, and cathelicidin, an antimicrobial peptide. In addition, neutrophils exposed to the bacterial proteins demonstrated elevated rates of interleukin 8 and tumour necrosis factor-α production. CONCLUSIONS: Proteins produced by a bacterium isolated from a Demodex mite have the ability to increase the migration, degranulation and cytokine production abilities of neutrophils. These results suggest that bacteria may play a role in the inflammatory erythema associated with rosacea.


Assuntos
Bacillus/imunologia , Proteínas de Bactérias/farmacologia , Ativação de Neutrófilo/efeitos dos fármacos , Rosácea/imunologia , Animais , Antígenos de Bactérias/imunologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Degranulação Celular/imunologia , Ensaios de Migração de Leucócitos , Movimento Celular/imunologia , Citocinas/biossíntese , Eletroforese em Gel de Poliacrilamida , Ensaio de Imunoadsorção Enzimática , Humanos , Metaloproteinase 9 da Matriz/metabolismo , Infestações por Ácaros/imunologia , Ácaros , Neutrófilos/metabolismo , Catelicidinas
15.
J Hosp Infect ; 126: 44-51, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35500765

RESUMO

BACKGROUND: A recent systematic review recommended time-varying methods for minimizing bias when estimating the excess length of stay (LOS) for healthcare-associated infections (HAIs); however, little evidence exists concerning which time-varying method is best used for HAI incidence studies. AIM: To undertake a retrospective analysis of data from a one-year prospective incidence study of HAIs, in one teaching hospital and one general hospital in NHS Scotland. METHODS: Three time-varying methods - multistate model, multivariable adjusted survival regression, and matched case-control approach - were applied to the data to estimate excess LOS and compared. FINDINGS: The unadjusted excess LOS estimated from the multistate model was 7.8 (95% confidence interval: 5.7-9.9) days, being shorter than the excess LOS estimated from survival regression adjusting for the admission characteristics (9.9; 8.4-11.7) days, and the adjusted estimates from matched case-control approach (10; 8.5-11.5) days. All estimates from the time-varying methods were much lower than the crude time-fixed estimates of 27 days. CONCLUSION: Studies examining LOS associated with HAI should consider a design which addresses time-dependent bias as a minimum. If there is an imbalance in patient characteristics between the HAI and non-HAI groups, then adjustment for patient characteristics is also important, where survival regression with time-dependent covariates is likely to provide the most flexible approach. Matched design is more likely to result in data loss, whereas a multistate model is limited by the challenge in adjusting for covariates. These findings have important implications for future cost-effectiveness studies of infection prevention and control programmes.


Assuntos
Infecção Hospitalar , Estudos de Casos e Controles , Infecção Hospitalar/epidemiologia , Atenção à Saúde , Humanos , Tempo de Internação , Estudos Prospectivos , Estudos Retrospectivos
16.
J Med Primatol ; 40(1): 27-36, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20637047

RESUMO

BACKGROUND: Causes of infant death remain unknown in significant proportions of human and non-human primate pregnancies. METHODS: A closed breeding colony with high rates of infant mortality had pregnancies assessed (n=153) by fetal measurements and maternal characteristics. Infant outcome was classified as neonatal death (stillborn or died <48 hours from birth), postnatal death (died 2-30 days) or surviving (alive after 30 days). RESULTS: Fetal size did not predict outcome. Poor maternal glycemic control and low social ranking increased odds for adverse outcome (OR=3.72, P=0.01 and 2.27, P=0.04, respectively). Male sex was over-represented in stillbirths (P=0.04), and many were macrosomic, but size did not associate with maternal glycemic control measured as glycated hemoglobin A1c. Postnatally dead infants were smaller (P<0.01), which associated with behavioral factors and glycemic control. CONCLUSIONS: Fetal growth estimates predicted gestational age but not fetal outcome. Maternal social status and metabolic health, particularly glycemic control, increased risks of adverse pregnancy outcome.


Assuntos
Chlorocebus aethiops , Doenças dos Macacos/etiologia , Complicações na Gravidez/veterinária , Natimorto/veterinária , Animais , Animais Recém-Nascidos , Diabetes Gestacional/veterinária , Feminino , Desenvolvimento Fetal , Macrossomia Fetal/mortalidade , Macrossomia Fetal/veterinária , Idade Gestacional , Hemoglobinas Glicadas/análise , Hierarquia Social , Hiperglicemia/complicações , Hiperglicemia/veterinária , Masculino , Gravidez , Resultado da Gravidez , Fatores Sexuais , Natimorto/epidemiologia , Ultrassonografia Pré-Natal/veterinária
17.
Euro Surveill ; 16(20): 19871, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21616049

RESUMO

Following the 2010/11 influenza season, we determined the age- and location-specific seroprevalence of antibodies against the influenza A(H1N1)2009 virus in Scotland. Samples were analysed by microneutralisation assay. Age/seropositivity profiles varied significantly between cities. The increases in seroprevalence relative to the previous influenza season (2009/10) were similar across age groups and geographic locations. However, the increased seropositivity in older adults appeared to be driven by exposure to vaccination, indicating significantly lower levels of infection than in younger age groups.


Assuntos
Anticorpos Antivirais/sangue , Vírus da Influenza A Subtipo H1N1/imunologia , Influenza Humana/epidemiologia , Adulto , Humanos , Influenza Humana/imunologia , Pessoa de Meia-Idade , Escócia/epidemiologia , Estudos Soroepidemiológicos , Adulto Jovem
18.
J Clin Virol ; 134: 104717, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33360857

RESUMO

BACKGROUND: Penile cancer (PeC) is a highly morbid disease which is rising in certain settings including Scotland. A component of PeC is associated with Human Papillomavirus (HPV) although its influence on clinical outcomes is debatable as is whether the fraction attributable to HPV is increasing. METHODS: A total of 122 archived tissue samples derived from patients diagnosed with PeC between 2006-2015 were collated and tested for HPV DNA using molecular PCR. HPV positivity was determined for the overall population and by calendar year of diagnosis to determine any temporal trends. The influence of age, deprivation, smoking, tumour stage and tumour grade on likelihood of HPV positivity was determined by logistic regression. In addition, the influence of HPV status and the other clinical and demographics variables on all-cause death and death from PeC was assessed. RESULTS: HPV was detected in 43 % (95 % CI: 34-52) of penile cancers and the majority of infections were HPV 16. The HPV component of PeC did not increase over the time period (p for linear trend - 0.226). No demographic or clinical variables were associated with HPV positivity neither was HPV status associated with improved all-cause or cancer-specific survival during the follow up period. CONCLUSION: The rise in PeC in Scotland may not be attributable to a rise in HPV-associated cancer; this is consistent with oropharyngeal cancer (OPC) in the UK where there is an increase in both HPV positive and negative cancer. This work calls for a larger multi centre study to enable further detailed investigation into the implications of HPV infection in PeC.


Assuntos
Alphapapillomavirus , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Neoplasias Penianas , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Neoplasias Penianas/epidemiologia , Estudos Retrospectivos , Escócia/epidemiologia
19.
J Hosp Infect ; 114: 10-22, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34301392

RESUMO

BACKGROUND: The measure of disease frequency most widely used to report healthcare-associated infection (HAI) is the point-prevalence survey. Incidence studies are rarely performed due to time and cost constraints; they show which patients are affected by HAI, when and where, and inform planning and design of infection prevention and control (IPC) measures. AIM: To determine the epidemiology of HAI within a general and a teaching hospital in Scotland. METHODS: A prospective observational incidence study was undertaken for one year from April 2018 using data collected as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. A novel, robust approach was undertaken, using record linkage to national administrative data to provide full admission and discharge information. Cases were recorded if they met international HAI definitions. FINDINGS: Incidence of HAI for the combined hospitals was 250 HAI cases per 100,000 acute occupied bed-days (AOBD). Highest frequency was in urinary tract (51.2 per 100,000 AOBD), bloodstream (44.7), and lower respiratory tract infection (42.2). The most frequently reported organisms were Escherichia coli, Staphylococcus aureus, and norovirus. Incidence of HAI was higher in older people and emergency cases. There was an increase in the rate of HAI in summer months (pneumonia, respiratory, surgical, and gastrointestinal infection) and in winter months norovirus gastrointestinal infection (P < 0.0001). The highest incidence specialties were intensive care, renal medicine, and cardiothoracic surgery. HAI occurred at a median of 9 days (interquartile range: 4-19) after admission. Incidence data were extrapolated to provide an annual national estimate of HAI in NHS Scotland of 7437 (95% confidence interval: 7021-7849) cases. CONCLUSION: This study provides a unique overview of incidence of HAI and identifies the burden of HAI at the national level for the first time. Understanding the incidence in different clinical settings, at different times, will allow targeting of IPC measures to those patients who would benefit the most.


Assuntos
Infecção Hospitalar , Idoso , Estudos de Coortes , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Hospitais de Ensino , Humanos , Incidência , Controle de Infecções
20.
J Hosp Infect ; 114: 32-42, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34301394

RESUMO

BACKGROUND: Few healthcare-associated infection (HAI) studies focus on risk of HAI at the point of admission. Understanding this will enable planning and management of care with infection prevention at the heart of the patient journey from the point of admission. AIM: To determine intrinsic characteristics of patients at hospital admission and extrinsic events, during the two years preceding admission, that increase risk of developing HAI. METHODS: An incidence survey of adults within two hospitals in NHS Scotland was undertaken for one year in 2018/19 as part of the Evaluation of Cost of Nosocomial Infection (ECONI) study. The primary outcome measure was developing any HAI using recognized case definitions. The cohort was derived from routine hospital episode data and linkage to community dispensed prescribing data. FINDINGS: The risk factors present on admission observed as being the most significant for the acquisition of HAI were: being treated in a teaching hospital, increasing age, comorbidities of cancer, cardiovascular disease, chronic renal failure and diabetes; and emergency admission. Relative risk of developing HAI increased with intensive care unit, high-dependency unit, and surgical specialties, and surgery <30 days before admission and a total length of stay of >30 days in the two years to admission. CONCLUSION: Targeting patients at risk of HAI from the point of admission maximizes the potential for prevention, especially when extrinsic risk factors are known and managed. This study proposes a new approach to infection prevention and control (IPC), identifying those patients at greatest risk of developing a particular type of HAI who might be potential candidates for personalized IPC interventions.


Assuntos
Infecção Hospitalar , Adulto , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Atenção à Saúde , Humanos , Incidência , Controle de Infecções , Unidades de Terapia Intensiva
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