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1.
Br J Dermatol ; 184(3): 538-544, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32407577

RESUMO

BACKGROUND: The rising incidence rates of skin cancer (SC) lead to an enormous burden on healthcare systems. General practitioners (GPs) might play an important part in SC care, but research has shown poor clinical recognition of SC, leading to a high rate of potentially unnecessary referrals. OBJECTIVES: The aim of this study was to evaluate if a dermato-oncological training programme (DOTP) for GPs improved their diagnostic skills and quality of referrals. METHODS: Out of 194 GPs in the Nijmegen area, 83 (42·8%) followed a DOTP on SC. Referrals from both a trained cohort (TC) and two cohorts of untrained GPs [untrained present cohort (UPC) and untrained historical cohort (UHC)] were included. Data on diagnostic skills, quality of referrals and the number of potentially unnecessary referrals were evaluated. RESULTS: A total number of 1662 referrals were analysed. The referral diagnosis was correct more often in the TC (70·3%) compared with the UPC (56·2%; P < 0·001) and the UHC (51·6%; P < 0·001). Furthermore, the TC also provided a better lesion description, mentioned a diagnosis more often in their referral letters and more often performed diagnostics before referral. In addition, fewer potentially unnecessary referrals were identified in the TC compared with the UPC (62·7% vs. 73·7%; P < 0·001) and the UHC (75·2%; P < 0·001). CONCLUSIONS: GPs who followed a DOTP had better diagnostic skills and quality of referrals than untrained GPs, leading to fewer potentially unnecessary referrals. This might enhance a more efficient use of the limited capacity in secondary dermatological care and consequently lead to lower healthcare costs.


Assuntos
Clínicos Gerais , Neoplasias Cutâneas , Custos de Cuidados de Saúde , Humanos , Encaminhamento e Consulta , Atenção Secundária à Saúde , Neoplasias Cutâneas/diagnóstico
2.
J Infect Dis ; 222(1): 62-73, 2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-31755920

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM) are at risk of anal squamous cell carcinoma. Data are limited on the natural history of the precursor to this carcinoma, anal squamous intraepithelial lesions (SILs). METHODS: HIV-positive MSM were screened for histopathological SILs by means of high-resolution anoscopy (HRA). For participants without SILs at baseline, we estimated the cumulative incidence and risk factors for SILs. For those with low-grade SILs (LSILs) at baseline, the risk of progression to high-grade SILs (HSILs) and the clearance rate were estimated at the lesion level. RESULTS: Of 807 men without SILs at baseline, 107 underwent follow-up HRA between 1 to 4.5 years later. At the second visit 18 men (16.8%) showed LSIL, and 25 (23.4%) HSIL. Age was associated with incident LSILs (adjusted odds ratio [aOR], 2.10 per 10-year increase in age; P = .01). Of 393 men with LSILs at baseline, 114 underwent follow-up HRA 0.5 to 2.5 years later. Of the 177 LSILs found at baseline, 87 (49.2%) had cleared at the second visit, and 29 (16.4%) had progressed to HSILs. CONCLUSION: Incident LSILs and HSILs were common during follow-up among HIV-positive MSM without dysplasia at baseline. Among men with LSILs at baseline, nearly half of these lesions cleared, and a small portion progressed.


Assuntos
Neoplasias do Ânus/etiologia , Neoplasias do Ânus/fisiopatologia , Progressão da Doença , Infecções por HIV/complicações , Homossexualidade Masculina , Lesões Intraepiteliais Escamosas/etiologia , Lesões Intraepiteliais Escamosas/fisiopatologia , Adulto , Fatores Etários , Infecções por HIV/epidemiologia , Infecções por HIV/fisiopatologia , Soropositividade para HIV , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Lesões Intraepiteliais Escamosas/epidemiologia
3.
Br J Surg ; 107(7): 917-926, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32207856

RESUMO

BACKGROUND: Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. METHODS: This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien-Dindo grade IIIA or higher) and 30-day or in-hospital mortality. RESULTS: A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20-69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non-CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher-volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. CONCLUSION: Hospital volume and postoperative outcomes were not associated.


ANTECEDENTES: La asociación entre el volumen hospitalario y los resultados de la cirugía hepática no está clara. Según la recomendación actual de las guías holandesas se requiere un volumen mínimo de 20 procedimientos anuales por centro. El objetivo de este estudio fue analizar la asociación entre el volumen hospitalario con los resultados postoperatorios en la auditoría hepatobiliar obligatoria holandesa a nivel nacional. MÉTODOS: Se realizó un estudio a nivel nacional en los Países Bajos. Se incluyeron todas las resecciones hepáticas registradas en la auditoría hepatobiliar holandesa entre 2014 y 2017. El volumen anual del centro se calculó y se clasificó en categorías de 20 procedimientos por año. Los objetivos principales fueron la morbilidad de mayor grado (Clavien-Dindo grado IIIA o superior) y la mortalidad hospitalaria o la mortalidad a los 30 días. RESULTADOS: Se realizaron un total de 5.590 resecciones en 34 centros con una mediana (rango intercuartílico) de volumen anual de 35 procedimientos (20-69). La tasa global de morbilidad mayor fue del 11% y la mortalidad del 2%. La mortalidad fue de 1,9% después de la resección por metástasis hepáticas colorrectales (colorectal liver metastases, CRLM), 1,2% para no CRLM, 0,4% para tumores benignos, 4,9% para carcinoma hepatocelular, y 10,3% para tumores biliares. Los centros de mayor volumen realizaron más resecciones hepáticas mayores y más resecciones por carcinoma hepatocelular y cáncer biliar. En el análisis multivariable después de ajustar por factores de riesgo conocidos de eventos adversos, no se observó ninguna asociación entre el volumen hospitalario y la morbilidad o mortalidad mayor. CONCLUSIÓN: No hubo asociación entre el volumen hospitalario y los resultados postoperatorios de la cirugía hepática en los Países Bajos.


Assuntos
Hepatectomia , Hospitais/estatística & dados numéricos , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatectomia/efeitos adversos , Hepatectomia/mortalidade , Hepatectomia/estatística & dados numéricos , Humanos , Fígado/cirurgia , Neoplasias Hepáticas/cirurgia , Masculino , Análise Multivariada , Países Baixos/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento
4.
Br J Dermatol ; 182(4): 1026-1033, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31302935

RESUMO

OBJECTIVES: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. METHODS: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0-4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0-2) to mark HPV production and life cycle completion. RESULTS: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. CONCLUSIONS: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a 'wait and see' policy for productive HSILs. What's already known about this topic? For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add? By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment.


Assuntos
Alphapapillomavirus , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Lesões Intraepiteliais Escamosas , Biomarcadores Tumorais , Inibidor p16 de Quinase Dependente de Ciclina , Homossexualidade Masculina , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/complicações
5.
Br J Dermatol ; 178(2): 357-362, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28386936

RESUMO

The prognostic significance of histological regression in primary melanoma has been debated for many years. We aim to review the evidence to see how histological regression may affect prognosis. A systematic review was performed by searching in MEDLINE, Scopus and the Cochrane Library from 1 January 1966 to 1 August 2015. All studies reporting hazard ratios or data on survival and histological regression were included. Primary random-effects meta-analyses were used to summarize outcome measures. Heterogeneity was assessed using the χ2 -test and I2 -statistic. To assess the potential bias of small studies we used funnel plots and the Begg and Mazumdar adjusted rank correlation method. Summaries of survival outcomes were measured as hazard ratios or relative risk of death at 5 years according to the presence of histological regression of primary melanoma. In total, 183 articles were reviewed out of 1876 retrieved. Ten studies comprising 8557 patients were included. Patients with histological regression had a lower relative risk of death (0·77, 95% confidence interval 0·61-0·97) than those without. Examination of the funnel plot did not provide evidence of publication bias. The results showed that histological regression is a protective factor for survival.


Assuntos
Melanoma/patologia , Neoplasias Cutâneas/patologia , Humanos , Melanoma/mortalidade , Regressão Neoplásica Espontânea/patologia , Prognóstico , Fatores de Risco , Neoplasias Cutâneas/mortalidade , Análise de Sobrevida
8.
Eur Rev Med Pharmacol Sci ; 17(7): 853-73, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23640431

RESUMO

Current Controlled Ovarian Stimulation (COH) for Assisted Reproductive Techniques (ART) pursues three main objectives: hypophyseal activity suppression, multiple follicle growth stimulation, and ovulation induction. By suppressing hypophyseal activity, it is possible to prevent untimely LH surge and allow the appropriate development of the leading follicle. The classical GnRH agonist long protocol is the most widely used in COH for ART. However, an alternative regimen based on GnRH antagonist has been recently introduced in clinical practice. As competitive antagonists, these drugs display an immediate and quickly reversible effect and they avoid hormonal withdrawal side effects. Moreover, this protocol shows undeniable advantages, including the shorter duration of the treatment, the lower amount of gonadotropin required, the shorter hormonal and ultrasound monitoring of patients, milder physical and emotional stress, and a lower risk of Ovarian Hyperstimulation Syndrome (OHSS). The use of GnRH antagonists was traditionally restricted to selected patients, as "poor responders" and women at high-risk of developing OHSS such as Polycystic Ovary Syndrome (PCOS) and patients who had previously experienced OHSS. These findings could prompt a trend to change from the standard agonist protocol to the antagonist protocol in all categories of patients. This review provides a comprehensive overview of the use of GnRH antagonist protocols applied both to IVF techniques and to IUI procedures in the Italian experience.


Assuntos
Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Técnicas de Reprodução Assistida , Feminino , Fertilização in vitro , Humanos , Itália , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Síndrome do Ovário Policístico/tratamento farmacológico , Injeções de Esperma Intracitoplásmicas
9.
Clin Exp Obstet Gynecol ; 40(2): 219-21, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23971242

RESUMO

The aim of this study was to assess the effects of three weeks of daily colostrum cream on vaginal cytology and local symptoms related to menopause. Genito-urinary symptoms and cell morphology were analyzed at time 0 (T0) and after three weeks (16 +/- days since the end of treatment) at time 1 (T1). Dyspareunia, vaginal dryness, and maturation index (MI) reached a statistically significant difference between T0 and T1. The results proved to be an alternative treatment for vaginal distress caused by lack of hormones in patients in which hormonal treatment is contraindicated.


Assuntos
Colostro , Menopausa , Doenças Vaginais/terapia , Dispareunia/terapia , Feminino , Humanos , Vagina/patologia , Cremes, Espumas e Géis Vaginais , Doenças Vaginais/patologia , Esfregaço Vaginal
10.
G Ital Dermatol Venereol ; 148(5): 453-63, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24005137

RESUMO

AIM: Objective of the study was to determine the most common cutaneous lesions in patients with haematologic malignancies observed at dermatologic consultation and to identify the impact parameters related to the haematologic condition, like disease type/duration, remission, chemotherapy and transplantation, have on skin manifestations. METHODS: A total of 101 consecutive patients with onco-haematological malignancies referred for dermatological consultation over a two-year period were included in this prospective single-centre observational cohort study. RESULTS: The most common finding was infection (19.8%), followed by drug adverse reactions (16.8%) and malignant neoplasia (11.9%). Elderly patients and those with a longer disease duration had a higher frequency of cutaneous neoplasia. Squamous cell carcinoma was the most frequent cutaneous neoplasia; three cases of melanoma were diagnosed and had a high Breslow thickness. Cutaneous involvement due to the haematological malignancies was observed in 5 patients. Common chronic dermatoses (psoriasis and eczema) were found in 10% of patients. Transplant had no effect on the percentage of infections or tumours. CONCLUSION: Patients with haematological malignancies have a higher incidence of adverse drug reactions with peculiar morphologic features and a lower incidence of common chronic dermatoses than patients referred for dermatological consultation by their general practitioner or other hospital services. Infectious dermatoses were less frequent than in solid organ transplanted patients. The complex variety of cutaneous lesions, the differential diagnostic pitfalls and the prognostic relevance of early skin tumour diagnosis, evidence the importance of a correct dermatological approach.


Assuntos
Transplante de Medula Óssea , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/cirurgia , Dermatopatias/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/epidemiologia , Estudos de Coortes , Terapia Combinada , Comorbidade , Toxidermias/epidemiologia , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Neoplasias Hematológicas/tratamento farmacológico , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Estudos Prospectivos , Psoríase/epidemiologia , Encaminhamento e Consulta , Dermatopatias Infecciosas/epidemiologia , Neoplasias Cutâneas/epidemiologia , Adulto Jovem
13.
Gene Ther ; 18(7): 727-33, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21390070

RESUMO

Small interfering RNAs (siRNAs) are emerging as promising therapeutic tools. However, the widespread clinical application of such molecules as modulators of gene expression is still dependent on several aspects that limit their bioavailability. One of the most promising strategies to overcome the barriers faced by gene silencing molecules involves the use of lipid-based nanoparticles (LNPs) and viral vectors, such as adenoviruses (Ads). The primary obstacle for translating gene silencing technology from an effective research tool into a feasible therapeutic strategy remains its efficient delivery to the targeted cell type in vivo. In this study, we tested the capability of LNPs and Ad to transduce and treat locally tumors in vivo. Efficient knockdown of a surrogate reporter (luciferase) and therapeutic target genes such as the kinesin spindle protein (KIF11) and polo-like kinase 1 were observed. Most importantly, this activity led to a cell cycle block as a consequence and slowed down tumor progression in tumor-bearing animals. Our data indicate that it is possible to achieve tumor transduction with si/short hairpin RNAs and further improve the delivery strategy that likely in the future will lead to the ideal non-viral particle for targeted cancer gene silencing.


Assuntos
Colesterol/análogos & derivados , Progressão da Doença , Marcação de Genes , Genes cdc , Lipossomos , Nanopartículas , Neoplasias/genética , Neoplasias/terapia , Polietilenoglicóis/administração & dosagem , Interferência de RNA , Adenoviridae/genética , Animais , Linhagem Celular Tumoral , Colesterol/administração & dosagem , Inativação Gênica , Vetores Genéticos , Humanos , Masculino , Camundongos , Camundongos Nus , Transdução Genética
14.
BJS Open ; 4(4): 605-621, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32374497

RESUMO

BACKGROUND: In patients with colorectal liver metastases (CRLM) preoperative imaging may include contrast-enhanced (ce) MRI and [18 F]fluorodeoxyglucose (18 F-FDG) PET-CT. This study assessed trends and variation between hospitals and oncological networks in the use of preoperative imaging in the Netherlands. METHODS: Data for all patients who underwent liver resection for CRLM in the Netherlands between 2014 and 2018 were retrieved from a nationwide auditing database. Multivariable logistic regression analysis was used to assess use of ceMRI, 18 F-FDG PET-CT and combined ceMRI and 18 F-FDG PET-CT, and trends in preoperative imaging and hospital and oncological network variation. RESULTS: A total of 4510 patients were included, of whom 1562 had ceMRI, 872 had 18 F-FDG PET-CT, and 1293 had combined ceMRI and 18 F-FDG PET-CT. Use of ceMRI increased over time (from 9·6 to 26·2 per cent; P < 0·001), use of 18 F-FDG PET-CT decreased (from 28·6 to 6·0 per cent; P < 0·001), and use of both ceMRI and 18 F-FDG PET-CT 16·9 per cent) remained stable. Unadjusted variation in the use of ceMRI, 18 F-FDG PET-CT, and combined ceMRI and 18 F-FDG PET-CT ranged from 5·6 to 100 per cent between hospitals. After case-mix correction, hospital and oncological network variation was found for all imaging modalities. DISCUSSION: Significant variation exists concerning the use of preoperative imaging for CRLM between hospitals and oncological networks in the Netherlands. The use of MRI is increasing, whereas that of 18 F-FDG PET-CT is decreasing.


ANTECEDENTES: En pacientes con metástasis hepáticas colorrectales (colorrectal liver metastases, CRLM), los estudios de imagen preoperatorios pueden incluir resonancia magnética con contraste (ce)MRI y 18 F-FDG-PET-CT. Este estudio evaluó las tendencias y la variación entre los hospitales y las redes oncológicas en el uso de estudios de imagen preoperatorios en los Países Bajos. MÉTODOS: Todos los pacientes que se sometieron a una resección hepática por CRLM en los Países Bajos entre 2014 y 2018 fueron seleccionados a partir de una base de datos a nivel nacional auditada. El análisis de regresión logística multivariable se utilizó para evaluar el uso de ceMRI, de 18 F-FDG-PET-CT y de ceMRI combinado con 18 F-FDG-PET-CT, así como para determinar las tendencias en los estudios de imagen preoperatorios y las variaciones hospitalarias y de la red oncológica. RESULTADOS: En total, se incluyeron 4.510 pacientes, de los cuales 1.562 se sometieron a ceMRI, 872 a 18 F-FDG-PET-CT y 1.293 a ceMRI combinado con 18 F-FDG-PET-CT. El uso de ceMRI aumentó con el tiempo del 9,6% al 26,2% (P < 0,001), el uso de 18 F-FDG-PET-CT disminuyó (25% a 6,0%, P < 0,001) y el uso de ceMRI y 18 F-FDG-PET- CT (17%) se mantuvo estable. La variación no ajustada entre hospitales en el uso de ceMRI, 18 F-FDG-PET-CT y la combinación de ceMRI y 18 F-FDG-PET-CT oscilaba del 5% al 10%. Después de la corrección por case-mix, la variación hospitalaria y de la red oncológica persistía en todas las pruebas de imagen. CONCLUSIÓN: En los Países Bajos existe una variación significativa entre hospitales y redes oncológicas respecto al uso de pruebas de imagen preoperatorias para el CRLM. El uso de MRI está aumentando, mientras que el uso de 18 F-FDG-PET-CT está disminuyendo.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Imageamento por Ressonância Magnética/estatística & dados numéricos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Institutos de Câncer/estatística & dados numéricos , Meios de Contraste , Bases de Dados Factuais , Feminino , Hospitais/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/cirurgia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos , Período Pré-Operatório
15.
Biochim Biophys Acta ; 1777(10): 1289-300, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18725189

RESUMO

Having confirmed that adenovirus-mediated overexpression of NH(2)-tau fragment lacking the first 25 aminoacids evokes a potent neurotoxic effect, sustained by protracted stimulation of NMDA receptors, in primary neuronal cultures we investigated whether and how chemically synthesized NH(2)-derived tau peptides, i.e. NH(2)-26-44 and NH(2)-1-25 fragments, affect mitochondrial function. We tested both fragments on each step of the processes leading to ATP synthesis via oxidative phosphorylation: i) electron flow via the respiratory chain from physiological substrates to oxygen with the activity of each individual complex of the respiratory chain investigated in some detail, ii) membrane potential generation arising from externally added succinate and iii) the activity of both the adenine nucleotide translocator and iv) ATP synthase. Oxidative phosphorylation is not affected by NH(2)-1-25 tau fragment, but dramatically impaired by NH(2)-26-44 tau fragment. Both cytochrome c oxidase and the adenine nucleotide translocator are targets of NH(2)-26-44 tau fragment, but adenine nucleotide translocator is the unique mitochondrial target responsible for impairment of oxidative phosphorylation by the NH(2)-26-44 tau fragment, which then exerts deleterious effects on cellular availability of ATP synthesized into mitochondria.


Assuntos
Mitocôndrias/metabolismo , Translocases Mitocondriais de ADP e ATP/metabolismo , Fosforilação Oxidativa , Fragmentos de Peptídeos/metabolismo , Proteínas tau/metabolismo , Difosfato de Adenosina/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/química , Translocases Mitocondriais de ADP e ATP/genética , ATPases Mitocondriais Próton-Translocadoras/metabolismo , Consumo de Oxigênio , Fragmentos de Peptídeos/genética , Ratos , Ratos Wistar , Proteínas tau/genética
16.
J Infect ; 76(4): 393-405, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29289562

RESUMO

BACKGROUND: We studied prevalence, risk factors and concordance of vaginal and anal HPV infection and L1 seropositivity among female sex workers (FSW) in Amsterdam. METHODS: In 2016, FSW aged ≥18 years having a sexually transmitted infections (STI) consultation were invited to participate. Participation entailed taking vaginal and anal self-swabs. Demographics and sexual behaviour data were collected. HPV DNA was analysed using the SPF10-PCR-DEIA-LiPA25-system-v1. Serum was tested for HPV L1 antibodies using multiplex serology assays. Determinants of vaginal and anal high risk HPV (hrHPV) infection and L1 seropositivity were assessed with logistic regression analyses. RESULTS: We included 304 FSW; median age was 29 years (IQR 25-37). Vaginal and anal hrHPV prevalence were 46% and 55%, respectively. HrHPV L1 seropositivity was 37%. Vaginal-anal hrHPV concordance was strong, but no significant association between vaginal or anal hrHPV infection and seropositivity was found. Having had anal sexual contact was not associated with anal hrHPV infection (P = 0.119). DISCUSSION: Vaginal and anal hrHPV prevalence is high among FSW in Amsterdam, the Netherlands. Promotion of HPV vaccination, preferably at the beginning of the sex (work) career, may be a useful prevention method against hrHPV infection and disease.


Assuntos
Doenças do Ânus/epidemiologia , Infecções por Papillomavirus/epidemiologia , Profissionais do Sexo/estatística & dados numéricos , Vagina/virologia , Adulto , Canal Anal/virologia , Doenças do Ânus/virologia , Estudos Transversais , DNA Viral/genética , Feminino , Humanos , Países Baixos/epidemiologia , Papillomaviridae/classificação , Papillomaviridae/genética , Prevalência , Fatores de Risco , Comportamento Sexual/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/virologia , Adulto Jovem
17.
Folia Microbiol (Praha) ; 52(3): 237-40, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17702461

RESUMO

Hydrogen peroxide production in yeast cells undergoing programmed cell death in response to acetic acid occurred in the majority of live cells 15 min after death induction and was no longer detectable after 60 min. Superoxide anion production was found later, 60 and 90 min after death induction when cells viability was 60 and 30%, respectively. In cells protected from death due to acid stress adaptation neither hydrogen peroxide nor superoxide anion could be observed after acetic acid treatment. The early production of hydrogen peroxide in cells in which survival was 100% could play a major role in acetic acid-induced programmed cell death signaling. Superoxide anion is assumed to be generated in cells already en route to acetic acid-induced programmed cell death.


Assuntos
Apoptose/fisiologia , Peróxido de Hidrogênio/metabolismo , Saccharomyces cerevisiae/enzimologia , Superóxidos/metabolismo , Ácido Acético/farmacologia , Ácidos/farmacologia , Catalase/metabolismo , Saccharomyces cerevisiae/fisiologia , Superóxido Dismutase/metabolismo
18.
Genet Test ; 10(3): 169-73, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17020467

RESUMO

Mutational analysis of the cystic fibrosis transmembrane regulator (CFTR) gene was performed in 98 unrelated CF chromosomes from 49 Lithuanian CF patients through a combined approach in which the p.F508del mutation was first screened by allele-specific PCR while CFTR mutations in nonp.F508del chromosomes have been screened for by denaturing gradient gel electrophoresis analysis. A CFTR mutation was characterized in 62.2% of CF chromosomes, two of which (2.0%) have been previously shown to carry a large gene deletion CFTRdele2,3(21 kb). The most frequent Lithuanian CF mutation is p.F508del (52.0%). Seven CFTR mutations, p.N1303K (2.0%), p.R75Q (1.0%), p.G314R (1.0%), p.R553X (4.2%), p.W1282X (1.0%), and g.3944delGT (1.0%), accounted for 10.1% of Lithuanian CF chromosomes. It was not possible to characterize 35.8% of the CF Lithuanian chromosomes. Analysis of intron 8 (TG)mTn and M470V polymorphic loci did not permit the characterization of the CFTR dysfunction underlying the CF phenotype in the patients for which no CFTR mutation was identified. Thus, screening of the eight CFTR mutations identified in this study and of the large deletion CFTRdele2,3(21 kb) allows the implementation of an early molecular or confirmatory CF diagnosis for 65% of Lithuanian CF chromosomes.


Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Testes Genéticos , Reação em Cadeia da Polimerase , Substituição de Aminoácidos/genética , Fibrose Cística/etiologia , Regulador de Condutância Transmembrana em Fibrose Cística/deficiência , Testes Genéticos/métodos , Humanos , Lituânia , Deleção de Sequência
19.
Transplant Proc ; 38(4): 1181-4, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16757300

RESUMO

The development of a small animal model for hepatitis C virus (HCV) infection is a critical issue for the development of novel anti-HCV drugs. To this aim, we have tried many different approaches for generating mice carrying humanized liver. Main efforts were focused on the transplantation of human hepatocytes into immunocompromised mice (SCID-/-, Bg-/-) carrying a genetic lethal liver disease (Alb-uPA). Survival of homozygotic animals should largely depend on early transplantation with healthy hepatocytes. In parallel to establishing a colony of Alb-uPA/SCID/Bg mice, we developed a microsurgical procedure for intrasplenic xenotransplantation of healthy hepatocytes in 1-week-old mice. So far, we generated several chimeras by xenotransplanting human hepatocytes in Alb-uPA+/+/SCID-/-/Bg-/- mice at 1 week after birth. In a first step, identification of successfully engrafted animals is possible by quantification of human serum albumin and human alpha 1 antitrypsin in mouse sera. Additional preliminary histomorphological analysis of liver sections from chimeric animals was also carried out. One of the mice was transiently infected with HCV, reaching viremia levels of approximately 10(5) genomes/mL. However, the efficiency of this system to generate chimeric mice is still very limited. We are currently exploring the use of more robust models of hepatic disease. Moreover, we have been also exploring novel strategies for the generation of chimeric mice by xenotransplanting human adult stem cells, instead of human hepatocytes, at preimmune stages of development.


Assuntos
Hepatite C/tratamento farmacológico , Hepatócitos/transplante , Animais , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Hepatopatias/cirurgia , Neoplasias Hepáticas , Camundongos , Camundongos SCID , Camundongos Transgênicos , Albumina Sérica/genética , Transplante Heterólogo , Ativador de Plasminogênio Tipo Uroquinase/genética
20.
Papillomavirus Res ; 2: 178-184, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-29074179

RESUMO

We explored HPV vaccination intention and its determinants among male clients of the sexually transmitted infections (STI) clinic in Amsterdam. In 2015, male clients aged ≥18 years were invited to complete a web-based questionnaire regarding HPV vaccination intention and socio-psychological determinants. Determinants (scale -3 to +3) were assessed with linear regression, stratified for men who have sex with men (MSM) (including men who have sex with men and women) and men who only have sex with women (MSW). Additionally, we explored the effect of out-of-pocket payment on intention. Of 1490 participants (median age 33 years [IQR:25-44]), 1,053(71%) were MSM. HPV vaccination intention was high (mean 1.68, 95%CI:1.55-1.81 among MSW; mean 2.35, 95%CI:2.29-2.42 among MSM). In multivariable analyses, socio-psychological determinants had similar effects on intention in both groups (R2=0.70 among MSW; R2=0.68 among MSM), except for subjective norms, self-efficacy, and HPV knowledge (significantly stronger associations among MSW). HPV vaccination intention decreased significantly when vaccination would require out-of-pocket payment; intention was negative at the current list price (€350). HPV vaccination intention among male clients of the Amsterdam STI-clinic is high and variance in intention was mostly be explained by socio-psychological factors. Out-of-pocket payment had a strong negative effect on HPV vaccination intention.


Assuntos
Imunização/estatística & dados numéricos , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Gastos em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Comportamento Sexual , Inquéritos e Questionários , Adulto Jovem
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