Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 26
Filtrar
1.
Oral Radiol ; 40(3): 445-453, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38587690

RESUMO

OBJECTIVES: The aim of this study was to evaluate, using cone-beam computed tomography (CBCT), the relationship of persistent foramen tympanicum (PFT) with degenerative changes in the temporomandibular joint (TMJ) and the presence of pneumatized glenoid fossae and articular eminences. METHOD: Two experienced oral and maxillofacial radiologists evaluated 510 CBCT scans, from which 94 patients were divided into two groups: G1-patients with PFT and G2-control group. The location of the PFT, presence, or absence of degenerative TMJ changes and morphology were evaluated. Similarly, all images were evaluated for the presence of pneumatized articular eminence and glenoid fossa. The Chi-square test and Fisher's Exact test were used for the categorical variables. A multinomial logistic regression model was performed for subgroup analysis. To assess the estimation-chance occurrence of TMJ alterations the Odds Ratio analysis was used. RESULTS: Statistically significant results were found for erosion, planning, and subchondral cyst. Regarding TMJ morphology, significant results were found for: round, flat, and others. Moreover, it was possible to observe that patients who had the PFT were approximately 48 times more likely to manifest TMJ alterations and approximately 3 times more likely to manifest articular eminence pneumatization. CONCLUSION: Since individuals who have FTP have a greater chance of having TMJ and PEA changes, it is important for the dental radiologist to be aware of these signs in CBCT scans for a correct diagnosis. TRIAL REGISTRATION NUMBER: CAAE: 34328214.3.0000.0104 (11/30/2014).


Assuntos
Tomografia Computadorizada de Feixe Cônico , Transtornos da Articulação Temporomandibular , Humanos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/diagnóstico por imagem , Idoso , Adolescente , Osso Temporal/diagnóstico por imagem , Adulto Jovem
2.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 42(4): 172-178, Abr. 2024. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-232171

RESUMO

Introducción: El programa de vacunación universal con la vacuna antineumocócica conjugada 13-valente (VNC13) se implantó en Andalucía en diciembre de 2016. Métodos: Estudio transversal de colonización nasofaríngea por Streptococcus pneumoniae. Se seleccionó a 397 niños sanos en centros de atención primaria de Sevilla durante los periodos 1/4/2018-28/2/2020 y 1/11/2021-28/2/2022 (periodo VNC13). Se utilizó una colección histórica de un estudio de colonización desarrollado en niños sanos y con infección respiratoria superior entre el 1/01/2006 y el 30/06/2008 (periodo VNC7) para comparar las distribuciones de serotipos/genotipos y las tasas de resistencias antibióticas. Resultados: Un total de 76 (19%) niños estaban colonizados con S. pneumoniae en el periodo VNC13 y se dispuso de 154 aislamientos del periodo VNC7. La colonización por serotipos incluidos en VNC13 disminuyó significativamente entre los periodos VNC13 y VNC7 (11 vs. 38%; p=0,0001); los serotipos 19F (8%), 3 (1%) y 6B (1%) fueron los únicos serotipos vacunales circulantes. Los serotipos 15B/C y 11A fueron los serotipos no VNC13 más prevalentes durante el periodo VNC13 (14% y 11%, respectivamente); este último se incrementó de forma significativa entre periodos de tiempo (p=0,04). El serotipo 11A solo se asoció en el periodo VNC13 con variantes resistentes a la ampicilina del clon Spain9V-ST156 (ST6521 y genéticamente relacionado ST14698), no detectados en el periodo anterior. Conclusiones: Hubo una circulación muy residual de los serotipos vacunales durante el periodo VNC13, con excepción del serotipo19F. El serotipo 11A se incrementó de forma significativa entre los periodos VNC13 y VNC7 por expansión clonal del genotipo resistente a la ampicilina ST6521.(AU)


Background: The 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination program was introduced in December 2016 in Andalusia. Methods: A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period) were used for comparison of serotype/genotype distributions and antibiotic resistance rates. Results: Overall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11 vs. 38%, P=0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (P=0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. Conclusions: There was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.(AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Epidemiologia Molecular , Programas de Imunização , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/genética , Infecções Pneumocócicas , Ampicilina , Espanha , Estudos Transversais , Portador Sadio
3.
Enferm Infecc Microbiol Clin (Engl Ed) ; 42(4): 172-178, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37085445

RESUMO

INTRODUCTION: The 13-valent pneumococcal conjugate vaccine (PCV13) universal vaccination programme was introduced in December 2016 in Andalusia. METHODS: A cross-sectional study was conducted on the molecular epidemiology of pneumococcal nasopharyngeal colonization. A total of 397 healthy children were recruited from primary healthcare centres in Seville for the periods 1/4/2018 to 28/2/2020 and 1/11/2021 to 28/2/2022 (PCV13 period). Data from a previous carriage study conducted among healthy and sick children from 1/01/2006 to 30/06/2008 (PCV7 period), were used for comparison of serotype/genotype distributions and antibiotic resistance rates. RESULTS: Overall, 76 (19%) children were colonized with S. pneumoniae during the PCV13 period and there were information available from 154 isolates collected during the PCV7 period. Colonization with PCV13 serotypes declined significantly in the PCV13 period compared with historical controls (11% vs 38%, p = 0.0001), being serotypes 19F (8%), 3 (1%) and 6B (1%) the only circulating vaccine types. Serotypes 15B/C and 11A were the most frequently identified non-PCV13 serotypes during the PCV13 period (14% and 11%, respectively); the later one increased significantly between time periods (p = 0.04). Serotype 11A was exclusively associated in the PCV13 period with ampicillin-resistant variants of the Spain9V-ST156 clone (ST6521 and genetically related ST14698), not detected in the preceding period. CONCLUSIONS: There was a residual circulation of vaccine types following PCV13 introduction, apart from serotype 19F. Serotype 11A increased between PCV13 and PCV7 periods due to emergence and clonal expansion of ampicillin-resistant genotype ST6521.


Assuntos
Infecções Pneumocócicas , Criança , Humanos , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Estudos Transversais , Epidemiologia Molecular , Espanha/epidemiologia , Portador Sadio/epidemiologia , Streptococcus pneumoniae/genética , Ampicilina , Programas de Imunização
4.
Viruses ; 14(9)2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36146844

RESUMO

SARS-CoV-2 infection has become a global health problem specially exacerbated with the continuous appearance of new variants. Healthcare workers (HCW) have been one of the most affected sectors. Children have also been affected, and although infection generally presents as a mild disease, some have developed the Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We recruited 190 adults (HCW and cohabitants, April to June 2020) and 57 children (April 2020 to September 2021), of whom 12 developed PIMS-TS, in a hospital-based study in Spain. Using an in-house Luminex assay previously validated, antibody levels were measured against different spike and nucleocapsid SARS-CoV-2 proteins, including the receptor-binding domain (RBD) of the Alpha, Beta, Gamma, and Delta variants of concern (VoC). Seropositivity rates obtained from children and adults, respectively, were: 49.1% and 11% for IgG, 45.6% and 5.8% for IgA, and 35.1% and 7.3% for IgM. Higher antibody levels were detected in children who developed PIMS-TS compared to those who did not. Using the COVID-19 IgM/IgA ELISA (Vircell, S.L.) kit, widely implemented in Spanish hospitals, a high number of false positives and lower seroprevalences compared with the Luminex estimates were found, indicating a significantly lower specificity and sensitivity. Comparison of antibody levels against RBD-Wuhan versus RBD-VoCs indicated that the strongest positive correlations for all three isotypes were with RBD-Alpha, while the lowest correlations were with RBD-Delta for IgG, RBD-Gamma for IgM, and RBD-Beta for IgA. This study highlights the differences in antibody levels between groups with different demographic and clinical characteristics, as well as reporting the IgG, IgM, and IgA response to RBD VoC circulating at the study period.


Assuntos
COVID-19 , Infecções por Coronavirus , Pneumonia Viral , Adulto , Anticorpos Antivirais , Betacoronavirus , COVID-19/complicações , COVID-19/epidemiologia , Criança , Infecções por Coronavirus/epidemiologia , Pessoal de Saúde , Humanos , Imunoensaio , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Pandemias , Pneumonia Viral/epidemiologia , SARS-CoV-2 , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus , Síndrome de Resposta Inflamatória Sistêmica
5.
Epidemiol Infect ; 150: e163, 2022 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-35993492

RESUMO

This study aimed to assess the impact of the introduction of pneumococcal conjugate vaccine 13 (PCV13) on the molecular epidemiology of invasive pneumococcal disease (IPD) in children from Andalusia. A population-based prospective surveillance study was conducted on IPD in children aged <14 years from Andalusia (2018-2020). Pneumococcal invasive isolates collected between 2006 and 2009 in the two largest tertiary hospitals in Andalusia were used as pre-PCV13 controls for comparison of serotype/genotype distribution. Overall IPD incidence rate was 3.55 cases per 100 000 in 2018; increased non-significantly to 4.20 cases per 100 000 in 2019 and declined in 2020 to 1.69 cases per 100 000 (incidence rate ratio 2020 vs. 2019: 0.40, 95% confidence interval (CI) 0.20-0.89, P = 0.01). Proportion of IPD cases due to PCV13 serotypes in 2018-2020 was 28% (P = 0.0001 for comparison with 2006-2009). Serotypes 24F (15%) and 11A (8.3%) were the most frequently identified non-PCV13 serotypes (NVT) in 2018-2020. Penicillin- and/or ampicillin-resistant clones mostly belonged to clonal complex 156 (serotype 14-ST156 and ST2944 and serotype 11A-ST6521). The proportion of IPD cases caused by PCV13 serotypes declined significantly after the initiation of the PCV13 vaccination programme in 2016. Certain NVT, such as serotypes 24F and 11A, warrant future monitoring in IPD owing to invasive potential and/or antibiotic resistance rates.


Assuntos
Infecções Pneumocócicas , Criança , Humanos , Epidemiologia Molecular , Infecções Pneumocócicas/epidemiologia , Vacinas Pneumocócicas , Estudos Prospectivos , Espanha/epidemiologia , Streptococcus pneumoniae , Vacinas Conjugadas
6.
J Clin Immunol ; 42(6): 1193-1204, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35507130

RESUMO

PURPOSE: STAT1 gain-of-function (GOF) and dominant-negative (DN) STAT3 syndromes share clinical manifestations including infectious and inflammatory manifestations. Targeted treatment with Janus-kinase (JAK) inhibitors shows promising results in treating STAT1 GOF-associated symptoms while management of DN STAT3 patients has been largely supportive. We here assessed the impact of ruxolitinib on the JAK-STAT1/3 pathway in DN STAT3 patients' cells. METHODS: Using flow cytometry, immunoblot, qPCR, and ELISA techniques, we examined the levels of basal STAT1 and phosphorylated STAT1 (pSTAT1) of cells obtained from DN STAT3, STAT1 GOF patients, and healthy donors following stimulation with type I/II interferons (IFNs) or interleukin (IL)-6. We also describe the impact of ruxolitinib on cytokine-induced STAT1 signaling in these patients. RESULTS: DN STAT3 and STAT1 GOF resulted in a similar phenotype characterized by increased STAT1 and pSTAT1 levels in response to IFNα (CD3+ cells) and IFNγ (CD14+ monocytes). STAT1-downstream gene expression and C-X-C motif chemokine 10 secretion were higher in most DN STAT3 patients upon stimulation compared to healthy controls. Ex vivo treatment with the JAK1/2-inhibitor ruxolitinib reduced cytokine responsiveness and normalized STAT1 phosphorylation in DN STAT3 and STAT1 GOF patient' cells. In addition, ex vivo treatment was effective in modulating STAT1 downstream signaling in DN STAT3 patients. CONCLUSION: In the absence of effective targeted treatment options for AD-HIES at present, modulation of the JAK/STAT1 pathway with JAK inhibitors may be further explored particularly in those AD-HIES patients with autoimmune and/or autoinflammatory manifestations.


Assuntos
Inibidores de Janus Quinases , Quimiocinas/genética , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Interferons/metabolismo , Interleucina-6/metabolismo , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , Mutação , Nitrilas , Fosforilação , Pirazóis , Pirimidinas , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT3/genética
7.
Front Pediatr ; 10: 899445, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36619503

RESUMO

The COVID-19 pandemic represents a valuable opportunity to carry out cohort studies that allow us to advance our knowledge on pathophysiological mechanisms of neuropsychiatric diseases. One of these opportunities is the study of the relationships between inflammation, brain development and an increased risk of suffering neuropsychiatric disorders. Based on the hypothesis that neuroinflammation during early stages of life is associated with neurodevelopmental disorders and confers a greater risk of developing neuropsychiatric disorders, we propose a cohort study of SARS-CoV-2-infected pregnant women and their newborns. The main objective of SIGNATURE project is to explore how the presence of prenatal SARS-CoV-2 infection and other non-infectious stressors generates an abnormal inflammatory activity in the newborn. The cohort of women during the COVID-19 pandemic will be psychological and biological monitored during their pregnancy, delivery, childbirth and postpartum. The biological information of the umbilical cord (foetus blood) and peripheral blood from the mother will be obtained after childbirth. These samples and the clinical characterisation of the cohort of mothers and newborns, are tremendously valuable at this time. This is a protocol report and no analyses have been conducted yet, being currently at, our study is in the recruitment process step. At the time of this publication, we have identified 1,060 SARS-CoV-2 infected mothers and all have already given birth. From the total of identified mothers, we have recruited 537 SARS-COV-2 infected women and all of them have completed the mental health assessment during pregnancy. We have collected biological samples from 119 mothers and babies. Additionally, we have recruited 390 non-infected pregnant women.

8.
Gen Dent ; 69(6): 69-73, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34678747

RESUMO

Paracoccidioidomycosis is an infectious disease caused by Paracoccidioides brasiliensis and is endemic in South America. A patient can be infected via fungus inhalation in the mycelium phase. Oral manifestations of paracoccidioidomycosis are often the first clinical sign of disease, but their appearance can vary. As a result, many clinicians are unable to identify this infection early. Late diagnosis can result in serious complications, such as pulmonary changes, or even death. This article reports 2 cases of paracoccidioidomycosis with different oral manifestations, reviews the literature, and discusses the various appearances of this infection and its differential diagnoses in order to emphasize the importance of performing a detailed clinical examination to make an accurate diagnosis and refer the patient for appropriate treatment.


Assuntos
Paracoccidioides , Paracoccidioidomicose , Diagnóstico Diferencial , Humanos , Paracoccidioidomicose/diagnóstico
9.
Pediatr Allergy Immunol ; 32(8): 1804-1812, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34289170

RESUMO

BACKGROUND: Inherited chronic mucocutaneous candidiasis (CMC) is often caused by inborn errors of immunity, impairing the response to, or the production of IL-17A and IL-17F. About half of the cases carry STAT1 gain-of-function (GOF) mutations. Only few patients have been reported with mutations of TRAF3IP2, a gene encoding the adaptor ACT1 essential for IL-17 receptor(R) signaling. We investigated a 10-year-old girl with CMC, carrying a heterozygous variant of STAT1 and compound heterozygous variants of TRAF3IP2. METHODS: By flow cytometry, STAT1 levels and phosphorylation (CD14+) as well as IL-17A, IL-22, IFN-γ, and IL-4 production (memory CD4+ T cells) were determined. ACT1 expression and binding to IL-17RA were assessed by Western blot and co-immunoprecipitation in HEK-293T cells transfected with plasmids encoding wild-type or mutant HA-tagged ACT1 and Flag-IL-17RA. We evaluated IL-17A responses by measuring luciferase induction under a NF-κB-driven reporter system in HEK-293T cells and Gro-α secretion in fibroblasts. RESULTS: A STAT1 variant (c.1363G>A/p.V455I) was identified by next-generation sequencing and classified as likely non-pathogenic as functional testing revealed normal STAT1 expression and phosphorylation upon IFN-γ. We also found compound heterozygous variants (c.1325A>G/p.D451G and c.1335delA/p.K454fs11*) of TRAF3IP2. By overexpression, despite normal protein expression, and impaired (K454fs11*) or normal (D451G) interaction with IL-17RA, both mutant alleles resulted in impaired NF-κB activation. Patient's fibroblasts displayed abolished GRO-α secretion upon IL-17A stimulation. Finally, ex vivo CD4+ T cells showed increased IL-17A, IL-22, and IL-4 and normal low IFN-γ expression upon stimulation. CONCLUSION: We identify novel compound heterozygous variants of TRAFP3IP2 causing autosomal recessive ACT1 deficiency in a child with CMC and provide a review of the current literature.


Assuntos
Candidíase Mucocutânea Crônica , Proteínas Adaptadoras de Transdução de Sinal , Alelos , Candidíase Mucocutânea Crônica/genética , Criança , Feminino , Humanos , Mutação , Fosforilação , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo , Linfócitos T/metabolismo
10.
Pathogens ; 10(6)2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34199852

RESUMO

BACKGROUND: Antibody dynamics over time after SARS-CoV-2 infection are still unclear, and data regarding children are scarce. METHODS: A prospective cohort study was performed including children infected by SARS-CoV-2 between March and May 2020. Patients were categorized into 3 groups: children admitted with COVID-19; outpatient children with mild COVID-19; and seropositive children participating in a seroprevalence study among cohabitants of infected healthcare workers (HCWs). Six months after the infection, a new serological control was performed. RESULTS: A total of 58 children were included, 50% male (median age 8.3 [IQR 2.8-13.5] years). The median time between the two serological studies was 186 (IQR 176-192) days, and 86% (48/56) of the children maintained positive IgG six months after the infection. This percentage was 100% in admitted patients and 78% among the rest of the included children (p = 0.022). The diagnoses of lower respiratory tract infection and multisystemic inflammatory syndrome were associated with persistence of IgG (p = 0.035). The children of HCWs in the seroprevalence study lost antibodies more often (p = 0.017). Initial IgG titers of the children who remained positive six months after the infection were significantly higher (p = 0.008). CONCLUSIONS: Most children infected by SARS-CoV-2 maintain a positive serological response six months after the infection. Those children who lost their IgG titer were more frequently asymptomatic or mildly symptomatic, presenting with low antibody titers after the infection.

12.
Pediatr Infect Dis J ; 40(5): e185-e188, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33591078

RESUMO

BACKGROUND: Data on SARS-CoV-2 transmission among children living with healthcare workers (HCWs) are scarce. METHODS: A cross-sectional study was performed at a tertiary Hospital in Madrid, including children of HCW who suffered from SARS-CoV-2 infection between March and May 2020. Children underwent enzyme-linked immunosorbent serological study for detecting SARS-CoV-2 antibodies: VIRCELL IgG assay. RESULTS: One hundred thirteen children from 69 HCWs with confirmed SARS-CoV-2 infection were recruited: 47 children had positive IgG (41.6%). Children secondary attack rate was 43.7% (25% if both parents have had asymptomatic infection; 39.5% if one parent was symptomatic; and 47% when both parents had symptoms). Having a positive sibling was associated with a positive IgG result (odds ratio = 12.2; 95% confidence interval: 4.4-33.7, P < 0.001). Median age was higher in IgG positive children (P = 0.022). Children who referred anosmia presented higher IgG titles (P < 0.04). CONCLUSIONS: We observed a very high SARS-CoV-2 transmission in children of HCW during the first pandemic wave, especially when both parents were symptomatic. Having a positive sibling was associated with seroconversion, supporting the important role of family clusters in the transmission of SARS-CoV-2.


Assuntos
COVID-19/transmissão , Pessoal de Saúde , Adolescente , Anticorpos Antivirais/sangue , Infecções Assintomáticas/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Transmissão de Doença Infecciosa , Família , Feminino , Humanos , Imunoglobulina G/sangue , Transmissão de Doença Infecciosa do Paciente para o Profissional , Masculino , Pandemias , SARS-CoV-2/isolamento & purificação , Soroconversão , Espanha/epidemiologia , Centros de Atenção Terciária
13.
J Acquir Immune Defic Syndr ; 85(2): 252-256, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32658127

RESUMO

OBJECTIVES: This study aims to analyze the association of the presence of common polymorphisms [single nucleotide polymorphisms (SNPs)] on Toll-like receptors (TLRs), such as TLR9-1635A/G, TLR2-1892A/C, TLR2-2258G/A, TLR4-899A/G, and TLR4-1196C/T, with the viral rebound after stopping antiretroviral treatment (ART). CCR5-Δ32 deletion and HLA-A/HLA-B alleles were also analyzed. DESIGN: Interruption of ART may be required to investigate the outcome of strategies aimed to achieve drug-free HIV remission or cure. However, interruption of ART is currently not indicated. This was a retrospective longitudinal study that included 57 long-term suppressed HIV-1-infected individuals. METHODS: TLR SNPs were detected by real-time polymerase chain reaction (PCR). CCR5-Δ32 was analyzed by conventional PCR and HLA-A and HLA-B alleles by PCR-SSOP Luminex. RESULTS: HIV-1 RNA rebound at week 4 after treatment interruption positively correlated with pre-ART HIV-1 load (P = 0.025). The TLR9-1635AA genotype was independently associated with a higher HIV-1 rebound compared with those with AG + GG genotype (multivariate stepwise regression analysis, P = 0.004). Women had lower HIV-1 RNA load both at rebound and during the 72 weeks of follow-up compared with men (P < 0.05 at all time-points), whereas CD4 nadir and CD4 count set-point were similar according to sex. The pre-ART viral load was independently associated with the viral set-point (P = 0.001), whereas the presence of the HLA-A01 allele (P = 0.027) and the CD4 nadir (P = 0.001) were associated with the CD4 count set-point. CONCLUSIONS: The association of the TLR9-1635AA genotype with a higher HIV-1 rebound suggests that this SNP may affect the results from strategies requiring interruption of ART aimed to cure HIV-1 infection.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Receptor Toll-Like 9/genética , Contagem de Linfócito CD4 , Feminino , HIV-1 , Humanos , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Carga Viral , Latência Viral
14.
Pediatr Infect Dis J ; 38(2): 157-160, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29613974

RESUMO

Newborn screening for severe combined immunodeficiency using T-cell receptor excision circles allows prompt diagnosis and initiation of supportive and curative therapy thereby reducing morbidity and mortality. However, profound combined immunodeficiencies with normal numbers of nonfunctional T cells will go undetected. We present a patient with calcium release-activated calcium channel gene (ORAI1) deficiency and normal T-cell receptor excision circle numbers observed after diagnosis at the age of 14 months who suffered from disseminated fatal cytomegalovirus and Pneumocystis jirovecii infection, demonstrating a potential pitfall of the current newborn screening program.


Assuntos
Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , Testes Diagnósticos de Rotina/métodos , Triagem Neonatal/métodos , Pneumocystis carinii/isolamento & purificação , Pneumonia por Pneumocystis/diagnóstico , Imunodeficiência Combinada Severa/diagnóstico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/patologia , Evolução Fatal , Feminino , Humanos , Lactente , Recém-Nascido , Pneumonia por Pneumocystis/complicações , Pneumonia por Pneumocystis/patologia , Imunodeficiência Combinada Severa/complicações , Linfócitos T/patologia
15.
Pediatr Allergy Immunol ; 27(1): 70-7, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26498110

RESUMO

BACKGROUND: Early diagnosis of primary immunodeficiency such as severe combined immunodeficiency (SCID) and X-linked agammaglobulinemia (XLA) improves outcome of affected children. T-cell-receptor-excision circles (TRECs) and kappa-deleting-recombination-excision circles (KRECs) determination from dried blood spots (DBS) identify neonates with severe T- and/or B-lymphopenia. No prospective data exist of the impact of gestational age (GA) and birth weight (BW) on TRECs and KRECs values. METHODS: TRECs and KRECs determination using triplex RT-PCR (TRECS-KRECS-ß-actin-Assay) from prospectively collected DBS between 02/2014 and 02/2015 in three hospitals in Seville, Spain. Cut-off levels were TRECs < 6/punch, KRECs < 4/punch and -ß-actin>700/punch. Internal (SCID, XLA, ataxia telangiectasia) and external controls (NBS quality assurance program, CDC) were included. RESULTS: A total of 5160 DBS were tested. Re-punch was needed in 77 samples (1.5%) due to insufficient ß-actin (<700 copies/punch). Pre-term neonates (GA<37 weeks) and neonates with a BW<2500 g showed significantly lower TRECs and KRECs levels (p < 0.001). Due to repeat positive results five neonates were re-called (<0.1%): Fatal chromosomopathy (n = 1; TRECs 1/KRECs 4); extreme pre-maturity (n = 2; TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch); neonates born to mothers receiving azathioprine during pregnancy (n = 2; TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch). All internal and external controls were correctly identified. CONCLUSIONS: TRECS-KRECS-ß-actin-Assay correctly identifies T- and B-cell lymphopenias. Pre-maturity and low BW is associated with lower TREC and KREC levels. Extreme pre-maturity and maternal immune suppressive therapy may be a cause for false positive results of TRECs and KRECs values, respectively. To reduce the rate of insufficient samples, DBS extraction and storage need to be improved.


Assuntos
Linfócitos B/imunologia , Teste em Amostras de Sangue Seco , Síndromes de Imunodeficiência/diagnóstico , Reação em Cadeia da Polimerase Multiplex , Triagem Neonatal/métodos , Reação em Cadeia da Polimerase em Tempo Real , Linfócitos T/imunologia , Artefatos , Peso ao Nascer , Estudos de Casos e Controles , Teste em Amostras de Sangue Seco/normas , Reações Falso-Positivas , Feminino , Marcadores Genéticos , Idade Gestacional , Humanos , Síndromes de Imunodeficiência/sangue , Síndromes de Imunodeficiência/genética , Síndromes de Imunodeficiência/imunologia , Recém-Nascido de Baixo Peso/sangue , Recém-Nascido de Baixo Peso/imunologia , Recém-Nascido , Recém-Nascido Prematuro/sangue , Recém-Nascido Prematuro/imunologia , Estudos Longitudinais , Masculino , Reação em Cadeia da Polimerase Multiplex/normas , Triagem Neonatal/normas , Valor Preditivo dos Testes , Estudos Prospectivos , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Fatores de Risco , Índice de Gravidade de Doença , Espanha
16.
Dis Model Mech ; 8(2): 157-68, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25540130

RESUMO

Embryopathies that develop as a consequence of maternal diabetes have been studied intensely in both experimental and clinical scenarios. Accordingly, hyperglycaemia has been shown to downregulate the expression of elements in the non-canonical Wnt-PCP pathway, such as the Dishevelled-associated activator of morphogenesis 1 (Daam1) and Vangl2. Daam1 is a formin that is essential for actin polymerization and for cytoskeletal reorganization, and it is expressed strongly in certain organs during mouse development, including the eye, neural tube and heart. Daam1(gt/gt) and Daam1(gt/+) embryos develop ocular defects (anophthalmia or microphthalmia) that are similar to those detected as a result of hyperglycaemia. Indeed, studying the effects of maternal diabetes on the Wnt-PCP pathway demonstrated that there was strong association with the Daam1 genotype, whereby the embryopathy observed in Daam1(gt/+) mutant embryos of diabetic dams was more severe. There was evidence that embryonic exposure to glucose in vitro diminishes the expression of genes in the Wnt-PCP pathway, leading to altered cytoskeletal organization, cell shape and cell polarity in the optic vesicle. Hence, the Wnt-PCP pathway appears to influence cell morphology and cell polarity, events that drive the cellular movements required for optic vesicle formation and that, in turn, are required to maintain the fate determination. Here, we demonstrate that the Wnt-PCP pathway is involved in the early stages of mouse eye development and that it is altered by diabetes, provoking the ocular phenotype observed in the affected embryos.


Assuntos
Polaridade Celular , Desenvolvimento Embrionário , Olho/embriologia , Via de Sinalização Wnt , Animais , Biomarcadores/metabolismo , Polaridade Celular/efeitos dos fármacos , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Diabetes Mellitus Experimental/patologia , Embrião de Mamíferos/anormalidades , Embrião de Mamíferos/efeitos dos fármacos , Embrião de Mamíferos/patologia , Desenvolvimento Embrionário/efeitos dos fármacos , Olho/patologia , Anormalidades do Olho/embriologia , Anormalidades do Olho/patologia , Proteínas do Olho/metabolismo , Feminino , Glucose/metabolismo , Glucose/farmacologia , Proteínas de Homeodomínio/metabolismo , Imuno-Histoquímica , Masculino , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Mutação/genética , Fator de Transcrição PAX6 , Fatores de Transcrição Box Pareados/metabolismo , Gravidez , Proteínas Repressoras/metabolismo , Via de Sinalização Wnt/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/metabolismo
17.
AIDS ; 28(13): 1989-92, 2014 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-25259707

RESUMO

A cross-sectional study of 77 chronic HIV-infected children revealed higher levels of biomarkers of inflammation (ultrasensitive C-reactive protein, D-dimer and ß-2-microglobulin), immune activation (HLA-DR+ CD38+ CD4+ and CD8+ T cells) and microbial translocation [lipopolysaccaride (LPS), microbial 16S rDNA and sCD14] than 32 healthy controls. Immune activation was higher in viremic children, but microbial translocation occurred independently of viraemia and T cell activation. Our results do not support a relevant role of microbial translocation in T cell activation in chronic HIV-infected children, proposing a need to develop strategies to minimize microbial translocation in the future.


Assuntos
Translocação Bacteriana/imunologia , Infecções por HIV/imunologia , Ativação Linfocitária , Linfócitos T/imunologia , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino
18.
Pediatr Crit Care Med ; 14(8): 796-800, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23925144

RESUMO

OBJECTIVES: To determine human beta-defensin-2 levels in term and preterm neonates at birth and to evaluate its impact on sepsis. DESIGN: Observational study. SETTING: Single tertiary care hospital. PATIENTS: Term neonates and preterm neonates were recruited and divided in groups according to important clinical events. INTERVENTIONS: Cord blood samples were drawn from all newborns immediately after birth. Human beta-defensin-2 levels were determined using enzyme-linked immunosorbent assay technology. All neonates were followed clinically during the first 30 days of life. MEASUREMENTS AND MAIN RESULTS: Forty-two term and 31 preterm neonates were enrolled. Human beta-defensin-2 levels in term neonates were higher compared with preterm infants (median, 1,882 vs 918 pg/mL; p = 0.003) and correlated with gestational age and birth weight. Of 31 preterm neonates, seven suffered from late-onset sepsis, and this was associated with lower human beta-defensin-2 levels (median, 513 vs 1,411 pg/mL; p = 0.006). CONCLUSION: Preterm neonates show lower human beta-defensin-2 levels in cord blood compared with term neonates. Low human beta-defensin-2 levels in preterm neonates might be associated with an increased risk of late-onset sepsis.


Assuntos
Doenças do Prematuro/sangue , Recém-Nascido Prematuro/sangue , Sepse/sangue , beta-Defensinas/sangue , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
19.
Dev Dyn ; 241(11): 1808-15, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22911573

RESUMO

BACKGROUND: The ventral ectodermal ridge (VER) is an important signalling centre in the mouse tail-bud following completion of gastrulation. BMP regulation is essential for VER function, but how these signals are transmitted between adjacent tissues is unclear. RESULTS: We investigated the idea that extracellular matrix components might be involved, using immunohistochemistry and in situ hybridisation to detect all known α, ß, and γ laminin chains and their mRNAs in the early tail bud. We identified an apparently novel laminin variant, comprising α5, ß3 and γ2 chains, as a major component of the VER basement membrane at E9.5. Strikingly, only the mRNAs for these chains were co-expressed in VER cells, suggesting that lamin532 may be the sole basement membrane laminin at this stage. Since α6 integrin was also expressed in VER cells, this raises the possibility of cell-matrix interactions regulating BMP signalling at this site of caudal morphogenesis. CONCLUSIONS: Laminin532 could interact with α6-containing integrin to direct differentiation of the specialised VER cells from surface ectoderm.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Ectoderma/metabolismo , Integrinas/metabolismo , Laminina/metabolismo , Animais , Proteínas Morfogenéticas Ósseas/genética , Ectoderma/embriologia , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Integrinas/genética , Laminina/genética , Camundongos , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
20.
Virol J ; 8: 416, 2011 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-21871090

RESUMO

BACKGROUND: Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations. METHODS: Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA. RESULTS: From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I. CONCLUSIONS: The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.


Assuntos
Farmacorresistência Viral , Emigrantes e Imigrantes , Infecções por HIV/epidemiologia , Protease de HIV/genética , Transcriptase Reversa do HIV/genética , HIV-1/efeitos dos fármacos , Mutação de Sentido Incorreto , Adulto , Fármacos Anti-HIV/farmacologia , Análise por Conglomerados , Feminino , Genótipo , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Dados de Sequência Molecular , Filogenia , Prevalência , Análise de Sequência de DNA , Espanha/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...