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1.
Immunogenetics ; 74(4): 381-407, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35348847

RESUMEN

COVID-19 is a new complex multisystem disease caused by the novel coronavirus SARS-CoV-2. In slightly over 2 years, it infected nearly 500 million and killed 6 million human beings worldwide, causing an unprecedented coronavirus pandemic. Currently, the international scientific community is engaged in elucidating the molecular mechanisms of the pathophysiology of SARS-CoV-2 infection as a basis of scientific developments for the future control of COVID-19. Global exome and genome analysis efforts work to define the human genetics of protective immunity to SARS-CoV-2 infection. Here, we review the current knowledge regarding the SARS-CoV-2 infection, the implications of COVID-19 to Public Health and discuss genotype to phenotype association approaches that could be exploited through the selection of candidate genes to identify the genetic determinants of severe COVID-19.


Asunto(s)
COVID-19 , COVID-19/genética , Predisposición Genética a la Enfermedad , Humanos , Pandemias , Salud Pública , SARS-CoV-2
2.
Cardiol Young ; 32(1): 132-134, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34134810

RESUMEN

CHD may, at times, occur in the framework of other rare pathologies. These, having similar clinical manifestations, present a diagnostic dilemma for the clinician.The authors present the case of an infant with non-syndromic complete atrioventricular septal defect, whose post-operative period was surprisingly complicated by progressive pulmonary hypertension. Despite intensive care, the infant ultimately died. The diagnosis of unilateral primary pulmonary lymphangiectasia was only possible post mortem.


Asunto(s)
Defectos de los Tabiques Cardíacos , Hipertensión Pulmonar , Enfermedades Pulmonares , Linfangiectasia , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Lactante , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico , Linfangiectasia/diagnóstico
3.
J Biol Chem ; 294(16): 6397-6404, 2019 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-30814250

RESUMEN

As anionic biopolymers, oligonucleotides can have biological functions independent from their roles as the medium for the storage and flow of genetic information. In this paper, we investigated the interaction between DNA and the pro-inflammatory cytokine tumor necrosis factor-α (TNFα). Although various forms of DNA bind to TNFα with low µm dissociation constants, the interaction stabilizes the trimeric form of TNFα and enhances its cytotoxic effect. Based on this mechanism, a photoswitchable TNFα (TNFα-2-nitroveratryloxycarbonyl) has been designed whose sensitivity to DNA-mediated up-regulation of TNFα activity can be tuned by light irradiation. The mechanism described in this study represents a general model to understand the involvement of nonspecific interactions among biomolecules in regulating their biological functions. Because the interaction is not DNA sequence-specific, the resulting effect should be considered for oligonucleotide-based therapeutics in general.


Asunto(s)
ADN/química , Multimerización de Proteína , Factor de Necrosis Tumoral alfa/química , Animales , Línea Celular , ADN/metabolismo , Humanos , Ratones , Factor de Necrosis Tumoral alfa/metabolismo
4.
Chembiochem ; 21(8): 1144-1149, 2020 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-31674719

RESUMEN

The study of populations of large size and high diversity is limited by the capability of collecting data. Moreover, for a pool of individuals, each associated with a unique characteristic feature, as the pool size grows, the possible interactions increase exponentially and quickly go beyond the limit of computation and experimental studies. Herein, the design of DNA libraries with various diversity is reported. By using a facile analytical method based on real-time PCR, the diversity of a pool of DNA can be evaluated to allow extraordinarily high heterogenicity (e.g., >1 trillion). It is demonstrated that these DNA libraries can be used to model heterogeneous populations; these libraries exhibit functions such as self-protection, suitability for biased expansion, and the possibility to evolve into amorphous structures. The method has shown the remarkable power of parallel computing with DNA, since it can resemble an analogue computer and be applied in selection-based biotechnology methods, such as DNA-encoded chemical libraries. As a chemical approach to solve problems traditionally for genetic and statistical analysis, the method provides a quick and cost-efficient evaluation of library diversity for intermediate steps through a selection process.


Asunto(s)
ADN/análisis , ADN/química , Descubrimiento de Drogas , Biblioteca de Genes , Reacción en Cadena de la Polimerasa/métodos , Bibliotecas de Moléculas Pequeñas/química , ADN/genética , Humanos
5.
Pediatr Cardiol ; 40(5): 892-900, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31069431

RESUMEN

The approach to pediatric asymptomatic Wolff-Parkinson-White (WPW) patients is controversial. The objective of this review is to update the last consensus of specialists of the Pediatric and Congenital Electrophysiology Society/Heart Rhythm Society on this subject in order to summarize the most recent evidence on the management of young patients with asymptomatic WPW pattern. A systematic review of the literature published between 2008 and 2018 was performed taking into account the protocol of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in PubMed (including Cochrane), Embase, and Web of Science. Observational, experimental, and multicentric studies were included. Out of a total of 37 articles selected, 4 were considered eligible. Most studies considered a cutoff age of 8 or greater as recommended in the 2012 consensus. The identification of a shortest pre-excitatory RR interval (SPERRI) ≤ 250 ms seems to be the best predictor for risk stratification. The importance of routine isoprenaline use to improve the sensitivity of the electrophysiological study to identify patients at high risk of sudden death was consensual. Prophylactic ablative therapy has been indicated in asymptomatic children with an accessory pathway (AP) who have a low SPERRI and/or a low effective anterograde period of the AP and/or multiple APs. Despite the evidence found in the most recent studies, more studies are warranted in this setting.


Asunto(s)
Enfermedades Asintomáticas , Síndrome de Wolff-Parkinson-White/terapia , Fascículo Atrioventricular Accesorio/congénito , Adolescente , Niño , Consenso , Electrocardiografía , Femenino , Humanos , Masculino , Síndrome de Wolff-Parkinson-White/diagnóstico por imagen , Síndrome de Wolff-Parkinson-White/mortalidad
6.
Cardiol Young ; 29(5): 711-713, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31044690

RESUMEN

Congenital stenosis of the pulmonary veins is a rare condition whose outcome is guarded despite the available treatment options. We report a case of a 6-month-old infant with significant stenosis of all four pulmonary veins.


Asunto(s)
Insuficiencia Cardíaca/etiología , Venas Pulmonares/anomalías , Venas Pulmonares/diagnóstico por imagen , Angiografía por Tomografía Computarizada , Constricción Patológica , Ecocardiografía Doppler , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Lactante
7.
Am J Epidemiol ; 187(12): 2541-2549, 2018 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-30099487

RESUMEN

Although the impact of deaths occurring during the 1918-1919 influenza pandemic has been assessed in many archeo-epidemiologic studies, detailed estimates are not available for Portugal. We applied negative binomial models to monthly data on respiratory-related and all-cause deaths at the national and district levels from Portugal for 1916-1922. Influenza-related excess mortality was computed as the difference between observed and expected deaths. Poisson regression was used to estimate the association of geographic and sociodemographic factors with excess mortality. Two waves of pandemic influenza-July 1918 to January 1919 and April to May 1919-were identified, for which the excess all-cause death rate was 195.7 per 10,000 persons. All districts of Portugal were affected. The pandemic hit earlier in southeastern districts and the main cities, but excess mortality was highest in the northeast, in line with the high death burden experienced by northern Spanish provinces. During the period of intense excess mortality (fall/winter 1918-1919), population density was negatively associated with pandemic impact. This pattern changed during the March 1919 to June 1920 wave, when excess mortality increased with population density and in northern and western directions. Portuguese islands were less and later affected. Given the geographic heterogeneity evidenced in our study, subnational sociodemographic characteristics and connectivity should be integrated in pandemic preparedness plans.


Asunto(s)
Influenza Pandémica, 1918-1919/historia , Gripe Humana/epidemiología , Gripe Humana/historia , Distribución por Edad , Causas de Muerte , Historia del Siglo XX , Humanos , Influenza Pandémica, 1918-1919/mortalidad , Gripe Humana/mortalidad , Modelos Estadísticos , Portugal/epidemiología , Enfermedades Respiratorias/mortalidad , Distribución por Sexo , Factores Socioeconómicos , Análisis Espacio-Temporal
8.
Immunogenetics ; 70(3): 169-177, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-28842783

RESUMEN

Influenza epidemics are a serious global public health and economic problem. The IFITM3 allele (rs12252-C) was suggested as a population-based genetic risk factor for severe influenza virus infection by A(H1N1)pdm09. We analyzed the population genetics of IFITM3 variants in the Portuguese general population (n = 200) and Central Africans (largely Angolan) (n = 148) as well as its association to influenza severity in Portuguese patients (n = 41). Seven SNPs, within the 352 bp IFITM3 amplicon around rs12252, were identified. SNP distributions in the Portuguese appeared at an intermediate level between the Africans and other Europeans. According to HapMap, rs34481144 belongs to the same linkage disequilibrium (LD) block as rs12252 and is in strong LD with rs6421983. A negative association with severe relative to mild disease was observed for allele rs34481144-A, indicating a protective effect under the dominant model. Moreover, haplotype Hap4 with rs34481144-A, not including rs12252-C, was significantly associated to mild influenza. Conversely, although with borderline significance, haplotype Hap1 with rs34481144-G, not including rs12252-C, was associated to severe disease. Moreover, in comparison to the general Portuguese population, statistical significant differences in the frequencies of the protective allele rs34481144-A in the severe disease group, the deleterious Hap1 in the mild disease group, and the protective Hap4 in the severe disease group were observed. The population attributable risk (PAR) for the targeted rs34481144 allele or genotype was of 55.91 and 64.44% in the general population and the mildly infected individuals, respectively. Implication of these variants in disease phenotype needs further validation, namely through functional analysis as is discussed.


Asunto(s)
Genética de Población , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/genética , Proteínas de la Membrana/genética , Proteínas de Unión al ARN/genética , Adulto , África Central/epidemiología , Alelos , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Subtipo H1N1 del Virus de la Influenza A/inmunología , Gripe Humana/epidemiología , Gripe Humana/inmunología , Gripe Humana/virología , Masculino , Proteínas de la Membrana/inmunología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Portugal/epidemiología , Proteínas de Unión al ARN/inmunología , Factores de Riesgo , Índice de Severidad de la Enfermedad
9.
Bull World Health Organ ; 96(2): 122-128, 2018 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-29403115

RESUMEN

The formulation of accurate clinical case definitions is an integral part of an effective process of public health surveillance. Although such definitions should, ideally, be based on a standardized and fixed collection of defining criteria, they often require revision to reflect new knowledge of the condition involved and improvements in diagnostic testing. Optimal case definitions also need to have a balance of sensitivity and specificity that reflects their intended use. After the 2009-2010 H1N1 influenza pandemic, the World Health Organization (WHO) initiated a technical consultation on global influenza surveillance. This prompted improvements in the sensitivity and specificity of the case definition for influenza - i.e. a respiratory disease that lacks uniquely defining symptomology. The revision process not only modified the definition of influenza-like illness, to include a simplified list of the criteria shown to be most predictive of influenza infection, but also clarified the language used for the definition, to enhance interpretability. To capture severe cases of influenza that required hospitalization, a new case definition was also developed for severe acute respiratory infection in all age groups. The new definitions have been found to capture more cases without compromising specificity. Despite the challenge still posed in the clinical separation of influenza from other respiratory infections, the global use of the new WHO case definitions should help determine global trends in the characteristics and transmission of influenza viruses and the associated disease burden.


La formulation de définitions précises de cas cliniques fait partie intégrante d'un processus efficace de surveillance de la santé publique. Alors que ces définitions devraient, dans l'idéal, s'appuyer sur un ensemble standardisé et fixe de critères de définition, elles nécessitent souvent une révision pour tenir compte des nouvelles connaissances relatives à la maladie concernée et des améliorations apportées aux tests diagnostiques. Pour être optimales, les définitions de cas doivent aussi établir un équilibre entre sensibilité et spécificité qui reflète leur utilisation aux fins prévues. À la suite de la pandémie de grippe H1N1 de 2009-2010, l'Organisation mondiale de la Santé (OMS) a lancé une consultation technique sur la surveillance mondiale de la grippe. Cela a conduit à des améliorations concernant la sensibilité et la spécificité de la définition de cas pour la grippe ­ c'est-à-dire une maladie respiratoire dont seule la symptomatologie reste à définir. Le processus de révision n'a pas seulement modifié la définition du syndrome de type grippal pour inclure une liste simplifiée des critères le mieux à même de prédire une infection grippale, il a également permis de clarifier le langage utilisé dans la définition pour en améliorer l'interprétation. Par ailleurs, afin de tenir compte des cas sévères de grippe qui nécessitaient une hospitalisation, une nouvelle définition de cas a été introduite concernant l'infection aigüe sévère des voies respiratoires dans tous les groupes d'âge. Il a été constaté que les nouvelles définitions reflétaient davantage de cas, sans pour autant compromettre la spécificité. S'il est vrai que la distinction clinique de la grippe des autres infections respiratoires continue de poser problème, l'utilisation mondiale des nouvelles définitions de cas de l'OMS devrait permettre de dégager des tendances mondiales concernant les caractéristiques et la transmission des virus grippaux ainsi que la charge de morbidité qui leur est associée.


La elaboración de definiciones precisas de los casos clínicos es una parte fundamental de un proceso efectivo de la vigilancia de la salud pública. Aunque tales definiciones deberían, idealmente, estar basadas en una recopilación estandarizada y fija de criterios de definición, a menudo necesitan una revisión para reflejar el nuevo conocimiento de la enfermedad existente y las mejoras en las pruebas de diagnóstico. Las definiciones óptimas de los casos también deben tener un equilibrio entre sensibilidad y especificidad que refleje su uso previsto. Después de la pandemia de gripe H1N1 en 2009-2010, la Organización Mundial de la Salud (OMS) inició una consulta técnica para la vigilancia mundial de la gripe. Esto dio lugar a mejoras en la sensibilidad y la especificidad de las definiciones de los casos de gripe, es decir, una enfermedad respiratoria que carece de una sintomatología definitoria singular. El proceso de revisión no solo modificó la definición de las enfermedades similares a la gripe para incluir una lista simplificada de los criterios que demostraron ser más predictivos de la infección por gripe, sino que también aclaró el lenguaje utilizado para la definición, con el fin de mejorar su interpretación. Para englobar los casos graves de gripe que requirieron hospitalización, también se desarrolló una nueva definición de los casos de la infección respiratoria aguda grave en todos los grupos de edad. Se ha descubierto que las nuevas definiciones engloban más casos sin comprometer la especificidad. A pesar del desafío que todavía plantea la separación clínica de la gripe de otras infecciones respiratorias, el uso global de las nuevas definiciones de los casos de la OMS debería ayudar a determinar las tendencias mundiales en las características y transmisión de los virus de la gripe y la carga de la enfermedad asociada.


Asunto(s)
Gripe Humana/diagnóstico , Infecciones del Sistema Respiratorio/diagnóstico , Niño , Preescolar , Tos , Hospitalización , Humanos , Lactante , Subtipo H1N1 del Virus de la Influenza A , Infecciones del Sistema Respiratorio/virología
10.
J Med Virol ; 87(1): 45-56, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25042157

RESUMEN

Neuraminidase inhibitors (NAIs) oseltamivir and zanamivir are currently the only effective antiviral drugs available worldwide for the management of influenza. The potential development of resistance is continually threatening their use, rationalizing and highlighting the need for a close and sustained evaluation of virus susceptibility. This study aimed to analyze and characterize the phenotypic and genotypic NAIs susceptibility profiles of A(H1N1)pdm09 viruses circulating in Portugal from 2009 to 2010/2011. A total of 144 cases of A(H1N1)pdm09 virus infection from community and hospitalized patients were studied, including three suspected cases of clinical resistance to oseltamivir. Oseltamivir resistance was confirmed for two of the suspected cases. Neuraminidase (NA) H275Y resistant marker was found in viruses from both cases but for one it was only present in 26.2% of virus population, raising questions about the minimal percentage of resistant virus that should be considered relevant. Cross-decreased susceptibility to oseltamivir and zanamivir (2-4 IC50 fold-change) was detected on viruses from two potentially linked community patients from 2009. Both viruses harbored the NA I223V mutation. NA Y155H mutation was found in 18 statistical non-outlier viruses from 2009, having no impact on virus susceptibility. The mutations at NA N369K and V241I may have contributed to the significantly higher baseline IC50 value obtained to oseltamivir for 2010/2011 viruses, compared to viruses from the pandemic period. These results may contribute to a better understanding of the relationship between phenotype and genotype, which is currently challenging, and to the global assessment of A(H1N1)pdm09 virus susceptibility profile and baseline level to NAIs.


Asunto(s)
Antivirales/farmacología , Farmacorresistencia Viral , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Oseltamivir/farmacología , Zanamivir/farmacología , Adulto , Femenino , Humanos , Lactante , Subtipo H1N1 del Virus de la Influenza A/enzimología , Subtipo H1N1 del Virus de la Influenza A/genética , Subtipo H1N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Humana/virología , Concentración 50 Inhibidora , Masculino , Persona de Mediana Edad , Mutación Missense , Neuraminidasa/genética , Portugal , Proteínas Virales/genética
11.
BMC Bioinformatics ; 15: 94, 2014 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-24684679

RESUMEN

BACKGROUND: In this study we consider DNA sequences as mathematical strings. Total and reduced alignments between two DNA sequences have been considered in the literature to measure their similarity. Results for explicit representations of some alignments have been already obtained. RESULTS: We present exact, explicit and computable formulas for the number of different possible alignments between two DNA sequences and a new formula for a class of reduced alignments. CONCLUSIONS: A unified approach for a wide class of alignments between two DNA sequences has been provided. The formula is computable and, if complemented by software development, will provide a deeper insight into the theory of sequence alignment and give rise to new comparison methods. AMS SUBJECT CLASSIFICATION: Primary 92B05, 33C20, secondary 39A14, 65Q30.


Asunto(s)
ADN/química , Alineación de Secuencia , Análisis de Secuencia de ADN/métodos , Secuencia de Bases , ADN/genética , Programas Informáticos
12.
Virology ; 578: 45-60, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36463618

RESUMEN

Influenza and COVID-19 are infectious respiratory diseases that represent a major concern to public health with social and economic impact worldwide, for which the available therapeutic options are not satisfactory. The RdRp has a central role in viral replication and thus represents a major target for the development of antiviral approaches. In this study, we focused on Influenza A virus PB1 polymerase protein and the betacoronaviruses nsp12 polymerase protein, considering their functional and structural similarities. We have performed conservation and druggability analysis to map conserved druggable regions, that may have functional or structural importance in these proteins. We disclosed the most promising and new targeting regions for the discovery of new potential polymerase inhibitors. Conserved druggable regions of putative interaction with favipiravir and molnupiravir were also mapped. We have also compared and integrated the current findings with previous research.


Asunto(s)
COVID-19 , Gripe Humana , Humanos , Antivirales/química , Proteinas del Complejo de Replicasa Viral , Gripe Humana/tratamiento farmacológico , ARN Polimerasa Dependiente del ARN/metabolismo , ARN Viral/genética
13.
Virology ; 578: 1-6, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36423573

RESUMEN

PB1 influenza virus retain traces of interspecies transmission and adaptation. Previous phylogenetic analyses highlighted mutations L298I, R386K and I517V in PB1 to have putatively ameliorated the A(H1N1)pdm09 adaptation to the human host. This study aimed to evaluate the reversal of these mutations and infer the role of these residues in the virus overall fitness and adaptation. We generate PB1-mutated viruses introducing I298L, K386R and V517I mutations in PB1 and evaluate their phenotypic impact on viral growth and on antigen yield. We observed a decrease in viral growth accompanied by a reduction in hemagglutination titer and neuraminidase activity, in comparison with wt. Our data indicate that the adaptive evolution occurred in the PB1 leads to an improved overall viral fitness; and such biologic advantaged has the potential to be applied to the optimization of influenza vaccine seed prototypes.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Filogenia , Proteínas Virales/genética , Virus de la Influenza A/genética , Vacunas contra la Influenza/genética
14.
Rev Port Cardiol ; 31(3): 241-5, 2012 Mar.
Artículo en Portugués | MEDLINE | ID: mdl-22284682

RESUMEN

Emery-Dreifuss muscular dystrophy type 1 (EDMD1) is a familial disease with X-Linked recessive transmission, caused by a mutation in a nuclear envelope protein, emerin. Clinical manifestations usually occur in adolescence and include contractures, muscle atrophy and weakness, and cardiac conduction disturbances. We describe the case of a young male, aged 16, with first-degree atrioventricular (AV) block and limited extension of both forearms. He had elevated CK, and cardiac monitoring showed severe conduction tissue disease, with significant sinus pauses, chronotropic incompetence and periods of AV dissociation during exercise. Immunohistochemical staining using an emerin antibody showed absence of the protein in a fragment of muscle tissue and genetic study identified a mutation associated with EDMD1. Study of his brother, aged 21, also established a diagnosis of EDMD1. Both individuals received a permanent pacemaker but musculoskeletal manifestations at that time did not warrant any other intervention: Screening for certain genetic diseases, including muscular dystrophies, is mandatory following identification of conduction abnormalities in young people.


Asunto(s)
Distrofia Muscular de Emery-Dreifuss , Adolescente , Humanos , Masculino , Distrofia Muscular de Emery-Dreifuss/diagnóstico
15.
Pharmaceutics ; 14(4)2022 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-35456711

RESUMEN

The development of effective antiviral drugs against SARS-CoV-2 is urgently needed and a global health priority. In light of the initial data regarding the repurposing of hydroxychloroquine (HCQ) to tackle this coronavirus, herein we present a quantitative synthesis and spectroscopic and thermal characterization of seven HCQ room temperature ionic liquids (HCQ-ILs) obtained by direct protonation of the base with two equivalents of organic sulfonic, sulfuric and carboxylic acids of different polarities. Two non-toxic and hydrophilic HCQ-ILs, in particular, [HCQH2][C1SO3]2 and [HCQH2][GlcCOO]2, decreased the virus-induced cytopathic effect by two-fold in comparison with the original drug, [HCQH2][SO4]. Despite there being no significant differences in viral RNA production between the three compounds, progeny virus production was significantly affected (p < 0.05) by [HCQH2][GlcCOO]2. Overall, the data suggest that the in vitro antiviral activities of the HCQ-ILs are most likely the result of specific intra- and intermolecular interactions and not so much related with their hydrophilic or lipophilic character. This work paves the way for the development of future novel ionic formulations of hydroxychloroquine with enhanced physicochemical properties.

16.
Virus Res ; 315: 198795, 2022 07 02.
Artículo en Inglés | MEDLINE | ID: mdl-35504447

RESUMEN

Vaccination prevents and reduces the severity of influenza virus infections. Continuous evolution of influenza hemagglutinin (HA) and neuraminidase (NA) supports the virus to evade pre-existing immunity, which demands vaccines to be reformulated every year. Incorporation of polymerase basic protein 1 (PB1) viral RNA (vRNA) of the same origin of HA and NA vRNA has been observed in previous pandemic viruses and occasionally reported for influenza A vaccine prototype strains of prior seasons. At this point, it remains to be explored whether this phenomenon translates into an improved growth phenotype. In this work, we showed that the HA vRNA of A(H1N1)pdm09 is generally incorporated with the PB1 vRNA of the same origin, establishing the beneficial effect of the presence of PB1 and the pattern of the PB1-HA co-incorporation in the A(H1N1)pdm09 model. We further investigated the putative interplay between PB1 and antigenic proteins regarding the vRNA composition of the progeny and observed that vRNA segregation does not appear to be mainly determined by protein-protein interactions; while vRNA-vRNA interactions can be suggested as the main driving force. Our data also indicate an increase in the hemagglutination capacity and neuraminidase activity due to incorporation of PB1, HA and NA from A(H1N1)pdm09, in comparison with the recombinant virus incorporating only HA and NA from A(H1N1)pdm09 - which have the potential to improve current limitations regarding antigenicity and immunogenicity of influenza vaccines. Further knowledge of the complex vRNA-vRNA interaction network between PB1 and HA will additionally contribute to improve current vaccine formulation, and to gradually optimize the production of A(H1N1)pdm09 reverse genetics vaccine seed virus towards a higher cost-effectiveness.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Gripe Humana , Glicoproteínas Hemaglutininas del Virus de la Influenza/genética , Hemaglutininas , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Vacunas contra la Influenza/genética , Neuraminidasa/genética , ARN Viral/genética , Proteínas Virales/metabolismo
17.
Virology ; 565: 106-116, 2022 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-34773868

RESUMEN

Influenza NS1 is a promising anti-influenza target, considering its conserved and druggable structure, and key function in influenza replication and pathogenesis. Notwithstanding, target identification and validation, strengthened by experimental data, are lacking. Here, we further explored our previously designed structure-based antiviral rationale directed to highly conserved druggable NS1 regions across a broad spectrum of influenza A viruses. We aimed to identify NS1-mutated viruses exhibiting a reduced growth phenotype and/or an altered cell apoptosis profile. We found that NS1 mutations Y171A, K175A (consensus druggable pocket 1), W102A (consensus druggable pocket 3), Q121A and G184P (multiple consensus druggable pockets) - located at hot spots amenable for pharmacological modulation - significantly impaired A(H1N1)pdm09 virus replication, in vitro. This is the first time that NS1-K175A, -W102A, and -Q121A mutations are characterized. Our map-and-mutate strategy provides the basis to establish the NS1 as a promising target using a rationale with a higher resilience to resistance development.


Asunto(s)
Virus de la Influenza A/genética , Virus de la Influenza A/patogenicidad , Gripe Humana/virología , Infecciones por Orthomyxoviridae/virología , Proteínas no Estructurales Virales/genética , Replicación Viral , Sustitución de Aminoácidos , Animales , Apoptosis , Línea Celular , Perros , Descubrimiento de Drogas , Células HEK293 , Interacciones Microbiota-Huesped , Humanos , Gripe Humana/metabolismo , Células de Riñón Canino Madin Darby , Mutación , Infecciones por Orthomyxoviridae/metabolismo
18.
J Clin Microbiol ; 48(4): 1391-6, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-20147640

RESUMEN

Human adenoviruses (AdVs) typically cause mild illnesses in otherwise healthy hosts. We investigated a pediatric outbreak of acute respiratory infection with fatal outcomes that occurred in Lisbon, Portugal, in 2004. Biological specimens were collected from 83 children attending two nurseries, a kinesiotherapy clinic, and the household of a nanny. Adenovirus infection was confirmed in 48 children by PCR and virus isolation. Most (96%) isolates were classified as being of subspecies B1. Phylogenetic analysis of fiber and hexon gene sequences revealed that most infants were infected with AdV serotype 3 (AdV3) strains. Infants attending one nursery harbored a new recombinant strain containing an AdV serotype 7 hexon and serotype 3 fiber (AdV7/3). Both the AdV3 and the AdV7/3 strains caused fatal infections. Two different serotype 3 strains were circulating in Lisbon in 2004, and the new AdV7/3 recombinant type originated from only one of those strains. These results demonstrate that recombination leads to the emergence of new adenovirus strains with epidemic and lethal potential.


Asunto(s)
Infecciones por Adenoviridae/epidemiología , Adenovirus Humanos/aislamiento & purificación , Brotes de Enfermedades , Infecciones del Sistema Respiratorio/epidemiología , Infecciones por Adenoviridae/virología , Adenovirus Humanos/clasificación , Adenovirus Humanos/genética , Adenovirus Humanos/inmunología , Proteínas de la Cápside/genética , Preescolar , Análisis por Conglomerados , ADN Viral/química , ADN Viral/genética , Genotipo , Humanos , Lactante , Recién Nacido , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Portugal/epidemiología , Recombinación Genética , Infecciones del Sistema Respiratorio/virología , Análisis de Secuencia de ADN
19.
Rev Port Cardiol ; 29(3): 413-32, 2010 Mar.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-20635566

RESUMEN

The definition of hypertension (HT) in the pediatric age group is based on the normal distribution of blood pressure (BP) in healthy children. Normal BP is defined as being below the 90th percentile for gender, age and height, and hypertension as equal to or higher than the 95th percentile on at least three separate occasions. If the values are above the 90th percentile but below the 95th percentile, the child should be considered prehypertensive. Ambulatory BP monitoring is useful in the assessment of BP levels in the young. P values in children and adolescents have creased in the last decade, in parallel with increases in body mass index, and HT now has a prevalence of 2-5%. Obesity in childhood and adolescence is one of the main predictors of HT in adulthood, but it is also associated with other cardiovascular risk factors such as dyslipidemia, abnormal glucose metabolism, insulin resistance, inflammation and impaired vascular function. Left ventricular hypertrophy is the most prominent evidence of target organ damage caused by hypertension in children and adolescents. The goal for antihypertensive treatment is to reduce BP below the 95th percentile. Weight control, with regular physical activity and dietary changes, is the primary therapy for obesity-related hypertension. Weight loss decreases not only BP but also other cardiovascular risk factors. The indications for use of antihypertensive drugs are: symptomatic hypertension, secondary hypertension, established hypertensive target organ damage, stage 2 hypertension and failure of nonpharmacologic measures.


Asunto(s)
Hipertensión , Adolescente , Factores de Edad , Niño , Humanos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/epidemiología , Hipertensión/etiología , Hipertensión/terapia , Factores de Riesgo
20.
J Optom ; 13(4): 257-261, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32711965

RESUMEN

The pandemic of the severe acute respiratory syndrome disease caused by the new coronavirus SARS-CoV-2 (COVID-19), had profound impact in many countries and their health care systems. Regarding Portugal, a suppression strategy with social distancing was adopted, attempting to break the transmission chains, bending the epidemy curve and reducing mortality. These measures seek to prevent an eventual National Health Service over-running, enforcing the suspension of all elective and non-urgent health care. Despite the success in so far, there is a consensus on the need to recover the previous level of health care provision and further enhance it. The Portuguese National Health Service, as a public, universal access, health care system funded by the State proved, in this context, its importance and relevance to the Portuguese population. However, long standing issues, such as the pre pandemic over long waiting lists for hospital ophthalmology attendance, whose determinants are fully identified but still unmet, emerge amplified from this pandemic. The lack of primary eye care in the National Health Service is a significant bottleneck, placing a huge stress on hospital-based care. An exclusive ophthalmologist's center care was over-runned before pandemic and will be even more so. The optometrist's exclusion from differentiated, multisectoral and multidisciplinary eye care teams remains the main hurdle to overcome and insure universal eye care in Portugal. National Health Service highlights the consequences of an overcome model. Universal eye care more than ever demands an evidence-based, integrated approach with primary eye care, in the community, on time and of proximity.


La pandemia del síndrome respiratorio agudo grave causado por el nuevo coronavirus SARS-CoV-2 (COVID-19) ha tenido amplias repercusiones en muchos países y en sus sistemas sanitarios. En Portugal, se ha adoptado una estrategia de contención basada en el distanciamiento social, con la cual se ha intentado cortar las cadenas de transmisión, frenar la curva de la epidemia y reducir la mortalidad. Con estas medidas se trataba de evitar un eventual desbordamiento del Servicio Nacional de Salud y se imponía la suspensión de toda la atención médica programada, que no fuera urgente. A pesar del éxito logrado hasta este momento, existe consenso sobre la necesidad de recuperar el nivel anterior de atención médica y fomentar su mejora. El Servicio Nacional de Salud de Portugal, como sistema sanitario público y de acceso universal, a cargo del Estado, ha demostrado, en este contexto, su importancia y pertinencia para la población portuguesa. Sin embargo, los problemas que acarrea desde hace mucho tiempo, como las largas listas de espera, anteriores a la pandemia, en la asistencia oftalmológica hospitalaria, cuyos factores determinantes están completamente identificados, pero que continúan sin solución, se han visto agravados a resultas de esta pandemia. La falta de atención primaria oftalmológica en el Servicio Nacional de Salud es un importante cuello de botella, que ejerce una enorme presión en la atención hospitalaria. La atención de un centro exclusivamente oftalmológico estaba desbordada antes de la pandemia y lo estará aún más después de esta. La exclusión de los optómetras de los equipos de atención oftalmológica diferenciados, multisectoriales y multidisciplinarios continúa siendo el principal obstáculo que debe superar y asegurar la atención oftalmológica universal en Portugal. El Servicio Nacional de Salud hace hincapié en las consecuencias de un modelo superado. La atención oftalmológica universal exige, más que nunca, un enfoque integral basado en la evidencia para abordar la atención primaria oftalmológica en la comunidad, puntual y de proximidad.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/epidemiología , Atención a la Salud/organización & administración , Oftalmopatías/terapia , Programas Nacionales de Salud/organización & administración , Neumonía Viral/epidemiología , COVID-19 , Infecciones por Coronavirus/prevención & control , Humanos , Control de Infecciones/métodos , Transmisión de Enfermedad Infecciosa de Paciente a Profesional/prevención & control , Oftalmólogos , Optometristas , Pandemias/prevención & control , Equipo de Protección Personal , Neumonía Viral/prevención & control , Portugal/epidemiología , SARS-CoV-2 , Medicina Estatal
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