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1.
Prenat Diagn ; 41(13): 1624-1633, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34671992

RESUMO

BACKGROUND/OBJECTIVE: Neural tube defects (NTDs) affect approximately 300,000 pregnancies worldwide each year. Many of these pregnancies are lost to miscarriage or termination of pregnancy. Here, we have analysed the trends of termination of pregnancy for NTDs from the national data for England and Wales. METHODS: Data for all terminations for residents in England and Wales for the period of 2007-2017 were obtained through Health and Social Act 4 (HSA4) submitted to the Department of Health. Using the ICD-10 codes, terminations for NTDs were selected for analysis. The statistical test Chi-squared was performed using SPSS-v25, where appropriate. RESULTS: In the 11-year period, there were 28,866 terminations under Ground E; of which 4425 (15.33%) had a diagnosis of NTD. The number of NTD cases increased over the time period from 308 in 2007 to 517 in 2017 (67.9%). Significant results were also seen when analysing the relationship between ethnicity, gestation and terminations where an NTD was diagnosed. CONCLUSION: With the availability of routine prenatal ultrasound, the termination for NTDs is on the rise in England and Wales, in spite of the health advice of periconceptional folic acid. This study demonstrates the need for implementation of further programmes to increase public health awareness of folic supplementation and government initiation of fortification to reduce NTDs.


Assuntos
Aborto Induzido/estatística & dados numéricos , Defeitos do Tubo Neural/cirurgia , Aborto Induzido/métodos , Adulto , Inglaterra/epidemiologia , Feminino , Humanos , Defeitos do Tubo Neural/epidemiologia , Gravidez , Prevalência , Estudos Prospectivos , País de Gales/epidemiologia
2.
Nat Chem Biol ; 16(11): 1255-1260, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32719558

RESUMO

The direct C-H carboxylation of aromatic compounds is an attractive route to the corresponding carboxylic acids, but remains challenging under mild conditions. It has been proposed that the first step in anaerobic microbial degradation of recalcitrant aromatic compounds is a UbiD-mediated carboxylation. In this study, we use the UbiD enzyme ferulic acid decarboxylase (Fdc) in combination with a carboxylic acid reductase to create aromatic degradation-inspired cascade reactions, leading to efficient functionalization of styrene through CO2 fixation. We reveal that rational structure-guided laboratory evolution can expand the substrate scope of Fdc, resulting in activity on a range of mono- and bicyclic aromatic compounds through a single mutation. Selected variants demonstrated 150-fold improvement in the conversion of coumarillic acid to benzofuran + CO2 and unlocked reactivity towards naphthoic acid. Our data demonstrate that UbiD-mediated C-H activation is a versatile tool for the transformation of aryl/alkene compounds and CO2 into commodity chemicals.


Assuntos
Dióxido de Carbono/química , Carboxiliases/metabolismo , Hidrocarbonetos Aromáticos/metabolismo , Oxirredutases/metabolismo , Sequência de Aminoácidos , Benzofuranos/química , Biocatálise , Biodegradação Ambiental , Carboxiliases/genética , Ácidos Carboxílicos/química , Descarboxilação , Avaliação Pré-Clínica de Medicamentos , Ativação Enzimática , Biblioteca Genômica , Hidrocarbonetos Aromáticos/química , Modelos Moleculares , Estrutura Molecular , Mutação , Naftalenos/química , Oxirredutases/genética , Relação Estrutura-Atividade , Estireno/química
3.
Vaccine ; 29(45): 7913-9, 2011 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-21875635

RESUMO

In 2009, 943 children aged 6 months to 10 years were randomised to receive two doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible predictors of immune response and reactogenicity. We used regression analysis to examine the effect of variables including past receipt of seasonal vaccine, antipyretics post-vaccination, interval between doses and pre-existing antibodies to H1N1 (2009) on immunogenicity. We also examined the relationship between immunogenicity and reactogenicity and whether prior infection or underlying conditions affected reactogenicity. For both vaccines, haemagglutination-inhibition titres were 60% higher in children with fever ≥38 °C after vaccination and 29% lower in those previously given seasonal vaccine. Early use of antipyretics did not affect immunogenicity. Post-vaccination titres were higher with longer intervals between doses and in those with evidence of prior infection, but reactogenicity in the latter was unaffected. In the adjuvanted vaccine group, reactions were more common in children with atopy. Both vaccines were safe and immunogenic in those with prior infection. Reduction in the interval between doses for earlier protection would be at the cost of reduced immunogenicity. The effect of seasonal vaccine on immunogenicity merits further investigation.


Assuntos
Adjuvantes Imunológicos/administração & dosagem , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Influenza Humana/prevenção & controle , Polissorbatos/administração & dosagem , Esqualeno/administração & dosagem , alfa-Tocoferol/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Anticorpos Antivirais/sangue , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Testes de Inibição da Hemaglutinação , Humanos , Lactente , Vacinas contra Influenza/administração & dosagem , Influenza Humana/imunologia , Masculino , Polissorbatos/efeitos adversos , Esqualeno/efeitos adversos , Vacinas de Produtos Inativados/administração & dosagem , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Vacinas de Subunidades Antigênicas/efeitos adversos , Vacinas de Subunidades Antigênicas/imunologia , alfa-Tocoferol/efeitos adversos
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