Adults aged ≥ 65 years contribute a large proportion of influenza-related hospitalizations and deaths due to increased risk of complications, which result in high medical costs and reduced health-related quality of life (HRQoL). Although seasonal influenza vaccines are recommended for older adults, the effectiveness of current vaccines is dependent on several factors including strain matching and recipient demographic factors. This systemic literature review aimed to explore the economic and humanistic burden of influenza in adults aged ≥ 65 years. An electronic database search was conducted to identify studies assessing the economic and humanistic burden of influenza, including influenza symptoms that impact the HRQoL and patient-related outcomes in adults aged ≥ 65 years. Studies were to be published in English and conducted in Germany, France, Spain, and Italy, the UK, USA, Canada, China, Japan, Brazil, Saudi Arabia, and South Africa. Thirty-eight studies reported on the economic and humanistic burden of influenza in adults aged ≥ 65 years. Higher direct costs were reported for people at increased risk of influenza-related complications compared to those at low risk. Lower influenza-related total costs were found in those vaccinated with adjuvanted inactivated trivalent influenza vaccine (aTIV) compared to high-dose trivalent influenza vaccine (TIV-HD). Older age was associated with an increased occurrence and longer duration of certain influenza symptoms. Despite the limited data identified, results show that influenza exerts a high humanistic and economic burden in older adults. Further research is required to confirm findings and to identify the unmet needs of current vaccines.
Influenza is a respiratory infection associated with a significant clinical burden globally. Adults aged ≥ 65 years are at increased risk of severe influenza-related symptoms and complications due to chronic comorbidity and immunosenescence. Annual influenza vaccination is recommended; however, current influenza vaccines confer suboptimal protection, in part due to antigen mismatch and poor durability. This systematic literature review characterizes the global clinical burden of seasonal influenza among adults aged ≥ 65 years. An electronic database search was conducted and supplemented with a conference abstract search. Included studies described clinical outcomes in the ≥ 65 years population across several global regions and were published in English between January 1, 2012 and February 9, 2022. Ninety-nine publications were included (accounting for > 156,198,287 total participants globally). Clinical burden was evident across regions, with most studies conducted in the USA and Europe. Risk of influenza-associated hospitalization increased with age, particularly in those aged ≥ 65 years living in long-term care facilities, with underlying comorbidities, and infected with A(H3N2) strains. Seasons dominated by circulating A(H3N2) strains saw increased risk of influenza-associated hospitalization, intensive care unit admission, and mortality within the ≥ 65 years population. Seasonal differences in clinical burden were linked to differences in circulating strains. Influenza exerts a considerable burden on adults aged ≥ 65 years and healthcare systems, with high incidence of hospitalization and mortality. Substantial influenza-associated clinical burden persists despite increasing vaccination coverage among adults aged ≥ 65 years across regions included in this review, which suggests limited effectiveness of currently available seasonal influenza vaccines. To reduce influenza-associated clinical burden, influenza vaccine effectiveness must be improved. Next generation vaccine production using mRNA technology has demonstrated high effectiveness against another respiratory virus—SARS-CoV-2—and may overcome the practical limitations associated with traditional influenza vaccine production.
Este artigo considera a marcante instabilidade da Filosofia nos curriculos da Educacao brasileira, assim como seu desaparecimento como disciplina, na versao aprovada da Base Nacional Comum Curricular (BNCC). Apresenta as provaveis alteracoes que esse documento promovera na Educacao, referente a formacao de professores, ao impacto politico e a autonomia docente na criacao de aulas, para, entao, dedicar-se aos espolios filosoficos restantes na Base, sobretudo aqueles relativos a etica. Mostra que a dimensao etica atravessa o documento e esta presente nas “Competencias Gerais” a serem desenvolvidas ao longo da Educacao Basica, sendo, portanto, uma preocupacao de todas as areas do conhecimento, sobretudo no que se refere as Tecnologias Digitais de Informacao e Comunicacao (TDICs) e a sustentabilidade ambiental. Volta a definicao de etica no documento e as suas bases, a saber, justica, solidariedade e livre-arbitrio; problematiza seus sentidos e marca algumas incoerencias. Evidencia que o documento, apesar de incentivar que a Educacao dos jovens esteja, de um lado, voltada aquilo que fizemos e sabemos do mundo, por outro, para o aberto e indeterminado; da enfase excessiva a busca de solucoes e ao aprendizado de respostas, dando prioridade, no que respeita a Filosofia, a resposta socratica para a questao “O que e o ser humano?” Destaca a ideia apresentada no documento de que o nosso tempo requer uma “nova mentalidade”, regida por uma “etica diferente”, e defende que e por meio do contato com modos de pensar filosoficos, presentes nos textos primarios de Filosofia, trabalhados por professores habilitados para isso, que os estudantes tornar-se-ao competentes e habeis nos dois principais sentidos eticos da Base – 1) da nossa relacao com a natureza, com o Planeta e seus bens finitos; e 2) da relacao consigo mesmo, o modo de ser. Afirma, por fim, que, apesar da espoliacao sofrida pela Filosofia na Base, nenhum projeto de Educacao pode ser sustentado sem ela. Palavras-chave: BNCC. Filosofia. Etica. Ensino de Filosofia
Sarcosine, an N-methylated amino acid, shows potential as antipsychotic, and serves as building block for peptide-based drugs, and acts as detergent when acetylated. N-methylated amino acids are mainly produced chemically or by biocatalysis, with either low yields or high costs for co-factor regeneration. Corynebacterium glutamicum, which is used for the industrial production of amino acids for decades, has recently been engineered for production of N-methyl-L-alanine and sarcosine. Heterologous expression of dpkA in a C. glutamicum strain engineered for glyoxylate overproduction enabled fermentative production of sarcosine from sugars and monomethylamine. Here, mutation of an amino acyl residue in the substrate binding site of DpkA (DpkAF117L) led to an increased specific activity for reductive alkylamination of glyoxylate using monomethylamine and monoethylamine as substrates. Introduction of DpkAF117L into the production strain accelerated the production of sarcosine and a volumetric productivity of 0.16 g L-1 h-1 could be attained. Using monoethylamine as substrate, we demonstrated N-ethylglycine production with a volumetric productivity of 0.11 g L-1 h-1, which to the best of our knowledge is the first report of its fermentative production. Subsequently, the feasibility of using rice straw hydrolysate as alternative carbon source was tested and production of N-ethylglycine to a titer of 1.6 g L-1 after 60 h of fed-batch bioreactor cultivation could be attained.
The aim of this work was to study the fermentative production of the N-methylated amino acid sarcosine by C. glutamicum. Characterization of the imine reductase DpkA from Pseudomonas putida revealed that it catalyses N-methylamination of glyoxylate to sarcosine. Heterologous expression of dpkA in a C. glutamicum strain engineered for glyoxylate overproduction enabled fermentative production of sarcosine from sugars and monomethylamine. Glucose-based fermentation reached sarcosine production titers of 2.4 +/- 0.1 g L-1. Sarcosine production based on the second generation feedstocks xylose and arabinose led to higher product titers of 2.7 +/- 0.1 g L-1 and 3.4 +/- 0.3 g L-1, respectively, than glucose-based production. Optimization of production conditions with xylose and potassium acetate blends increased sarcosine titers to 8.7 +/- 0.2 g L-1 with a yield of 0.25 g g(-1). This is the first example in which a C. glutamicum process using lignocellulosic pentoses is superior to glucose-based production.