Saccharomyces cerevisiae Cells Lacking the Zinc Vacuolar Transporter Zrt3 Display Improved Ethanol Productivity in Lignocellulosic Hydrolysates.

Yeast-based bioethanol production from lignocellulosic hydrolysates (LH) is an attractive and sustainable alternative for biofuel production. However, the presence of acetic acid (AA) in LH is still a major problem. Indeed, above certain concentrations, AA inhibits yeast fermentation and triggers a regulated cell death (RCD) process mediated by the mitochondria and vacuole. Understanding the mechanisms involved in AA-induced RCD (AA-RCD) may thus help select robust fermentative yeast strains, providing novel insights to improve lignocellulosic ethanol (LE) production. Herein, we hypothesized that zinc vacuolar transporters are involved in vacuole-mediated AA-RCD, since zinc enhances ethanol production and zinc-dependent catalase and superoxide dismutase protect from AA-RCD. In this work, zinc limitation sensitized wild-type cells to AA-RCD, while zinc supplementation resulted in a small protective effect. Cells lacking the vacuolar zinc transporter Zrt3 were highly resistant to AA-RCD, exhibiting reduced vacuolar dysfunction. Moreover, zrt3Δ cells displayed higher ethanol productivity than their wild-type counterparts, both when cultivated in rich medium with AA (0.29 g L-1 h-1 versus 0.11 g L-1 h-1) and in an LH (0.73 g L-1 h-1 versus 0.55 g L-1 h-1). Overall, the deletion of ZRT3 emerges as a promising strategy to increase strain robustness in LE industrial production.

Drug Targeting of Inflammatory Bowel Diseases by Biomolecules.

Inflammatory bowel disease (IBD) is a group of disabling, destructive and incurable immune-mediated inflammatory diseases comprising Crohn's disease (CD) and ulcerative colitis (UC), disorders that are highly prevalent worldwide and demand a large investment in healthcare. A persistent inflammatory state enables the dysfunction and destruction of healthy tissue, hindering the initiation and endurance of wound healing. Current treatments are ineffective at counteracting disease progression. Further, increased risk of serious side effects, other comorbidities and/or opportunistic infections highlight the need for effective treatment options. Gut microbiota, the key to preserving a healthy state, may, alternatively, increase a patient's susceptibility to IBD onset and development given a relevant bacterial dysbiosis. Hence, the main goal of this review is to showcase the main conventional and emerging therapies for IBD, including microbiota-inspired untargeted and targeted approaches (such as phage therapy) to infection control. Special recognition is given to existing targeted strategies with biologics (via monoclonal antibodies, small molecules and nucleic acids) and stimuli-responsive (pH-, enzyme- and reactive oxygen species-triggered release), polymer-based nanomedicine that is specifically directed towards the regulation of inflammation overload (with some nanosystems additionally functionalized with carbohydrates or peptides directed towards M1-macrophages). The overall goal is to restore gut balance and decrease IBD's societal impact.

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, detection of seroconversion after vaccination, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests have a long history in blood typing, and general serology through linkage of reporter molecules to the red cell surface. They do not require special equipment, are read by eye, have short development times, low cost and can be applied as a Point of Care Test (POCT). We describe a red cell agglutination test for the detection of antibodies to the SARS-CoV-2 receptor binding domain (RBD). We show that the Haemagglutination Test ("HAT") has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. The HAT can be titrated, detects rising titres in the first five days of hospital admission, correlates well with a commercial test that detects antibodies to the RBD, and can be applied as a point of care test. The developing reagent is composed of a previously described nanobody to a conserved glycophorin A epitope on red cells, linked to the RBD from SARS-CoV-2. It can be lyophilised for ease of shipping. We have scaled up production of this reagent to one gram, which is sufficient for ten million tests, at a cost of [~]0.27 UK pence per test well. Aliquots of this reagent are ready to be supplied to qualified groups anywhere in the world that need to detect antibodies to SARS-CoV-2, but do not have the facilities for high throughput commercial tests.

Deprescription in Advanced Cancer Patients Referred to Palliative Care.

In palliative care, drugs are considered futile if they do not have a short-term benefit in symptom control or quality of life. The authors examined pharmacotherapy prescribed for patients referred to palliative care to identify futile drugs. This was a retrospective analysis of patients referred over 6 months, focusing on the prescription of gastric protectants, antidiabetic agents, bisphosphonates, anticoagulants, antidementia drugs, statins, and antihypertensive agents. The sample consisted of 448 patients. Gastric protectants were prescribed futilely in 50% of cases (125/248), statins in 97% (69/71), antihypertensive agents in 27% (42/155), antidiabetic drugs in 1% (1/70), bisphosphonates in 27% (4/15), and antidementia drugs in 100% (9/9). This study reveals that many patients with advanced cancer continue to be treated with inappropriate drugs and points to the need for medical training in palliative care, drawing attention to the need for therapeutic review at each medical visit.

Unlocking the in vitro anti-Trypanosoma cruzi activity of halophyte plants from the southern Portugal

OBJECTIVE@#To evaluate the in vitro anti-Trypanosoma cruzi (T. cruzi) activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal (Algarve), and chemically characterize the most active samples.@*METHODS@#Acetone, dichloromethane and methanol extracts were prepared from 31 halophyte species and tested in vitro against trypomastigotes and intracellular amastigotes of the Tulahuen strain of T. cruzi. The most active extract was fractionated by preparative HPLC-DAD, affording 11 fractions. The most selective fraction was fully characterized by (1)H NMR.@*RESULTS@#From 94 samples tested, one was active, namely the root dichloromethane extract of Juncus acutus (IC50 < 20 μg/mL). This extract was fractionated by HPLC, affording 11 fractions, one of them containing only a pure compound (juncunol), and tested for anti-parasitic activity. Fraction 8 (IC50 = 4.1 μg/mL) was the most active, and was further characterized by (1)H NMR. The major compounds were phenanthrenes, 9,10-dihydrophenanthrenes and benzocoumarins.@*CONCLUSION@#Our results suggest that the compounds identified in fraction 8 are likely responsible for the observed anti parasitic activity. Further research is in progress aiming to isolate and identify the specific active molecules. To the best of our knowledge, this is the first report on the in vitro anti T. cruzi activity of halophyte species.

Unlocking the in vitro anti-Trypanosoma cruzi activity of halophyte plants from the southern Portugal

Objective To evaluate the in vitro anti-Trypanosoma cruzi (T. cruzi) activity of organic extracts prepared from halophyte species collected in the southern coast of Portugal (Algarve), and chemically characterize the most active samples. Methods Acetone, dichloromethane and methanol extracts were prepared from 31 halophyte species and tested in vitro against trypomastigotes and intracellular amastigotes of the Tulahuen strain of T. cruzi. The most active extract was fractionated by preparative HPLC-DAD, affording 11 fractions. The most selective fraction was fully characterized by

[Decision modeling for economic evaluation of health technologies]. / Modelos de decisão para avaliações econômicas de tecnologias em saúde.

Most economic evaluations that participate in decision-making processes for incorporation and financing of technologies of health systems use decision models to assess the costs and benefits of the compared strategies. Despite the large number of economic evaluations conducted in Brazil, there is a pressing need to conduct an in-depth methodological study of the types of decision models and their applicability in our setting. The objective of this literature review is to contribute to the knowledge and use of decision models in the national context of economic evaluations of health technologies. This article presents general definitions about models and concerns with their use; it describes the main models: decision trees, Markov chains, micro-simulation, simulation of discrete and dynamic events; it discusses the elements involved in the choice of model; and exemplifies the models addressed in national economic evaluation studies of diagnostic and therapeutic preventive technologies and health programs.

Modelos de decisão para avaliações econômicas de tecnologias em saúde / Decision modeling for economic evaluation of health technologies

A maioria das avaliações econômicas que participam dos processos de decisão de incorporação e financiamento de tecnologias dos sistemas de saúde utiliza modelos de decisão para avaliar os custos e benefícios das estratégias comparadas. Apesar do grande número de avaliações econômicas conduzidas no Brasil, há necessidade de aprofundamento metodológico sobre os tipos de modelos de decisão e sua aplicabilidade no nosso meio. O objetivo desta revisão de literatura é contribuir para o conhecimento e o uso de modelos de decisão nos contextos nacionais das avaliações econômicas de tecnologias em saúde. Este artigo apresenta definições gerais sobre modelos e preocupações com o seu uso; descreve os principais modelos: árvore de decisão, Markov, microssimulação, simulação de eventos discretos e dinâmicos; discute os elementos envolvidos na escolha do modelo; e exemplifica os modelos abordados com estudos de avaliação econômica nacionais de tecnologias preventivas e de programas de saúde, diagnósticas e terapêuticas.

Most economic evaluations that participate in decision-making processes for incorporation and financing of technologies of health systems use decision models to assess the costs and benefits of the compared strategies. Despite the large number of economic evaluations conducted in Brazil, there is a pressing need to conduct an in-depth methodological study of the types of decision models and their applicability in our setting. The objective of this literature review is to contribute to the knowledge and use of decision models in the national context of economic evaluations of health technologies. This article presents general definitions about models and concerns with their use; it describes the main models: decision trees, Markov chains, micro-simulation, simulation of discrete and dynamic events; it discusses the elements involved in the choice of model; and exemplifies the models addressed in national economic evaluation studies of diagnostic and therapeutic preventive technologies and health programs.

Incidência de aids e estimativa de riscos relativos por categoria de exposição no Estado de São Paulo, Brasil, de 1998 a 2005 / Incidence of AIDS and estimate of relative risks by transmission category in the State of São Paulo, Brazil, 1998 to 2005

Em 2004, a Pesquisa de Conhecimentos, Atitudes e Práticas da População Brasileira (PCAP) mostrou que entre indivíduos de 15 a 54 anos de idade, no Estado de São Paulo, 1,3% dos homens eram usuários de drogas injetáveis (UDI), 3,9% eram homens que fazem sexo com homens (HSH) e 89% eram heterossexuais. Entre as mulheres, 0,7% eram UDI e 90,3% heterossexuais. Os dados permitiram estimar essas populações específicas e calcular as taxas de incidência (TI) por categoria de exposição ao HIV. Este estudo estimou as TI de aids no Estado, de 1998 a 2005, e os riscos relativos de desenvolver a doença nas principais categorias de exposição: HSH, UDI masculino e UDI feminino, heterossexuais masculinos e femininos, na faixa de 15 a 49 anos de idade. Foram utilizadas três fontes de dados: Sinan Aids, população calculada pela Fundação Seade e PCAP. Para o cálculo dos denominadores, considerou-se que não houve alteração do comportamento, no período analisado, utilizando-se as mesmas proporções do PCAP 2004. As TI entre os UDI em 1998 foram as mais altas em homens e mulheres (1.735 e 614,8 por 100.000 habitantes, respectivamente), seguidos pelos HSH (450,4) e heterossexuais (22,7 nos homens). O risco relativo para UDI masculino foi 76,3 mais alto que os homens heterossexuais, em 1998. Todas as TI diminuíram de 1998 a 2005, mas a epidemia continua concentrada em grupos específicos (UDI e HSH)

[Reflections on the psychoanalytic representations of nurses about themselves and about nursing]. / Reflexão na abordagem psicanalitica das representações do enfermeiro sobre si e sobre a enfermagem.

This study describes some reflections on the representations of nurses about themselves and about nursing, in order to analyze them within a psychoanalytic framework of the constitution of the subject in the sphere of the desire which motivates them, at the levels of the imaginary and the symbolic. The analysis adopted was the discursive practices proposed by Spink, using association of ideas in the hermeneutical tradition. Considering the subject, eight nurses were interviewed whose interpretations were displayed on graphs and tables. From discourse analysis emerged meanings in the symbolic sphere and the production of meanings. It is possible to understand that the desire of the nurse shows itself as the desire of others' desire, an imaginary desire and therefore, it is imaginary and to be constituted. This object which appears identified with the self, may appear over-valued or commonplace, depreciated or punished. From this point of view, new horizons may open up in practice and professional training for nurses, which brings them together around a signifier which can give them a meaning, enabling them to see themselves as subjects in their professional expressiveness.

Diagnóstico de saúde das mulheres em idade fértil de Sergipe / Women's health during fertility - Sergipe

Relato parcial de uma pesquisa realizada pela Secretaria de Estado da Saúde em parceria com o UNICEF, intitulado de Diagnóstico Materno-Infantil do Estado de Sergipe. Nesta pesquisa as autoras realizam uma abordagem parcial sobre a saúde das mulheres em idade fértil. Objetivo: Medir por amostragem a nível estadual os indicadores: estado civil, idade da menarca, início da vida sexual, gravidez, abortos, prevençäo do câncer cérvico-uterino e mama, anticoncepçäo e utilizaçäo dos serviços de saúde. Os resultados foram coletados através da aplicaçäo de um formulário estruturado, abrangendo variáveis pré-concepcionais, biológicas e sociais. Os dados obtidos fornecem subsídos para ampla discussäo sobre a saúde das mulheres em Sergipe.