A metabolomic approach to animal vitreous humor topographical composition: A pilot study

The purpose of this study was to evaluate the feasibility of a 1H-NMR-based metabolomic approach to explore the metabolomic signature of different topographical areas of vitreous humor (VH) in an animal model. Five ocular globes were enucleated from five goats and immediately frozen at 280uC. Once frozen, three of them were sectioned, and four samples corresponding to four different VH areas were collected: the cortical, core, and basal, which was further divided into a superior and an inferior fraction. An additional two samples were collected that were representative of the whole vitreous body. 1H-NMR spectra were acquired for twenty-three goat vitreous samples with the aim of characterizing the metabolomic signature of this biofluid and identifying whether any site-specific patterns were present. Multivariate statistical analysis (MVA) of the spectral data were carried out, including Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), and Partial Least Squares Discriminant Analysis (PLS-DA). A unique metabolomic signature belonging to each area was observed. The cortical area was characterized by lactate, glutamine, choline, and its derivatives, N-acetyl groups, creatine, and glycerol; the core area was characterized by glucose, acetate, and scyllo-inositol; and the basal area was characterized by branched-chain amino acids (BCAA), betaine, alanine, ascorbate, lysine, and myo-inositol. We propose a speculative approach on the topographic role of these molecules that are mainly responsible for metabolic differences among the as-identified areas. 1H-NMR-based metabolomic analysis has shown to be an important tool for investigating the VH. In particular, this approach was able to assess in the samples here analyzed the presence of different functional areas on the basis of a different metabolite distribution.The purpose of this study was to evaluate the feasibility of a 1H-NMR-based metabolomic approach to explore the metabolomic signature of different topographical areas of vitreous humor (VH) in an animal model. Five ocular globes were enucleated from five goats and immediately frozen at -80°C. Once frozen, three of them were sectioned, and four samples corresponding to four different VH areas were collected: the cortical, core, and basal, which was further divided into a superior and an inferior fraction. An additional two samples were collected that were representative of the whole vitreous body. 1H-NMR spectra were acquired for twenty-three goat vitreous samples with the aim of characterizing the metabolomic signature of this biofluid and identifying whether any site-specific patterns were present. Multivariate statistical analysis (MVA) of the spectral data were carried out, including Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), and Partial Least Squares Discriminant Analysis (PLS-DA). A unique metabolomic signature belonging to each area was observed. The cortical area was characterized by lactate, glutamine, choline, and its derivatives, N-acetyl groups, creatine, and glycerol; the core area was characterized by glucose, acetate, and scyllo-inositol; and the basal area was characterized by branched-chain amino acids (BCAA), betaine, alanine, ascorbate, lysine, and myo-inositol. We propose a speculative approach on the topographic role of these molecules that are mainly responsible for metabolic differences among the as-identified areas. 1H-NMR-based metabolomic analysis has shown to be an important tool for investigating the VH. In particular, this approach was able to assess in the samples here analyzed the presence of different functional areas on the basis of a different metabolite distribution. © 2014 Locci et al

Combined use of a femtosecond laser and a microkeratome in obtaining thin grafts for Descemet stripping automated endothelial keratoplasty: an eye bank study

Purpose: To evaluate the use of a femtosecond laser combined with a microkeratome in the preparation of posterior corneal disks for Descemet stripping automated endothelial keratoplasty (DSAEK).
Methods: This experimental study involved ultrathin DSAEK tissue preparation of 22 donor corneas unsuitable for transplantation. The first cut was performed with an Intralase® FS60 laser and the second cut with a Moria CBm 300-µm microkeratome. The thickness of the first cut was modified for each cornea to obtain a final graft thickness of less than 110 µm. Precut and postcut central pachymetry were performed with an ultrasonic pachymeter. Central endothelial cell density (ECD) was calculated before and 24 hours after tissue preparation. 
Results: Final graft thickness was 105.0 ± 26.1 (SD) µm (range 65-117). The mean microkeratome head cut thickness was 324.5 ± 10.9 µm (range 310-345). Precut and postcut ECDs averaged 2250 ± 222 and 2093 ± 286 cells/mm2, respectively, representing 6.9% of cell loss. No corneas were perforated.
Conclusion: Femtosecond FS60 lasers and Moria CBm 300-µm microkeratomes can be used sequentially to prepare consistently thin DSAEK grafts with no irregular cuts or cornea perforations

Optimising mRNA vaccines manufacturing by using Machine learning approaches

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Femtosecond laser and microkeratome-assisted Descemet stripping endothelial keratoplasty: first clinical results

Purpose: To evaluate the use of a femtosecond laser combined with a microkeratome in the preparation of posterior corneal disks for Descemet stripping automated endothelial keratoplasty (DSAEK).
Methods: This experimental study involved ultrathin DSAEK tissue preparation of 22 donor corneas unsuitable for transplantation. The first cut was performed with an Intralase® FS60 laser and the second cut with a Moria CBm 300-µm microkeratome. The thickness of the first cut was modified for each cornea to obtain a final graft thickness of less than 110 µm. Precut and postcut central pachymetry were performed with an ultrasonic pachymeter. Central endothelial cell density (ECD) was calculated before and 24 hours after tissue preparation. 
Results: Final graft thickness was 105.0 ± 26.1 (SD) µm (range 65-117). The mean microkeratome head cut thickness was 324.5 ± 10.9 µm (range 310-345). Precut and postcut ECDs averaged 2250 ± 222 and 2093 ± 286 cells/mm2, respectively, representing 6.9% of cell loss. No corneas were perforated.
Conclusion: Femtosecond FS60 lasers and Moria CBm 300-µm microkeratomes can be used sequentially to prepare consistently thin DSAEK grafts with no irregular cuts or cornea perforations

Comportamentos de risco e excesso de peso na adolescência: revisão da literatura

A adolescência é uma fase de maior vulnerabilidade para o envolvimento em comportamentos de risco. Paralelamente, o excesso de peso pode ter implicações pessoais e inter-pessoais que podem pôr em causa o bem-estar psicológico dos adolescentes e potenciar o envolvimento em comportamentos de risco. Objectivo: Analisar estudos sobre comportamentos de risco (ferimentos auto-infligidos e consumo de substâncias) num contexto de obesidade ou sobrepeso na adolescência, observando o papel que certas variáveis psico-sociais podem ter na sua moderação. Métodos: Pesquisa de livros e em bases de dados de artigos científicos sobre o tema. Resultados: Os resultados das investigações que procuram associações entre o excesso de peso na adolescência e o cometimento de ferimentos auto-infligidos e/ou consumo de substâncias são pouco consistentes. Alguns estudos mostram que os adolescentes obesos apresentam mais comportamentos de risco, ao passo que outros mostram que o excesso de peso e a obesidade nos jovens parecem estar associados a uma frequência menor ou idêntica deste tipo de comportamentos nos seus pares de peso saudável. Existem evidências de que a regulação emocional, a participação em actividades sociais e o suporte social proporcionado pelos pares e família podem moderar estes comportamentos de risco nos adolescentes com excesso de peso. Conclusão: O excesso de peso não é necessariamente um factor de risco para que os adolescentes cometam ferimentos auto-infligidos ou enveredem por padrões de consumo de álcool e tabaco mais problemáticos, podendo no entanto existir factores psico-sociais que tornem os adolescentes com excesso de peso mais vulneráveis a este tipo de comportamentos. (Discussão) A investigação sobre a associação entre o excesso de peso e o desenvolvimento de comportamentos de risco é reduzida. O número de estudos torna-se ainda mais escasso se reduzirmos os estudos existentes à população adolescente. Relativamente aos ferimentos auto-infligidos, a investigação tem vindo a estudar a relação entre suicídio e obesidade, mas pouco se sabe sobre a prevalência dos vários tipos de comportamentos auto-infligidos e dos perfis de auto-regulação mais frequentes na população jovem obesa. Apesar disso a presença de ferimentos auto-infligidos na adolescência demonstra que é independente da condição de excesso de peso. No entanto outros estudos mostram que o excesso de peso pode traduzir-se em maior vulnerabilidade para cometer ferimentos auto-infligidos. A ausência de resultados consensuais a este nível alerta para o facto de ser urgente explorar esta relação ao mesmo nível do que já foi efectuado no âmbito das perturbações alimentares como a bulimia e a anorexia nervosa. Diversos autores têm encontrado níveis elevados de co-ocorrência da bulimia nervosa e de ferimentos auto-infligidos, tendo ambos sido conceptualizados como estratégias mal-adaptativas de regulação emocional ou de lidar com a insatisfação com a imagem corporal. Nesta linha comprova-se que as dificuldades de auto-regulação também podem ser comuns à obesidade, tornando-se fundamental aprofundar a sua ligação aos ferimentos auto-infligidos. Reflectindo sobre o impacto do sobrepeso no consumo de álcool, surge uma grande diversidade de resultados. Se por um lado encontramos estudos que reforçaram uma relação directa entre o IMC dos adolescentes e o consumo de substâncias, por outro outras investigações mais recentes apontam na direcção contrária. Esta incongruência pode dever-se a aspectos sócio-demográficos específicos da amostra seleccionada para cada estudo (como o sexo e a idade), ou a outros factores de ordem psico-social. Quanto ao consumo de tabaco as investigações mais recentes indicam um aumento do seu consumo nos jovens com excesso de peso em relação aos jovens de peso saudável. A ideia partilhada pelos adolescentes de que o uso de tabaco faz perder peso pode explicar a maior prevalência do uso de tabaco nos adolescentes com excesso de peso em relação a adolescentes com peso normal. A literatura refere ainda que as dificuldades de integração no grupo de pares, sentidas por vezes pelos adolescentes obesos, podem levar a um maior envolvimento nestes comportamentos. Factores como o estado emocional, o suporte familiar, o grau de participação em actividades sociais e a relação com os pares podem assim exercer uma influência negativa ou positiva na prevalência dos comportamentos de risco nos adolescentes com excesso de peso. Também aqui os resultados dos estudos empíricos não permitem dados conclusivos. (...) (Conclusão) O excesso de peso por si só não é necessariamente um factor de risco para o cometimento de ferimentos auto-infligidos e para o consumo de substâncias. No entanto existem factores demográficos e psico-sociais que podem interferir nesta relação, podendo tornar os adolescentes com excesso de peso mais ou menos vulneráveis à adopção destes comportamentos. Os profissionais de saúde desempenham aqui um papel importante na educação para a saúde, podendo alertar os adolescentes para as consequências deste tipo de comportamentos, principalmente os associados ao excesso de peso

Maximizing mRNA vaccine production with Bayesian optimization

Messenger RNA (mRNA) vaccines are a new alternative to conventional vaccines with a prominent role in infectious disease control. These vaccines are produced in in vitro transcription (IVT) reactions, catalyzed by RNA polymerase in cascade reactions. To ensure an efficient and cost-effective manufacturing process, essential for a large-scale production and effective vaccine supply chain, the IVT reaction needs to be optimized. IVT is a complex reaction that contains a large number of variables that can affect its outcome. Traditional optimization methods rely on classic Design of Experiments methods, which are time-consuming and can present human bias or based on simplified assumptions. In this contribution, we propose the use of Machine Learning approaches to perform a data-driven optimization of an mRNA IVT reaction. A Bayesian optimization method and model interpretability techniques were used to automate experiment design, providing a feedback loop. IVT reaction conditions were found under 60 optimization runs that produced 12 g · L−1 in solely 2 h. The results obtained outperform published industry standards and data reported in literature in terms of both achievable reaction yield and reduction of production time. Furthermore, this shows the potential of Bayesian optimization as a cost-effective optimization tool within (bio)chemical applications

Encerramento Percutâneo de Comunicação Interauricular Residual por Falência de Dispositivo

A 39-year-old woman underwent uneventful percutaneous occlusion of an ostium secundum atrial septal defect (ASD) with a 22 mm Ultrasept ASD Occluder®. Transesophageal echocardiography (TEE) performed two years after implantation revealed a de novo residual left-to-right shunt through the correctly implanted device. Three-dimensional transesophageal echocardiography (3D TEE) further clarified this finding by showing a perforation of the device membrane coating. The patient underwent transcatheter closure of the residual shunt with a 20 mm Ultrasept PFO®device. The procedure was guided by fluoroscopy and real-time 3D TEE. At the end of the procedure 3D TEE documented correct device deployment with complete defect coverage and absence of residual shunt.info:eu-repo/semantics/publishedVersio