Analysis of the Accuracy of CAM-type Deformity Resection on a Low-cost Arthroscopic Simulator in a Training Scenario.

Objective To evaluate surgeons' performance in resecting CAM-type deformities using a realistic arthroscopic surgery simulator. Methods An arthroscopic simulator was created using low-cost materials with the help of a GTMax Core A1 3D printer and the programs Invesalius and Meshmixer 2017, which were used to develop femoral head parts in ABS material, with the presence of a CAM-type deformity, to mimic a femoroacetabular impact situation. After the operations were performed by 16 surgeons, the femurs were compared to a previous model with deformity and another without, using Cloudcompare, and parameters such as the volumetric difference between the operated femurs, with and without deformity, the minimum and maximum distance between them, the percentage of the deformity resected, the estimated time for total resection of the deformity, as well as a qualitative analysis based on the images and graphs provided by the program representing the areas of the parts resected, were evaluated at the end. Results The average resection speed was 34.66 mm 3 /min (SD = 46 mm 3 /min, max = 147.33; min = -2.66). The average resection rate was 26.2% (SD = 34.7%, max = 111; min = -2). Qualitative analysis showed hyporesection of deformities and sometimes hyperresection of nondeformed areas. The simulator was highly rated by the surgeons, with a tactile sensation very similar to real surgery, according to them. Conclusion Arthroscopic simulators have proved very useful in training less experienced surgeons.

Analysis of the Accuracy of CAM-type Deformity Resection on a Low-cost Arthroscopic Simulator in a Training Scenario / Análise da acurácia da ressecção de deformidades tipo CAME em simulador artroscópico de baixo custo em um cenário de treinamento

Abstract Objective To evaluate surgeons' performance in resecting CAM-type deformities using a realistic arthroscopic surgery simulator. Methods An arthroscopic simulator was created using low-cost materials with the help of a GTMax Core A1 3D printer and the programs Invesalius and Meshmixer 2017, which were used to develop femoral head parts in ABS material, with the presence of a CAM-type deformity, to mimic a femoroacetabular impact situation. After the operations were performed by 16 surgeons, the femurs were compared to a previous model with deformity and another without, using Cloudcompare, and parameters such as the volumetric difference between the operated femurs, with and without deformity, the minimum and maximum distance between them, the percentage of the deformity resected, the estimated time for total resection of the deformity, as well as a qualitative analysis based on the images and graphs provided by the program representing the areas of the parts resected, were evaluated at the end. Results The average resection speed was 34.66 mm3/min (SD = 46 mm3/min, max = 147.33; min = −2.66). The average resection rate was 26.2% (SD = 34.7%, max = 111; min = −2). Qualitative analysis showed hyporesection of deformities and sometimes hyperresection of nondeformed areas. The simulator was highly rated by the surgeons, with a tactile sensation very similar to real surgery, according to them. Conclusion Arthroscopic simulators have proved very useful in training less experienced surgeons.

Resumo Objetivo Avaliar o desempenho de cirurgiões na ressecção de deformidades tipo CAME fazendo uso de um simulador realista de cirurgia artroscópica. Métodos Um simulador artroscópico foi criado a partir de materiais de baixo custo com auxílio de uma impressora 3D GTMax Core A1 e dos programas Invesalius e Meshmixer 2017, que foram utilizados para criar peças de cabeça de fêmur em material ABS, com a presença de uma deformidade tipo CAME, a fim de mimetizar uma situação de impacto femoroacetabular. Após as operações serem realizadas por 16 cirurgiões, os fêmures foram comparados a um modelo prévio com e outro sem deformidade pelo programa Cloudcompare, sendo avaliados ao final parâmetros como diferença volumétrica entre os fêmures operados, com e sem deformidade, distância mínima e máxima entre eles, porcentagem da deformidade ressecada, tempo estimado para ressecção total da deformidade, além de uma análise qualitativa feita com base nas imagens e gráficos fornecidos pelo programa representando as áreas das peças efetivamente ressecadas. Resultados A velocidade média de resseção foi de 34,66mm3/minuto (DP = 46 mm3/min, max = 147,33 mm3/min; min = −2,66 mm3/min). A média de ressecção obtida foi de 26,2% (DP = 34,7%, max = 111%; min = −2%). A análise qualitativa demonstrou uma hiporresecção das deformidades e, por vezes, hiperresecção de áreas não deformadas. O simulador foi muito bem avaliado pelos cirurgiões, tendo uma sensação tátil bem semelhante à cirurgia real segundo os mesmos. Conclusão Simuladores artroscópicos se mostraram muito úteis no treinamento de cirurgiões menos experientes.

Potencial terapêutico dos canabinoides na ansiedade e depressão: uma revisão integrativa da literatura / Therapeutic potential of cannabinoids in anxiety and depression: an integrative review of the literature / Potencial terapéutico de canabinoides en ansiedad y depresión: una revisión integrativa de la literatura

Introdução: Os transtornos psiquiátricos, principalmente ansiedade e depressão, são queixas muito prevalentes na população mundial. Atualmente, esse fato move a comunidade científica a realizar estudos para avaliar alternativas que possam contribuir no tratamento dessas doenças. Por isso, a Cannabis Medicinal (CM) vem ganhando espaço na sociedade e parece ser uma opção terapêutica viável e vantajosa. Objetivo: Evidenciar os possíveis usos terapêuticos dos componentes presentes na planta Cannabis no manejo da ansiedade e depressão. Métodos: Trata-se de uma revisão bibliográfica integrativa, elaborada a partir de trabalhos científicos acerca da ação da Cannabis Medicinal como uma alternativa para o tratamento da ansiedade e depressão. Foram considerados artigos originais e completos publicados em português, espanhol e inglês nos últimos dez anos, de 2013 até 2023, obtidos nas plataformas SCIELO, PUBMED e LILACS. Resultados: As substâncias presentes na planta Cannabis, principalmente o Canabidiol (CBD), parecem ser uma opção promissora e potencialmente benéfica, especialmente para os casos que não respondem aos tratamentos convencionais. Conclusão: A partir dos estudos analisados, evidencia-se que os estudos atuais disponíveis sobre a eficácia dos canabinoides no tratamento dos transtornos mentais são de qualidade variável. Sendo assim, apesar da CM ser uma possível opção para o tratamento de transtornos mentais, ainda se faz necessária a realização de mais pesquisas para elucidar plenamente como funcionaria sua utilização na prática clínica. PALAVRAS-CHAVE: Uso Terapêutico da Cannabis; Depressão; Ansiedade; Revisão Integrativa.

Introduction: Psychiatric disorders, mainly anxiety and depression, are very prevalent complaints in the world population. At the moment, this fact is driving the scientific community to carry out studies to evaluate alternatives that may contribute towards the treatment of these diseases. For this reason, Medicinal Cannabis (CM) has been gaining space in society and seems to be a viable and advantageous therapeutic option. Objective: To show the possible therapeutic uses of the components present in the Cannabis plant in the management of anxiety and depression. Methods: It is an integrative bibliographic review, elaborated from scientific papers about the action of Medicinal Cannabis as an alternative for the treatment of anxiety and depression. They were considered original and complete articles published in Portuguese, Spanish and English in the last ten years, from 2013 until 2023, obtained on the platforms SCIELO, PUBMED and LILACS. Results: The substances present in the Cannabis plant, mainly Cannabidiol (CBD), seem to be a promising and potentially beneficial option, especially for cases that do not respond to conventional treatments. Conclusion: From the studies analyzed, it is evident that the current available studies on the efficacy of cannabinoids in the treatment of mental disorders are of variable quality. Therefore, although CM is a possible option for the treatment of mental disorders, it is still necessary to carry out more research to fully elucidate how its use would work in clinical practice.

Introducción: los trastornos psiquiátricos, principalmente la ansiedad y la depresión, son quejas muy frecuentes en la población mundial. Por el momento, este hecho está llevando a la comunidad científica a realizar estudios para evaluar alternativas que puedan contribuir al tratamiento de estas enfermedades. Por esta razón, el Medicamento de Cannabis (CM) ha venido ganando espacio en la sociedad y parece ser una opción terapéutica viable y ventajosa. Objetivo: destacar los posibles usos terapéuticos de los componentes presentes en la planta de Cannabis en el manejo de la ansiedad y la depresión. Métodos: Se trata de una revisión bibliográfica integradora, elaborada sobre la base de un trabajo científico sobre la acción del Medicinal Cannabis como alternativa para el tratamiento de la ansiedad y la depresión. Se consideraron artículos originales y completos publicados en portugués, español e inglés en los últimos 10 años de 2013 a 2023, obtenidos en las plataformas SCIELO, PUBMED y LILACS. Resultados: Las sustancias presentes en la planta Cannabis, principalmente Canabidiol (CBD), parecen ser una opción prometedora y potencialmente beneficiosa, especialmente en los casos que no responden a tratamientos convencionales. Conclusión: De los estudios analizados se desprende que los estudios actuales disponibles sobre la eficacia de los cannabinoides en el tratamiento de los trastornos mentales son de calidad variable. Por lo tanto, aunque la MPC es una posible opción para el tratamiento de los trastornos mentales, todavía se necesita una investigación más profunda para explicar plenamente cómo funcionaría su uso en la práctica clínica.

O exercício físico como uma alternativa para o controle da pressão arterial em hipertensos: uma revisão integrativa da literatura / Physical exercise as an alternative for blood pressure control in hypertensive individuals: an integrative literature review / El ejercicio físico como alternativa para el control de la presión arterial en hipertensos: una revisión bibliográfica integradora

Introdução: A Hipertensão Arterial Sistêmica (HAS) é uma doença crônica de alta prevalência que pode provocar consequências desastrosas em indivíduos não tratados. Por isso, a comunidade científica busca encontrar formas para mitigar os efeitos danosos da hipertensão. Nesse sentido, a prática de exercícios físicos (EF) surge como uma medida não farmacológica interessante para o controle da pressão arterial (PA). Objetivo: Evidenciar os potencias benefícios do exercício físico no controle da PA. Métodos: Trata-se de uma revisão bibliográfica integrativa da literatura, elaborada a partir de trabalhos científicos acerca dos benefícios da prática de exercícios físicos no controle da pressão arterial. Foram considerados artigos originais e completos publicados em português, espanhol e inglês nos últimos dez anos, de 2013 até 2023, obtidos nas plataformas SCIELO, PUBMED e LILACS. Resultados: Os estudos atuais disponíveis sobre o tema mostram grande eficácia da realização de atividades físicas na prevenção e no tratamento da HAS. Algumas evidências sugerem que a prática regular de EF possui muitos benefícios para diversos órgãos e sistemas do corpo humano, principalmente para o coração e o sistema cardiovascular. Conclusão: A partir dos estudos analisados, evidencia-se que a prática regular de atividades físicas resulta em uma série de benefícios para a saúde no geral, como melhora na capacidade cognitiva, diminuição da gordura visceral e controle dos níveis pressóricos. O EF possui relação significativa com a HAS, sendo comprovadamente benéfica. A prática prolongada de atividades físicas teve um efeito protetor na incidência de doenças cardiovasculares e na mortalidade em comparação aos indivíduos sedentários. É importante que comunidade científica busque formas de realizar mais estudos, a fim de informar e influenciar pessoas a praticarem atividades físicas.

Introduction: Systemic Arterial Hypertension (SAH) is a chronic disease of high prevalence that can cause disastrous consequences in untreated individuals. Therefore, the scientific community seeks to find ways to mitigate the harmful effects of hypertension. In this sense, the practice of physical exercises (PE) emerges as an interesting non-pharmacological measure for the control of blood pressure (BP). Objective: To highlight the potential benefits of physical exercise in BP control. Methods: This is an integrative literature review, based on scientific papers about the benefits of physical exercise in blood pressure control. Original and complete articles published in Portuguese, Spanish and English in the last ten years, from 2013 to 2023, obtained from SCIELO, PUBMED and LILACS platforms were considered.Results: The current studies available on the subject show great effectiveness of performing physical activities in the prevention and treatment of SAH. Some evidence suggests that the regular practice of PE has many benefits for various organs and systems of the human body, especially for the heart and cardiovascular system. Conclusion: From the studies analyzed, it is evident that regular physical activity results in a series of benefits for overall health, such as improved cognitive ability, decreased visceral fat, and control of blood pressure levels. PE has a significant relation with SAH, being proven beneficial. Long-term physical activity had a protective effect on the incidence of cardiovascular disease and mortality compared to sedentary individuals. It is important that the scientific community seek ways to conduct further studies in order to inform and influence people to practice physical activities.

Introducción: La hipertensión arterial sistémica (HSA) es una enfermedad crónica de alta prevalencia que puede causar consecuencias desastrosas en individuos no tratados. Por isso, a comunidade científica procura encontrar formas de mitigar os efeitos nocivos da hipertensão. En este sentido, la práctica de ejercicios físicos (EF) surge como una medida no farmacológica interesante para el control de la presión arterial (PA). Objetivo: Demostrar los beneficios del ejercicio físico en el control de la PA. Métodos: Se trata de una revisión bibliográfica integradora de la literatura, elaborada a partir de trabajos científicos acerca de los beneficios de la práctica de ejercicios físicos en el control de la presión arterial. Fueron considerados artículos originales y completos publicados en portugués, español e inglés en los últimos diez años, de 2013 a 2023, obtenidos de las plataformas SCIELO, PUBMED y LILACS. Resultados: Los estudios actuales disponibles sobre el tema muestran gran eficacia de la realización de actividades físicas en la prevención y tratamiento de la HSA. Algunas evidencias sugieren que la práctica regular de EF tiene muchos beneficios para diversos órganos y sistemas del cuerpo humano, especialmente para el corazón y el sistema cardiovascular. Conclusión: De los estudios analizados se desprende que la práctica regular de actividades físicas conlleva una serie de beneficios para la salud en general, como la mejora de la capacidad cognitiva, la disminución de la grasa visceral y el control de los niveles de presión arterial. La PE tiene una relación significativa con la HSA, demostrándose beneficiosa. La práctica prolongada de actividades físicas tuvo un efecto protector sobre la incidencia de enfermedades cardiovasculares y la mortalidad en comparación con los individuos sedentarios. Es importante que la comunidad científica busque la forma de realizar más estudios para informar e influenciar a las personas para que practiquen actividades físicas.

Os desafios enfrentados na amamentação para a mulher cega: uma revisão integrativa da literatura / The challenges faced in breastfeeding by blind women: an integrative literature review / Los retos de la lactancia materna en mujeres ciegas: una revisión bibliográfica integradora

Introdução: A maternidade para mulheres cegas é um processo de modificação descrito como um evento crítico, marcado por inseguranças e preocupações. Essas mulheres sofrem preconceito e além de lidarem com uma limitação física, também precisam vivenciar limitações impostas pela sociedade. Objetivo: Esse estudo teve como objetivo destacar a prática da amamentação e os desafios para as mulheres cegas. Métodos: Trata-se de uma revisão bibliográfica integrativa, elaborada a partir de trabalhos científicos acerca dos desafios enfrentados na amamentação para a mulher cega. Foram considerados artigos originais e completos publicados em português, espanhol e inglês nos últimos dez anos, de 2013 até 2023, obtidos nas plataformas SCIELO, PUBMED, LILACS e BVS. Resultados: Os estudos atuais mostram que os desafios enfrentados pelas mulheres cegas durante a amamentação são pouco discutidos e podem levar ao distanciamento das recém-mães dessa prática. Deve-se sempre ser alertado sobre a importância da amamentação, pois está associada não apenas à saúde da criança, mas também à saúde materna e ao maior vínculo entre mãe e filho. Conclusão: Fica nítido a necessidade de desenvolver ações de educação em saúde, orientações, informações no pré-natal sobre as mudanças que ocorrerão no período gestacional, cuidados de enfermagem no parto e pós-parto direcionados às especificidades da mulher cega, além de orientações sobre cuidados iniciais do bebê, como banho, amamentação e prevenção de acidentes.

Introduction: Motherhood for blind women is a process of change described as a critical event, marked by insecurities and concerns. These women suffer prejudice and besides dealing with a physical limitation, they also need to experience limitations imposed by society. Objective: This study aimed to highlight the practice of breastfeeding and the challenges for blind women. Methods: This is an integrative literature review, based on scientific papers about the challenges faced by blind women in breastfeeding. Original and complete articles published in Portuguese, Spanish and English in the last ten years, from 2013 to 2023, obtained from the SCIELO, PUBMED, LILACS and BVS platforms were considered. Results: The current studies show that the challenges faced by blind women during breastfeeding are little discussed and may lead to the distancing of new mothers from this practice. One should always be alerted about the importance of breastfeeding, since it is associated not only with the child's health, but also with maternal health and the greater bond between mother and child. Conclusion: It is clear the need to develop health education actions, guidelines, information in prenatal care about the changes that will occur during pregnancy, nursing care during delivery and postpartum directed to the specificities of blind women, as well as guidelines on initial care of the baby, such as bathing, breastfeeding and accident prevention.

Introducción: La maternidad para las mujeres ciegas es un proceso de cambio descrito como un acontecimiento crítico, marcado por inseguridades y preocupaciones. Estas mujeres sufren prejuicios y, además de lidiar con una limitación física, también tienen que experimentar las limitaciones impuestas por la sociedad. Objetivo: Este estudio tuvo como objetivo destacar la práctica de la lactancia materna y los desafíos para las mujeres ciegas. Métodos: Trata-se de uma revisão bibliográfica integrativa, elaborada a partir de trabalhos científicos acerca dos desafios enfrentados na amamentação para a mulher cega. Se consideraron artículos originales y completos publicados en portugués, español e inglés en los últimos diez años, de 2013 a 2023, obtenidos de las plataformas SCIELO, PUBMED, LILACS y BVS. Resultados: Los estudios actuales muestran que los desafíos enfrentados por las mujeres ciegas durante la lactancia materna son poco discutidos y pueden llevar al distanciamiento de las nuevas madres de esta práctica. Se debe alertar siempre sobre la importancia de la lactancia materna, pues está asociada no sólo a la salud del niño, sino también a la salud materna y al mayor vínculo entre madre e hijo. Conclusão: Fica nítida a necessidade de desenvolver ações de educação em saúde, orientações, informações no pré-natal sobre as mudanças que ocorrerão no período gestacional, cuidados de enfermagem no parto e pós-parto direcionados às especificidades da mulher cega, além de orientações sobre cuidados iniciais do bebê, como banho, amamentação e prevenção de acidentes.

Quantitative assessment of emphysema and bronchial wall thickness in patients with stable chronic obstructive pulmonary disease: comparison between the eosinophilic and non-eosinophilic phenotypes.

Objective: To perform a quantitative assessment of bronchial wall thickening and the emphysema score in patients with stable chronic obstructive pulmonary disease (COPD), comparing the eosinophilic and non-eosinophilic COPD phenotypes. Materials and Methods: This was a retrospective observational study of patients with COPD followed between August 2018 and July 2019. The patients were divided into two groups by the eosinophil count in peripheral blood: eosinophilic (≥ 300 cells/µL); and non-eosinophilic (< 300 cells/µL). Quantitative, automated assessments of emphysema and bronchial wall thickness were performed by evaluating computed tomography scans of the chest. Results: We evaluated the records of 110 patients diagnosed with COPD: 28 (25.5%) in the eosinophilic group; and 82 (74.5%) in the non-eosinophilic group. The demographic, clinical, functional, and therapeutic variables were comparable between the two groups. There were no significant differences between the two groups in terms of the emphysema score or bronchial wall thickness (p > 0.05 for both). Conclusion: Patients with eosinophilic COPD do not appear to have lower emphysema scores or greater bronchial wall thickening than do those with non-eosinophilic phenotypes of the disease.

Objetivo: Avaliar quantitativamente o escore de enfisema e o espessamento da parede brônquica de pacientes com doença pulmonar obstrutiva crônica (DPOC) estável e comparar os fenótipos eosinofílico e não eosinofílico. Materiais e Métodos: Estudo observacional, transversal, retrospectivo, que avaliou pacientes com DPOC no período de agosto de 2018 a julho de 2019. Os pacientes foram separados dois grupos, de acordo com o número de eosinófilos periféricos: os eosinofílicos (≥ 300 células/µL) e os não eosinofílicos (< 300 células/µL). Foram realizadas avaliações quantitativas e automatizadas de enfisema e de espessamento brônquico para os dois grupos por meio de tomografia computadorizada de tórax. Resultados: Foram coletados dados de 110 pacientes com o diagnóstico de DPOC, dos quais 28 (25,5%) apresentaram perfil eosinofílico. As variáveis demográficas, clínicas, funcionais e terapêuticas do grupo dos pacientes com perfil eosinofílico foram semelhantes às do grupo não eosinofílico. Não se observaram diferenças significativas em relação ao escore de enfisema e à medida de espessura de parede brônquica entre os dois grupos (p > 0,05). Conclusão: Neste estudo, os pacientes com fenótipo eosinofílico não apresentaram menor escore de enfisema e nem maior espessamento parietal brônquico.

Quantitative assessment of emphysema and bronchial wall thickness in patients with stable chronic obstructive pulmonary disease: comparison between the eosinophilic and non-eosinophilic phenotypes / Avaliação quantitativa de enfisema e espessamento parietal brônquico em pacientes com doença pulmonar obstrutiva crônica estável: comparação entre os fenótipos eosinofílico e não eosinofílico

Abstract Objective: To perform a quantitative assessment of bronchial wall thickening and the emphysema score in patients with stable chronic obstructive pulmonary disease (COPD), comparing the eosinophilic and non-eosinophilic COPD phenotypes. Materials and Methods: This was a retrospective observational study of patients with COPD followed between August 2018 and July 2019. The patients were divided into two groups by the eosinophil count in peripheral blood: eosinophilic (≥ 300 cells/µL); and non-eosinophilic (< 300 cells/µL). Quantitative, automated assessments of emphysema and bronchial wall thickness were performed by evaluating computed tomography scans of the chest. Results: We evaluated the records of 110 patients diagnosed with COPD: 28 (25.5%) in the eosinophilic group; and 82 (74.5%) in the non-eosinophilic group. The demographic, clinical, functional, and therapeutic variables were comparable between the two groups. There were no significant differences between the two groups in terms of the emphysema score or bronchial wall thickness (p > 0.05 for both). Conclusion: Patients with eosinophilic COPD do not appear to have lower emphysema scores or greater bronchial wall thickening than do those with non-eosinophilic phenotypes of the disease.

Resumo Objetivo: Avaliar quantitativamente o escore de enfisema e o espessamento da parede brônquica de pacientes com doença pulmonar obstrutiva crônica (DPOC) estável e comparar os fenótipos eosinofílico e não eosinofílico. Materiais e Métodos: Estudo observacional, transversal, retrospectivo, que avaliou pacientes com DPOC no período de agosto de 2018 a julho de 2019. Os pacientes foram separados dois grupos, de acordo com o número de eosinófilos periféricos: os eosinofílicos (≥ 300 células/µL) e os não eosinofílicos (< 300 células/µL). Foram realizadas avaliações quantitativas e automatizadas de enfisema e de espessamento brônquico para os dois grupos por meio de tomografia computadorizada de tórax. Resultados: Foram coletados dados de 110 pacientes com o diagnóstico de DPOC, dos quais 28 (25,5%) apresentaram perfil eosinofílico. As variáveis demográficas, clínicas, funcionais e terapêuticas do grupo dos pacientes com perfil eosinofílico foram semelhantes às do grupo não eosinofílico. Não se observaram diferenças significativas em relação ao escore de enfisema e à medida de espessura de parede brônquica entre os dois grupos (p > 0,05). Conclusão: Neste estudo, os pacientes com fenótipo eosinofílico não apresentaram menor escore de enfisema e nem maior espessamento parietal brônquico.

A pipeline for the reconstruction and evaluation of context-specific human metabolic models at a large-scale.

Constraint-based (CB) metabolic models provide a mathematical framework and scaffold for in silico cell metabolism analysis and manipulation. In the past decade, significant efforts have been done to model human metabolism, enabled by the increased availability of multi-omics datasets and curated genome-scale reconstructions, as well as the development of several algorithms for context-specific model (CSM) reconstruction. Although CSM reconstruction has revealed insights on the deregulated metabolism of several pathologies, the process of reconstructing representative models of human tissues still lacks benchmarks and appropriate integrated software frameworks, since many tools required for this process are still disperse across various software platforms, some of which are proprietary. In this work, we address this challenge by assembling a scalable CSM reconstruction pipeline capable of integrating transcriptomics data in CB models. We combined omics preprocessing methods inspired by previous efforts with in-house implementations of existing CSM algorithms and new model refinement and validation routines, all implemented in the Troppo Python-based open-source framework. The pipeline was validated with multi-omics datasets from the Cancer Cell Line Encyclopedia (CCLE), also including reference fluxomics measurements for the MCF7 cell line. We reconstructed over 6000 models based on the Human-GEM template model for 733 cell lines featured in the CCLE, using MCF7 models as reference to find the best parameter combinations. These reference models outperform earlier studies using the same template by comparing gene essentiality and fluxomics experiments. We also analysed the heterogeneity of breast cancer cell lines, identifying key changes in metabolism related to cancer aggressiveness. Despite the many challenges in CB modelling, we demonstrate using our pipeline that combining transcriptomics data in metabolic models can be used to investigate key metabolic shifts. Significant limitations were found on these models ability for reliable quantitative flux prediction, thus motivating further work in genome-wide phenotype prediction.

Toward 3D-bioprinting of an endocrine pancreas: A building-block concept for bioartificial insulin-secreting tissue.

Three-dimensional bioprinting of an endocrine pancreas is a promising future curative treatment for patients with insulin secretion deficiency. In this study, we present an end-to-end concept from the molecular to the macroscopic level. Building-blocks for a hybrid scaffold device of hydrogel and functionalized polycaprolactone were manufactured by 3D-(bio)printing. Pseudoislet formation from INS-1 cells after bioprinting resulted in a viable and proliferative experimental model. Transcriptomics showed an upregulation of proliferative and ß-cell-specific signaling cascades, downregulation of apoptotic pathways, overexpression of extracellular matrix proteins, and VEGF induced by pseudoislet formation and 3D-culture. Co-culture with endothelial cells created a natural cellular niche with enhanced insulin secretion after glucose stimulation. Survival and function of pseudoislets after explantation and extensive scaffold vascularization of both hydrogel and heparinized polycaprolactone were demonstrated in vivo. Computer simulations of oxygen, glucose and insulin flows were used to evaluate scaffold architectures and Langerhans islets at a future perivascular transplantation site.

Reconstruction of tissue-specific genome-scale metabolic models for human cancer stem cells.

Cancer Stem Cells (CSCs) contribute to cancer aggressiveness, metastasis, chemo/radio-therapy resistance, and tumor recurrence. Recent studies emphasized the importance of metabolic reprogramming of CSCs for the maintenance and progression of the cancer phenotype through both the fulfillment of the energetic requirements and the supply of substrates fundamental for fast-cell growth, as well as through metabolite-induced epigenetic regulation. Therefore, it is of paramount importance to develop therapeutic strategies tailored to target the metabolism of CSCs. In this work, we built computational Genome-Scale Metabolic Models (GSMMs) for CSCs of different tissues. Flux simulations were then used to predict metabolic phenotypes, identify potential therapeutic targets, and spot already-known Transcription Factors (TFs), miRNAs and antimetabolites that could be used as part of drug repurposing strategies against cancer. Results were in accordance with experimental evidence, provided insights of new metabolic mechanisms for already known agents, and allowed for the identification of potential new targets and compounds that could be interesting for further in vitro and in vivo validation.

The novel Outer Plug Standardization (OPS) calibration strategy applied in a new method for the high-throughput determination of Cl-, NO3- and SO4-2 in rainwater samples.

This paper presents the Outer Plug Standardization - OPS, a novel technique as an alternative for the classic internal standardization using multiple injection in capillary zone electrophoresis is proposed herein. This technique was applied in a new method for the determination of chloride, nitrate and sulfate in rainwater samples. After the injection accuracy was tested and proved to be a minor error source (average 1.26% RSD), the OPS was applied and it improved the intra-day and inter-day precision of the analytical method by 32.5% and 24.7%, respectively. Using a capillary with effective length of 23.5 cm the electrophoretic separation of the three inorganic anions could be achieved in <1 min, with detection limits of 0.05, 0.09 and 0.11 mg L-1 for chloride, nitrate and sulfate, respectively. Also, the statistical t-test was applied to the results obtained for 82 rainwater samples that were collected and analyzed applying both the method developed in this study and the official APHA 4140 method where no statistical difference was noted within a 95% confidence level.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology.

Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

Cannabinoids in Neurology - Position paper from Scientific Departments from Brazilian Academy of Neurology / Canabinoides em Neurologia - Artigo de posicionamento dos Departamentos Científicos da Academia Brasileira de Neurologia

ABSTRACT Cannabinoids comprehend endocannabinoids, phytocannabinoids, and synthetic cannabinoids, with actions both in the central and peripherical nervous systems. A considerable amount of publications have been made in recent years, although cannabis has been known for over a thousand years. Scientific Departments from the Brazilian Academy of Neurology described evidence for medical use in their areas. Literature is constantly changing, and possible new evidence can emerge in the next days or months. Prescription of these substances must be discussed with patients and their families, with knowledge about adverse events and their efficacy.

RESUMO Os canabinoides compreendem os endocanabinoides, fitocanabinoides e os canabinoides sintéticos e desempenham ações no sistema nervoso central e periférico. Uma quantidade enorme de publicações tem sido lançada nos últimos anos, embora a cannabis seja conhecida por milênios. Os Departamentos Científicos da Academia Brasileira de Neurologia descreveram as evidências do uso médico em suas áreas. A literatura está em constantes mudanças e possíveis novas evidências podem surgir nos próximos dias ou meses. A prescrição dessas substâncias deve ser discutida com os pacientes e suas famílias, com conhecimento sobre eventos adversos e sua eficácia.

Causal integration of multi-omics data with prior knowledge to generate mechanistic hypotheses.

Multi-omics datasets can provide molecular insights beyond the sum of individual omics. Various tools have been recently developed to integrate such datasets, but there are limited strategies to systematically extract mechanistic hypotheses from them. Here, we present COSMOS (Causal Oriented Search of Multi-Omics Space), a method that integrates phosphoproteomics, transcriptomics, and metabolomics datasets. COSMOS combines extensive prior knowledge of signaling, metabolic, and gene regulatory networks with computational methods to estimate activities of transcription factors and kinases as well as network-level causal reasoning. COSMOS provides mechanistic hypotheses for experimental observations across multi-omics datasets. We applied COSMOS to a dataset comprising transcriptomics, phosphoproteomics, and metabolomics data from healthy and cancerous tissue from eleven clear cell renal cell carcinoma (ccRCC) patients. COSMOS was able to capture relevant crosstalks within and between multiple omics layers, such as known ccRCC drug targets. We expect that our freely available method will be broadly useful to extract mechanistic insights from multi-omics studies.

Information geometric analysis of long range topological superconductors.

The Uhlmann connection is a mixed state generalisation of the Berry connection. The latter has a very important role in the study of topological phases at zero temperature. Closely related, the quantum fidelity is an information theoretical quantity which is a measure of distinguishability of quantum states. Moreover, it has been extensively used in the analysis of quantum phase transitions. In this work, we study topological phase transitions in 1D and 2D topological superconductors with long-range hopping and pairing amplitudes, using the fidelity and the quantity [Formula: see text] closely related to the Uhlmann connection. The drop in the fidelity and the departure of [Formula: see text] from zero signal the topological phase transitions in the models considered. The analysis of the ground state fidelity susceptibility and its associated critical exponents are also applied to the study of the aforementioned topological phase transitions.

CoBAMP: a Python framework for metabolic pathway analysis in constraint-based models.

SUMMARY: CoBAMP is a modular framework for the enumeration of pathway analysis concepts, such as elementary flux modes (EFM) and minimal cut sets in genome-scale constraint-based models (CBMs) of metabolism. It currently includes the K-shortest EFM algorithm and facilitates integration with other frameworks involving reading, manipulation and analysis of CBMs. AVAILABILITY AND IMPLEMENTATION: The software is implemented in Python 3, supported on most operating systems and requires a mixed-integer linear programming optimizer supported by the optlang framework. Source-code is available at https://github.com/BioSystemsUM/cobamp.

Comparison of pathway analysis and constraint-based methods for cell factory design.

BACKGROUND: Computational strain optimisation methods (CSOMs) have been successfully used to exploit genome-scale metabolic models, yielding strategies useful for allowing compound overproduction in metabolic cell factories. Minimal cut sets are particularly interesting since their definition allows searching for intervention strategies that impose strong growth-coupling phenotypes, and are not subject to optimality bias when compared with simulation-based CSOMs. However, since both types of methods have different underlying principles, they also imply different ways to formulate metabolic engineering problems, posing an obstacle when comparing their outputs. RESULTS: In this work, we perform an in-depth analysis of potential strategies that can be obtained with both methods, providing a critical comparison of performance, robustness, predicted phenotypes as well as strategy structure and size. To this end, we devised a pipeline including enumeration of strategies from evolutionary algorithms (EA) and minimal cut sets (MCS), filtering and flux analysis of predicted mutants to optimize the production of succinic acid in Saccharomyces cerevisiae. We additionally attempt to generalize problem formulations for MCS enumeration within the context of growth-coupled product synthesis. Strategies from evolutionary algorithms show the best compromise between acceptable growth rates and compound overproduction. However, constrained MCSs lead to a larger variety of phenotypes with several degrees of growth-coupling with production flux. The latter have proven useful in revealing the importance, in silico, of the gamma-aminobutyric acid shunt and manipulation of cofactor pools in growth-coupled designs for succinate production, mechanisms which have also been touted as potentially useful for metabolic engineering. CONCLUSIONS: The two main groups of CSOMs are valuable for finding growth-coupled mutants. Despite the limitations in maximum growth rates and large strategy sizes, MCSs help uncover novel mechanisms for compound overproduction and thus, analyzing outputs from both methods provides a richer overview on strategies that can be potentially carried over in vivo.