Potato waste as feedstock to produce biohydrogen and organic acids: A comparison of acid and alkaline pretreatments using response surface methodology.

The effects of physicochemical pre-treatment were evaluated on hydrogen (H2) production and organic acids from hydrolyzed potato peel. Central composite design (CCD) and response surface methodology (RSM) were used to evaluate the effects of different substrate concentrations on a wet basis (38.8-81.2 g.L-1) and hydrolyser ratios (6M NaOH and 30% HCl: 1.6-4.4% v.v-1; and H2SO4: 2.2-7.8% v.v-1). The experiments were conducted in batch reactors at 37 °C, using a heat-treated microbial consortium. The maximum H2 production potential (P), lag phase (λ), and maximum H2 production rate (Rm) were evaluated for untreated and pre-treated potato peel waste. H2 production was positively influenced under hydrolyzed substrate concentrations ≥75 g.L-1 in the three CCDs performed. Only the increase in the H2SO4 proportions (≥5% v.v-1) had a negative influence on H2 production. Increasing the 30% HCl and 6M NaOH proportions did not significantly influence the cumulative H2 production. The highest hydrogen production was obtained after alkaline pre-treatment by dark fermentation (P: 762.09 mL H2.L-1; λ: 14.56 h; Rm: 38.39 mL H2.L-1.h-1). Based on the CCD and RSM, the highest H2 production (1060.10 mL H2.L-1) was observed with 81.2 g.L-1 hydrolyzed potato peel with 3.0% v.v-1 of 6M NaOH. The highest yield liquid metabolites were acetic (513.70 mg. g-1 COD) and butyric acids (491.90 mg. g-1 COD).

Perspectives on the evaluation and adoption of complex in vitro models in drug development: Workshop with the FDA and the pharmaceutical industry (IQ MPS Affiliate).

Complex in vitro models (CIVM) offer the potential to improve pharmaceutical clinical drug attrition due to safety and/ or efficacy concerns. For this technology to have an impact, the establishment of robust characterization and qualifi­cation plans constructed around specific contexts of use (COU) is required. This article covers the output from a workshop between the Food and Drug Administration (FDA) and Innovation and Quality Microphysiological Systems (IQ MPS) Affiliate. The intent of the workshop was to understand how CIVM technologies are currently being applied by pharma­ceutical companies during drug development and are being tested at the FDA through various case studies in order to identify hurdles (real or perceived) to the adoption of microphysiological systems (MPS) technologies, and to address evaluation/qualification pathways for these technologies. Output from the workshop includes the alignment on a working definition of MPS, a detailed description of the eleven CIVM case studies presented at the workshop, in-depth analysis, and key take aways from breakout sessions on ADME (absorption, distribution, metabolism, and excretion), pharmacology, and safety that covered topics such as qualification and performance criteria, species differences and concordance, and how industry can overcome barriers to regulatory submission of CIVM data. In conclusion, IQ MPS Affiliate and FDA scientists were able to build a general consensus on the need for animal CIVMs for preclinical species to better determine species concordance. Furthermore, there was acceptance that CIVM technologies for use in ADME, pharmacology and safety assessment will require qualification, which will vary depending on the specific COU.

3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration.

Nonclinical testing has served as a foundation for evaluating potential risks and effectiveness of investigational new drugs in humans. However, the current two-dimensional (2D) in vitro cell culture systems cannot accurately depict and simulate the rich environment and complex processes observed in vivo, whereas animal studies present significant drawbacks with inherited species-specific differences and low throughput for increased demands. To improve the nonclinical prediction of drug safety and efficacy, researchers continue to develop novel models to evaluate and promote the use of improved cell- and organ-based assays for more accurate representation of human susceptibility to drug response. Among others, the three-dimensional (3D) cell culture models present physiologically relevant cellular microenvironment and offer great promise for assessing drug disposition and pharmacokinetics (PKs) that influence drug safety and efficacy from an early stage of drug development. Currently, there are numerous different types of 3D culture systems, from simple spheroids to more complicated organoids and organs-on-chips, and from single-cell type static 3D models to cell co-culture 3D models equipped with microfluidic flow control as well as hybrid 3D systems that combine 2D culture with biomedical microelectromechanical systems. This article reviews the current application and challenges of 3D culture systems in drug PKs, safety, and efficacy assessment, and provides a focused discussion and regulatory perspectives on the liver-, intestine-, kidney-, and neuron-based 3D cellular models.

Characterizing the reproducibility in using a liver microphysiological system for assaying drug toxicity, metabolism, and accumulation.

Liver microphysiological systems (MPSs) are promising models for predicting hepatic drug effects. Yet, after a decade since their introduction, MPSs are not routinely used in drug development due to lack of criteria for ensuring reproducibility of results. We characterized the feasibility of a liver MPS to yield reproducible outcomes of experiments assaying drug toxicity, metabolism, and intracellular accumulation. The ability of the liver MPS to reproduce hepatotoxic effects was assessed using trovafloxacin, which increased lactate dehydrogenase (LDH) release and reduced cytochrome P450 3A4 (CYP3A4) activity. These observations were made in two test sites and with different batches of Kupffer cells. Upon culturing equivalent hepatocytes in the MPS, spheroids, and sandwich cultures, differences between culture formats were detected in CYP3A4 activity and albumin production. Cells in all culture formats exhibited different sensitivities to hepatotoxicant exposure. Hepatocytes in the MPS were more functionally stable than those of other culture platforms, as CYP3A4 activity and albumin secretion remained prominent for greater than 18 days in culture, whereas functional decline occurred earlier in spheroids (12 days) and sandwich cultures (7 days). The MPS was also demonstrated to be suitable for metabolism studies, where CYP3A4 activity, troglitazone metabolites, diclofenac clearance, and intracellular accumulation of chloroquine were quantified. To ensure reproducibility between studies with the MPS, the combined use of LDH and CYP3A4 assays were implemented as quality control metrics. Overall results indicated that the liver MPS can be used reproducibly in general drug evaluation applications. Study outcomes led to general considerations and recommendations for using liver MPSs. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Microphysiological systems (MPSs) have been designed to recreate organ- or tissue-specific characteristics of extracellular microenvironments that enhance the physiological relevance of cells in culture. Liver MPSs enable long-lasting and stable culture of hepatic cells by culturing them in three-dimensions and exposing them to fluid flow. WHAT QUESTION DID THIS STUDY ADDRESS? What is the functional performance relative to other cell culture platforms and the reproducibility of a liver MPS for assessing drug development and evaluation questions, such as toxicity, metabolism, and pharmacokinetics? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? The liver MPS systematically detected the toxicity of trovafloxacin. When compared with spheroids and sandwich cultures, this system had a more stable function and different sensitivity to troglitazone, tamoxifen, and digoxin. Quantifying phase II metabolism of troglitazone and intracellular accumulation of chloroquine demonstrated the potential use of the liver MPS for studying drug metabolism and pharmacokinetics. Quality control criteria for assessing chip function were key for reliably using the liver MPS. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Due to its functional robustness and physiological relevance (3D culture, cells expose to fluid flow and co-culture of different cell types), the liver MPS can, in a reproducible manner: (i) detect inflammatory-induced drug toxicity, as demonstrated with trovafloxacin, (ii) detect the toxicity of other drugs, such as troglitazone, tamoxifen, and digoxin, with different effects than those detected in spheroids and sandwich cultures, (iii) enable studies of hepatic function that rely on prolonged cellular activity, and (iv) detect phase II metabolites and drug accumulation to potentially support the interpretation of clinical data. The integration of MPSs in drug development will be facilitated by careful evaluation of performance and reproducibility as performed in this study.

Perspectivas da Prática Avançada de Enfermagem no processo de cuidado gerontológico: revisão integrativa / Perspectives of the Advanced Practice Nursing in the gerontological care process: an integrative review

Objetivo: Identificar as características da Prática Avançada de Enfermagem na atenção à saúde da pessoa idosa. Métodos: Revisão integrativa da literatura para responder o questionamento: "Quais as características da Prática Avançada de Enfermagem na atenção à saúde da pessoa idosa?". A busca ocorreu nas bases LILACS, Science Direct, PubMed, Web of Science, CINAHL e Scopusem novembro de 2020. Resultados: Após leitura e análise, 17 artigos compuseram a amostra final desta revisão. Os dados foram analisados por meio de categorias temáticas. Conclusão: A Prática Avançada de Enfermagem no cuidado gerontológico perpassa todos os níveis de complexidade e contempla o planejamento do cuidado com base na avaliação clínica precisa do paciente idoso, a implementação da educação em saúde para melhoria da qualidade de vida dos idosos e a educação em saúde e capacitação profissional para o cuidado gerontológico, assim como a utilização de teorias e modelos assistenciais para gestão do cuidado.

Objective: To identify the characteristics of the Advanced Practice Nursing in health care for the elderly. Methods: Integrative literature review to answer the question: "What are the characteristics of Advanced Practice Nursing in health care for the elderly?". LILACS, Science Direct, PubMed, Web of Science, CINAHL and Scopus databases were used for the research, carried out in November 2020. Results: After reading and analysis, 17 articles comprised the final sample of this review. Data were analyzed using thematic categories. Conclusion: Advanced Practice Nursing in gerontological care encompasses all levels of complexity and includes the planning of care based on the accurate clinical assessment of the elderly patient, the implementation of health education to improve the quality of life of the elderly and education in health and professional training for geriatric care, as well as the use of theories and care models for care management.

Quantifying drug-induced structural toxicity in hepatocytes and cardiomyocytes derived from hiPSCs using a deep learning method.

Cardiac and hepatic toxicity result from induced disruption of the functioning of cardiomyocytes and hepatocytes, respectively, which is tightly related to the organization of their subcellular structures. Cellular structure can be analyzed from microscopy imaging data. However, subtle or complex structural changes that are not easily perceived may be missed by conventional image-analysis techniques. Here we report the evaluation of PhenoTox, an image-based deep-learning method of quantifying drug-induced structural changes using human hepatocytes and cardiomyocytes derived from human induced pluripotent stem cells. We assessed the ability of the deep learning method to detect variations in the organization of cellular structures from images of fixed or live cells. We also evaluated the power and sensitivity of the method for detecting toxic effects of drugs by conducting a set of experiments using known toxicants and other methods of screening for cytotoxic effects. Moreover, we used PhenoTox to characterize the effects of tamoxifen and doxorubicin-which cause liver toxicity-on hepatocytes. PhenoTox revealed differences related to loss of cytochrome P450 3A4 activity, for which it showed greater sensitivity than a caspase 3/7 assay. Finally, PhenoTox detected structural toxicity in cardiomyocytes, which was correlated with contractility defects induced by doxorubicin, erlotinib, and sorafenib. Taken together, the results demonstrated that PhenoTox can capture the subtle morphological changes that are early signs of toxicity in both hepatocytes and cardiomyocytes.

The Effects of Strength Training Combined with Vitamin C and E Supplementation on Skeletal Muscle Mass and Strength: A Systematic Review and Meta-Analysis.

Intense muscle contractile activity can result in reactive oxygen species production in humans. Thus, supplementation of antioxidant vitamins has been used to prevent oxidative stress, enhance performance, and improve muscle mass. In this sense, randomized controlled studies on the effect of vitamin C and E supplementation combined with strength training (ST) on skeletal muscle mass and strength have been conducted. As these studies have come to ambiguous findings, a better understanding of this topic has yet to emerge. The purpose of the present review is to discuss the current knowledge about the effect of vitamin C and E supplementation on muscle mass and strength gains induced by ST. Search for articles was conducted in the following databases: PubMed/Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, and Google Scholar. This work is in line with the recommendations of the PRISMA statement. Eligible studies were placebo-controlled trials with a minimum of four weeks of ST combined with vitamin C and E supplementation. The quality of each included study was evaluated using the Physiotherapy Evidence Database Scale (PEDro). 134 studies were found to be potentially eligible, but only seven were selected to be included in the qualitative synthesis. A meta-analysis of muscle strength was conducted with 3 studies. Findings from these studies indicate that vitamins C and E has no effect on muscle force production after chronic ST. Most of the evidence suggests that this kind of supplementation does not potentiate muscle growth and could possibly attenuate hypertrophy over time.

Liver Microphysiological Systems for Predicting and Evaluating Drug Effects.

Liver plays a major role in drug metabolism and is one of the main sites of drug adverse effects. Microphysiological systems (MPS), also known as organs-on-a-chip, are a class of microfluidic platforms that recreate properties of tissue microenvironments. Among different properties, the liver microenvironment is three-dimensional, fluid flows around its cells, and different cell types regulate its function. Liver MPS aim to recreate these properties and enable drug testing and measurement of functional endpoints. Tests with these systems have demonstrated their potential for predicting clinical drug effects. Properties of liver MPS that improve the physiology of cell culture are reviewed, specifically focusing on the importance of recreating a physiological microenvironment to evaluate and model drug effects. Advances in modeling hepatic function by leveraging MPS are addressed, noting the need for standardization in the use, quality control, and interpretation of data from these systems.

Experiências de adoecimento por condições crônicas transmissíveis: revisão integrativa da literatura / Illness experiences due to communicable chronic conditions: integrative literature review

Resumo O objetivo deste artigo é identificar e descrever as experiências de adoecimento de pessoas que vivem com condições crônicas transmissíveis. Revisão integrativa da literatura foi realizada em maio de 2015 nas bases de dados PubMed, Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) e Scopus. A partir do cruzamento de palavras-chave e de descritores controlados, foram adotadas oito estratégias de busca, que resultaram na seleção final de 12 artigos. Realizou-se fichamento dos artigos, sendo elaboradas duas categorias temáticas, tendo em vista o agrupamento de temas coincidentes: (1) experiências com as condições crônicas transmissíveis; e (2) estratégias de enfrentamento das condições crônicas transmissíveis. Identificou-se o estigma como sendo a experiência de maior impacto na vida dos sujeitos, o qual reverberou em sentimentos negativos. Apesar disso, os sujeitos adoecidos adotaram hábitos de vida saudáveis, bem como apoiaram-se na religiosidade/espiritualidade e no dimensionamento do tempo como forma de harmonizar sua convivência com as doenças. Observou-se, ainda, que a rede de apoio (família, serviços de saúde) tem papel fundamental na vivência das condições crônicas transmissíveis. Os sujeitos experimentam sensações e sentimentos negativos desde o diagnóstico, seja pela fragilidade que a doença impõe ao seu organismo, seja pela manutenção da condição que os torna mais vulneráveis à discriminação, ao preconceito e ao estigma. Torna-se necessário fortalecer a rede de apoio em torno do sujeito, no sentido de favorecer a melhoria na qualidade de vida das pessoas que vivem com condições crônicas transmissíveis.

Abstract The objective of this article is to identify and describe the illness experiences of people living with communicable chronic conditions. An integrative literature review was carried out in May 2015 in the PubMed, the Literature in the Health Sciences in Latin America and the Caribbean (LILACS) and in the Scopus databases. Through the intersection of keywords and controlled descriptors, eight search strategies were conducted and resulted in the final selection of 12 articles, which were catalogued into two theme categories, in order to group matching themes: (1) experiences with communicable chronic conditions; (2) coping strategies for communicable chronicle diseases. Stigma was identified as the most impacting experience in subjects' lives, which reverberated negatives feelings. In spite of their illness, subjects adopted healthy lifestyle habits and found support on religiosity/spirituality and on the dimensionality of time as a way to live harmoniously with diseases. We also noticed that the support network (family, health services) plays a key role in the process of living with communicable chronicle diseases. Since the diagnostic, the subjects experience negative feelings and sensations not only because of the fragileness that the disease imposes on their body but also because of the maintenance of the condition, which make them more vulnerable to discrimination, prejudice and stigma. It becomes necessary to strengthen the support network around the subject, in order to encourage improvements in the quality of life of people living with communicable diseases.

Effects of antiproteolytic agents on corneal epithelial viability and matrix metalloproteinase-2 and metalloproteinase-9 activity in alkali-burned corneas of rats.

OBJECTIVE: To evaluate the effects of agents on corneal re-epithelization and metalloproteinase-2 and metalloproteinase-9 (MMP-2 and MMP-9) activities in corneas of rats submitted to ulceration. ANIMALS STUDIED: Ninety eight healthy rats. PROCEDURES: Corneal ulcers were created using 1N NaOH in their left eye. Eyes were treated every 6 h with 1% ethylenediaminetetraacetic acid (EDTA), 3% chondroitin sulfate (CS), 10% N-acetylcysteine NAc and saline (S) at 6-h intervals. Corneas were stained with fluorescein and photographed at the same time points. Following 20 h and 40-42 h of corneal injury, corneas were processed for scanning electron microscopy (SEM) to quantify microvilli density, and MMPs activities were analyzed using zymography. RESULTS: The percentage of wound area and the time in hours for corneal re-epithelization did not differ significantly among treatment groups (P > 0.05). In first and the second moments, latent MMP-2 was significantly elevated in the eyes treated with NAC and CS (P < 0.001). Active MMP-2 did not change significantly among treatment groups in the first moment (P > 0.05); significantly higher activity was observed in the second moment in the eyes treated with CS (P <0.001). In the second moment, latent MMP-9 decreased significantly in eyes treated with EDTA and S (P < 0.01). Microvilli corneal density did not change significantly between healthy subjects and treatment groups (P > 0.05). CONCLUSION: Any of the studied substances did not accelerate corneal re-epithelization and did not add protection to the corneal microvilli. Significant higher levels of active form of MMP-2 in 3% chondroitin sulfate-treated group may indicate that the agent acts as substrate for such enzyme. At the end of the experiment, 1% EDTA was the most efficient agent to inhibit significantly the latent form of MMP-9. However, any of the substances add benefit over saline on reducing the proteolytic activity in the cornea of rats after alkali injury.