Microphysiological systems to study tumor-stroma interactions in brain cancer.

Brain tumors still lack effective treatments, and the mechanisms of tumor progression and therapeutic resistance are unclear. Multiple parameters affect cancer prognosis (e.g., type and grade, age, location, size, and genetic mutations) and election of suitable treatments is based on preclinical models and clinical data. However, most candidate drugs fail in human trials due to inefficacy. Cell lines and tissue culture plates do not provide physiologically relevant environments, and animal models are not able to adequately mimic characteristics of disease in humans. Therefore, increasing technological advances are focusing on in vitro and computational modeling to increase the throughput and predicting capabilities of preclinical systems. The extensive use of these therapeutic agents requires a more profound understanding of the tumor-stroma interactions, including neural tissue, extracellular matrix, blood-brain barrier, astrocytes and microglia. Microphysiological brain tumor models offer physiologically relevant vascularized 'minitumors' that can help deciphering disease mechanisms, accelerating the drug discovery and predicting patient's response to anticancer treatments. This article reviews progress in tumor-on-a-chip platforms that are designed to comprehend the particular roles of stromal cells in the brain tumor microenvironment.

Microphysiological models of the central nervous system with fluid flow.

There are over 1,000 described neurological and neurodegenerative disorders affecting nearly 100 million Americans - roughly one third of the U.S. population. Collectively, treatment of neurological conditions is estimated to cost $800 billion every year. Lowering this societal burden will require developing better model systems in which to study these diverse disorders. Microphysiological systems are promising tools for modeling healthy and diseased neural tissues to study mechanisms and treatment of neuropathology. One major benefit of microphysiological systems is the ability to incorporate biophysical forces, namely the forces derived from biological fluid flow. Fluid flow in the central nervous system (CNS) is a complex but important element of physiology, and pathologies as diverse as traumatic or ischemic injury, cancer, neurodegenerative disease, and natural aging have all been found to alter flow pathways. In this review, we summarize recent advances in three-dimensional microphysiological systems for studying the biology and therapy of CNS disorders and highlight the ability and growing need to incorporate biological fluid flow in these miniaturized model systems.

From 3D Back to 2D Monolayer Stomach Organoids-on-a-Chip.

2D monolayer gastric organoids (2DMGOs)-on-a-chip have consistent structures and can live for more than a year in culture. This state-of-the-art cell physiological system in a microfluidic device provides a way to investigate biomedically relevant, stimuli-dependent cellular responses in a variety of differentiated 2DMGOs.

Sensor Technologies to Manage the Physiological Traits of Chronic Pain: A Review.

Non-oncologic chronic pain is a common high-morbidity impairment worldwide and acknowledged as a condition with significant incidence on quality of life. Pain intensity is largely perceived as a subjective experience, what makes challenging its objective measurement. However, the physiological traces of pain make possible its correlation with vital signs, such as heart rate variability, skin conductance, electromyogram, etc., or health performance metrics derived from daily activity monitoring or facial expressions, which can be acquired with diverse sensor technologies and multisensory approaches. As the assessment and management of pain are essential issues for a wide range of clinical disorders and treatments, this paper reviews different sensor-based approaches applied to the objective evaluation of non-oncological chronic pain. The space of available technologies and resources aimed at pain assessment represent a diversified set of alternatives that can be exploited to address the multidimensional nature of pain.

Tissue mechanics, an important regulator of development and disease.

A growing body of work describes how physical forces in and around cells affect their growth, proliferation, migration, function and differentiation into specialized types. How cells receive and respond biochemically to mechanical signals is a process termed mechanotransduction. Disease may arise if a disruption occurs within this mechanism of sensing and interpreting mechanics. Cancer, cardiovascular diseases and developmental defects, such as during the process of neural tube formation, are linked to changes in cell and tissue mechanics. A breakdown in normal tissue and cellular forces activates mechanosignalling pathways that affect their function and can promote disease progression. The recent advent of high-resolution techniques enables quantitative measurements of mechanical properties of the cell and its extracellular matrix, providing insight into how mechanotransduction is regulated. In this review, we will address the standard methods and new technologies available to properly measure mechanical properties, highlighting the challenges and limitations of probing different length-scales. We will focus on the unique environment present throughout the development and maintenance of the central nervous system and discuss cases where disease, such as brain cancer, arises in response to changes in the mechanical properties of the microenvironment that disrupt homeostasis. This article is part of a discussion meeting issue 'Forces in cancer: interdisciplinary approaches in tumour mechanobiology'.

A lifetime of pulmonary gas exchange.

Pulmonary gas exchange is the primary function of the lung, and during my lifetime, its measurement has passed through many stages. When I was born, many physiologists still believed that the lung secreted oxygen. When I was a medical student, the only way we had to recognize defective gas exchange was whether the patient was cyanosed. The advent of the oximeter soon showed that this sign could be very misleading. A breakthrough was the introduction of blood gas electrodes that could measure the PO2 , PCO2 , and pH of a small sample of arterial blood. It was soon recognized that the commonest cause of hypoxemia was ventilation-perfusion inequality, and that this could also be responsible for CO2 retention. In the early days, the understanding of the mechanisms of pulmonary gas exchange relied on graphical analysis because the oxygen and carbon dioxide dissociation curves are nonlinear and interdependent which precluded algebraic methods. However, with the introduction of digital computing, problems that had hitherto been impossible to tackle became amenable to study. A key advance was the development of the Multiple Inert Gas Elimination Technique. Now, noninvasive methods for measuring gas exchange show promise, and the whole subject continues to develop.

Same Redox Evidence But Different Physiological "Stories": The Rashomon Effect in Biology.

The Rashomon effect - a phenomenon studied in the arts and social sciences - occurs when the same event is given contradictory interpretations by different individuals involved. The effect was named after Akira Kurosawa's 1950 film Rashomon, in which a murder is described in four contradictory ways by four witnesses. In the film, a samurai has been killed under mysterious circumstances. Four people give contradictory reports about the crime. In particular, the samurai's wife claims that she was sexually abused by a bandit, fainted, and then awoke to find her husband dead; the bandit claims that he seduced the wife and challenged the samurai in a battle to victory or at least to an honorable death; the woodcutter (who may have been an onlooker) claims that he witnessed the rape and murder but was not involved; and the dead samurai's spirit claims that he committed suicide. The Rashomon effect is not only about constructing different versions of the world based on differences in perspective; it occurs when such differences appear together with the absence of evidence to assess any version of the truth, plus "the social pressure for closure on the question." In this commentary, we describe the relevance of the Rashomon effect beyond the arts and social sciences, namely in the field of biology. We use examples from redox biology, which is full of contradictions, thus making it fertile ground on which to apply reasoning derived from the Rashomon effect.

Multi-response optimization of Artemia hatching process using split-split-plot design based response surface methodology.

A novel method, BBD-SSPD is proposed by the combination of Box-Behnken Design (BBD) and Split-Split Plot Design (SSPD) which would ensure minimum number of experimental runs, leading to economical utilization in multi- factorial experiments. The brine shrimp Artemia was tested to study the combined effects of photoperiod, temperature and salinity, each with three levels, on the hatching percentage and hatching time of their cysts. The BBD was employed to select 13 treatment combinations out of the 27 possible combinations that were grouped in an SSPD arrangement. Multiple responses were optimized simultaneously using Derringer's desirability function. Photoperiod and temperature as well as temperature-salinity interaction were found to significantly affect the hatching percentage of Artemia, while the hatching time was significantly influenced by photoperiod and temperature, and their interaction. The optimum conditions were 23 h photoperiod, 29 °C temperature and 28 ppt salinity resulting in 96.8% hatching in 18.94 h. In order to verify the results obtained from BBD-SSPD experiment, the experiment was repeated preserving the same set up. Results of verification experiment were found to be similar to experiment originally conducted. It is expected that this method would be suitable to optimize the hatching process of animal eggs.

Improving respiration measurements with gas exchange analyzers.

Dark respiration measurements with open-flow gas exchange analyzers are often questioned for their low accuracy as their low values often reach the precision limit of the instrument. Respiration was measured in five species, two hypostomatous (Vitis Vinifera L. and Acanthus mollis) and three amphistomatous, one with similar amount of stomata in both sides (Eucalyptus citriodora) and two with different stomata density (Brassica oleracea and Vicia faba). CO2 differential (ΔCO2) increased two-fold with no change in apparent Rd, when the two leaves with higher stomatal density faced outside. These results showed a clear effect of the position of stomata on ΔCO2. Therefore, it can be concluded that leaf position is important to guarantee the improvement of respiration measurements increasing ΔCO2 without affecting the respiration results by leaf or mass units. This method will help to increase the accuracy of leaf respiration measurements using gas exchange analyzers.

Does allostatic load calculation method matter? Evaluation of different methods and individual biomarkers functioning by race/ethnicity and educational level.

OBJECTIVES: Using nationally representative data for adults of age 25 years and older from four waves of the National Health and Nutrition Examination Survey (NHANES), collected from 2003 through 2010, this study examines differences in individual health markers used to calculate allostatic load, with particular attention given to stratification by race/ethnicity and educational level. METHODS: Factor analysis with maximum likelihood estimation was used. Fisher's r to z transformation test was used to determine whether or not observed differences in factor loadings were statistically significant. RESULTS: The findings reveal the unidimensionality of the concept of allostatic load and the underlying differences in associations between individual biomarkers and summary measures of allostatic load. Additionally, metabolic processes tend to be the most important predictor of allostatic load for all adults; however, inflammatory measures are more important in determining allostatic load scores for non-Hispanic blacks compared to non-Hispanic whites and for adults with less than a college education compared to adults with some college or a college degree. CONCLUSIONS: These findings highlight the continued importance of studying the concept of "weathering" or allostatic load at the population level and need to better understand how population groups facing exclusion from economic, social, and political power may internalize this position which may cause early health deterioration and ultimate mortality chance through different expression of health insults and premature aging. Am. J. Hum. Biol. 28:627-635, 2016. © 2016 Wiley Periodicals, Inc.

[18F]-FDG positron emission tomography--an established clinical tool opening a new window into exercise physiology.

Positron emission tomography (PET) with [(18)F]-fluorodeoxyglucose (FDG) is an established clinical tool primarily used to diagnose and evaluate disease status in patients with cancer. PET imaging using FDG can be a highly valuable tool to investigate normal human physiology by providing a noninvasive, quantitative measure of glucose uptake into various cell types. Over the past years it has also been increasingly used in exercise physiology studies to identify changes in glucose uptake, metabolism, and muscle activity during different exercise modalities. Metabolically active cells transport FDG, an (18)fluorine-labeled glucose analog tracer, from the blood into the cells where it is then phosphorylated but not further metabolized. This metabolic trapping process forms the basis of this method's use during exercise. The tracer is given to a participant during an exercise task, and the actual PET imaging is performed immediately after the exercise. Provided the uptake period is of sufficient duration, and the imaging is performed shortly after the exercise; the captured image strongly reflects the metabolic activity of the cells used during the task. When combined with repeated blood sampling to determine tracer blood concentration over time, also known as the input function, glucose uptake rate of the tissues can be quantitatively calculated. This synthesis provides an accounting of studies using FDG-PET to measure acute exercise-induced skeletal muscle activity, describes the advantages and limitations of this imaging technique, and discusses its applications to the field of exercise physiology.

Seventy years of pancreatic physiology: take a look back.

This review article has 4 major objectives to follow pancreatic physiology development more than close to 70 years of intensive and productive basic research. At first, the review will focus on secretion of the pancreatic enzymes with (1) the controls involved, (2) the interrelations existing between secretion and synthesis of these enzymes, (3) the enzymes' adaptation to the constituents of the diet, and (4) whether secretion of the different enzymes is parallel or nonparallel. Second, growth and regeneration of the pancreatic gland will be looked at in relation to the factors involved and the target cells implicated.

A new method for non-invasive estimation of human muscle fiber type composition.

BACKGROUND: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT) or type-II fibers and slow-twitch (ST) or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative. METHODOLOGY: Eighty-three control subjects, 15 talented young track-and-field athletes, 51 elite athletes and 14 ex-athletes volunteered to participate in the current study. The carnosine content of all 163 subjects was measured in the gastrocnemius muscle by proton magnetic resonance spectroscopy ((1)H-MRS). Muscle biopsies for fiber typing were taken from 12 untrained males. PRINCIPAL FINDINGS: A significant positive correlation was found between muscle carnosine, measured by (1)H-MRS, and percentage area occupied by type II fibers. Explosive athletes had ∼30% higher carnosine levels compared to a reference population, whereas it was ∼20% lower than normal in typical endurance athletes. Similar results were found in young talents and ex-athletes. When active elite runners were ranked according to their best running distance, a negative sigmoidal curve was found between logarithm of running distance and muscle carnosine. CONCLUSIONS: Muscle carnosine content shows a good reflection of the disciplines of elite track-and-field athletes and is able to distinguish between individual track running distances. The differences between endurance and sprint muscle types is also observed in young talents and former athletes, suggesting this characteristic is genetically determined and can be applied in early talent identification. This quick method provides a valid alternative for the muscle biopsy method. In addition, this technique may also contribute to the diagnosis and monitoring of many conditions and diseases that are characterized by an altered muscle fiber type composition.

Identification of Staphylococcus spp. isolated during the ripening process of a traditional minas cheese / Identificação de Staphylococcus spp. isolados durante o processo de maturação de um queijo-de-minas tradicional

The population dynamics of Staphylococcus spp. was studied during the ripening of Canastra Minas cheese at three farms located in the State of Minas Gerais, Brazil. The presence of coagulase (coa), thermonuclease (nuc), and enterotoxin (sea, seb, sec, and sed) genes was investigated in Staphylococcus strains isolated during the 60-day cheese-ripening period. The presence of the staphylococcal enterotoxins A, C, and D was also investigated in the cheese samples. Cheese samples that were matured for 0, 7, 15, 30, and 45 days presented staphylococci counts from 10³ to 10(8)cfu/g. All isolates considered coagulase-positive by physiological tests had the coa gene. However, no association was observed between the results obtained with biochemical tests and those obtained by PCR using gene-specific primers for coagulase-negative strains. Coagulase and thermonuclease genes occurred simultaneously in 41.3 percent of Staphylococcus spp. tested. None of the investigated Staphylococcus strains expressed enterotoxins SEA, SEB, SEC, and SED. Enterotoxins A, C, and D were not detected in any of the cheese samples.

Estudou-se a dinâmica das populações de Staphylococcus spp. durante a maturação do queijo Canastra, em três fazendas localizadas no estado de Minas Gerais. A presença dos genes que codificam para a produção das enzimas coagulase (coa), termonuclease (nuc) e produção de enterotoxinas (sea, seb, sec e sed), em linhagens de Staphylococcus isoladas durante os 60 dias de maturação do queijo foi analisada. Também foi investigada a presença de enterotoxina estafilocócica A, C e D nas amostras de queijo. As amostras de queijo com 0, 7, 15, 30 e 45 dias de maturação apresentaram contagens de Staphylococcus spp. entre 10³ e 10(8)ufc / g. Todos os isolados coagulase positivo nos testes fisiológicos apresentaram o gene coa. Não foi observada associação entre os resultados obtidos com os testes bioquímicos e aqueles obtidos com a PCR usando iniciadores gene-específicos para linhagens coagulase negativa. Os genes da coagulase e termonuclease ocorreram simultaneamente em 41,3 por cento dos Staphylococcus spp. testados. Nenhum dos isolados de Staphylococcus apresentou os genes que codificam para a produção das enterotoxinas SEA, SEB, SEC ou SED. As enterotoxinas A, C ou D não foram detectadas em nenhuma das amostras de queijo analisadas.

Conservação e fisiologia pós-colheita de folhas de Capuchinha (Tropaeolum majus L. ) / Conservation and postharvest physiology of leaves Capuchin (Tropaeolum majus L. )

Este trabalho teve como objetivo avaliar a vida útil pós-colheita de folhas de Capuchinha (Tropaeolum majus L.) embaladas com filme PVC de baixa densidade e proteínas nas concentrações de 1, 3 e 5 por cento. O experimento foi conduzido no Laboratório de Química e Bioquímica do Centro de Ciências Agrárias (CCA) da Universidade Federal da Paraíba (UFPB) Areia - PB. As folhas de Capuchinha colhidas no CCA foram levadas imediatamente ao Laboratório de Química e Bioquímica, para pré-seleção, desinfestação em água clorada contendo 100mg.L-1 de cloro ativo, e seca à temperatura ambiente. Após o controle fitossanitário, as folhas foram submetidas aos seguintes tratamentos: solução de proteína nas concentrações de 1, 3 e 5 por cento, filme PVC de baixa densidade e a testemunha sem recobrimento. As folhas foram armazenadas durante cinco dias em temperatura média de 26 - 29ºC e umidade relativa média de 59,5 - 71,5 por cento e outra parte foi armazenada em câmara fria com temperatura média de 12 ± 0,5 ºC e umidade relativa média de 95 ± 3 por cento. Durante o período de armazenamento as folhas foram avaliadas quanto à perda de massa fresca, determinação de ácido ascórbico, sólidos solúveis e acidez titulável. O armazenamento durante quatro dias sob refrigeração a temperatura média de 12 ± 0,5ºC associada ao recobrimento com filme PVC mostrou melhores resultados na conservação da vida útil pós-colheita das folhas de Capuchinha.

This study aimed to evaluate the shelf-life of Capuchin sheets (Tropaeolum majus L.) packed with plastic wrap and low density proteins at concentrations of 1, 3 and 5 percent. The experiment was conducted at the Laboratório de Química e Bioquímica and the Centro de Ciências Agrárias (CCA) of the Universidade Federal da Paraíba (UFPB) Areia - PB. Capuchin leaves harvested in the CCA were taken immediately to the Laboratório de Química e Bioquímica, for pre-screening, disinfection in chlorinated water containing 100mg.L-1 of active chlorine, and dried at room temperature. After spraying, the leaves were treated as follows: protein solution at concentrations of 1, 3 and 5 percent, low density plastic wrap and uncoated witness. The leaves were stored for five days in average temperature from 26 to 29ºC and relative humidity from 59.5 to 71.5 percent and another part was stored in cold with average temperature of 12 ± 0.5ºC and relative humidity of 95 ± 3 percent. During the storage period the leaves were evaluated for weight loss, determination of ascorbic acid, soluble solids and titratable acidity. Storage for four days under refrigeration at an average temperature of 12 ± 0.5ºC associated with PVC film coating showed better results in the conservation of shelf-life of Capuchin sheets.

A reproducible and inexpensive method of measuring hip abductor strength.

The evaluation of hip abductor strength is useful in assessing of the outcome of hip surgery. Hand-held dynamometers are available, but they are less reliable in assessing hip abductor strength than some other muscle groups. We describe a new device designed to measure hip abductor strength, which is practical in a clinical setting. A system of constraints, pads and reference points was devised to make force measurements as little examiner-dependent as possible. Reproducibility was assessed in a controlled setting. The abductor strength of ten healthy young subjects (average age 28 years) was tested twice on each side by two independent examiners. Tests were performed in a supine position, eliminating the influence of gravity and examiner intervention. The results indicated high reproducibility, the maximal measurement uncertainty being within 1 N. Intra-class correlation coefficients ranged from 0.85-0.98 for intra-rater reproducibility, and 0.81-0.96 for inter-rater reporoducibility. The coefficient of variation was lower than 10%. The device described may be suitable for routine clinical assessment of patients after hip surgery.

Physiological and health implications of a sedentary lifestyle.

Sedentary behaviour is associated with deleterious health outcomes, which differ from those that can be attributed to a lack of moderate to vigorous physical activity. This has led to the field of "sedentary physiology", which may be considered as separate and distinct from exercise physiology. This paper gives an overview of this emerging area of research and highlights the ways that it differs from traditional exercise physiology. Definitions of key terms associated with the field of sedentary physiology and a review of the self-report and objective methods for assessing sedentary behaviour are provided. Proposed mechanisms of sedentary physiology are examined, and how they differ from those linking physical activity and health are highlighted. Evidence relating to associations of sedentary behaviours with major health outcomes and the population prevalence and correlates of sedentary behaviours are reviewed. Recommendations for future research are proposed.