Proximate and fatty acid profile analysis of Tenebrio molitor and Zophobas morio using different killing methods.

The present work aimed to quantify the macronutrients and the fatty acid (FA) profile in different killing methods, blanching (BC) and freezing (FR), on edible insects of the speciesTenebrio molitor(TM) andZophobas morio(ZM). Concerning macronutrients TM-BC and TM-FR presented 51.2% and 50.6% of protein, 28% and 29.4% of lipids, and 12.4% and 11.4%. Meanwhile, ZM-BC and ZM-FR expressed 42.8% and 43.7% of protein, 39.1% and 40.1% of lipids, and 10.7% and 8.9% of carbohydrates. The FA of TM and ZM shows respectively values of Saturated Fatty Acids (∑SFA) 30% - 45%, Monounsaturated (MUFA) 47% - 32%, Polyunsaturated (∑PUFA) 23% - 22%, Atherogenicity Index (AI) 0.64 - 0.75, Thrombogenicity Index (TI) 0.77 - 1.44 and hypocholesterolemic/hypercholesterolemic index (h/H) of 2.50-1.51. Based on the results obtained, the slaughter methods showed statistically differences in relation to MUFA's in TM, and ZM larvae only in the minority fraction of FA.

Effect of Atomized Black Maca (Lepidium meyenii) Supplementation in the Cryopreservation of Alpaca (Vicugna pacos) Epididymal Spermatozoa.

Artificial insemination is an important assisted reproductive technology that has been applied in several mammalian species. However, successful cryopreservation of semen of South American camelids has been limited, hindering the commercial application of artificial insemination in alpaca species. In this scenario, the addition of antioxidants to semen extenders provides a strategy to improve the freezability of mammalian sperm. Bioactive metabolites from natural extracts of black maca have shown valuable antioxidant properties. Thus, the objective of this study was to evaluate the effect of the addition of atomized black maca in the freezing medium of epididymal spermatozoa of alpacas. Fifteen pairs of epididymis were collected from a local slaughterhouse. Each sample was divided into six groups: (1) fresh, (2) yolk medium (YM), (3) 10 mg/mL maca, (4) 20 mg/mL maca, (5) 30 mg/mL maca, and (6) resveratrol (as an antioxidant control). Sperm cryopreservation was performed through the slow freezing method. Markers associated with functionality, such as motility, viability, and plasma membrane integrity, as well as markers associated with oxidative damage, such as DNA integrity, total ROS production, and mitochondrial function, were analyzed. The results show that the supplementation with black maca (20 mg/mL) improved the sperm motility, viability, plasma membrane integrity, and mitochondrial function evaluated according to an index of formazan deposits. Similarly, the ROS production decreased with maca at 20 mg/mL, although the DNA integrity did not show any differences among the groups. These results suggest that maca at 20 mg/mL has cytoprotective effects during freezing/thawing of epididymal sperm of alpaca species. Further research will be focused on assessing the effects of maca supplementation on semen extenders by using biomolecular markers (proAKAP4) associated with fertility.

Biofortification of cow milk through dietary supplementation with sunflower oil: fatty acid profile, atherogenicity, and thrombogenic index.

The present study aimed to assess the effects of replacing the starchy ingredients of concentrate by increasing the levels of sunflower oil on the production, composition, fatty acid profile, and evaluate the atherogenicity and thrombogenic index of Jersey cow's milk. Eight Jersey cows were arranged in a double Latin square and distributed in treatments consisting of supplementation with increasing levels of sunflower oil replacing the corn grain and wheat bran of concentrate, including the following: T0 (control diet), without sunflower oil and with 38 g ether extract (EE)/kg dry matter (DM); T1 = 65 g EE/kg DM; T2 = 86 g EE/kg DM; and T3 = 110 g EE/kg DM. The daily milk production was measured, and the corrected milk production was calculated. Milk samples were analyzed by infrared spectroscopy to determine fat, protein, lactose, and total solids, whereas the lipid profile was assessed by gas chromatography. Milk production, energy-corrected milk production, fat content, daily fat production, lactose, and total solids were not affected by the treatments. Protein, lactose, and total solids concentrations decreased. Short-, medium-, and odd-chain fatty acids decreased with an increase in sunflower oil levels. Conversely, linear increases in long-chain, monounsaturated, and polyunsaturated fatty acid concentrations were observed. There were significant increases in stearic and elaidic acids and conjugated linoleic acid isomers, especially in vaccenic and rumenic acids. There was a positive effect on the milk atherogenicity, thrombogenicity, and nutraceutical indices. Dietary supplementation with sunflower oil changes the milk FA profile, decreases the atherogenicity and the thrombogenicity indices, and improve the nutraceutical index up to the addition of 86 g EE/kg DM de sunflower oil in the diets of Jersey cows.

Tissue-specific parameters for the design of ECM-mimetic biomaterials.

The extracellular matrix (ECM) is a complex network of biomolecules that mechanically and biochemically directs cell behavior and is crucial for maintaining tissue function and health. The heterogeneous organization and composition of the ECM varies within and between tissue types, directing mechanics, aiding in cell-cell communication, and facilitating tissue assembly and reassembly during development, injury and disease. As technologies like 3D printing rapidly advance, researchers are better able to recapitulate in vivo tissue properties in vitro; however, tissue-specific variations in ECM composition and organization are not given enough consideration. This is in part due to a lack of information regarding how the ECM of many tissues varies in both homeostatic and diseased states. To address this gap, we describe the components and organization of the ECM, and provide examples for different tissues at various states of disease. While many aspects of ECM biology remain unknown, our goal is to highlight the complexity of various tissues and inspire engineers to incorporate unique components of the native ECM into in vitro platform design and fabrication. Ultimately, we anticipate that the use of biomaterials that incorporate key tissue-specific ECM will lead to in vitro models that better emulate human pathologies. STATEMENT OF SIGNIFICANCE: Biomaterial development primarily emphasizes the engineering of new materials and therapies at the expense of identifying key parameters of the tissue that is being emulated. This can be partially attributed to the difficulty in defining the 3D composition, organization, and mechanics of the ECM within different tissues and how these material properties vary as a function of homeostasis and disease. In this review, we highlight a range of tissues throughout the body and describe how ECM content, cell diversity, and mechanical properties change in diseased tissues and influence cellular behavior. Accurately mimicking the tissue of interest in vitro by using ECM specific to the appropriate state of homeostasis or pathology in vivo will yield results more translatable to humans.

Simulating flow induced migration in vascular remodelling.

Shear stress induces directed endothelial cell (EC) migration in blood vessels leading to vessel diameter increase and induction of vascular maturation. Other factors, such as EC elongation and interaction between ECs and non-vascular areas are also important. Computational models have previously been used to study collective cell migration. These models can be used to predict EC migration and its effect on vascular remodelling during embryogenesis. We combined live time-lapse imaging of the remodelling vasculature of the quail embryo yolk sac with flow quantification using a combination of micro-Particle Image Velocimetry and computational fluid dynamics. We then used the flow and remodelling data to inform a model of EC migration during remodelling. To obtain the relation between shear stress and velocity in vitro for EC cells, we developed a flow chamber to assess how confluent sheets of ECs migrate in response to shear stress. Using these data as an input, we developed a multiphase, self-propelled particles (SPP) model where individual agents are driven to migrate based on the level of shear stress while maintaining appropriate spatial relationship to nearby agents. These agents elongate, interact with each other, and with avascular agents at each time-step of the model. We compared predicted vascular shape to real vascular shape after 4 hours from our time-lapse movies and performed sensitivity analysis on the various model parameters. Our model shows that shear stress has the largest effect on the remodelling process. Importantly, however, elongation played an especially important part in remodelling. This model provides a powerful tool to study the input of different biological processes on remodelling.

Intercellular Adhesion Stiffness Moderates Cell Decoupling as a Function of Substrate Stiffness.

The interplay between cell-cell and cell-substrate interactions is complex yet necessary for the formation and healthy functioning of tissues. The same mechanosensing mechanisms used by the cell to sense its extracellular matrix also play a role in intercellular interactions. We used the discrete element method to develop a computational model of a deformable cell that includes subcellular components responsible for mechanosensing. We modeled a three-dimensional cell pair on a patterned (two-dimensional) substrate, a simple laboratory setup to study intercellular interactions. We explicitly modeled focal adhesions and adherens junctions. These mechanosensing adhesions matured, becoming stabilized by force. We also modeled contractile stress fibers that bind the discrete adhesions. The mechanosensing fibers strengthened upon stalling. Traction exerted on the substrate was used to generate traction maps (along the cell-substrate interface). These simulated maps are compared to experimental maps obtained via traction force microscopy. The model recreates the dependence on substrate stiffness of the tractions' spatial distribution, contractile moment of the cell pair, intercellular force, and number of focal adhesions. It also recreates the phenomenon of cell decoupling, in which cells exert forces separately when substrate stiffness increases. More importantly, the model provides viable molecular explanations for decoupling: mechanosensing mechanisms are responsible for competition between different fiber-adhesion configurations present in the cell pair. The point at which an increasing substrate stiffness becomes as high as that of the cell-cell interface is the tipping point at which configurations that favor cell-substrate adhesion dominate over those favoring cell-cell adhesion. This competition is responsible for decoupling.

Modeling of Mechanosensing Mechanisms Reveals Distinct Cell Migration Modes to Emerge From Combinations of Substrate Stiffness and Adhesion Receptor-Ligand Affinity.

Mesenchymal cell migration is an integral process in development and healing. The process is regulated by both mechanical and biochemical properties. Mechanical properties of the environment are sensed through mechanosensing, which consists of molecular responses mediated by mechanical signals. We developed a computational model of a deformable 3D cell on a flat substrate using discrete element modeling. The cell is polarized in a single direction and thus moves along the long axis of the substrate. By modeling discrete focal adhesions and stress fibers, we implement two mechanosensing mechanisms: focal adhesion stabilization by force and stress fiber strengthening upon contraction stalling. Two substrate-associated properties, substrate (ligand) stiffness and adhesion receptor-ligand affinity (in the form of focal adhesion disassembly rate), were varied for different model setups in which the mechanosensing mechanisms are set as active or inactive. Cell displacement, focal adhesion number, and cellular traction were quantified and tracked in time. We found that varying substrate stiffness (a mechanical property) and adhesion receptor-ligand affinity (a biochemical property) simultaneously dictate the mode in which cells migrate; cells either move in a smooth manner reminiscent of keratocytes or in a cyclical manner reminiscent of epithelial cells. Mechanosensing mechanisms are responsible for the range of conditions in which a cell adopts a particular migration mode. Stress fiber strengthening, specifically, is responsible for cyclical migration due to build-up of enough force to elicit rupture of focal adhesions and retraction of the cellular rear. Together, both mechanisms explain bimodal dependence of cell migration on substrate stiffness observed in the literature.

The role of actin protrusion dynamics in cell migration through a degradable viscoelastic extracellular matrix: Insights from a computational model.

Actin protrusion dynamics plays an important role in the regulation of three-dimensional (3D) cell migration. Cells form protrusions that adhere to the surrounding extracellular matrix (ECM), mechanically probe the ECM and contract in order to displace the cell body. This results in cell migration that can be directed by the mechanical anisotropy of the ECM. However, the subcellular processes that regulate protrusion dynamics in 3D cell migration are difficult to investigate experimentally and therefore not well understood. Here, we present a computational model of cell migration through a degradable viscoelastic ECM. This model is a 2D representation of 3D cell migration. The cell is modeled as an active deformable object that captures the viscoelastic behavior of the actin cortex and the subcellular processes underlying 3D cell migration. The ECM is regarded as a viscoelastic material, with or without anisotropy due to fibrillar strain stiffening, and modeled by means of the meshless Lagrangian smoothed particle hydrodynamics (SPH) method. ECM degradation is captured by local fluidization of the material and permits cell migration through the ECM. We demonstrate that changes in ECM stiffness and cell strength affect cell migration and are accompanied by changes in number, lifetime and length of protrusions. Interestingly, directly changing the total protrusion number or the average lifetime or length of protrusions does not affect cell migration. A stochastic variability in protrusion lifetime proves to be enough to explain differences in cell migration velocity. Force-dependent adhesion disassembly does not result in faster migration, but can make migration more efficient. We also demonstrate that when a number of simultaneous protrusions is enforced, the optimal number of simultaneous protrusions is one or two, depending on ECM anisotropy. Together, the model provides non-trivial new insights in the role of protrusions in 3D cell migration and can be a valuable contribution to increase the understanding of 3D cell migration mechanics.

Lifestyle and comorbid conditions as risk factors for community-acquired pneumonia in outpatient adults (NEUMO-ES-RISK project).

Introduction: Information about community-acquired pneumonia (CAP) risk in primary care is limited. We assess different lifestyle and comorbid conditions as risk factors (RF) for CAP in adults in primary care. Methods: A retrospective-observational-controlled study was designed. Adult CAP cases diagnosed at primary care in Spain between 2009 and 2013 were retrieved using the National Surveillance System of Primary Care Data (BiFAP). Age-matched and sex-matched controls were selected by incidence density sampling (ratio 2:1). Associations are presented as percentages and OR. Binomial regression models were constructed to avoid bias effects. Results: 51 139 patients and 102 372 controls were compared. Mean age (SD) was 61.4 (19.9) years. RF more significantly linked to CAP were: HIV (OR [95% CI]: 5.21 [4.35 to 6.27]), chronic obstructive pulmonary disease (COPD) (2.97 [2.84 to 3.12]), asthma (2.16 [2.07,2.26]), smoking (1.96 [1.91 to 2.02]) and poor dental hygiene (1.45 [1.41 to 1.49]). Average prevalence of any RF was 82.2% in cases and 69.2% in controls (2.05 [2.00 to 2.10]). CAP rate increased with the accumulation of RF and age: risk associated with 1RF was 1.42 (1.37 to 1.47) in 18-60-year-old individuals vs 1.57 (1.49 to 1.66) in >60 years of age, with 2RF 1.88 (1.80 to 1.97) vs 2.35 (2.23, 2.48) and with ≥ 3 RF 3.11 (2.95, 3.30) vs 4.34 (4.13 to 4.57). Discussion: Prevalence of RF in adult CAP in primary care is high. Main RFs associated are HIV, COPD, asthma, smoking and poor dental hygiene. Our risk stacking results could help clinicians identify patients at higher risk of pneumonia.

Spatiotemporal Analyses of Cellular Tractions Describe Subcellular Effect of Substrate Stiffness and Coating.

Cells interplay with their environment through mechanical and chemical interactions. To characterize this interplay, endothelial cells were cultured on polyacrylamide hydrogels of varying stiffness, coated with either fibronectin or collagen. We developed a novel analysis technique, complementary to traction force microscopy, to characterize the spatiotemporal evolution of cellular tractions: We identified subpopulations of tractions, termed traction foci, and tracked their magnitude and lifetime. Each focus consists of tractions associated with a local single peak of maximal traction. Individual foci were spread over a larger area in cells cultured on collagen relative to those on fibronectin and exerted higher tractions on stiffer hydrogels. We found that the trends with which forces increased with increasing hydrogel stiffness were different for foci and whole-cell measurements. These differences were explained by the number of foci and their average strength. While on fibronectin multiple short-lived weak foci contributed up to 30% to the total traction on hydrogels with intermediate stiffness, short-lived foci in such a number were not observed on collagen despite the higher tractions. Our approach allows for the use of existing traction force microscopy data to gain insight at the subcellular scale without molecular probes or spatial constraining of cellular tractions.

Case Report: Squamous Cell Carcinoma Referred for Mohs Surgery Found to be Cutaneous Leishmaniasis.

Chronic skin lesions constitute a clinical diagnostic challenge. We report the case of a patient whose facial lesion was histopathologically compatible with squamous cell carcinoma and hence programmed for Mohs surgery. However, review of the clinical and epidemiological history led to laboratory diagnosis of cutaneous leishmaniasis, treatment with miltefosine, and complete resolution of the lesion.

Perception of Patients Regarding Burdens and Benefits of Vitamin K Antagonists Among Patients with Nonvalvular Atrial Fibrillation.

BACKGROUND: Achieving a good satisfaction with anticoagulant treatment should be a target in Atrial Fibrillation (AF) patients. OBJECTIVE: To ascertain the perception of patients regarding burdens and benefits of anticoagulation with Vitamin K Antagonists (VKA). METHODS: This was a multicenter cross-sectional/retrospective study conducted throughout Spain, in which AF patients taking VKA during the last year, attended at primary care setting were included. The Anti-Clot-Treatment Scale (ACTS) was used to determine perceived burdens and benefits with anticoagulation. RESULTS: Overall, 1,386 patients (mean age 77.4 ± 8.7 years; 48.6% women; 64.2% permanent AF; CHA2DS2-VASc 3.9 ± 1.5; HAS-BLED 1.6 ± 0.9) were analyzed. The adequate anticoagulation control was achieved by 56.9/60.6% of patients according to direct method/Rosendaal method, respectively. Overall, mean ACTS Burdens scale score was 49.4 ± 8.8 and mean ACTS Benefits scale score 11.2 ± 2.2. Active patients, polymedication, elderly and visits to the nurse were associated with higher scores in the ACTS Burdens scale (lower perceived burden), whereas visits to the emergency department and primary care physician were associated with lower scores in the ACTS Burdens scale (higher perceived burden). Active patients, number of INR determinations, visits to the nurse, and an adequate INR control were associated with higher scores in the ACTS Benefits scale (higher perceived benefit), whereas visits to the emergency department and to the primary care physician were associated with lower scores in the ACTS Benefits scale (lower perceived benefit). CONCLUSION: Satisfaction with treatment was high among patients with AF chronically anticoagulated with VKA, suggesting that quality of life is not impaired in this population.

Causas de morte e razões para eutanásia em gatos na Região Central do Rio Grande do Sul (1964-2013) / Causes of death and reason for euthanasia in cats in the central region of Rio Grande do Sul, Brazil (1964-2013)

Este trabalho tem por objetivo determinar a prevalência das doenças que causam a morte ou levam à eutanásia de gatos da região central do Rio Grande do Sul. Para isto, foram revisados os arquivos do Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Santa Maria (UFSM) entre 1964 a 2013, e foram encontrados um total de 1.247 protocolos de necropsias de gatos. Em 878 protocolos (70,4%) a causa da morte e/ou razão para eutanásia foi estabelecida e em 369 casos (29,6%) não foi possível estabelecer uma causa definitiva. Os diagnósticos encontrados foram avaliados e distribuídos em diferentes categorias. Os grupos responsáveis pelo maior número de causas de morte ou razão para eutanásia em gatos foram os distúrbios causados por agentes físicos (15,6%), seguidos das doenças infecciosas e parasitárias (13,2%) e dos tumores (10,50%). Intoxicações e toxi-infecções (5,3%), doenças degenerativas (4,8%), distúrbios iatrogênicos (3,8%), doenças metabólicas e endocrinológicas (2,7%) foram categorias comuns. Doenças imunomediadas (2,1%), doenças nutricionais (1,6%), eutanásia por conveniência (1,4%) e distúrbios congênitos (1%) foram categorias incomuns. Outros distúrbios perfizeram 8,34% dos casos, As doenças mais importantes também foram avaliadas com relação à idade e os resultados obtidos demonstram que os adultos são mais acometidos pelo distúrbio do trato urinário inferior dos felinos, por traumas e por distúrbios iatrogênicos. Os gatos idosos são mais afetados por tumores e por doenças degenerativas, como a insuficiência renal crônica. Nos filhotes a principal doença que causa a morte ou eutanásia é a peritonite infecciosa feline.(AU)

The objective of this study was to determine the main diseases that cause death or euthanasia in cats in the central region of Rio Grande do Sul, Brazil. The Veterinary Pathology Laboratory (LPV-UFSM) files were reviewed from 1964 to 2013 and a total of 1,247 cat necropsies protocols were found. In 878 (70.40%) protocols the cause of death and/or reason for euthanasia has been established while in 369 (29.59%) cases it was not possible to be determined and these were classified as inconclusive. The final diagnosis were evaluated and classified into different categories. The category which includes the largest number of causes of death or reason for euthanasia in cats are disorders due to physical agents (15.63%), followed by infectious and parasitic diseases (13.15%), tumors (10.50%), other disorders (8.34%), poisoning and toxinfections (5.29%), degenerative diseases (4.81%), iatrogenic disorders (3.76%), metabolic and endocrinological diseases (2.72%), immune-mediated diseases (2.08%), nutritional diseases (1.60), convenience euthanasia (1.44%) and congenital disorders (1.04%). The most important diseases were also evaluated according to age and the results demonstrated that adult cats are most affected by lower urinary tract disease, trauma and iatrogenic disorders. Elderly cats are most affected by tumors and chronic renal failure. However, in young cats, feline infections peritonitis were found to be the most important cause of death or euthanasia.(AU)

Formation of homogeneous groups of bovine milk production units via multivariate statistical techniques / Formação de grupos homogêneos de unidades de produção de leite bovino através de técnicas estatísticas multivariadas

ABSTRACT: Milk supply chain in Brazil exhibits significant production system heterogeneity in all federal units. Thus, the objective of this study was to form homogeneous groups of bovine milk production units based on the chemical and microbiological quality of the milk via multivariate statistical techniques. A total of 1,541 milk producing units (MPUs), corresponding to 44,089 samples, were analyzed. The first three principal components accounted for 81.38% of the total variation in the data. Principal component 1 (PC1) was associated with the chemical quality of milk (fat, protein [PROT] and total dry extract [TDE] content), while PC2 and PC3 were associated with microbiological quality (somatic cell count [SCC] and total bacterial count [TBC]). The concurrent analysis of the two two-dimensional projections characterized the different productive strata by their quality attributes and identified the positive/negative points of milk microbiological characteristics in each production group. Thus, the dimensionality of the set of 1,541 MPUs was reduced to 15 homogeneous production groups. This method optimizes the use of the dairy industry monthly database and characterizes all the heterogeneities present in dairy production systems.

RESUMO: A cadeia produtiva brasileira de leite possui expressiva heterogeneidade de sistemas de produção em todas as unidades federativas. Assim, objetivou-se formar grupos homogêneos de unidades de produção de leite bovino através de técnicas estatísticas multivariadas, com base na qualidade química e microbiológica do leite. Foram utilizadas 1.541 unidades produtoras de leite (UPL), totalizando 44.089 amostras analisadas. Os três primeiros componentes principais explicaram 81,38% da variação total dos dados. O componente principal 1 associou-se à qualidade química do leite (gordura, proteína e extrato seco total), enquanto os componentes principais 2 e 3 com a qualidade microbiológica (contagem de células somáticas e contagem bacteriana total). Com a análise conjunta das três projeções bidimensionais, caracterizaram-se os distintos estratos produtivos quanto aos seus atributos de qualidade e identificaram-se os pontos positivos/negativos das características microbiológicas do leite de cada um dos grupos de produção. Assim, obteve-se uma redução da dimensionalidade do conjunto de 1.541UPL em 15 grupos de produção homogêneos, otimizando a utilização da base de informações mensais das indústrias lácteas, e caracterizando a totalidade das heterogeneidades presentes em sistemas de produção leiteiros.

Evaluación de la actividad física en pacientes con enfermedad pulmonar obstructiva crónica / Tools for physical activity assessment in chronic obstructive pulmonary disease

The prevalence and mortality of chronic obstructive pulmonary disease (COPD) is increasing in Chile, constituting a public health problem. Pulmonary and systemic consequences of COPD affect physical activity, as the disease progresses. There are multiple means for physical activity assessment, from low cost and easily applicable questionnaires to sophisticated laboratory tests. Physical inactivity is a modifiable risk factor for morbidity and mortality in patients with COPD. Physical activity interventions not only contribute to decrease the likelihood of mortality, but also protect from comorbidities, especially cardiovascular ones. It also plays a major role avoiding functional limitations of these subjects. Dyspnea and fatigue render exercise as an unpleasant activity for most patients with COPD. If psychological alterations such as anxiety and depression are summed, these patients drift towards an inactive lifestyle. This article analyzes several tools available to assess physical activity is patients with COPD, useful in clinical practice.

Estimating the economic consequences of an increased medication adherence due to a potential improvement in the inhaler technique with Spiromax® compared with Turbuhaler® in patients with moderate-to-severe chronic obstructive pulmonary disease in Spain.

OBJECTIVE: The objective of this study was to estimate the economic impact of the introduction of DuoResp® Spiromax®, budesonide/formoterol fixed-dose combination (FDC), focusing on an increase in medication adherence due to an enhancement of the inhalation technique for the treatment of COPD patients in Spain and 5 regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. METHODS: A 4-year budget impact model was developed for the time period of 2015-2018. This study aimed at evaluating the budget impact associated with the introduction of DuoResp Spiromax in comparison with Symbicort® Turbuhaler® and Rilast® Turbuhaler. National and regional data on COPD prevalence were obtained from the literature. Input data on health care resource utilization were obtained by clinical consultation. Resource included primary care visits, specialist visits, hospitalization, and emergency room visits as well as the length of hospital stay. Based on both pharmacological and health care resource costs, overall annual treatment cost per patient was estimated in EUR 2015. RESULTS: It was calculated that 130,777 adults were treated with budesonide/formoterol FDC delivered by a dry powder inhaler, Turbuhaler, in Spain in 2015. However, the target population decreases over the next 4 years. This pattern was observed in 4 regions, but for Andalusia, the treated population increased slightly. The overall budget savings in Spain with the market share of DuoResp Spiromax were estimated to be €6.01 million for the time period of 2015-2018. Region-specific data resulted in savings of €902,133 in Andalusia, €740,520 in Catalonia, €464,281 in Galicia, €748,996 in Madrid, and €495,812 in Valencia for the time period of 2015-2018. CONCLUSION: The introduction of budesonide/formoterol FDC delivered by Spiromax for COPD treatment is likely to contribute in a reduction of health care costs for Spain and in 5 Spanish regions. This model forecasts that Spain and these 5 Spanish regions were likely to have savings, which might be due to fewer days of hospitalization, avoided emergency room, and primary care visits.

[Tools for physical activity assessment in chronic obstructive pulmonary disease]. / Evaluación de la actividad física en pacientes con enfermedad pulmonar obstructiva crónica.

The prevalence and mortality of chronic obstructive pulmonary disease (COPD) is increasing in Chile, constituting a public health problem. Pulmonary and systemic consequences of COPD affect physical activity, as the disease progresses. There are multiple means for physical activity assessment, from low cost and easily applicable questionnaires to sophisticated laboratory tests. Physical inactivity is a modifiable risk factor for morbidity and mortality in patients with COPD. Physical activity interventions not only contribute to decrease the likelihood of mortality, but also protect from comorbidities, especially cardiovascular ones. It also plays a major role avoiding functional limitations of these subjects. Dyspnea and fatigue render exercise as an unpleasant activity for most patients with COPD. If psychological alterations such as anxiety and depression are summed, these patients drift towards an inactive lifestyle. This article analyzes several tools available to assess physical activity is patients with COPD, useful in clinical practice.

A budget impact analysis of Spiromax(®) compared with Turbuhaler(®) for the treatment of moderate to severe asthma: a potential improvement in the inhalation technique to strengthen medication adherence could represent savings for the Spanish Healthcare System and five Spanish regions.

OBJECTIVE: To assess the economic impact of the introduction of DuoResp(®) Spiromax(®) by focusing on a potential improvement in the inhalation technique to strengthen medication adherence for the treatment of moderate to severe asthmatics in Spain and five Spanish regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. METHODS: A 4-year budget impact model was developed for the period 2015-2018 from the Spanish Healthcare System perspective. Budesonide-formoterol fixed-dose combination delivered by Turbuhaler(®) was considered to be the most appropriate comparator for assessing the budget impact with the introduction of DuoResp(®) Spiromax(®). National and regional data on asthma prevalence were obtained from the literature. Input parameters on health care resources were obtained by consulting experts from different Spanish hospitals. Resources used included medical visits, emergency room visits, and hospitalizations. The average numbers of primary care and specialist visits per year were also gathered. Based on health care resource use per patient, the total treatment cost per patient was estimated. RESULTS: The population with moderate to severe asthma treated with budesonide-formoterol fixed-dose combinations delivered by Turbuhaler(®) in 2015 was estimated to be 166,985 in Spain. Region-specific prevalence data resulted in 25,081, 12,392, 16,097, 17,829, and 15,148 patients in Andalusia, Catalonia, Galicia, Madrid, and Valencia, respectively. Based on the forecast uptake of DuoResp(®) Spiromax(®), the total budget savings in Spain were expected to be €1.509 million over the next 4 years. Region-specific rates imply that the total savings were expected to be €229,706 in Andalusia, €90,145 in Catalonia, €188,327 in Galicia, €122,669 in Madrid, and €165,796 in Valencia over 2015-2018. CONCLUSION: The introduction of DuoResp(®) Spiromax(®), which represents a potential improvement in the inhalation technique to strengthen medication adherence for the treatment of moderate to severe asthma, could represent savings for the Spanish National Health Society and five Spanish regions.

The Integrated Role of Wnt/ß-Catenin, N-Glycosylation, and E-Cadherin-Mediated Adhesion in Network Dynamics.

The cellular network composed of the evolutionarily conserved metabolic pathways of protein N-glycosylation, Wnt/ß-catenin signaling pathway, and E-cadherin-mediated cell-cell adhesion plays pivotal roles in determining the balance between cell proliferation and intercellular adhesion during development and in maintaining homeostasis in differentiated tissues. These pathways share a highly conserved regulatory molecule, ß-catenin, which functions as both a structural component of E-cadherin junctions and as a co-transcriptional activator of the Wnt/ß-catenin signaling pathway, whose target is the N-glycosylation-regulating gene, DPAGT1. Whereas these pathways have been studied independently, little is known about the dynamics of their interaction. Here we present the first numerical model of this network in MDCK cells. Since the network comprises a large number of molecules with varying cell context and time-dependent levels of expression, it can give rise to a wide range of plausible cellular states that are difficult to track. Using known kinetic parameters for individual reactions in the component pathways, we have developed a theoretical framework and gained new insights into cellular regulation of the network. Specifically, we developed a mathematical model to quantify the fold-change in concentration of any molecule included in the mathematical representation of the network in response to a simulated activation of the Wnt/ ß-catenin pathway with Wnt3a under different conditions. We quantified the importance of protein N-glycosylation and synthesis of the DPAGT1 encoded enzyme, GPT, in determining the abundance of cytoplasmic ß-catenin. We confirmed the role of axin in ß-catenin degradation. Finally, our data suggest that cell-cell adhesion is insensitive to E-cadherin recycling in the cell. We validate the model by inhibiting ß-catenin-mediated activation of DPAGT1 expression and predicting changes in cytoplasmic ß-catenin concentration and stability of E-cadherin junctions in response to DPAGT1 inhibition. We show the impact of pathway dysregulation through measurements of cell migration in scratch-wound assays. Collectively, our results highlight the importance of numerical analyses of cellular networks dynamics to gain insights into physiological processes and potential design of therapeutic strategies to prevent epithelial cell invasion in cancer.

Qualidade do leite em diferentes sistemas de produção, ano e estação climática / Milk quality in different production systems, year and weather seasons

Objetivou-se avaliar a qualidade do leite produzido sob distintos níveis tecnológicos, durante três anos nas quatro estações climáticas, na região sul do Brasil. Os parâmetros de qualidade do leite avaliados foram: gordura, proteína, lactose, sólidos totais, contagem de células somáticas e contagem bacteriana total, oriundas de 346 propriedades classificadas em três sistemas de produção (não especializado, semi especializado, especializado). Os dados foram analisados por modelo misto com medida repetida no tempo, tendo como efeito fixo o sistema de produção, ano e estação, e efeito aleatório a propriedade designada em cada sistema de produção. Observou-se percentual elevado de amostras em desacordo com a Instrução Normativa Brasileira nº 62/2011. O sistema de produção afetou a contagem bacteriana total e o teor de gordura, com valores superiores para ambas no sistema não especializado. Todas as variáveis foram influenciadas pela estação do ano, sendo que no outono o leite apresentou percentuais superiores de gordura, proteína, sólidos totais e inferior de CBT. O teor de lactose foi influenciada pelo sistema de produção e pela estação do ano, demonstrando a influência dos fatores estudados na qualidade do leite produzido.

This study aimed evaluate the quality of milk yield under different technological levels, for three years in the four seasons, in southern Brazil. The quality parameter of milk were evaluated: fat, protein, lactose, total solids, somatic cell count and total bacterial count, collected from 346 dairy farms classified in three levels of the production systems (specialized, partially specializes and nonspecialized). Data were analyzed by mixed model with repeated measures in time, with the fixed effect production systems, years and seasons, and random effect property designated in each production system. We observed a high percentage of samples in disagreement with Federal Normative Instruction 62/2011 (IN 62), created to establish quality parameters for milk in the country. The production system affected the total bacterial count and fat content, with higher values for both in the nonspecialized system. All variables were influenced by the season, and in the fall the milk had a higher percentage of fat, protein, total solids and lower CBT. The lactose content was influenced by production systema and the season, demonstrating the influence of the factors studied in the quality of milk yield.