Application of a generic PBK model for beef cattle: Tissue/fluid correlations of paracetamol and NSAIDs.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and paracetamol can be administered off-label to cattle. Since the use of these veterinary medicines in cattle may pose a public health risk after meat consumption, it is important to translate measured concentrations in urine and tissues into concentrations in meat for human consumption. A generic physiologically-based kinetic (PBK) model for cattle can enable this translation. In this work, a beef cattle PBK model was applied to calculate the relationships between concentrations in different bovine tissues and those were compared to measured concentrations in different matrices. Sixty-seven kidney samples, the corresponding urine and meat samples, and available 19 serum samples were analysed. Overall, 70% of the PBK model predictions are within a 2-fold factor and relationships for kidney/meat, urine/meat, and plasma/meat ratios were established. The conversions of measured kidney concentrations into meat concentrations were mostly within a factor two, while those based on plasma and urine were underpredicted. Based on these ratios, plasma and urine could be used as an appropriate surrogate matrix for a fast, simple in vivo sample screening test under field conditions, such as in local farms and slaughterhouses, to predict a maximum residue level exceedance in meat, reducing the number of test samples.

Chemical food safety hazards in circular food systems: a review.

Food production has increasingly become effective but not necessarily sustainable. Transitioning toward circular production systems aiming to minimize waste and reuse materials is one of the means to obtain a more sustainable food production system. However, such a circular food production system can also lead to the accumulation and recirculation of chemical hazards. A literature review was performed to identify potential chemical hazards related to the use of edible and non-edible resources in agriculture and horticulture, and edible plant and animal by-products in feed production. The review revealed that limited information was available on the chemical hazards that could occur when reusing crop residues in circular agriculture. Frequently mentioned hazards present in edible and non-edible resources are heavy metals, process and environmental contaminants, pesticides and pharmaceuticals. For feed, natural toxins and pharmaceutical residues are of potential concern. Studies, furthermore, indicated that plants are capable of taking up chemical hazards when grown on contaminated soil. The presence of chemical hazards in manure, sewage sludge, crop residues, and animal by-products may lead to accumulation in a circular food production system. Therefore, it is relevant to identify these hazards prior to application in food production and, if needed, take precautionary measures to prevent food safety risks.

Tertiary wastewater treatment combined with high dilution rates fails to eliminate impacts on receiving stream invertebrate assemblages.

The amount of wastewater processed in treatment plants is increasing following more strict environmental regulations. Treatment facilities are implementing upgrades to abate the concentrations of nutrients and contaminants and, thus, reduce their effects on receiving systems. Although many studies characterized the chemical composition and ecotoxicological effects of treated wastewater, its environmental effects are still poorly known, as receiving water bodies are often subjected to other stressors. We performed a field manipulative experiment to measure the response of invertebrate assemblages to one year of tertiary-treated wastewater discharges. We poured treated wastewater from an urban wastewater treatment plant into the lower-most 100-m of a previously unpolluted stream (3.6 % daily flow on average) while using another upstream reach as control. The positive correlation between effect sizes of abundance changes and IBMWP scores suggested assemblage modifications were following taxa tolerance to ecological impairment. The treatment increased the temporal variability of SPEARorganic, EPT relative abundance, and invertebrate functional redundancy. Our results show that even in this best-case scenario of tertiary-treated and highly diluted wastewater, the abundance of the most sensitive taxa in the aquatic assemblages is reduced. Further improvements in wastewater treatments seem necessary to ensure these effluents do not modify receiving water ecosystems.

Exploiting the layer-by-layer nanoarchitectonics for the fabrication of polymer capsules: A toolbox to provide multifunctional properties to target complex pathologies.

Polymer capsules fabricated via the layer-by-layer (LbL) approach have attracted a great deal of attention for biomedical applications thanks to their tunable architecture. Compared to alternative methods, in which the precise control over the final properties of the systems is usually limited, the intrinsic versatility of the LbL approach allows the functionalization of all the constituents of the polymeric capsules following relatively simple protocols. In fact, the final properties of the capsules can be adjusted from the inner cavity to the outer layer through the polymeric shell, resulting in therapeutic, diagnostic, or theranostic (i.e., combination of therapeutic and diagnostic) agents that can be adapted to the particular characteristics of the patient and face the challenges encountered in complex pathologies. The biomedical industry demands novel biomaterials capable of targeting several mechanisms and/or cellular pathways simultaneously while being tracked by minimally invasive techniques, thus highlighting the need to shift from monofunctional to multifunctional polymer capsules. In the present review, those strategies that permit the advanced functionalization of polymer capsules are accordingly introduced. Each of the constituents of the capsule (i.e., cavity, multilayer membrane and outer layer) is thoroughly analyzed and a final overview of the combination of all the strategies toward the fabrication of multifunctional capsules is presented. Special emphasis is given to the potential biomedical applications of these multifunctional capsules, including particular examples of the performed in vitro and in vivo validation studies. Finally, the challenges in the fabrication process and the future perspective for their safe translation into the clinic are summarized.

Determination of banned dyes in red spices by ultra-high-performance liquid chromatography-atmospheric pressure ionization-tandem mass spectrometry.

This paper reports the development of an ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC‒MS/MS) method to determine eight banned dyes (Sudan I-IV, Sudan Orange, Sudan Red 7B, Para Red, Rhodamine B) in turmeric, curry, and chili products. For this purpose, the feasibility of electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) for the ionization of these compounds was evaluated. The tandem mass spectrometry (MS/MS) fragmentation of all targeted compounds was studied and both multistage mass spectrometry and high-resolution mass spectrometry were used to establish the fragmentation pathways and identify common fragmentation behaviors. Among the most significant ions, the most characteristic and abundant product ions observed on the triple quadrupole were selected to propose a selective and sensitive UHPLC‒MS/MS method (multiple reaction monitoring mode, MRM) of these target compounds in spices samples after a quick and easy extraction with acetonitrile. Matrix effect (ME) studies carried out in the three atmospheric pressure ionization sources have demonstrated that APCI showed the best performance with ME values ranging from 2 to 25%. Furthermore, the estimated quality parameters indicated the good performance of the proposed method, providing low method limits of detection (MLODs) (1-48 µg kg-1), good intra-day precision (RSD % < 15%), and accurate quantitation (relative error % < 15%). Finally, the applicability of the developed method was demonstrated by the analysis of turmeric, curry, and chili products. In total, 36 diverse samples coming from different countries were analyzed and although none of these compounds were detected above the MLODs, the analysis of spiked samples showed that the method was able to detect this family of compounds at low µg kg-1.

Encapsulation of manganese dioxide nanoparticles into layer-by-layer polymer capsules for the fabrication of antioxidant microreactors.

Oxidative stress is caused by the accumulation of reactive oxygen and nitrogen species (ROS and RNS) in the cellular microenvironment. These ROS and RNS damage important cell structures leading to cell apoptosis and senescence, thus causing a detrimental effect on numerous disease pathologies such as osteoarthritis, neurodegeneration and cardiovascular diseases. For this reason, there is a growing interest in the development of antioxidant biomaterials that can eventually regulate the levels of ROS/RNS and prevent oxidative stress. The encapsulation of antioxidant enzymes (e.g., catalase or superoxide dismutase) on polymer microcapsules fabricated via the layer-by-layer (LbL) approach represents a promising strategy within this context. The diffusion of reagents and by-products through the shell of these microcapsules is timely and spatially controlled, allowing the bio-chemical reaction between ROS/RNS and the encapsulated enzyme. However, natural enzymes usually present low stability, high cost and difficult storage, which could limit their potential application in the biomedical field. Hence, nanomaterials with intrinsic enzyme-like characteristics (i.e., nanozymes) have been considered as inorganic alternatives. In the present work, manganese dioxide nanoparticles were encapsulated into LbL polymer microcapsules to yield synthetic antioxidant microreactors. These microreactors efficiently scavenged hydrogen peroxide (H2O2) from solution and protected cells from oxidative stress in an in vitro model. The versatility of the synthetic procedure presented herein allows the fabrication of capsules with either positive or negative surface charge, which has a direct impact on the cytotoxicity and cell interaction. This study represents accordingly a novel strategy to obtain antioxidant polymer microreactors based on synthetic (nano)materials for the treatment of oxidative stress.

The WHO active ageing pillars and its association with survival: Findings from a population-based study in Spain.

BACKGROUND: The World Health Organization's active ageing model is based on the optimisation of four key "pillars": health, lifelong learning, participation and security. It provides older people with a policy framework to develop their potential for well-being, which in turn, may facilitate longevity. We sought to assess the effect of active ageing on longer life expectancy by: i) operationalising the WHO active ageing framework, ii) testing the validity of the factors obtained by analysing the relationships between the pillars, and iii) exploring the impact of active ageing on survival through the health pillar. METHODS: Based on data from a sample of 801 community-dwelling older adults, we operationalised the active ageing model by taking each pillar as an individual construct using principal component analysis. The interrelationship between components and their association with survival was analysed using multiple regression models. RESULTS: A three-factor structure was obtained for each pillar, except for lifelong learning with a single component. After adjustment for age, gender and marital status, survival was only significantly associated with the physical component of health (HR = 0.66; 95% CI = 0.47-0.93; p = 0.018). In turn, this component was loaded with representative variables of comorbidity and functionality, cognitive status and lifestyles, and correlated with components of lifelong learning, social activities and institutional support. CONCLUSION: According to how the variables clustered into the components and how the components intertwined, results suggest that the variables loading on the biomedical component of the health pillar (e.g. cognitive function, health conditions or pain), may play a part on survival chances.

Multimorbidity and functional impairment-bidirectional interplay, synergistic effects and common pathways.

This review discusses the interplay between multimorbidity (i.e. co-occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians' fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug-drug and drug-disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age-related health deterioration; this review provides an overview of knowledge gaps and future directions.

Rapidly developing multimorbidity and disability in older adults: does social background matter?

BACKGROUND: Multimorbidity is among the most disabling geriatric conditions. In this study, we explored whether a rapid development of multimorbidity potentiates its impact on the functional independence of older adults, and whether different sociodemographic factors play a role beyond the rate of chronic disease accumulation. METHODS: A random sample of persons aged ≥60 years (n = 2387) from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) was followed over 6 years. The speed of multimorbidity development was estimated as the rate of chronic disease accumulation (linear mixed models) and further dichotomized into the upper versus the three lower rate quartiles. Binomial negative mixed models were used to analyse the association between speed of multimorbidity development and disability (impaired basic and instrumental activities of daily living), expressed as the incidence rate ratio (IRR). The effect of sociodemographic factors, including sex, education, occupation and social network, was investigated. RESULTS: The risk of new activity impairment was higher among participants who developed multimorbidity faster (IRR 2.4, 95% CI 1.9-3.1) compared with those who accumulated diseases more slowly overtime, even after considering the baseline number of chronic conditions. Only female sex (IRR for women vs. men 1.6, 95% CI 1.2-2.0) and social network (IRR for poor vs. rich social network 1.7, 95% CI 1.3-2.2) showed an effect on disability beyond the rate of chronic disease accumulation. CONCLUSIONS: Rapidly developing multimorbidity is a negative prognostic factor for disability. However, sociodemographic factors such as sex and social network may determine older adults' reserves of functional ability, helping them to live independently despite the rapid accumulation of chronic conditions.

Effect of food shortage and temperature on age 0+ salmonids: a contribution to predict the effects of climate change.

Brown trout Salmo trutta alevins were maintained at 8 and 11° C at three conditions over a 9 day period from yolk sac exhaustion: fed ad libitum, starved or fed ad libitum after starvation. Whole-body gene expressions for proteins involved in energy metabolism and the two primary proteolytic pathways were assessed. This study is the first to show an over-expression of proteasome and autophagy-related genes in young stages of salmonids, particularly at 11° C.

Thermal stability increase in metallic nanoparticles-loaded cellulose nanocrystal nanocomposites.

Due to the potential of CNC-based flexible materials for novel industrial applications, the aim of this work is to improve the thermal stability of cellulose nanocrystals (CNC) films through a straightforward and scalable method. Based of nanocomposite approach, five different metallic nanoparticles (ZnO, SiO2, TiO2, Al2O3 and Fe2O3) have been co-assembled in water with CNCs to obtain free-standing nanocomposite films. Thermogravimetric analysis (TGA) reveals an increased thermal stability upon nanoparticle. This increase in the thermal stability reaches a maximum of 75°C for the nanocomposites having 10wt% of Fe2O3 and ZnO. The activation energies of thermodegradation process (Ea) determined according to Kissinger and Ozawa-Flynn-Wall methods further confirm the delayed degradation of CNC nanocomposites upon heating. Finally, the changes induced in the crystalline structure during thermodegradation were followed by wide angle X-ray diffraction (WAXD). It is also observed that thermal degradation proceeds at higher temperatures for nanocomposites having metallic nanoparticles. Overall, experimental findings here showed make nanocomposite approach a simple low-cost environmentally-friendly strategy to overcome the relatively poor thermal stability of CNCs when extracted via sulfuric acid assisted hydrolysis of cellulose.

Global health care use by patients with type-2 diabetes: Does the type of comorbidity matter?

AIM: To identify patterns of health care use among diabetic patients with multimorbidity across primary, specialised, hospital and emergency care, depending on their type of chronic comorbidity. METHODS: Longitudinal study of a population-based retrospective cohort conformed by adult patients with type-2 diabetes assigned to any of the primary care centres in Aragon during 2010 and 2011 (n=65,716). Negative binomial regressions were run to model the effect of the type of comorbidity on the number of visits to each level of care. Comorbidities were classified as concordant, discordant or mental based on expert consensus and depending on whether they shared the same overall pathophysiologic risk profile and disease management plan designed for type-2 diabetes. RESULTS: Mental comorbidity was independently associated with total and unplanned admissions (incidence rate ratio [IRR]:1.25; 95% confidence interval [CI]:1.12-1.39, IRR:1.21; 95% CI:1.06-1.39), average length of stay (IRR:1.47; 95% CI:1.25-1.73), and total and priority emergency room visits (IRR:1.26; 95% CI:1.17-1.35, IRR:1.30; 95% CI:1.18-1.42). Patients with discordant comorbidities showed the strongest associations with the number of visits to specialists (IRR:1.38; 95% CI:1.33-1.43) and to different specialties (IRR:1.36; 95% CI:1.32-1.39). Differences regarding GP visits were lower but still significant for patients with discordant comorbidity (IRR:1.08; 95% CI:1.06-1.11), but especially for those with mental comorbidity (IRR:1.17; 95% CI:1.14-1.21). CONCLUSION: In patients with type-2 diabetes, the coexistence of mental comorbidity significantly increases the use of unplanned hospital services, and discordant comorbidities have an important effect on specialised care use. Differences with respect to primary care use are not as prominent.

Geomorphic status of regulated rivers in the Iberian Peninsula.

River regulation by dams modifies flow regimes, interrupts the transfer of sediment through channel networks, and alters downstream bed dynamics, altogether affecting channel form and processes. So far, most studies on the geomorphic impacts of dams are restricted to single rivers, or even single river stretches. In this paper we analyse the geomorphic status of 74 river sites distributed across four large basins in the Iberian Peninsula (i.e. 47 sites located downstream of dams). For this purpose, we combine field data with hydrological data available from water agencies, and analyse historical (1970) and current aerial photographs. In particular, we have developed a Geomorphic Status (GS) index that allows us to assess the physical structure of a given channel reach and its change through time. The GS encompasses a determination of changes in sedimentary units, sediment availability, bar stability and channel flow capacity. Sites are statistically grouped in four clusters based on contrasted physical and climate characteristics. Results emphasise that regulation changes river's flow regime with a generalized reduction of the magnitude and frequency of floods (thus flow competence). This, in addition to the decrease downstream sediment supply, results in the loss of active bars as they are encroached by vegetation, to the point that only reaches with little or no regulation maintain exposed sedimentary deposits. The GS of regulated river reaches is negatively correlated with magnitude of the impoundment (regulation). Heavily impacted reaches present channel stabilization and, in contrast to the hydrological response, the distance and number of tributaries do not reverse the geomorphic impact of the dams. Stabilization limits river dynamics and may contribute to the environmental degradation of the fluvial ecosystem. Overall, results describe the degree of geomorphological alteration experienced by representative Iberian rivers mostly because of regulation, challenging the successful long-term implementation of river basin management programmes.

Crystallization and its effect on the mechanical properties of a medium chain length polyhydroxyalkanoate.

Medium chain length polyhydroxyalkanoates (mcl-PHAs) could play a role in the growing demand for highly elastic and biodegradable materials in the medical field. In this study, a poly(3-hydroxyoctanoate-co-3-hydroxyhexanoate) (P(3HO-co-3HH)) was first fully characterized in terms of molecular weight, microstructural chain parameters and chemical structure by means of gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR). As determined by NMR, the synthesized polymer contained 94.3% and 5.7% molar content of 3-hydroxyoctanoate and 3-hydroxyhexanoate, respectively. Since mechanical properties are closely related to thermal history, the effect of crystallization on tensile properties was also investigated in the present study. Three crystallization temperatures were selected (0, 23 and 37°C), the conclusion reached is that the maximum crystallization rate for this copolymer was achieved at 0°C. On the other hand, evolution of tensile properties of P(3HO-co-3HH) films stored at room temperature demonstrated that, as crystallization occurred toward the equilibrium state, the polymer underwent a stiffening process. In this sense, secant modulus and tensile strength increased respectively from 8.3 ± 1.0 MPa and 6.4 ± 0.8 MPa after 1 day stored at room temperature to 36.2 ± 3.3 MPa and 16.3 ± 2.1 MPa after 16 weeks.

A study of the mechanical properties and cytocompatibility of lactide and caprolactone based scaffolds filled with inorganic bioactive particles.

The mechanical properties of highly porous (90% porosity) poly(l-lactide) (PLLA), poly(ε-caprolactone) (PCL) and poly(l-lactide/ε-caprolactone) (PLCL) were investigated. Young's modulus of non-porous PLLA, PCL and PLCL dropped from 2263.4, 183.7 and 5.7 MPa to 16.8, 1.0 and 1.0 MPa, respectively, for their ~90% porous counterparts. Elongation at break of PCL decreased noticeably with porosity fraction while PLCL maintained a highly elastomeric character and strain recovery capacity even in the presence of pores. Inorganic bioactive particles (hydroxyapatite or bioglass) were added to confer bioactivity to the aforementioned synthetic bioresorbable polymers, and their effect on the mechanical properties was also investigated. Addition of 15 vol.% of inorganic bioactive particles increased the Young's modulus of highly porous PLLA from 16.2 to ~30 MPa. On the contrary, the difference between Young's modulus of filled and unfilled PCL and PLCL scaffolds was not statistically significant. Finally, an in vitro study of the cytocompatibility and adhesion of adipose derived stem cells (ADSCs) was conducted. The observed viability and excellent adhesion of these cells to both porous and non-porous templates indicate that the employed materials can be good candidates for application in tissue engineering.

Tensile behavior and dynamic mechanical analysis of novel poly(lactide/δ-valerolactone) statistical copolymers.

Lactide-co-δ-valerolactone copolymers (PLVL) have not attracted as much research interest as the more popular poly(lactide-co-ε-caprolactone) (PLCL) elastomeric materials. In this work the study of the mechanical performance is focused on the former with the aim of identifying the potential advantages of these thermoplastic elastomers for their application in the biomedical field. Mechanical testing (at 21°C and at 37°C) of at least 5 specimens and dynamic mechanical analysis (DMA) in duplicate were carried out on various PLVL, which include a moderately blocky l-lactide/δ-valerolactone copolymer (~70% of l-LA and R=0.68) and several that showed a random distribution of sequences (R~1): some terpolymers based on l-lactide, d-lactide and δ-valerolactone (with a lactone content of ~25 and ~14%) and a series of copolymers of l-LA and δ-VL having l-LA molar contents ranging from 69 to 74%. In view of the results, it can be concluded that noteworthy improvements in stiffness and strength were achieved by adding δ-VL to the reaction mix instead of ε-CL, although both monomers have analogous chemical properties. For example, a PLVL with a 75:25M composition of l-LA/δ-VL at 21°C presented a secant modulus of 213.7±36.5MPa and σu=14.7±1.4MPa whereas a previously studied PLCL of equal composition had a secant modulus and an ultimate stress value of 19.4±1.3MPa and 3.2±0.6MPa, respectively. At 37°C, the differences in the mechanical properties between the different PLVLs of this work were far less relevant, with most of them showing a fully elastomeric behavior. Referring to the DMA measurements, the reduction in the peak of tan δ (from ~2.5 to 0.5) through the glass transition was a clear indicator that crystalline domains formed during hydrolytic degradation in some of the polymers. However, the more amorphous PLVLs with short l-LA average sequence lengths (ll-LA<2.91) did not undergo changes in the storage modulus and tan δ curves after two weeks submerged in PBS at 37°C.

Does higher quality of primary healthcare reduce hospital admissions for diabetes complications? A national observational study.

AIM: To determine if hospital admission rates for diabetes complications (acute complications, chronic complications, no complications and hypoglycaemia) were associated with primary care diabetes management. METHODS: We performed an observational study in the population in England during the period 2004-2009 (54 741 278 people registered with 8140 general practices). We used multivariable negative binomial regression to model the associations between indirectly standardized hospital admission rates for complications and primary healthcare quality, supply and access indicators, diabetes prevalence and population factors. RESULTS: In multivariate regression models, increasing deprivation (incidence rate ratio: 1.0154; P < 0.001, 95% CI 1.0141-1.0166) and diabetes prevalence (incidence rate ratio: 1.0956; P < 0.001, 95% CI 1.0677-1.1241) were risk factors for admission, while most healthcare covariates, i.e. a larger practice population (incidence rate ratio 0.9999, P = 0.013, 95% CI 0.9999-0.9999), better patient-perceived urgent and non-urgent access to primary care (incidence rate ratio: 0.9989, P = 0.023; 95% CI 0.9979-0.9998 and incidence rate ratio: 0.9988; P = 0.003, 95% CI 0.9980-0.9996, respectively) and better HbA1c target achievement (incidence rate ratio: 0.9971; P < 0.001, 95% CI 0.9958-0.9984), were protective. Diabetes admissions decreased significantly during the period 2004-2009. CONCLUSIONS: After controlling for population factors, better scheduled primary care access and glycaemic control were associated with lower hospital admission rates across most complications. There is little rationale to restrict primary care-sensitive condition definitions to acute complications. They should be revised to improve the usefulness of hospital admission data as an outcome measure, and to facilitate international comparisons. The risk of emergency hospital admission should be monitored routinely.