Resveratrol-loaded octenyl succinic anhydride modified starch emulsions and hydroxypropyl methylcellulose (HPMC) microparticles: Cytotoxicity and antioxidant bioactivity assessment after in vitro digestion.

Hydroxypropyl methylcellulose (HPMC)-based microparticles and modified starch emulsions (OSA-MS) were loaded with resveratrol and characterized regarding their physicochemical and thermal properties. Both delivery systems were subject to an in vitro gastrointestinal digestion to assess the bioaccessibility of resveratrol. In addition, cell-based studies were conducted after in vitro digestion and cytotoxicity and oxidative stress were assessed. HPMC-based microparticles displayed higher average sizes (d) and lower polydispersity index (PDI) (d = 948 nm, PDI < 0.2) when compared to OSA-MS-based emulsions (d = 217 nm, PDI < 0.3). Both proved to protect resveratrol under digestive conditions, leading to an increase in bioaccessibility. Resveratrol-loaded HPMC-microparticles showed a higher bioaccessibility (56.7 %) than resveratrol-loaded emulsions (19.7 %). Digested samples were tested in differentiated co-cultures of Caco-2 and HT29-MTX, aiming at assessing cytotoxicity and oxidative stress, and a lack of cytotoxicity was observed for all samples. Results displayed an increasing antioxidant activity, with 1.6-fold and 1.4-fold increases over the antioxidant activity of free resveratrol, for HPMC-microparticles and OSA-MS nanoemulsions, respectively. Our results offer insight into physiological relevancy due to assessment post-digestion and highlight the protection that the use of micro-nano delivery systems can confer to resveratrol and their potential to be used as functional food ingredients capable of providing antioxidant benefits upon consumption.

Recent advances in oral delivery systems of resveratrol: foreseeing their use in functional foods.

Herein, we review the current state-of-the-art on the use of micro- and nano-delivery systems, a possible solution to some of the drawbacks associated with the incorporation of resveratrol in foods. Specifically, we present an overview of a wide range of micro-nanostructures, namely, lipidic and polymeric, used for the delivery of resveratrol. Also, the gastrointestinal fate of resveratrol-loaded micro-nanostructures, as a critical parameter for their use as functional food, is explored in terms of stability, bioaccessibility, and bioavailability. Different micro-nanostructures are of interest for the development of functional foods given that they can provide different advantages and properties to these foods and even be tailor-made to address specific issues (e.g., controlled or targeted release). Therefore, we discuss a wide range of micro-nanostructures, namely, lipidic and polymeric, used to deliver resveratrol and aimed at the development of functional foods. It has been reported that the use of some production methodologies can be of greater interest than others, for example, emulsification, solvent displacement and electrohydrodynamic processing (EHDP) enable a greater increase in bioaccessibility. Additionally, the use of coatings facilitates further improvements in bioaccessibility, which is likely due to the increased gastric stability of the coated micro-nanostructures. Other properties, such as mucoadhesion, can also help improve bioaccessibility due to the increase in gut retention time. Additionally, cytotoxicity (e.g., biocompatibility, antioxidant, and anti-inflammatory) and possible sensorial impact of resveratrol-loaded micro- and nano-systems in foods are highlighted.

Exploring the Mechanisms behind the Anti-Tumoral Effects of Model C-Scorpionate Complexes.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2](NO3)2 (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), were studied as potential scaffolds for future anticancer drug development. Their cytotoxicity and cell migration inhibitory activity were analyzed, and an untargeted metabolomics approach was employed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2](NO3)2 was particularly cytotoxic against the HCT116 cell line. While [Co(κ3-TpmOH)2](NO3)2 significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] was associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2](NO3)2 was associated with dysregulation of cell adhesion and membrane structural pathways, suggesting that its antiproliferative and anti-migration properties could be due to changes in the overall cellular adhesion mechanisms.

Missing data imputation techniques for wireless continuous vital signs monitoring.

Wireless vital signs sensors are increasingly used for remote patient monitoring, but data analysis is often challenged by missing data periods. This study explored the performance of various imputation techniques for continuous vital signs measurements. Wireless vital signs measurements (heart rate, respiratory rate, blood oxygen saturation, axillary temperature) from surgical ward patients were used for repeated random simulation of missing data periods (gaps) of 5-60 min in two-hour windows. Gaps were imputed using linear interpolation, spline interpolation, last observation- and mean carried forwards technique, and cluster-based prognosis. Imputation performance was evaluated using the mean absolute error (MAE) between original and imputed gap samples. Besides, effects on signal features (window's slope, mean) and early warning scores (EWS) were explored. Gaps were simulated in 1743 data windows, obtained from 52 patients. Although MAE ranges overlapped, median MAE was structurally lowest for linear interpolation (heart rate: 0.9-2.6 beats/min, respiratory rate: 0.8-1.8 breaths/min, temperature: 0.04-0.17 °C, oxygen saturation: 0.3-0.7% for 5-60 min gaps) but up to twice as high for other techniques. Three techniques resulted in larger ranges of signal feature bias compared to no imputation. Imputation led to EWS misclassification in 1-8% of all simulations. Imputation error ranges vary between imputation techniques and increase with gap length. Imputation may result in larger signal feature bias compared to performing no imputation, and can affect patient risk assessment as illustrated by the EWS. Accordingly, careful implementation and selection of imputation techniques is warranted.

Alginate Particles for Encapsulation of Phenolic Extract from Spirulina sp. LEB-18: Physicochemical Characterization and Assessment of In Vitro Gastrointestinal Behavior.

Encapsulation can be used as a strategy to protect and control the release of bioactive extracts. In this work, an extract from Spirulina sp. LEB-18, rich in phenolic compounds, was encapsulated in biopolymeric particles (i.e., composed of alginate) and characterized concerning their thermal behavior using differential scanning calorimetry (DSC), size, morphology, swelling index (S), and encapsulation efficiency (EE%); the release profile of the phenolic compounds at different pHs and the particle behavior under in vitro gastrointestinal digestion were also evaluated. It was shown that it is possible to encapsulate the phenolic extract from Spirulina sp. LEB-18 in alginate particles with high encapsulation efficiency (88.97%). It was also observed that the particles are amorphous and that the encapsulated phenolic compounds were released at a pH 7.2 but not at pH 1.5, which means that the alginate particles are able to protect the phenolic compounds from the harsh stomach conditions but lose their integrity under intestinal pH conditions. Regarding bioaccessibility, it was observed that the encapsulated phenolic compounds showed higher bioaccessibility compared to phenolic compounds in free form. This work increases the knowledge about the behavior of alginate particles encapsulating phenolic compounds during in vitro gastrointestinal digestion. It also provides essential information for designing biopolymeric particle formulations encapsulating phenolic compounds for application in pharmaceutical and food products.

Modulation and Characterization of Wax-Based Olive Oil Organogels in View of Their Application in the Food Industry.

Olive oil has recognized health benefits but lacks structural resilience to act in a similar fashion as do the typically used triglycerides (TAGs) when applied in food manufacturing. Therefore, olive oil structuring is critical to widening its use as a healthier alternative in spreadable products. Foreseeing the development of an application for the food industry, three types of natural waxes were used as organogelators, generating olive oil organogels with distinct properties. Retail-simulated storage conditions were used to mimic real-life industrial and commercial use. Organogel systems were evaluated according to their oxidation stability and textural and rheological properties. Textural and rheological parameters increased in response to increasing gelator concentration, while oxidation values (below 1.5 meq O2·kg-1) remained within legal limits. Organogels displayed similar textural properties to those of commercially available spreadable products, while displaying a low critical gelation concentration. In short, it was shown that tailoring the physicochemical properties of organogels towards specific applications is possible. The produced organogels showed similar properties to the ones of commercially available spreadable products, revealing favourable oxidative profiles. Therefore, an industrial application can be easily foreseen, building on the natural characteristics of olive oil as a healthier alternative to current spreadable products.

Solid and aqueous magnetoliposomes as nanocarriers for a new potential drug active against breast cancer.

Iron oxide nanoparticles, with diameters around 12nm, were synthesized by coprecipitation method. The magnetic properties indicate a superparamagnetic behavior with a coercive field of 9.7Oe and a blocking temperature of 118K. Both aqueous and solid magnetoliposomes containing magnetite nanoparticles have sizes below 150nm, suitable for biomedical applications. Interaction between both types of magnetoliposomes and models of biological membranes was proven. A new antitumor compound, a diarylurea derivative of thienopyridine, active against breast cancer, was incorporated in both aqueous and solid magnetoliposomes, being mainly located in the lipid membrane. A promising application of these magnetoliposomes in oncology is anticipated, allowing a combined therapeutic approach, using both chemotherapy and magnetic hyperthermia.

Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs.

Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers.

Reliability and validity of Yo-Yo tests in 9- to 16-year-old football players and matched non-sports active schoolboys.

The purpose of this study was to examine the test-retest reliability and construct validity of three age-adapted Yo-Yo intermittent tests in football players aged 9-16 years (n = 70) and in age-matched non-sports active boys (n = 72). Within 7 days, each participant performed two repetitions of an age-related intensity-adapted Yo-Yo intermittent test, i.e. the Yo-Yo intermittent recovery level 1 children's test for 9- to 11-year-olds; the Yo-Yo intermittent endurance level 1 for 12- to 13-year-olds and the Yo-Yo intermittent endurance level 2 test for 14- to 16-year-olds. Peak heart rate (HRpeak) was determined for all tests. The distance covered in the tests was 57% (1098 ± 680 vs. 700 ± 272 m), 119% (2325 ± 778 vs. 1062 ± 285 m) and 238% (1743 ± 460 vs. 515 ± 113 m) higher (p ≤ .016), respectively for football-trained than for non-sports active boys aged 9-11, 12-13 and 14-16 years. The typical errors of measurement for Yo-Yo distance, expressed as a percentage of the coefficient of variation (confidence interval), were 11.1% (9.0-14.7%), 10.1% (8.1-13.7%) and 8.5% (6.7-11.7%) for football players aged 9-11, 12-13 and 14-16 years, respectively, with corresponding values of 9.3% (7.4-12.8%), 10.2% (8.1-14.0%) and 8.5% (6.8-11.3%) for non-sports active boys. Intraclass correlation coefficient values for test-retest were excellent in both groups (range: 0.844-0.981). Relative HRpeak did not differ significantly between the groups in test and retest. In conclusion, Yo-Yo intermittent test performances and HRpeak are reliable for 9- to 16-year-old footballers and non-sports active boys. Additionally, performances of the three Yo-Yo tests were seemingly better for football-trained than for non-sports active boys, providing evidence of construct validity.

Persistent lipid abnormalities in patients with hypertension and dyslipidemia treated with statins: results of the Portuguese hypertensive subpopulation of the Dyslipidemia International Study (DYSIS).

This study aimed to assess the treatment patterns and prevalence of persistent lipid abnormalities in Portuguese hypertensive patients concomitantly treated with statins. Only 25% of the 656 hypertensive patients achieved the blood pressure goals in use during the study period. Similarly, only 33% and 37% attained the recommended levels of total cholesterol<4.5 mmol/L and LDL cholesterol<2.5 mmol/L, respectively. Relatively low doses of medium potency statins were the mainstay of therapy. There seems to be considerable room for improvement through the use of more potent statins, dose up-titration, and/or addition of other lipid-modifying therapies.

Genome sequencing highlights the dynamic early history of dogs.

To identify genetic changes underlying dog domestication and reconstruct their early evolutionary history, we generated high-quality genome sequences from three gray wolves, one from each of the three putative centers of dog domestication, two basal dog lineages (Basenji and Dingo) and a golden jackal as an outgroup. Analysis of these sequences supports a demographic model in which dogs and wolves diverged through a dynamic process involving population bottlenecks in both lineages and post-divergence gene flow. In dogs, the domestication bottleneck involved at least a 16-fold reduction in population size, a much more severe bottleneck than estimated previously. A sharp bottleneck in wolves occurred soon after their divergence from dogs, implying that the pool of diversity from which dogs arose was substantially larger than represented by modern wolf populations. We narrow the plausible range for the date of initial dog domestication to an interval spanning 11-16 thousand years ago, predating the rise of agriculture. In light of this finding, we expand upon previous work regarding the increase in copy number of the amylase gene (AMY2B) in dogs, which is believed to have aided digestion of starch in agricultural refuse. We find standing variation for amylase copy number variation in wolves and little or no copy number increase in the Dingo and Husky lineages. In conjunction with the estimated timing of dog origins, these results provide additional support to archaeological finds, suggesting the earliest dogs arose alongside hunter-gathers rather than agriculturists. Regarding the geographic origin of dogs, we find that, surprisingly, none of the extant wolf lineages from putative domestication centers is more closely related to dogs, and, instead, the sampled wolves form a sister monophyletic clade. This result, in combination with dog-wolf admixture during the process of domestication, suggests that a re-evaluation of past hypotheses regarding dog origins is necessary.

Persistent lipid abnormalities in statin-treated patients and predictors of LDL-cholesterol goal achievement in clinical practice in Europe and Canada.

BACKGROUND: The prevalence of persistent lipid abnormalities in patients receiving statins in primary and secondary care is needed to formulate recommendations for future treatment. Studies associating cardiovascular risk factors with lipid target goal achievement are lacking. DESIGN: A cross-sectional, observational study that assessed the prevalence of persistent dyslipidemia in patients treated with statins and analyzed predictors of lipid target achievement. METHODS: Serum lipid values of 22,063 statin-treated patients were studied in the context of their cardiovascular risk factors, and the potency and composition of their lipid-lowering treatment. European Society of Cardiology recommendations were used to classify patient risk, and to define LDL-cholesterol goal and normal levels for HDL-cholesterol and triglycerides. RESULTS: Overall, 48.2% of patients did not achieve the therapeutic goal for LDL-cholesterol, either as a single lipid anomaly or associated with low HDL-cholesterol, elevated triglycerides, or both. Lack of goal achievement was more prevalent among low-risk patients (55.8%) than high-risk patients (46.8%). Serum LDL-cholesterol levels were lower in high-risk patients. Predictors associated with LDL-cholesterol goal achievement were higher statin dose (odds ratio (OR): 0.35), specialist treatment (OR: 0.74), or combined lipid-lowering therapy (OR: 0.80). CONCLUSIONS: Nearly half of statin-treated patients missed their therapeutic LDL-cholesterol goal, highlighting a gap between recommendations and clinical practice. Better achievement of LDL-cholesterol therapeutic goal was found among patients at high cardiovascular risk, those on high statin doses or using combination therapy, and patients managed by specialists. Results suggest that residual dyslipidemia in statin-treated patients at low cardiovascular risk may be reduced by increasing statin dose.

350 ambulatory hemorrhoidectomies using a scanner coupled to a CO2 laser.

OBJECTIVE: The purpose of this study was to investigate how a scanner device would improve the outcome of laser hemorrhoidectomy regarding pain, healing, secretion, and hemostasis. BACKGROUND DATA: The technology of the laser has been applied since the 1960s in several clinical and surgical specialties. The inherent advantages, due to the biological characteristics of this instrument are: (1) it does not affect the neighborning tissues, (2) it is hemostatic, (3) it favors healing, (4) it is bactericidal, and (5) it presents less postoperative pain. Several authors have questioned these supposed advantages. After scanners were introduced, better results were accomplished, including in proctological surgery. METHODS: A total of 350 patients, consecutively, went through a laser hemorrhoidectomy using a CO2 laser coupled to a scanner device in a 3-year period. Patients were monitored for pain, healing, bleeding, and local secretion for up to 36 months. RESULTS: Almost 13% of the patients required bondage of arteries during the operation; 96% used analgesics for up to 3 days; and 5 patients (1.42%) complained of strong pain for several days. Only 2 patients (0.6%) reported intense pain for more than 7 days. All patients presented complete healing between the 30th and the 40th POD. In the 90th POD tissue regeneration appeared healthy. The immediate complications included 2 cases of nipple hemorrhage that demanded a review. Stenosis occurred in 4 patients. Residual "plicoma" was often present with the laser technique (20%). Return to work, regardless of its nature, was an average, on the 3rd postoperative day. CONCLUSIONS: Our evaluation of the results led to the conclusion that the scanner coupled to the CO2 laser was fundamental for better postoperative outcome in our patients, at least compared to other laser techniques.