Novel chitosan-based hydrogels as promising wound dressing materials with advanced properties.

Herein, four different grafted chitosans were synthesized by covalent attachment of glycine, L-arginine, L-glutamic acid, or L-cysteine to the chitosan chains. All products were subsequently permethylated to obtain their corresponding quaternary ammonium salts to enhance the inherent antimicrobial properties of native chitosan. In all cases, transparent hydrogels with the following remarkable characteristics were obtained: i) high-water absorption capacity (32-44 g H2O per g of polymer), ii) viscoelastic behavior at low deformations, iii) flexibility when subjected to deformations and iv) stability over long time scales. All the permethylated derivatives successfully inhibited 100 % of the growth of S. aureus. They also exhibited higher antimicrobial activity against E. coli than native chitosan. The structure of the chemically crosslinked products was more stable under external perturbations than that of the physically crosslinked ones. Between the chemically crosslinked products, the permethylated glutamic acid-grafted chitosan exhibited a noteworthy higher water absorption capacity with respect to that modified with cysteine, which makes it the most promising material for various industrial applications, including biomedical and food industries. Regarding biomedical applications, this derivative met the required physicochemical criteria for wound dressings, which encourages the pursuit of biological studies necessary to ensure the safety of its use for this application.

Production of resistant starches via citric acid modification: Effects of reaction conditions on chemical structure and final properties.

Aiming to contribute to the current knowledge on the impact of reaction conditions on the chemical structure and target properties of starch citrates, in the current contribution different corn starch citrates were prepared by manipulation of reaction time, temperature and citric acid concentration. Modified starches were characterized in terms of chemical structure, morphology, crystallinity, swelling power and resistant starch content. For the first time, total substitution, crosslinking and monosubstitution degrees were quantitatively determined; and the relationship among final chemical structure, reaction conditions and target starch citrates properties was comprehensively analyzed. Products with total substitution values in the range of 0.075-0.24, crosslinking degrees in the 0.005-0.11 interval, and monosubstitution extents within the 0.05-0.12 range, were produced. By proper selection of reaction conditions products with almost 100 % of resistant starch were obtained. Results evidenced that starch citrates properties (mainly swelling power and RS content) depend on both chemical structure and the reaction conditions employed. Actually, the reaction temperature set (120 °C or 150 °C) proved to play a determinant role in the final products properties as evidenced from starch citrates with similar chemical structure and substantially different swelling and digestibility properties.

Carbohydrate-Derived Polytriazole Nanoparticles Enhance the Anti-Inflammatory Activity of Cilostazol.

Poly(amide-triazole) and poly(ester-triazole) synthesized from d-galactose as a renewable resource were applied for the synthesis of nanoparticles (NPs) by the emulsification/solvent evaporation method. The NPs were characterized as stable, spherical particles, and none of their components, including the stabilizer poly(vinyl alcohol), were cytotoxic for normal rat kidney cells. These NPs proved to be useful for the efficient encapsulation of cilostazol (CLZ), an antiplatelet and vasodilator drug currently used for the treatment of intermittent claudication, which is associated with undesired side-effects. In this context, the nanoencapsulation of CLZ was expected to improve its therapeutic administration. The carbohydrate-derived polymeric NPs were designed taking into account that the triazole rings of the polymer backbone could have attractive interactions with the tetrazole ring of CLZ. The activity of the nanoencapsulated CLZ was measured using a matrix metalloproteinase model in a lipopolysaccharide-induced inflammation system. Interestingly, the encapsulated drug exhibited enhanced anti-inflammatory activity in comparison with the free drug. The results are very promising since the stable, noncytotoxic NP systems efficiently reduced the inflammation response at low CLZ doses. In summary, the NPs were obtained through an innovative methodology that combines a carbohydrate-derived synthetic polymer, designed to interact with the drug, ease of preparation, adequate biological performance, and environmentally friendly production.

Long transient response of vegetation dynamics after four millennia of anthropogenic impacts in an island ecosystem.

Agents of global change commonly have a higher impact on island ecosystem dynamics. In the Mediterranean region, those dynamics have historically been influenced by anthropogenic impacts, for example, the introduction of invasive species and overharvesting of resources. Here, we analysed the spatio-temporal dynamics of vegetation in sa Dragonera island, which experienced a large environmental change ca. 4000 years ago by the arrival of humans. Anthropogenic impacts, such as herbivory by goats and over-logging, ended in the 1970s, while in 2011 the site became the largest Mediterranean island where rats were eradicated. Invasive rats and goats played the ecological role of two endemic species, the cave goat and the giant dormouse, which inhabited the island for more than 5 million years and were rapidly extinct by humans. We used Landsat imagery to explore NDVI as a proxy of vegetation productivity over the years 1984-2021, orthophotos to assess changes in land and vegetation covers and historical plant inventories to study the dynamics in plant diversity. Results showed that those indicators steadily increased both in spring and in summer, while the noise around the trends was partially explained by climate variability. The regime shifts in the temporal dynamics of vegetation productivity suggested a transient from a perturbed to a non-perturbed stable state. Trends in successional dynamics, spatial self-organization and plant diversity also showed the same type of transient dynamics. Historical perturbations related to harvesting (mainly the synergies between goat browsing, burning and forest over-logging) were more important than rat eradication or the influence of climate to explain the vegetation dynamics. Our study shows the transient nature of this small island ecosystem after 4000 years of perturbations and its current path towards vegetation dynamics more controlled by ecological interactions lacking large herbivores and omnivores, drought dynamics and the carrying capacity of the island.

Los agentes del cambio global suelen tener un mayor impacto en la dinámica de los ecosistemas insulares. En la región Mediterránea, esas dinámicas se han visto influenciadas históricamente por impactos antropogénicos, e.g. la introducción de especies invasoras y la sobreexplotación de los recursos. Analizamos aquí la dinámica espacio-temporal de la vegetación en la isla de sa Dragonera, que experimentó un gran cambio ambiental hace unos 4000 años por la llegada de los humanos. Los impactos antropogénicos, como la herbivoría de las cabras y la tala excesiva, terminaron en la década de 1970, mientras que en 2011 se convirtió en la isla mediterránea más grande donde se erradicaron las ratas. Las ratas y cabras invasoras desempeñaron el papel ecológico de dos especies endémicas, el miotrago y el lirón gigante, que habitaron la isla durante más de 5 millones de años y fueron rápidamente extinguidos por los humanos. Usamos imágenes de Landsat para explorar el NDVI (indicador de la productividad de la vegetación) durante los años 1984-2021, ortofotos para evaluar los cambios en la cobertura de la tierra y la vegetación e inventarios históricos de plantas para estudiar la dinámica de su diversidad. Los resultados mostraron que esos indicadores aumentaron constantemente tanto en primavera como en verano, mientras que el ruido en torno a las tendencias se explicaba en parte por la variabilidad climática. Los cambios de régimen en la dinámica temporal de la productividad de la vegetación sugirieron un transitorio de un estado estable perturbado a uno no perturbado. Las tendencias en la dinámica sucesional, la autoorganización espacial y la diversidad de plantas también mostraron el mismo tipo de dinámica transitoria. Las perturbaciones históricas relacionadas con la recolección (principalmente las sinergias entre el pastoreo de cabras, la quema y la tala excesiva de bosques) fueron más importantes que la erradicación de ratas o la influencia del clima para explicar la dinámica de la vegetación. Nuestro estudio muestra la naturaleza transitoria de este ecosistema después de 4000 años de perturbaciones y su trayectoria actual hacia una dinámica de la vegetación más controlada por interacciones ecológicas (que carecen de grandes herbívoros y omnívoros), dinámicas de sequía y la capacidad de carga de la isla.

Perceived Health and Earnings: Evidence from the European Working Conditions Survey 2015.

This paper aims to analyse the relationship between perceived health and earnings across Europe. Empirical analysis is based on the last published round from the European Working Conditions Survey (N = 43,850) and offers updated evidence on the effect of earnings on perceived health in 35 countries. The main findings show a positive and significant relationship between earnings and health, which is consistent with the existing literature. Moreover, health seems to be U-shaped relative to earnings. On the other hand, age is negatively related to health, which is consistent with previous research. This paper shows the health differences between countries, where cultural, geographic, and economic differences imply health inequalities across countries. From a practical perspective, understanding the dynamics of perceived health and earnings' processes can contribute to health policy.

Detection of chlorantraniliprole residues in tomato using field-deployable MIP photonic sensors.

A photonic sensor based on inversed opal molecular imprinted polymer (MIP) film to detect the presence of chlorantraniliprole (CHL) residue in tomatoes was developed. Acrylic acid was polymerized in the presence of CHL inside the structure of a colloidal crystal, followed by etching of the colloids and CHL elution. Colloidal crystals and MIP films were characterized by scanning electron microscopy and FT-IR, confirming the inner structure and chemical structure of the material. MIP films supported on polymethylmethacrylate (PMMA) slides were incubated in aqueous solutions of the pesticide and in blended tomato samples. The MIP sensor displayed shifts of the peak wavelength of the reflection spectra in the visible range when incubated in CHL concentrations between 0.5 and 10 µg L-1, while almost no peak displacement was observed for non-imprinted (NIP) films. Whole tomatoes were blended into a liquid and spiked with CHL; the sensor was able to detect CHL residues down to 0.5 µg kg-1, significantly below the tolerance level established by the US Environmental Protection Agency of 1.4 mg kg-1. Stable values were reached after about 30-min incubation in test samples. Control samples (unspiked processed tomatoes) produced peak shifts both in MIP and NIP films; however, this matrix effect did not affect the detection of CHL in the spiked samples. These promising results support the application of photonic MIP sensors as an economical and field-deployable screening tool for the detection of CHL in crops.

Cost-benefit analysis of the use of tranexamic acid in total replacement hip surgery.

STUDY OBJECTIVE: To establish the best dose regimen for tranexamic acid (TXA) in total hip replacement surgery. DESIGN: Secondary analysis based on data from a multicenter double-blind randomized clinical trial. SETTING: Two hospitals in Spain. INTERVENTIONS: TXA (2 doses) versus placebo. PATIENTS: Consecutive adults who underwent uncemented unilateral total replacement hip surgery. MEASUREMENTS: We estimated the costs associated with TXA use (including consumables, drugs and nurse time) and allogeneic and autologous blood transfusions. For the cost-benefit analysis, we considered the spending on controls to estimate the benefits and the spending on patients in the intervention arms to estimate the costs. The net cost-benefit of TXA administration was calculated by subtracting the costs incurred per patient given TXA from the costs per patient given placebo. MAIN RESULTS: The median total costs per patient were €2.7 (2.4-3.0) in the single-dose group, €6.5 (6.5-7.1) in the two-dose group and €0 (0-190) in the control group (p = 0.001). The blood transfusion costs were €1607.8, €1041.8 and €3115.3 in the single-dose, two-dose and control groups, respectively. The administration of two doses of TXA achieved a greater net cost-benefit than a single dose, the difference being €566 in terms of overall costs. CONCLUSIONS: The administration of TXA is cost-effective, especially in the case of the two-dose regimen studied.

Sulfated Polysaccharides in the Freshwater Green Macroalga Cladophora surera Not Linked to Salinity Adaptation.

The presence of sulfated polysaccharides in cell walls of seaweeds is considered to be a consequence of the physiological adaptation to the high salinity of the marine environment. Recently, it was found that sulfated polysaccharides were present in certain freshwater Cladophora species and some vascular plants. Cladophora (Ulvophyceae, Chlorophyta) is one of the largest genera of green algae that are able to grow in both, seas and freshwater courses. Previous studies carried out on the water-soluble polysaccharides of the marine species C. falklandica established the presence of sulfated xylogalactoarabinans constituted by a backbone of 4-linked ß-L-arabinopyranose units partially sulfated mainly on C3 and also on C2 with partial glycosylation, mostly on C2, with terminal ß-D-xylopyranose or ß-D-galactofuranose units. Besides, minor amounts of 3-, 6- and/or 3,6-linked ß-D-galactan structures, with galactose in the pyranosic form were detected. In this work, the main water soluble cell wall polysaccharides from the freshwater alga Cladophora surera were characterized. It was found that this green alga biosynthesizes sulfated polysaccharides, with a structure similar to those found in marine species of this genus. Calibration of molecular clock with fossil data suggests that colonization of freshwater environments occurred during the Miocene by its ancestor. Therefore, the presence of sulfated polysaccharides in the freshwater green macroalga C. surera could be, in this case, an adaptation to transient desiccation and changes in ionic strength. Retention of sulfated polysaccharides at the cell walls may represent a snapshot of an evolutionary event, and, thus constitutes an excellent model for further studies on the mechanisms of sulfation on cell wall polysaccharides and environmental stress co-evolution.

Comorbid pathological gambling, mental health, and substance use disorders: Health-care services provision by clinician specialty.

Background and aims Pathological gambling (PG) is an impulse control disorder. This study assessed the burden of co-occurring behavioral addictions and mental health disorders in treatment-seeking patients and estimated the likelihood of receiving care for these disorders by clinician specialty. Methods Study data were derived from the Massachusetts All-Payer Claims Database, a representative database, for the period 2009-2013. The sample included commercially insured adult residents of Massachusetts. Univariate and multivariate logistic regressions were used to estimate the likelihood of provision of care by clinician specialty adjusting for patient's demographic characteristics and level of care. Bonferroni correction was applied to adjust for multiple testing. Results The study sample included 869 patients. Treatment-seeking patients who had a diagnosis of PG were mostly males (71%), aged 45-54 years (26.7%) and enrolled in a health maintenance organization (47%). The most prevalent co-occurring disorders among patients with PG as principal diagnosis were anxiety disorders (28%), mood disorders (26%), and substance use disorders (18%). PG was associated with a more than twofold likelihood of receiving care from social workers and psychologists (p < .05). Depressive disorders were associated with a three times greater likelihood of receiving care from primary care physicians (PCPs) (p < .05). Having three and four or more diagnosis was associated with a greater likelihood of receiving care from PCPs. Discussion and conclusions Psychiatric and substance use disorders are prevalent among treatment-seeking pathological gamblers. The likelihood of receiving care from specialty clinicians significantly varies by clinical diagnosis and patient clinical complexity.

Imidazothiazole and related heterocyclic systems. Synthesis, chemical and biological properties.

Fused heterobicyclic systems have gained much importance in the field of medicinal chemistry because of their broad spectrum of physiological activities. Among the heterocyclic rings containing bridgehead nitrogen atom, imidazothiazoles derivatives are especially attractive because of their different biological activities. Since many imidazothiazoles derivatives are effective for treating several diseases, is interesting to analyze the behavior of some isosteric related heterocycles, such as pirrolothiazoles, imidazothiadiazoles and imidazotriazoles. In this context, this review summarizes the current knowledge about the syntheses and biological behavior of these families of heterocycles. Traditional synthetic methodologies as well as alternative synthetic procedures are described. Among these last methodologies, the use of multicomponent reaction, novel and efficient coupling reagents, and environmental friendly strategies, like microwave assistance and solvent-free condition in ionic liquids are also summarized. This review includes the biological assessments, docking research and studies of mechanism of action performed in order to obtain the compounds leading to the development of new drugs.

Dealing with the health state 'dead' when using discrete choice experiments to obtain values for EQ-5D-5L heath states.

OBJECTIVE: To evaluate two different methods to obtain a dead (0)--full health (1) scale for EQ-5D-5L valuation studies when using discrete choice (DC) modeling. METHOD: The study was carried out among 400 respondents from Barcelona who were representative of the Spanish population in terms of age, sex, and level of education. The DC design included 50 pairs of health states in five blocks. Participants were forced to choose between two EQ-5D-5L states (A and B). Two extra questions concerned whether A and B were considered worse than dead. Each participant performed ten choice exercises. In addition, values were collected using lead-time trade-off (lead-time TTO), for which 100 states in ten blocks were selected. Each participant performed five lead-time TTO exercises. These consisted of DC models offering the health state 'dead' as one of the choices--for which all participants' responses were used (DCdead)--and a model that included only the responses of participants who chose at least one state as worse than dead (WTD) (DCWTD). The study also estimated DC models rescaled with lead-time TTO data and a lead-time TTO linear model. RESULTS: The DC(dead) and DCWTD models produced relatively similar results, although the coefficients in the DCdead model were slightly lower. The DC model rescaled with lead-time TTO data produced higher utility decrements. Lead-time TTO produced the highest utility decrements. CONCLUSIONS: The incorporation of the state 'dead' in the DC models produces results in concordance with DC models that do not include 'dead'.

Synthesis of imidazo[2,1-b]thiazoles linked to an unprotected carbohydrate moiety.

Two series of imidazo[2,1-b]thiazoles substituted on C-3 or C-5 with an unprotected carbohydrate moiety were synthesized. Different protective groups for position 3 of the carbohydrate moiety were tested (acetyl, tert-butyldimethylsilyl (TBDMS), and p-methoxybenzyl (PMB)) and the latter turn out to be the best strategy to obtain the desired products. Full deprotection of the carbohydrate was performed successfully in only one step.

1,2,4-Triazole D-ribose derivatives: design, synthesis and antitumoral evaluation.

Herein we report the design, synthesis and characterization of novel 1,2,4-triazole d-ribose derivatives, as well as their synthetic precursors. The antitumoral activity against T cell lymphoma cell line of these products was studied. Structures containing a 1,2,4-triazolic ring linked by sulfur to the carbohydrate moiety showed a moderate antiproliferative activity. The presence of the second heterocyclic ring did not show significant changes in their biological activity. Meanwhile, structures with 3-thiobenzyl-5-substituted-1,2,4-triazole ring linked by nitrogen leads to compounds with a biphasic behavior, stimulating cell proliferation at low concentrations and inhibiting it at higher ones. An increment in the polarity was associated with a decrease in the activity of the evaluated compounds. A preliminary antitumoral screening pointed the 1,2,4-triazolic structures linked to protected sugars as promising leaders for further studies.

Imidazo[2,1-b]thiazole carbohydrate derivatives: Synthesis and antiviral activity against Junin virus, agent of Argentine hemorrhagic fever.

Herein, we describe the syntheses of 3,5-disubstituted imidazo[2,1-b]thiazole. The cyclization step was performed in two different conditions by using either thermal or microwave heating. Comparing the results of both methodologies, we found that the microwave assistance is an improved alternative to obtain this family of heterocyclic compound. Compounds were first evaluated for cytotoxicity in Vero cells by MTT method and then, the antiviral activity was assayed by a virus yield inhibition assay in the range of concentrations lower than the corresponding CC(50), using JUNV strain IV4454 as the model system. The most active compounds (3 and 4), showed a level of antiviral activity against JUNV in monkey Vero cells better than the reference substance ribavirin. Then, they are promising lead compound for further analysis and characterization to establish their therapeutic potential against hemorrhagic fever viruses.

Synthesis and antiviral activity of azoles obtained from carbohydrates.

Herein we describe the synthesis of 1,2,4-triazolyl-3-thione;1,3,4-oxadiazole, and imidazo[2,1-b]thiazole derivatives from carbohydrates. The antiviral activity of these compounds was tested against Dengue and Junin virus (the etiological agent of Argentine hemorrhagic fever). The 3-(p-bromobenzoyl)-5-(1,2-O-isopropylidene-3-O-methyl-alpha-d-xylofuranos-5-ulos-5-yl)imidazo[2,1-b]thiazole was able to inhibit the replication of both viruses in Vero cells at concentration significantly lower than the CC(50).

Unusual structures in the polysaccharides from the red seaweed Pterocladiella capillacea (Gelidiaceae, Gelidiales).

Sequential extraction of tetrasporic Pterocladiella capillacea with water at room temperature and then at 50 degrees C led to the isolation of two products that were each fractionated with cetrimide to give a soluble fraction and a precipitate. The precipitates were then subjected to fractional solubilization in solutions of increasing sodium chloride concentration. The whole treatment yielded two major fractions in each case, one soluble in the cetrimide medium and the other soluble in 0.5 M NaCl, which were further fractionated by anion-exchange chromatography. Structural analysis, carried out by methylation, desulfation-methylation, 13C NMR spectroscopy and determination of the absolute configuration of the 2,6-di-O-methylgalactose units in the permethylated products, indicated the presence of xylogalactans, with low content of 3,6-anhydrogalactose and low molecular weight. These polysaccharides varied in the level of xylopyranosyl and sulfate substitution, primarily on the 6-position of the 3-linked beta-D-galactopyranosyl and on the 3-position of the 4-linked alpha-galactopyranosyl units. Moreover, herein we report, for the first time, the presence of 3-substituted, 4-linked D-galactopyranosyl residues in an alga belonging to the Gelidiales.