The current technology of air‐filtration materials for protection against highly toxic chemicals, that is, chemical‐warfare agents, is mainly based on the broad and effective adsorptive properties of ...hydrophobic activated carbons. However, adsorption does not prevent these materials from behaving as secondary emitters once they are contaminated. Thus, the development of efficient self‐cleaning filters is of high interest. Herein, we report how we can take advantage of the improved phosphotriesterase catalytic activity of lithium alkoxide doped zirconium(IV) metal–organic framework (MOF) materials to develop advanced self‐detoxifying adsorbents of chemical‐warfare agents containing hydrolysable PF, PO, and CCl bonds. Moreover, we also show that it is possible to integrate these materials onto textiles, thereby combining air‐permeation properties of the textiles with the self‐detoxifying properties of the MOF material.
The silk of human kindness: Insertion of lithium alkoxides in zirconium metal–organic frameworks (MOF) which are then deposited on silk fibers gives rise to protective fabrics capable of self‐detoxifying chemical‐warfare agents. The fabrics combine the air‐permeation properties of the textiles with the highly active phosphotriesterase catalytic activity of the MOF for the hydrolysis of PF, PO, and CCl bonds.
Chiral graphene quantum dots were prepared by acidic exfoliation and oxidation of graphite, dialysis, and esterification with enantiomerically pure (R) or (S)-2-phenyl-1-propanol. Circular dichroism ...studies support the formation of supramolecular aggregates with pyrene molecules, where a transfer of chirality occurs from the chiral graphene quantum dots to the pyrene.
Background: The risks and benefits of coxibs, non-steroidal anti-inflammatory drugs (NSAIDs), and aspirin treatment are under intense debate. Objective: To determine the risk of peptic ulcer upper ...gastrointestinal bleeding (UGIB) associated with the use of coxibs, traditional NSAIDs, aspirin or combinations of these drugs in clinical practice. Methods: A hospital-based, case–control study in the general community of patients from the National Health System in Spain. The study included 2777 consecutive patients with endoscopy-proved major UGIB because of the peptic lesions and 5532 controls matched by age, hospital and month of admission. Adjusted relative risk (adj RR) of UGIB determined by conditional logistic regression analysis is provided. Results: Use of non-aspirin-NSAIDs increased the risk of UGIB (adj RR 5.3; 95% confidence interval (CI) 4.5 to 6.2). Among non-aspirin-NSAIDs, aceclofenac (adj RR 3.1; 95% CI 2.3 to 4.2) had the lowest RR, whereas ketorolac (adj RR 14.4; 95% CI 5.2 to 39.9) had the highest. Rofecoxib treatment increased the risk of UGIB (adj RR 2.1; 95% CI 1.1 to 4.0), whereas celecoxib, paracetamol or concomitant use of a proton pump inhibitor with an NSAID presented no increased risk. Non-aspirin antiplatelet treatment (clopidogrel/ticlopidine) had a similar risk of UGIB (adj RR 2.8; 95% CI 1.9 to 4.2) to cardioprotective aspirin at a dose of 100 mg/day (adj RR 2.7; 95% CI 2.0 to 3.6) or anticoagulants (adj RR 2.8; 95% CI 2.1 to 3.7). An apparent interaction was found between low-dose aspirin and use of non-aspirin-NSAIDs, coxibs or thienopyridines, which increased further the risk of UGIB in a similar way. Conclusions: Coxib use presents a lower RR of UGIB than non-selective NSAIDs. However, when combined with low-dose aspirin, the differences between non-selective NSAIDs and coxibs tend to disappear. Treatment with either non-aspirin antiplatelet or cardioprotective aspirin has a similar risk of UGIB.
Summary
Background
The application of specific immunotherapy to stimulate oral tolerance towards food allergens is hampered by the high frequency of adverse side‐effects and the excessive duration of ...the treatments.
Objective
In this work, a hydrolysate of ovalbumin with pepsin (OP), selected for its low IgE reactivity and Th2‐stimulating capacity, was assayed for its ability to prevent and treat allergy to egg white (EW).
Methods
As a first step, the safety of OP, in terms of the absence of sensitizing and eliciting potential, was evaluated in BALB/c mice. Then, its suitability for prophylactic and therapeutic applications was compared with that of the intact allergen, paying attention to the molecular and cellular mechanisms involved in the control of the allergic process. To this aim, IgE, IgG1, IgG2a and IgA levels, allergic reactions, expression of genes related to Th1, Th2, Th17 and Treg responses, dendritic and T cell populations were assessed in intestinal tissues and spleens of EW‐allergic mice, either untreated or treated with intact ovalbumin (OVA) or OP.
Results
The hydrolysate of OVA with pepsin was hypoallergenic, lacked sensitizing potential and offered preventive and therapeutic protection against allergy to EW through the induction of Treg cells and the up‐regulation of TGF‐β, IL‐10, IL‐17, Foxp3 and RORγt in intestinal tissues. This restrained the expression of GATA3 and the differentiation of Th2 cells, leading to low cytokine responses following ex vivo spleen cell stimulation. As compared with intact OVA, OP was more effective against sensitization. In addition, in the therapeutic setting, OP provided quicker desensitization that lasted for at least 3 weeks after discontinuation of the therapy.
Conclusions and Clinical Relevance
This study provides evidence for the superior role of hydrolysed, as compared to intact allergens, in the prevention of allergy development and in the promotion of long‐term desensitization, as well as of intermolecular tolerance.
The only glaciers existing today in the Iberian Peninsula are small features located in the Pyrenees, though their number and extension has undergone significant changes over the Late Quaternary. The ...wide range of glacial landforms and deposits distributed across different Iberian ranges suggests the occurrence of several past periods with larger glacial systems. The objective of this research is to summarize the current knowledge on the spatial and temporal patterns of glacial activity in the Iberian mountains during the Late Quaternary. To this purpose, the chronological framework was divided in six periods: glaciations prior to the Last Glacial Cycle (Middle Pleistocene), Last Glacial Cycle (Late Pleistocene), Termination-1, Holocene, Little Ice Age (LIA) and present-day. The data were geographically divided considering the mountain systems where glacial evidence exists: Pyrenees, Cantabrian Range, NW ranges, Central Range, Iberian Range and Sierra Nevada. During Quaternary cold stages, ice accumulated in the head valleys of these mountain ranges and glaciers flowed down-valleys. In all cases, glaciers remained confined within the mountain systems and did not reach the surrounding lowlands. Depending on the combination of temperatures and moisture conditions, more or less ice was stored. In some ranges, there is evidence of Middle Pleistocene glaciations, one potentially correlating with marine isotope stage (MIS) 12 and another correlating with MIS 6 with glaciation dated to ca. 130-170 ka. However, most of the glacial records correspond to the Last Glacial Cycle and subsequent Termination. The maximum glacial expansion of this last Pleistocene glaciation stage occurred well before the global Last Glacial Maximum (LGM) between 30 and 60 ka in the Cantabrian Mountains and Pyrenees, at ca. 30 ka in Sierra Nevada and NW ranges, and (almost) synchronously to the LGM in the Central Range and Iberian Range. A massive glacial retreat occurred in all ranges at 19-20 ka, but the long-term deglaciation process was interrupted by cold intervals, such as the Oldest and Younger Dryas, which favoured glacial expansion in the highest mountains. Temperature increase recorded during the Holocene conditioned the melting of glaciers, which only reappeared in the highest massifs during the coldest periods, such as the LIA. However, post-LIA warming led to glacier disappearance in the Cantabrian Mountains, Sierra Nevada and most massifs of the Pyrenees, together with an accelerated shrinkage of the small glaciers still existing in this range at elevations near 3000 m.
Diabetes is a disease that can be treated with oral antidiabetic agents and/or insulin. However, patients’ metabolic control is inadequate in a high percentage of them and a major cause of chronic ...diseases like diabetic retinopathy. Approximately 15% of patients have some degree of diabetic retinopathy when diabetes is first diagnosed, and most will have developed this microvascular complication after 20 years. Early diagnosis of the disease is the best tool to prevent or delay vision loss and reduce the involved costs. However, diabetic retinopathy is an asymptomatic disease and its development to advanced stages reduces the effectiveness of treatments. Today, the recommended treatment for severe nonproliferative and proliferative diabetic retinopathy is photocoagulation with an argon laser and intravitreal injections of anti-VEGF associated with, or not, focal laser for diabetic macular oedema. The use of these therapeutic approaches is severely limited, such as uncomfortable administration for patients, long-term side effects, the costs they incur, and the therapeutic effectiveness of the employed management protocols. Hence, diabetic retinopathy is the widespread diabetic eye disease and a leading cause of blindness in adults in developed countries. The growing interest in using polyphenols, e.g., resveratrol, in treatments related to oxidative stress diseases has spread to diabetic retinopathy. This review focuses on analysing the sources and effects of oxidative stress and inflammation on vascular alterations and diabetic retinopathy development. Furthermore, current and antioxidant therapies, together with new molecular targets, are postulated for diabetic retinopathy treatment.
Female birds may adjust their offspring phenotype to the specific requirements of the environment by differential allocation of physiologically active substances into yolks, such as androgens. Yolk ...androgens have been shown to accelerate embryonic development, growth rate and competitive ability of nestlings, but they can also entail immunological costs. The balance between costs and benefits of androgen allocation is expected to depend on nestling environment. We tested this hypothesis in a multibrooded passerine, the spotless starling, Sturnus unicolor. We experimentally manipulated yolk androgen levels using a between‐brood design and evaluated its effects on nestling development, survival and immune function. Both in first and replacement broods, the embryonic development period was shorter for androgen‐treated chicks than controls, but there were no differences in second broods. In replacement broods, androgen‐treated chicks were heavier and larger than those hatched from control eggs, but this effect was not observed in the other breeding attempts. Androgen exposure reduced survival with respect to controls only in second broods. Regarding immune function, we detected nonsignificant trends for androgen treatment to activate two important components of innate and adaptive immunity (IL‐6 and Ig‐A levels, respectively). Similarly, androgen‐treated chicks showed greater lymphocyte proliferation than controls in the first brood and an opposite trend in the second brood. Our results indicate that yolk androgen effects on nestling development and immunity depend on the environmental conditions of each breeding attempt. Variation in maternal androgen allocation to eggs could be explained as the result of context‐dependent optimal strategies to maximize offspring fitness.
Gestational Diabetes Mellitus (GDM) and obesity affect the functioning of multiple maternal systems and influence colonization of the newborn gastrointestinal through the breastmilk microbiota (BMM). ...It is currently unclear how GDM and obesity affect the human BMM composition. Here, we applied 16S-rRNA high-throughput sequencing to human colostrum milk to characterize BMM taxonomic changes in a cohort of 43 individuals classified in six subgroups according to mothers patho-physiological conditions (healthy control (n = 18), GDM (n = 13), or obesity (n = 12)) and newborn gender. Using various diversity indicators, including Shannon/Faith phylogenetic index and UniFrac/robust Aitchison distances, we evidenced that BMM composition was influenced by the infant gender in the obesity subgroup. In addition, the GDM group presented higher microbial diversity compared to the control group. Staphylococcus, Corynebacterium 1, Anaerococcus and Prevotella were overrepresented in colostrum from women with either obesity or GDM, compared to control samples. Finally, Rhodobacteraceae was distinct for GDM and 5 families (Bdellovibrionaceae, Halomonadaceae, Shewanellaceae, Saccharimonadales and Vibrionaceae) were distinct for obesity subgroups with an absolute effect size greater than 1 and a q-value ≤ 0.05. This study represents the first effort to describe the impact of maternal GDM and obesity on BMM.
Alcohol is part of the usual diet of millions of individuals worldwide. However, not all individuals who drink alcohol experience the same effects, nor will everyone develop an alcohol use disorder. ...Here we propose that the intestinal microbiota (IMB) helps explain the different consumption patterns of alcohol among individuals. 507 humans participated in this study and alcohol consumption and IMB composition were analyzed. On the other hand, in 80 adult male Wistar rats, behavioral tests, alcohol intoxication, fecal transplantation, administration of antibiotics and collection of fecal samples were performed. For identification and relative quantification of bacterial taxa was used the bacterial 16 S ribosomal RNA gene. In humans, we found that heavy episodic drinking is associated with a specific stool type phenotype (type 1, according to Bristol Stool Scale; p < 0.05) and with an increase in the abundance of Actinobacteria (p < 0.05). Next, using rats, we demonstrate that the transfer of IMB from alcohol-intoxicated animals causes an increase in voluntary alcohol consumption in transplant-recipient animals (p < 0.001). The relative quantification data indicate that the genus Porphyromonas could be associated with the effect on voluntary alcohol consumption. We also show that gut microbiota depletion by antibiotics administration causes a reduction in alcohol consumption (p < 0.001) and altered the relative abundance of relevant phyla such as Firmicutes, Bacteroidetes or Cyanobacteria (p < 0.05), among others. Benjamini-Hochberg false discovery rate (FDR) correction was performed for multiple comparisons. These studies reveal some of the consequences of alcohol on the IMB and provide evidence that manipulation of IMB may alter voluntary alcohol consumption.
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