Correction: Facing the escalating burden of dengue: Challenges and perspectives.

[This corrects the article DOI: 10.1371/journal.pgph.0002598.].

How to treat localized Hodgkin lymphoma?

PURPOSE OF REVIEW: We aim to summarize the current knowledge on the management of early-stage classical Hodgkin lymphoma, with a focus on conventional strategies, incorporation of immunotherapies and exploration of novel prognostic markers. RECENT FINDINGS: Long-term data on combined modalities (associating chemotherapy and radiotherapy) still supports their benefit in terms of progression free survival compared to chemotherapy alone in both early favourable and early unfavourable interim PET-negative classical Hodgkin Lymphoma. Novel agents, such as Brentuximab Vedotin and checkpoints inhibitors show promising and impressive results when added to first-line treatment. Various strategies have been used, mainly in phase 2 non randomized clinical trials. Interim PET-scan has limited prognostic value and its role in regimens incorporating immunotherapies is yet unknown. Other prognosis markers emerge, such as metabolic tumour volume and circulating tumour DNA. By reflecting tumour burden pretreatment and minimal residual disease on treatment, they might be useful tools guiding treatment decisions. SUMMARY: Novel immunotherapy agents are likely to change the landscape in front-line management of classical early-stage Hodgkin lymphoma by combined modality treatment. Despite encouraging recent data, proof of their efficacy and safety on the longer term are still needed. Treatment decisions might be guided by new promising prognosis markers but their use in clinical practice is still to be determined.

Hypoxia Promotes Invadosome Formation by Lung Fibroblasts.

Lung parenchymal hypoxia has emerged as a cardinal feature of idiopathic pulmonary fibrosis (IPF). Hypoxia promotes cancer cell invasion and metastasis through signaling that is dependent upon the lysophosphatidic acid (LPA) receptor, LPA1 (LPAR1). Abundant data indicate that LPA1-dependent signaling also enhances lung fibrogenesis in IPF. We recently reported that fibroblasts isolated from the lungs of individuals with IPF have an increased capacity to form subcellular matrix-degradative structures known as invadosomes, an event that correlates with the degree of lung fibrosis. We therefore hypothesized that hypoxia promotes invadosome formation in lung fibroblasts through LPA1-dependent signaling. Here, it is demonstrated that invadosome formation by fibroblasts from the lungs of individuals with advanced IPF is inhibited by both the tyrosine receptor kinase inhibitor nintedanib and inhibition of LPA1. In addition, exposure of normal human lung fibroblasts to either hypoxia or LPA increased their ability to form invadosomes. Mechanistically, the hypoxia-induced invadosome formation by lung fibroblasts was found to involve LPA1 and PDGFR-Akt signaling. We concluded that hypoxia increases the formation of invadosomes in lung fibroblasts through the LPA1 and PDGFR-Akt signaling axis, which represents a potential target for suppressing lung fibrosis.

Pharmacokinetics in regional anesthesia.

PURPOSE OF REVIEW: Pharmacokinetics of local anesthetics are one of the main determinants of success and safety of regional anesthesia and comprise local and systemic distribution phases. This review aims to summarize the latest research findings on this topic in the context of various regional blocks performed for different surgeries and patient populations. RECENT FINDINGS: Research into local kinetics and systemic absorption of local anesthetics has chiefly been focused on novel fascial plane blocks, especially the erector spinae plane block, as these are increasingly adopted for regional anesthesia and pain management. As their clinical efficacy is very dependent on injection of large volumes of local anesthetic, doses over typically recommended limits are often administered. SUMMARY: Fascial plane blocks are the regional anesthesia techniques in need of the most pharmacokinetic characterization, not only to better understand their complex mechanisms of action but also to avoid harm from excessive doses of local anesthetics. Further mapping of risk factors for systemic toxicity from administration in different block sites is crucial. Extremes of age and pregnancy are vulnerable patient populations but in whom regional anesthesia, including novel techniques, has been performed with few complications.

Zinc/Magnesium Ferrite Nanoparticles Functionalized with Silver for Optimized Photocatalytic Removal of Malachite Green.

Water pollution is a major environmental challenge. Due to the inefficiency of conventional wastewater treatment plants in degrading many organic complex compounds, these recalcitrant pollutants end up in rivers, lakes, oceans and other bodies of water, affecting the environment and human health. Semiconductor photocatalysis is considered an efficient complement to conventional methods, and the use of various nanomaterials for this purpose has been widely explored, with a particular focus on improving their activity under visible light. This work focuses on developing magnetic and photoactive zinc/magnesium mixed ferrites (Zn0.5Mg0.5Fe2O4) by sol-gel and solvothermal synthesis methods, which are two of the most important and efficient methods used for the synthesis of ferrite nanoparticles. The nanoparticles (NPs) synthesized by the sol-gel method exhibited an average size of 14.7 nm, while those synthesized by the solvothermal method had an average size of 17.4 nm. Both types possessed a predominantly cubic structure and demonstrated superparamagnetic behavior, reaching a magnetization saturation value of 60.2 emu g-1. Due to the high recombination rate of electrons/holes, which is an intrinsic feature of ferrites, surface functionalization with silver was carried out to enhance charge separation. The results demonstrated a strong influence of adsorption and of the deposition of silver. Several optimization steps were performed during synthesis, allowing us to create efficient catalysts, as proved by the almost full removal of the dye malachite green attaining 95.0% (at a rate constant of 0.091 min-1) and 87.6% (at a rate constant of 0.017 min-1) using NPs obtained by the sol-gel and solvothermal methods, respectively. Adsorption in the dark accounted for 89.2% of the dye removal for nanoparticles prepared by sol-gel and 82.8% for the ones obtained by the solvothermal method. These results make mixed zinc/magnesium ferrites highly promising for potential industrial application in effluent photoremediation using visible light.

A [2.2]Isoindolinophanyl-Based Carbene (iPC) Ligand: Synthesis, Electronic and Photophysical Properties, and Application in Photocatalysis*.

Cyclic amino(alkyl) and cyclic amino(aryl) carbenes (cAACs/cAArCs) have been established as very useful ligands for catalytic and photonic applications of transition metal complexes. Herein, we describe the synthesis of a structurally related sterically demanding, electrophilic [2.2]isoindolinophanyl-based carbene (iPC) with a [2.2]paracyclophane moiety. The latter leads to more delocalized frontier orbitals and intense green fluorescence of (HiPC)OTf (2) from an intra-ligand charge transfer (1ILCT) state in the solid state. Base-promoted synthesis of the free carbene led to an unusual ring expansion and subsequent dimerization reaction, but the beneficial ligand properties can be exploited by trapping in situ at a metal center. The iPC ligand is a very potent π-chromophore, which participates in low energy metal-to-ligand (ML)CT transitions in [RhCl(CO)2(iPC)] (4) and IL-"through-space"-CT transitions in [Au(iPC)2]OTf (5). The steric demand of the iPC leads to high stability of 5 against air, moisture, or solvent attack, and ultralong-lived green phosphorescence with a lifetime of 185 µs is observed in solution. The beneficial photophysical and electronic properties of the iPC ligand, including a large accessible π surface area, were exploited by employing highly efficient energy transfer (EnT) photocatalysis in a [2+2] styrene cycloaddition reaction using 5, which outperformed other established photocatalysts in comparison.

Glycosylated flavonoid kaempferitrin: Electroanalytical detection and the proposal of an oxidation mechanism supported by quantum chemical calculations.

In this work, the electrochemical behavior of the glycosylated flavonoid kaempferitrin was studied, and an electroanalytical methodology was developed for its determination in infusions of Bauhinia forficata using a boron-doped diamond electrode (BDD). The electrochemical behavior of the flavonoid was studied by cyclic voltammetry, and two irreversible oxidation peaks at 0.80 and 1.0 V vs Ag/AgCl were observed. The influence of the pH on the voltammograms was examined, and higher sensitivity was found at pH 7.0. The electrochemical process corresponding to peak 1 at 0.80 V is predominantly diffusion-controlled, as the study shows at varying scan rates. An analytical plot was obtained by square wave voltammetry at optimized experimental conditions (frequency = 100 s-1, amplitude = 90 mV, and step potential = 8 mV) in the concentration range from 3.4 µmol L-1 to 58 µmol L-1, with a linearity of 0.99. The limit of detection and limit of quantification values were 1.0 µmol L-1 and 3.4 µmol L-1, respectively. Three samples of Bauhinia forficata infusions (2 g of sample in 100 mL of water) were analyzed, and the KF values found were 5.0 × 10-4 mol L-1, 3.0 × 10-4 mol L-1, and 7.0 × 10-4 mol L-1, with recovery percentages of 98 %, 106 % and 94 %, respectively. Finally, experiments were performed with two other flavonoids (chrysin and apeginin) to compare and propose an electrochemical oxidation mechanism for kaempferitrin, which was supported by quantum chemical calculations.

Premature mortality trends in 183 countries by cancer type, sex, WHO region, and World Bank income level in 2000-19: a retrospective, cross-sectional, population-based study.

BACKGROUND: Cancer is a leading cause of mortality worldwide. By 2040, over 30 million new cancers are predicted, with the greatest cancer burden in low-income countries. In 2015, the UN passed the Sustainable Development Goal 3.4 (SDG 3.4) to tackle the rising burden of non-communicable diseases, which calls for a reduction by a third in premature mortality from non-communicable diseases, including cancer, by 2030. However, there is a paucity of data on premature mortality rates by cancer type. In this study, we examine annual rates of change for cancer-specific premature mortality and classify whether countries are on track to reach SDG 3.4 targets. METHODS: This is a retrospective, cross-sectional, population-based study investigating premature mortality trends from 2000-19 using the WHO Global Health Estimates data. All cancers combined and thirteen individual cancers in 183 countries were examined by WHO region, World Bank income level, and sex. The risk of premature mortality was calculated for ages 30-69 years, independent of other competing causes of death, using standard life table methods. The primary objective was to compute average annual rate of change in premature mortality from 2000 to 2019. Secondary objectives assessed whether this annual rate of change would be sufficient to reach SDG 3.4. targets for premature mortality by 2030. FINDINGS: This study was conducted using data retrieved for the years 2000-19. Premature mortality rates decreased in 138 (75%) of 183 countries across all World Bank income levels and WHO regions, however only eight (4%) countries are likely to meet the SDG 3.4 targets for all cancers combined. Cancers where early detection strategies exist, such as breast and colorectal cancer, have higher declining premature mortality rates in high-income countries (breast cancer 48 [89%] of 54 and colorectal cancer 45 [83%]) than in low-income countries (seven [24%] of 29 and four [14%]). Cancers with primary prevention programmes, such as cervical cancer, have more countries with declining premature mortality rates (high-income countries 50 [93%] of 54 and low-income countries 26 [90%] of 29). Sex-related disparities in premature mortality rates vary across WHO regions, World Bank income groups, and by cancer type. INTERPRETATION: There is a greater reduction in premature mortality for all cancers combined and for individual cancer types in high-income countries compared with lower-middle-income and low-income countries. However, most countries will not reach the SDG 3.4 target. Cancers with early detection strategies in place, such as breast and colorectal cancers, are performing poorly in premature mortality compared with cancers with primary prevention measures, such as cervical cancer. Investments toward prevention, early detection, and treatment can potentially accelerate declines in premature mortality. FUNDING: WHO.

A single-cell transcriptomic atlas of sensory-dependent gene expression in developing mouse visual cortex.

Sensory experience drives the refinement and maturation of neural circuits during postnatal brain development through molecular mechanisms that remain to be fully elucidated. One likely mechanism involves the sensory-dependent expression of genes that encode direct mediators of circuit remodeling within developing cells. However, while studies in adult systems have begun to uncover crucial roles for sensory-induced genes in modifying circuit connectivity, the gene programs induced by brain cells in response to sensory experience during development remain to be fully characterized. Here, we present a single-nucleus RNA-sequencing dataset describing the transcriptional responses of cells in mouse visual cortex to sensory deprivation or sensory stimulation during a developmental window when visual input is necessary for circuit refinement. We sequenced 118,529 individual nuclei across sixteen neuronal and non-neuronal cortical cell types isolated from control, sensory deprived, and sensory stimulated mice, identifying 1,268 unique sensory-induced genes within the developing brain. To demonstrate the utility of this resource, we compared the architecture and ontology of sensory-induced gene programs between cell types, annotated transcriptional induction and repression events based upon RNA velocity, and discovered Neurexin and Neuregulin signaling networks that underlie cell-cell interactions via CellChat . We find that excitatory neurons, especially layer 2/3 pyramidal neurons, are highly sensitive to sensory stimulation, and that the sensory-induced genes in these cells are poised to strengthen synapse-to-nucleus crosstalk by heightening protein serine/threonine kinase activity. Altogether, we expect this dataset to significantly broaden our understanding of the molecular mechanisms through which sensory experience shapes neural circuit wiring in the developing brain.

On-line coupling of hollow-fiber flow field-flow fractionation and depolarized multi-angle static light scattering (HF5/D-MALS). Proof of principle.

Introduced here is the on-line coupling of hollow-fiber flow field-flow fractionation (HF5) to depolarized multi-angle static light scattering (D-MALS). HF5 is a size-based separation alternative to size-exclusion and hydrodynamic chromatography and asymmetric flow field-flow fractionation. HF5 can separate larger sizes than its chromatographic counterparts and provides several advantages over its fractionation counterpart, including reduced sample consumption and greater ease of operation. D-MALS is a variant of MALS in which the depolarized scattering from the analyte solution is measured at a variety of angles simultaneously. Measurements of depolarized scattering have previously been employed in studying the optical properties of solutions or suspensions, to determine the length of rod-like analytes, and to gain increased accuracy in the determination of analyte molar mass. The coupling HF5/D-MALS allows for the depolarization ratio of a solution or suspension to be measured continuously across the fractogram. This is demonstrated here for a Teflon latex the size range of which extends beyond that accessible to commercial size-exclusion columns. The results presented provide the first reported on-line HF5/D-MALS coupling, showing the feasibility of the technique as well as its realized potential for providing continuous depolarization measurements, inter alia.

Non-Steroidal Anti-Inflammatory Drugs in the Aquatic Environment and Bivalves: The State of the Art.

In recent years, contaminants of emerging concern have been reported in several environmental matrices due to advances in analytical methodologies. These anthropogenic micropollutants are detected at residual levels, representing an ecotoxicological threat to aquatic ecosystems. In particular, the pharmacotherapeutic group of non-steroidal anti-inflammatories (NSAIDs) is one of the most prescribed and used, as well as one of the most frequently detected in the aquatic environment. Bivalves have several benefits as a foodstuff, and also as an environment bioindicator species. Therefore, they are regarded as an ideal tool to assess this issue from both ecotoxicological and food safety perspectives. Thus, the control of these residues in bivalves is extremely important to safeguard environmental health, also ensuring food safety and public health. This paper aims to review NSAIDs in bivalves, observing their consumption, physicochemical characteristics, and mechanisms of action; their environmental occurrence in the aquatic environment and aquatic biota; and their effects on the ecosystem and the existent legal framework. A review of the analytical methodologies for the determination of NSAIDs in bivalves is also presented.

A multi-tissue de novo transcriptome assembly and relative gene expression of the vulnerable freshwater salmonid Thymallus ligericus.

Freshwater ecosystems are among the most endangered ecosystems worldwide. While numerous taxa are on the verge of extinction as a result of global changes and direct or indirect anthropogenic activity, genomic and transcriptomic resources represent a key tool for comprehending species' adaptability and serve as the foundation for conservation initiatives. The Loire grayling, Thymallus ligericus, is a freshwater European salmonid endemic to the upper Loire River basin. The species is comprised of fragmented populations that are dispersed over a small area and it has been identified as a vulnerable species. Here, we provide a multi-tissue de novo transcriptome assembly of T. ligericus. The completeness and integrity of the transcriptome were assessed before and after redundancy removal with lineage-specific libraries from Eukaryota, Metazoa, Vertebrata, and Actinopterygii. Relative gene expression was assessed for each of the analyzed tissues, using the de novo assembled transcriptome and a genome-based analysis using the available T. thymallus genome as a reference. The final assembly, with a contig N50 of 1221 and Benchmarking Universal Single-Copy Orthologs (BUSCO) scores above 94%, is made accessible along with structural and functional annotations and relative gene expression of the five tissues (NCBI SRA and FigShare databases). This is the first transcriptomic resource for this species, which provides a foundation for future research on this and other salmonid species that are increasingly exposed to environmental stressors.

Unveiling the power of proteomics in advancing tropical animal health and production.

Proteomics, the large-scale study of proteins in biological systems has emerged as a pivotal tool in the field of animal and veterinary sciences, mainly for investigating local and rustic breeds. Proteomics provides valuable insights into biological processes underlying animal growth, reproduction, health, and disease. In this review, we highlight the key proteomics technologies, methodologies, and their applications in domestic animals, particularly in the tropical context. We also discuss advances in proteomics research, including integration of multi-omics data, single-cell proteomics, and proteogenomics, all of which are promising for improving animal health, adaptation, welfare, and productivity. However, proteomics research in domestic animals faces challenges, such as sample preparation variation, data quality control, privacy and ethical considerations relating to animal welfare. We also provide recommendations for overcoming these challenges, emphasizing the importance of following best practices in sample preparation, data quality control, and ethical compliance. We therefore aim for this review to harness the full potential of proteomics in advancing our understanding of animal biology and ultimately improve animal health and productivity in local breeds of diverse animal species in a tropical context.

CGG repeats in the human FMR1 gene regulate mRNA localization and cellular stress in developing neurons.

The human genome has many short tandem repeats, yet the normal functions of these repeats are unclear. The 5' untranslated region (UTR) of the fragile X messenger ribonucleoprotein 1 (FMR1) gene contains polymorphic CGG repeats, the length of which has differing effects on FMR1 expression and human health, including the neurodevelopmental disorder fragile X syndrome. We deleted the CGG repeats in the FMR1 gene (0CGG) in human stem cells and examined the effects on differentiated neurons. 0CGG neurons have altered subcellular localization of FMR1 mRNA and protein, and differential expression of cellular stress proteins compared with neurons with normal repeats (31CGG). In addition, 0CGG neurons have altered responses to glucocorticoid receptor (GR) activation, including FMR1 mRNA localization, GR chaperone HSP90α expression, GR localization, and cellular stress protein levels. Therefore, the CGG repeats in the FMR1 gene are important for the homeostatic responses of neurons to stress signals.

Piglets performance, nutrient digestibility and gut health in response to feeding Ulva lactuca seaweed supplemented with a recombinant ulvan lyase or a commercial carbohydrase mixture.

Ulva lactuca, a green seaweed, may be an alternative source of nutrients and bioactive compounds for weaned piglets. However, it has a recalcitrant cell wall rich in a sulphated polysaccharide - ulvan - that is indigestible to monogastrics. The objective of this study was to evaluate the effect of dietary incorporation of 7% U. lactuca, combined with carbohydrases supplementation (commercial carbohydrase mixture or recombinant ulvan lyase), on growth performance, nutrient digestibility and gut health parameters (morphology and microbiota) of weaned piglets. The experiment was conducted over 14 days using 40 weaned piglets randomly allocated to one of four experimental diets: a control diet based on wheat-maize-soybean meal, a diet with 7% U. lactuca replacing the control diet (UL), a diet with UL supplemented with 0.005% Rovabio® Excel AP, and a diet with UL supplemented with 0.01% of a recombinant ulvan lyase. The dietary treatments had no major effects on growth performance, nitrogen balance and gut content variables, as well as histological measurements. Contrarily, dry matter and organic matter digestibility decreased with dietary seaweed inclusion, while hemicellulose digestibility increased, suggesting a high fermentability of this cell wall fraction independently of carbohydrases supplementation. Some beneficial microbial populations increased as a consequence of enzymatic supplementation (e.g., Prevotella), while seaweed diets as a whole led to an increased abundance of Shuttleworthia, Anaeroplasma and Lachnospiraceae_NK3A20_group, all related with a healthier gut. It also decreased Lactobacillus when compared to controls, which is possibly related to increased bioavailability of seaweed zinc. This study indicates that, under these experimental conditions, up to 7% dietary U. lactuca has no detrimental effect on piglet growth, despite decreasing acid detergent fibre digestibility. Carbohydrases supplementation of Ulva diets is not required at this incorporation level.

Treatment Strategies for Bile Leak Following Pediatric Liver Transplantation.

There are no standard management protocols for the treatment of bile leak (BL) after liver transplantation. The objective of this study is to describe treatment options for BL after pediatric LT. METHODS: Retrospective analysis (January 2010-March 2023). VARIABLES STUDIED: preoperative data, status at diagnosis, and postoperative outcome. Four groups: observation (n = 9), percutaneous transhepatic cholangiography (PTC, n = 38), ERCP (2), and surgery (n = 27). RESULTS: Nine hundred and thirty-one pediatric liver transplantation (859 LDLT and 72 DDT); 78 (8.3%) patients had BL, all in LDLT. The median (IQR) peritoneal bilirubin (PB) level and fluid-to-serum bilirubin ratio (FSBR) at diagnosis was 14.40 mg/dL (8.5-29), and 10.7 (4.1-23.7). Patients who required surgery for treatment underwent the procedure earlier, at a median of 14 days (IQR: 7-19) versus 22 days for PTC (IQR: 15-27, p = 0.002). PB and FSBR were significantly lower in the observation group. In 11 cases, conservative management had resolution of the BL in an average time of 35 days, and 38 patients underwent PTC in a median time of 22 days (15-27). Twenty-seven (34.6%) patients were reoperated as initial treatment for BL in a median time of 17 days (1-108 days); 25 (33%) patients evolved with biliary stricture, 5 (18.5%) after surgery, and 20 (52.6%) after PTC (p = 0.01). CONCLUSION: Patients with BL who were observed presented significantly lower levels of PB and FSBR versus those who underwent PTC or surgery. Patients treated with PTC presented higher rates of biliary stricture during the follow-up.

A systematic review of recruitment and retention of ethnic minorities and migrants in obesity prevention randomised controlled trials.

BACKGROUND: Participants' recruitment and retention into community-based interventions can be challenging, especially in research involving ethnic minorities and migrants. Despite known challenges, there are limited reviews that probe recruitment and retention strategies involving ethnic minorities and migrants in the Organisation for Economic Cooperation and Development (OECD) countries. This systematic review aimed to measure recruitment and retention rates and identify the barriers and facilitators to effective recruitment and retention of ethnic minorities and migrants in community-based obesity prevention Randomised Control Trials (RCTs) in OECD countries. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Five databases (CINAHL, Cochrane, Embase, Medline and PsychInfo) were searched from January 2000 to March 2022, in addition to Google and Google Scholar. Methodological quality and risk of bias were assessed, and pooled analysis and meta-ethnographic analysis were conducted on the included studies. RESULTS: Twenty-five studies were included in the review. The pooled analysis found a 64% rate of recruitment of ethnic minorities in RCTs, with a retention rate of 71%. Key facilitators identified were-use of multiple communication channels, incentives, recruiting community champions, participant convenience and employing culturally sensitive strategies. Key barriers to participation were limited access to study sites, time constraints, limited trust, perceived fear, and anxiety. CONCLUSION: Findings suggest the importance of undertaking culturally appropriate recruitment and retention strategies to minimise barriers and facilitate effective recruitment and retention of low-income ethnic minorities and migrants in community-based research.

Role of Deep Eutectic Solvent Precursors as Hydrotropes: Unveiling Synergism/Antagonism for Enhanced Kraft Lignin Dissolution.

Lignin holds significant potential as a feedstock for generating valuable aromatic compounds, fuels, and functional materials. However, achieving this potential requires the development of effective dissolution methods. Previous works have demonstrated the remarkable capability of hydrotropes to enhance the aqueous solubility of lignin, an amphiphilic macromolecule. Notably, deep eutectic solvents (DESs) have exhibited hydrotropic behavior, significantly increasing the aqueous solubility of hydrophobic solutes, making them attractive options for lignin dissolution. This study aimed at exploring the influence of hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) on the performance of DESs as hydrotropes for lignin dissolution, while possible dissolution mechanisms in different water/DES compositions were discussed. The capacity of six alcohols (glycerol, ethylene glycol, 1,3-propanediol, 1,4-butanediol, 1,5-pentanediol, and 1,6-hexanediol) and cholinium chloride to enhance the solubility of Kraft lignin in aqueous media was investigated. A correlation between solubility enhancement and the alkyl chain length of the alcohol was observed. This was rationalized upon the competition between hydrotrope-hydrotrope and solute-hydrotrope aggregates with the latter being maximized for 1,4-butanediol. Interestingly, the hydrotropic effect of DESs on lignin solubility is well represented by the independent sum of the dissolving contributions from the corresponding HBAs and HBDs in the diluted region. Conversely, in the concentrated region, the solubility of lignin for a certain hydrotrope concentration was always found to be higher for the pure hydrotropes rather than their combined HBA/HBD counterparts.

The iron(III) coordinating properties of citrate and α-hydroxycarboxylate containing siderophores.

The iron(III) binding properties of citrate and rhizoferrin, a citrate containing siderophore, are compared. Citrate forms many oligonuclear complexes, whereas rhizoferrin forms a single mononuclear complex. The α-hydroxycarboxylate functional group, which is present in both citrate, and rhizoferrin, has a high affinity and selectivity for iron(III) under most biological conditions. The nature of the toxic form of iron found in the blood of patients suffering from many haemoglobinopathies and haemochromatosis is identified as a mixture of iron(III)citrate complexes. The significance of the presence of this iron pool to patients suffering from systemic iron overload is discussed. The wide utilisation of the α-hydroxycarboxylate functional group in siderophore structures is described, as is their photo-induced decarboxylation leading to the release of iron(II) ions. The importance of this facile dissociation to algal iron uptake is discussed.

Large-vessel involvement in ANCA-associated vasculitis: A multicenter case-control study.

OBJECTIVE: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) primarily affects small vessels. Large-vessel involvement (LVI) is rare. We aimed to describe the characteristics of LVI, to identify associated risk factors, and to describe its therapeutic management. METHODS: This multicenter case-control (1:2) study included patients with AAV according to the ACR/EULAR classification and LVI as defined by the Chapel Hill nomenclature, together with controls matched for age, sex, and AAV type. RESULTS: We included 26 patients, 15 (58 %) of whom were men, with a mean age of 56.0 ± 17.1 years. The patients had granulomatosis with polyangiitis (n = 20), or microscopic polyangiitis (n = 6). The affected vessels included the aorta (n = 18; 69 %) supra-aortic trunks (n = 9; 35 %), lower-limb arteries (n = 5; 19 %), mesenteric arteries (n = 5; 19 %), renal arteries (n = 4; 15 %), and upper-limb arteries (n = 2; 8 %). Imaging showed wall thickening (n = 10; 38 %), perivascular inflammation (n = 8; 31 %), aneurysms (n = 5; 19 %), and stenosis (n = 4; 15 %). Comparisons with the control group revealed that LVI was significantly associated with neurological manifestations (OR=3.23 [95 % CI: 1.11-10.01, p = 0.03]), but not with cardiovascular risk factors (OR=0.70 [95 % CI: 0.23-2.21, p = 0.60]), or AAV relapse (OR=2.01 [95 % CI: 0.70-5.88, p = 0.16]). All patients received corticosteroids, in combination with an immunosuppressant in 24 (92 %), mostly cyclophosphamide (n = 10, 38 %) or rituximab (n = 9, 35 %). CONCLUSION: Regardless of distinctions based on vessel size, clinicians should consider LVI as a potential manifestation of AAV, with the aorta commonly affected. The risk of developing LVI appears to be greater for clinical phenotypes of AAV with neurological involvement. Standard AAV treatment can be used to manage LVI.