Time to diagnosis in systemic lupus erythematosus: Associated factors and its impact on damage accrual and mortality. Data from a multi-ethnic, multinational Latin American lupus cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort. METHODS: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality. RESULTS: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200). CONCLUSIONS: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality).

Unveiling the Collaborative Effect at the Cucurbit[8]uril-MoS2 Hybrid Interface for Electrochemical Melatonin Determination.

Host-guest interactions are of paramount importance in supramolecular chemistry and in a wide range of applications. Particularly well known is the ability of cucurbit[n]urils (CB[n]) to selectively host small molecules. We show that the charge transfer and complexation capabilities of CB[n] are retained on the surface of 2D transition metal dichalcogenides (TMDs), allowing the development of efficient electrochemical sensing platforms. We unveil the mechanisms of host-guest recognition between the MoS2 -CB[8] hybrid interface and melatonin (MLT), an important molecular regulator of vital constants in vertebrates. We find that CB[8] on MoS2 organizes the receptor portals perpendicularly to the surface, facilitating MLT complexation. This advantageous adsorption geometry is specific to TMDs and favours MLT electro-oxidation, as opposed to other 2D platforms like graphene, where one receptor portal is closed. This study rationalises the cooperative interaction in 2D hybrid systems to improve the efficiency and selectivity of electrochemical sensing platforms.

Unveiling the Collaborative Effect at the Cucurbit [8] uril-MoS2 Hybrid Interface for Electrochemical Melatonin Determination.

Invited for the cover of this issue are two collaborating groups: one at the Universidad Autónoma de Madrid and the other at the Instituto de Ciencia de Materiales de Madrid. The image depicts Cucurbit[8]uril adsorbed on a transition metal dichalcogenide surface letting the cavity open for complex formation with melatonin and allowing efficient electrochemical sensing. Read the full text of the article at 10.1002/chem.202203244.

Unmasking Retinitis Pigmentosa complex cases by a whole genome sequencing algorithm based on open-access tools: hidden recessive inheritance and potential oligogenic variants.

BACKGROUND: Retinitis Pigmentosa (RP) is a clinically and genetically heterogeneous disorder that results in inherited blindness. Despite the large number of genes identified, only ~ 60% of cases receive a genetic diagnosis using targeted-sequencing. The aim of this study was to design a whole genome sequencing (WGS) based approach to increase the diagnostic yield of complex Retinitis Pigmentosa cases. METHODS: WGS was conducted in three family members, belonging to one large apparent autosomal dominant RP family that remained unsolved by previous studies, using Illumina TruSeq library preparation kit and Illumina HiSeq X platform. Variant annotation, filtering and prioritization were performed using a number of open-access tools and public databases. Sanger sequencing of candidate variants was conducted in the extended family members. RESULTS: We have developed and optimized an algorithm, based on the combination of different open-access tools, for variant prioritization of WGS data which allowed us to reduce significantly the number of likely causative variants pending to be manually assessed and segregated. Following this algorithm, four heterozygous variants in one autosomal recessive gene (USH2A) were identified, segregating in pairs in the affected members. Additionally, two pathogenic alleles in ADGRV1 and PDZD7 could be contributing to the phenotype in one patient. CONCLUSIONS: The optimization of a diagnostic algorithm for WGS data analysis, accompanied by a hypothesis-free approach, have allowed us to unmask the genetic cause of the disease in one large RP family, as well as to reassign its inheritance pattern which implies differences in the clinical management of these cases. These results contribute to increasing the number of cases with apparently dominant inheritance that carry causal mutations in recessive genes, as well as the possible involvement of various genes in the pathogenesis of RP in one patient. Moreover, our WGS-analysis approach, based on open-access tools, can easily be implemented by other researchers and clinicians to improve the diagnostic yield of additional patients with inherited retinal dystrophies.

Serum Phospholipid Fatty Acids and Mammographic Density in Premenopausal Women.

BACKGROUND: The role of fatty acids (FAs) on mammographic density (MD) is unclear, and available studies are based on self-reported dietary intake. OBJECTIVES: This study assessed the association between specific serum phospholipid fatty acids (PLFAs) and MD in premenopausal women. METHODS: The cross-sectional study DDM-Madrid recruited 1392 Spanish premenopausal women, aged 39-50 y, who attended a screening in a breast radiodiagnosis unit of Madrid City Council. Women completed lifestyle questionnaires and FFQs. Percentage MD was estimated using a validated computer tool (DM-Scan), and serum PLFA percentages were measured by GC-MS. Multivariable linear regression models were used to quantify the association of FA tertiles with MD. Models were adjusted for age, education, BMI, waist circumference, parity, oral contraceptive use, previous breast biopsies, and energy intake, and they were corrected for multiple testing. RESULTS: Women in the third tertile of SFAs showed significantly higher MD compared with those in the first tertile (ßT3vsT1 = 7.53; 95% CI: 5.44, 9.61). Elevated relative concentrations of palmitoleic (ßT3vsT1 = 3.12; 95% CI: 0.99, 5.25) and gondoic (ßT3vsT1 = 2.67; 95% CI: 0.57, 4.77) MUFAs, as well as high relative concentrations of palmitelaidic (ßT3vsT1 = 5.22; 95% CI: 3.15, 7.29) and elaidic (ßT3vsT1 = 2.69; 95% CI: 0.59, 4.79) trans FAs, were also associated with higher MD. On the contrary, women with elevated relative concentrations of n-6 (ω-6) linoleic (ßT3vsT1 = -5.49; 95% CI; -7.62, -3.35) and arachidonic (ßT3vsT1 = -4.68; 95% CI: -6.79, -2.58) PUFAs showed lower MD. Regarding desaturation indices, an elevated palmitoleic to palmitic ratio and a low ratio of oleic to steric and arachidonic to dihomo-γ-linolenic acids were associated with higher MD. CONCLUSIONS: Spanish premenopausal women with high relative concentrations of most SFAs and some MUFAs and trans FAs showed an increased MD, whereas those with high relative concentrations of some n-6 PUFAs presented lower density. These results, which should be confirmed in further studies, underscore the importance of analyzing serum FAs individually.

A Multi-Strategy Sequencing Workflow in Inherited Retinal Dystrophies: Routine Diagnosis, Addressing Unsolved Cases and Candidate Genes Identification.

The management of unsolved inherited retinal dystrophies (IRD) cases is challenging since no standard pipelines have been established. This study aimed to define a diagnostic algorithm useful for the diagnostic routine and to address unsolved cases. Here, we applied a Next-Generation Sequencing-based workflow, including a first step of panel sequencing (PS) followed by clinical-exome sequencing (CES) and whole-exome sequencing (WES), in 46 IRD patients belonging to 42 families. Twenty-six likely causal variants in retinal genes were found by PS and CES. CES and WES allowed proposing two novel candidate loci (WDFY3 and a X-linked region including CITED1), both abundantly expressed in human retina according to RT-PCR and immunohistochemistry. After comparison studies, PS showed the best quality and cost values, CES and WES involved similar analytical efforts and WES presented the highest diagnostic yield. These results reinforce the relevance of panels as a first step in the diagnostic routine and suggest WES as the next strategy for unsolved cases, reserving CES for the simultaneous study of multiple conditions. Standardizing this algorithm would enhance the efficiency and equity of clinical genetics practice. Furthermore, the identified candidate genes could contribute to increase the diagnostic yield and expand the mutational spectrum in these disorders.

Differential pulse voltammetric determination of the carcinogenic diamine 4,4'-oxydianiline by electrochemical preconcentration on a MoS2 based sensor.

An electrochemical sensor for the carcinogen 4,4'-oxydianiline (Oxy) is described. The method is based on the ability of MoS2 nanosheets to preconcentrate Oxy. A glassy carbon electrode (GCE) was covered, by drop-casting, with MoS2 nanosheets that were obtained by exfoliation. X-Ray photoemission spectroscopy indicates that Oxy accumulates on the MoS2 nanosheets through an electropolymerization process similar to that reported for aniline. Both electrochemical impedance spectroscopy and atomic force microscopy were used to characterize the electrode surface at the different stages of device fabrication. Employing the current measured at +0.27 V vs. Ag/AgCl after Oxy adsorption, the modified GCE enables the voltammetric detection of Oxy at 80 nM levels with relative errors and relative standard deviations of <8.3 and <5.6%, respectively, at all the concentrations studied. The method was applied to the selective determination of Oxy in spiked river water samples. Very good selectivity and recoveries of around 95% in average are found. Graphical abstractSchematic representation of 4,4-oxydianiline electrochemical polymerization and preconcentration onto molybdenum disulfide nanosheets for the diamine determination in river waters.

Synergistic effect of MoS2 and diamond nanoparticles in electrochemical sensors: determination of the anticonvulsant drug valproic acid.

The authors describe an electrochemical sensor based on the use of diamond nanoparticles (DNPs) and molybdenum disulfide (MoS2) platelets. The sensor was applied to the voltammetric determination of the anticonvulsant valproic acid which was previously derivatized with ferrocene. The MoS2 platelets were obtained by an exfoliation method, and the DNPs were directly dispersed in water and subsequently deposited on a glassy carbon electrode (GCE). The sensor response was optimized in terms of the solvent employed for dispersing the MoS2 nanomaterial and the method for modifying the GCE. Sensors consisting of a first layer of MoS2 dispersed in ethanol/water and a second layer of DNPs give better response. The single steps of sensor construction were characterized by atomic force microscopy and electrochemical impedance spectroscopy. The differential pulse voltammetric response of the GCE (measured at +0.18 V vs. Ag/AgCl) was compared to that of sensors incorporating only one of the nanomateriales (DNPs or MoS2). The formation of a hybrid MoS2-DNP structure clearly improves performance. The GCE containing both nanomaterials exhibits high sensitivity (740 µA ⋅ mM-1 ⋅ cm-2), a 0.27 µM detection limit, and an 8% reproducibility (RSD). The sensor retained 99% of its initial response after 45 days of storage. Graphical abstract Electrochemical sensor by co-immobilization of MoS2 and diamond nanoparticles (DNP). The formation of a hybrid MoS2-DNP structure enhances the performance of the sensor towards valproic acid derivatized with a ferrocene group, when compared with sensors incorporating only DNP or MoS2.

Novel RP1 mutations and a recurrent BBS1 variant explain the co-existence of two distinct retinal phenotypes in the same pedigree.

BACKGROUND: Molecular diagnosis of Inherited Retinal Dystrophies (IRD) has long been challenging due to the extensive clinical and genetic heterogeneity present in this group of disorders. Here, we describe the clinical application of an integrated next-generation sequencing approach to determine the underlying genetic defects in a Spanish family with a provisional clinical diagnosis of autosomal recessive Retinitis Pigmentosa (arRP). RESULTS: Exome sequencing of the index patient resulted in the identification of the homozygous BBS1 p.M390R mutation. Sanger sequencing of additional members of the family showed lack of co-segregation of the p.M390R variant in some individuals. Clinical reanalysis indicated co-ocurrence of two different phenotypes in the same family: Bardet-Biedl syndrome in the individual harboring the BBS1 mutation and non-syndromic arRP in extended family members. To identify possible causative mutations underlying arRP, we conducted disease-targeted gene sequencing using a panel of 26 IRD genes. The in-house custom panel was validated using 18 DNA samples known to harbor mutations in relevant genes. All variants were redetected, indicating a high mutation detection rate. This approach allowed the identification of two novel heterozygous null mutations in RP1 (c.4582_4585delATCA; p.I1528Vfs*10 and c.5962dupA; p.I1988Nfs*3) which co-segregated with the disease in arRP patients. Additionally, a mutational screening in 96 patients of our cohort with genetically unresolved IRD revealed the presence of the c.5962dupA mutation in one unrelated family. CONCLUSIONS: The combination of molecular findings for RP1 and BBS1 genes through exome and gene panel sequencing enabled us to explain the co-existence of two different retinal phenotypes in a family. The identification of two novel variants in RP1 suggests that the use of panels containing the prevalent genes of a particular population, together with an optimized data analysis pipeline, is an efficient and cost-effective approach that can be reliably implemented into the routine diagnostic process of diverse inherited retinal disorders. Moreover, the identification of these novel variants in two unrelated families supports the relatively high prevalence of RP1 mutations in Spanish population and the role of private mutations for commonly mutated genes, while extending the mutational spectrum of RP1.

'Conceptualizations and implementation of user engagement in Weather and climate services: A climateservicesproviders' perspective by Di Fant, V., del Pozo, M., Gulikers, J. and Paparrizos, S.

Weather and Climate Information Services are increasingly used worldwide to facilitate the provision of information to their intended users. Despite this, the definition, classification and evaluation of climate services remains highly debated, particularly regarding user engagement. High forms of user engagement like co-production and co-creation are the least understood. This study looks at three case studies to clarify the current understanding of user engagement in climate services. The research identifies explicit and implicit conceptualizations of user engagement by service providers and characterizes their implementation. The study confirms the current lack of clarity for providers regarding the terminology used to describe user engagement in climate services, which calls for a different understanding of user engagement that allows to better embrace its complexity. Furthermore, our findings reveal that the highest form of user engagement occurred in the case study where there was a shared understanding of how service providers conceptualized user engagement. This conceptualization was aligned with the actual user engagement strategies implemented in the project. This stresses the importance of a shared understanding of user engagement terminology. Finally, the same service is often found to have implemented different user engagement levels at different stages and for different elements of the products. This brings up the issue of how to best describe user engagement in such situations. We recommend embracing the multi-faceted nature of user engagement in climate services by characterizing different elements and stages differently.

Long-read sequencing improves the genetic diagnosis of retinitis pigmentosa by identifying an Alu retrotransposon insertion in the EYS gene.

BACKGROUND: Biallelic variants in EYS are the major cause of autosomal recessive retinitis pigmentosa (arRP) in certain populations, a clinically and genetically heterogeneous disease that may lead to legal blindness. EYS is one of the largest genes (~ 2 Mb) expressed in the retina, in which structural variants (SVs) represent a common cause of disease. However, their identification using short-read sequencing (SRS) is not always feasible. Here, we conducted targeted long-read sequencing (T-LRS) using adaptive sampling of EYS on the MinION sequencing platform (Oxford Nanopore Technologies) to definitively diagnose an arRP family, whose affected individuals (n = 3) carried the heterozygous pathogenic deletion of exons 32-33 in the EYS gene. As this was a recurrent variant identified in three additional families in our cohort, we also aimed to characterize the known deletion at the nucleotide level to assess a possible founder effect. RESULTS: T-LRS in family A unveiled a heterozygous AluYa5 insertion in the coding exon 43 of EYS (chr6(GRCh37):g.64430524_64430525ins352), which segregated with the disease in compound heterozygosity with the previously identified deletion. Visual inspection of previous SRS alignments using IGV revealed several reads containing soft-clipped bases, accompanied by a slight drop in coverage at the Alu insertion site. This prompted us to develop a simplified program using grep command to investigate the recurrence of this variant in our cohort from SRS data. Moreover, LRS also allowed the characterization of the CNV as a ~ 56.4kb deletion spanning exons 32-33 of EYS (chr6(GRCh37):g.64764235_64820592del). The results of further characterization by Sanger sequencing and linkage analysis in the four families were consistent with a founder variant. CONCLUSIONS: To our knowledge, this is the first report of a mobile element insertion into the coding sequence of EYS, as a likely cause of arRP in a family. Our study highlights the value of LRS technology in characterizing and identifying hidden pathogenic SVs, such as retrotransposon insertions, whose contribution to the etiopathogenesis of rare diseases may be underestimated.

Whole-exome sequencing identifies novel compound heterozygous mutations in USH2A in Spanish patients with autosomal recessive retinitis pigmentosa.

PURPOSE: Retinitis pigmentosa (RP) is an inherited retinal dystrophy characterized by extreme genetic and clinical heterogeneity. Thus, the diagnosis is not always easily performed due to phenotypic and genetic overlap. Current clinical practices have focused on the systematic evaluation of a set of known genes for each phenotype, but this approach may fail in patients with inaccurate diagnosis or infrequent genetic cause. In the present study, we investigated the genetic cause of autosomal recessive RP (arRP) in a Spanish family in which the causal mutation has not yet been identified with primer extension technology and resequencing. METHODS: We designed a whole-exome sequencing (WES)-based approach using NimbleGen SeqCap EZ Exome V3 sample preparation kit and the SOLiD 5500×l next-generation sequencing platform. We sequenced the exomes of both unaffected parents and two affected siblings. Exome analysis resulted in the identification of 43,204 variants in the index patient. All variants passing filter criteria were validated with Sanger sequencing to confirm familial segregation and absence in the control population. In silico prediction tools were used to determine mutational impact on protein function and the structure of the identified variants. RESULTS: Novel Usher syndrome type 2A (USH2A) compound heterozygous mutations, c.4325T>C (p.F1442S) and c.15188T>G (p.L5063R), located in exons 20 and 70, respectively, were identified as probable causative mutations for RP in this family. Family segregation of the variants showed the presence of both mutations in all affected members and in two siblings who were apparently asymptomatic at the time of family ascertainment. Clinical reassessment confirmed the diagnosis of RP in these patients. CONCLUSIONS: Using WES, we identified two heterozygous novel mutations in USH2A as the most likely disease-causing variants in a Spanish family diagnosed with arRP in which the cause of the disease had not yet been identified with commonly used techniques. Our data reinforce the clinical role of WES in the molecular diagnosis of highly heterogeneous genetic diseases where conventional genetic approaches have previously failed in achieving a proper diagnosis.

2D-ReS2 & diamond nanoparticles-based sensor for the simultaneous determination of sunset yellow and tartrazine in a multiple-pulse amperometry FIA system.

We present a flow injection system with a multiple pulse amperometric detection (FIA-MPA)-based methodology for the simultaneous analysis of sunset yellow and tartrazine. As transducer, we have developed a novel electrochemical sensor based on the synergistic effect of ReS2 nanosheets and diamond nanoparticles (DNPs). Among several transition dichalcogenides for the sensor development, we have selected ReS2 nanosheets since it yields a better response towards both colourants. Scanning probe microscopy characterization shows that the surface sensor is composed by scattered and stacked ReS2 flakes and large aggregates of DNPs. With this system, the gap between the oxidation potential values of sunset yellow and tartrazine is wide enough to allow the simultaneous determination of both dyes. Under the optimum potential pulse conditions (0.8 and 1.2 V) during 250 ms, a flow rate of 3 mL/min and a volume injection of 250 µL, detection limits of 3.51 × 10-7 M and 2.39 × 10-7 M for sunset yellow and tartrazine, respectively, were obtained. This method exhibits good accuracy and precision with Er minor than 13% and RSD lower than 8% with a sampling frequency of 66 samples per hour. Pineapple jelly samples were analyzed by the standard addition method, obtaining 53.7 mg/kg and 29.0 mg/kg of sunset yellow and tartrazine, respectively. From the analysis of fortified samples, recoveries of 94% and 105% were obtained.

MoS2 quantum dots-based optical sensing platform for the analysis of synthetic colorants. Application to quinoline yellow determination.

In this work, a novel fluorescence sensor has been designed to solve the actual need of new fast and inexpensive sensing platforms for the analysis of synthetic colorants. It is based on MoS2 quantum dots obtained by a hydrothermal method and incorporated as fluorophore into the matrix of PVC membranes, which are deposited on quartz substrates by spin-coating. It was proven, as in these conditions, MoS2 quantum dots maintain the fluorescent properties that they present in solution. Experiments carried out in solution displayed a maximum emission when they were excited under 310 nm. This initial fluorescence decreases linearly in presence of increasing concentrations of various synthetic colorants namely quinoline yellow, tartrazine, sunset yellow, allura red, ponceau 4R and carmoisine. The two possible mechanisms that can explain this quenching effect, colorants absorbing photons emitted by quantum dots and/or competing with the nanomaterial for photons coming from the excitation source, were evaluated. The most pronounced effect was observed with quinoline yellow, as a result of a mixed mechanism. The optimized methodology developed for the determination of quinoline yellow showed a linear concentration range between 5.4 and 55.0 µg with a limit of detection of 1.6 µg. The sensor was applied to the determination of quinoline yellow in a food colour paste obtaining results in good agreement with those obtained by HPLC-UV-vis measurements.

Electrochemical sensor based on the synergy between Cucurbit[8]uril and 2D-MoS2 for enhanced melatonin quantification.

We present the development of an electrochemical sensor towards melatonin determination based on the synergistic effect between MoS2 nanosheets and cucurbit[8]uril. For the sensor construction cucurbit[8]uril suspensions were prepared in water, and MoS2 nanosheets were obtained by liquid exfoliation in ethanol:water. The sensing platform was topographically characterized by Atomic Force Microscopy. Electrochemical Impedance Spectroscopy experiments allowed us to study the charge transfer process during melatonin oxidation. Moreover, stoichiometry of the resulting complex has also been determined. After the optimization of the sensor construction and the experimental variables involved in the Differential Pulse Voltammetric response of melatonin, detection limit of 3.80 × 10-7 M, relative errors minor than 3.8% and relative standard deviation lower than 4.4% were obtained. The proposed sensor has been successfully applied to melatonin determination in pharmaceutical and biological samples as human urine and serum, with very good recoveries ranging from 90 to 102%.

Expanding the phenotype of THRB: a range of macular dystrophies as the major clinical manifestations in patients with a dominant splicing variant.

Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders that often severely impair vision. Some patients manifest poor central vision as the first symptom due to cone-dysfunction, which is consistent with cone dystrophy (COD), Stargardt disease (STGD), or macular dystrophy (MD) among others. Here, we aimed to identify the genetic cause of autosomal dominant COD in one family. WGS was performed in 3 affected and 1 unaffected individual using the TruSeq Nano DNA library kit and the NovaSeq 6,000 platform (Illumina). Data analysis identified a novel spliceogenic variant (c.283 + 1G>A) in the thyroid hormone receptor beta gene (THRB) as the candidate disease-associated variant. Further genetic analysis revealed the presence of the same heterozygous variant segregating in two additional unrelated dominant pedigrees including 9 affected individuals with a diagnosis of COD (1), STGD (4), MD (3) and unclear phenotype (1). THRB has been previously reported as a causal gene for autosomal dominant and recessive thyroid hormone resistance syndrome beta (RTHß); however, none of the IRD patients exhibited RTHß. Genotype-phenotype correlations showed that RTHß can be caused by both truncating and missense variants, which are mainly located at the 3' (C-terminal/ligand-binding) region, which is common to both THRB isoforms (TRß1 and TRß2). In contrast, the c.283 + 1G>A variant is predicted to disrupt a splice site in the 5'-region of the gene that encodes the N-terminal domain of the TRß1 isoform protein, leaving the TRß2 isoform intact, which would explain the phenotypic variability observed between RTHß and IRD patients. Interestingly, although monochromacy or cone response alterations have already been described in a few RTHß patients, herein we report the first genetic association between a pathogenic variant in THRB and non-syndromic IRDs. We thereby expand the phenotype of THRB pathogenic variants including COD, STGD, or MD as the main clinical manifestation, which also reflects the extraordinary complexity of retinal functions mediated by the different THRB isoforms.

Anti-malarials exert a protective effect while Mestizo patients are at increased risk of developing SLE renal disease: data from a Latin-American cohort.

OBJECTIVE: To examine the role of ethnicity and the use of anti-malarials (protective) on lupus renal disease. METHODS: A nested case-control study (1:2 proportion, n = 265 and 530) within GLADEL's (Grupo Latino Americano De Estudio de Lupus) longitudinal inception cohort was carried out. The end-point was ACR renal criterion development after diagnosis. Cases and controls were matched for follow-up time (end-point or a comparable time, respectively). Renal disease predictors were examined by univariable and multivariable analyses. Additional analyses were done to determine if the protective effect of anti-malarials persisted after adjusting for intake-associated confounders. RESULTS: Of the cases, 233 (87.9%) were women; their mean (s.d.) age at diagnosis was 28.0 (11.9) years and their median (Q3-Q1 interquartile range) follow-up time for cases and controls was 8.3 months (Q3-Q1: 23.5); 56.6% of the cases and 74.3% of the controls were anti-malarial users. Mestizo ethnicity [odds ratio (OR) 1.72, 95% CI 1.19, 2.48] and hypertension (OR 2.26, 95% CI 1.38, 3.70) were independently associated with a higher risk of renal disease, whereas anti-malarial use (OR 0.39, 95% CI 0.26, 0.58), older age at disease onset (OR 0.98, 95% CI 0.96, 0.99) and female gender (OR 0.56, 95% CI 0.32, 0.99) were negatively associated with such occurrence. After adjusting for variables associated with their intake, the protective effect of anti-malarials on renal disease occurrence persisted (OR 0.38, 95% CI 0.25, 0.58). CONCLUSION: Mestizo patients are at increased risk of developing renal disease, whereas anti-malarial use protects patients from such an occurrence.

Chitosan sulfate-lysozyme hybrid hydrogels as platforms with fine-tuned degradability and sustained inherent antibiotic and antioxidant activities.

The control of the properties and biological activities of chitosan-lysozyme hybrid hydrogels to exploit their interesting biomedical applications depends largely on the chitosan acetylation pattern, a difficult parameter to control. Herein, we have prepared sulfated chitosan-lysozyme hydrogels as versatile platforms with fine-tuned degradability and persistent bactericidal and antioxidant properties. The use of chitosan sulfates instead of chitosan has the advantage that the rate and mechanisms of lysozyme release, as well as antibacterial and antioxidant activities, depend on the sulfation profile, a structural parameter that is easily controlled by simple chemical modifications. Thus, while 6-O-sulfated chitosan hydrogels allow the release of loaded lysozyme in a short time (60% in 24 h), due to a high rate of degradation that allows rapid antibiotic and antioxidant activities, in 3-O-sulfated systems there is a slow release of lysozyme (80% in 21 days), resulting in long-lasting antibiotic and antioxidant activities.