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The shortage of fresh water resources has made the desalination of seawater a widely adopted technology. Seawater reverse osmosis (SWRO) is the most commonly used method for desalination. The SWRO process is energy-intensive, and most of the energy in SWRO is spent on pressurizing the seawater to overcome the osmotic barrier for producing fresh water. The pressure needed depends on the salinity of the seawater, its temperature, and the membrane surface properties. Membrane compaction occurs in SWRO due to hydraulic pressure application for long-term operations and operating temperature fluctuations due to seasonal seawater changes. This study investigates the effects of short-term feed water temperature increase on the SWRO process in a full-scale pilot with pretreatment and a SWRO installation consisting of a pressure vessel which contains seven industrial-scale 8” diameter spiral wound membrane elements. A SWRO feed water temperature of 40 °C, even for a short period of 7 days, caused a permanent performance decline illustrated by a strong specific energy consumption increase of 7.5%. This study highlights the need for membrane manufacturer data that account for the water temperature effect on membrane performance over a broad temperature range. There is a need to develop new membranes that are more tolerant to temperature fluctuations.

Anionic species are one of the most common pollutants in residual and freshwaters. The presence of anthropogenic anions in water drastically increases the toxicity to living beings. Here, we report the preparation of a new optical active material based on tri(tosylamino)phthalocyanines grafted to ferromagnetic silica nanoparticles for anion detection and removal. The new unsymmetrical phthalocyanines (Pcs) proved to be excellent chemosensors for several anions (AcO−, Br−, Cl−, CN−, F−, H2PO4−, HSO4−, NO2−, NO3−, and OH−) in dimethyl sulfoxide (DMSO). Furthermore, the Pcs were grafted onto magnetic nanoparticles. The resulting novel hybrid material showed selectivity and sensitivity towards CN−, F−, and OH− anions in DMSO with limit of detection (LoD) of ≈4.0 µM. In water, the new hybrid chemosensor demonstrated selectivity and sensitivity for CN− and OH− anions with LoD of ≈0.2 µM. The new hybrids are easily recovered using a magnet, allowing recyclability and reusability, after acidic treatment, without losing the sensing proprieties.

Designing new metallodrugs for anticancer therapy is a driving force in the scientific community. Aiming to contribute to this field, we hereby report the development of a Schiff base (H2L) derived from the condensation of 2-carbaldehyde-8-hydroxyquinoline with 2-hydrazinobenzothiazole and its complexation with transition metal ions. All compounds were characterised by analytical and spectroscopic techniques, which disclosed their structure: [Cu(HL)Cl], [Cu(HL)2], [Ni(HL)(acetate)], [Ni(HL)2], [Ru(HL)Cl(DMSO)], [VO(HL)2] and [Fe(HL)2Cl(H2O)]. Different binding modes were proposed, showing the ligand’s coordination versatility. The ligand proton dissociation constants were determined, and the tested compounds showed high lipophilicity and light sensitivity. The stability of all complexes in aqueous media and their ability to bind to albumin were screened. Based on an antiproliferative in vitro screening, [Ni(HL)(acetate)] and [Ru(HL)Cl(DMSO)] were selected for further studies aiming to investigate their mechanisms of action and therapeutic potential towards colon cancer. The complexes displayed IC50 < 21 μM towards murine (CT-26) and human (HCT-116) colon cancer cell lines. Importantly, both complexes exhibited superior antiproliferative properties compared to the clinically approved 5-fluorouracil. [Ni(HL)(acetate)] induced cell cycle arrest in S phase in CT-26 cells. For [Ru(HL)Cl(DMSO)] this effect was observed in both colon cancer cell lines. Additionally, both compounds significantly inhibited cell migration particularly in the human colon cancer cell line, HCT-116. Overall, the therapeutic potential of both metal complexes was demonstrated.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown origin, in which both genetic and environmental factors are involved. One such environmental factor is vitamin D, a vital hormone that plays a specific function in the immune system homeostasis, acting through a nuclear receptor (VDR) expressed in all immune cells. Several polymorphisms of the gene that encodes this receptor have been described. Though inconsistently, these polymorphisms have been associated with clinical manifestations and SLE development. The aim of this study was to determine the possible association between VDR gene polymorphisms (BsmI, ApaI, TaqI e FokI) and SLE susceptibility and severity, in a cohort of lupus patients from the north of Portugal. A total of 170 patients (F = 155, M = 15; age = 45 ± 13.4 years) with SLE (diagnosed according the American College of Rheumatology criteria) with at least five years of disease evolution and followed in the Autoimmune Disease Clinical Immunology Unit of Centro Hospitalar do Porto were studied. Patients and 192 ethnicity-matched controls were genotyped for BsmI (rs1544410), ApaI (rs7975232), TaqI (rs731236) and FokI (rs2228570) polymorphisms by TaqMan allelic discrimination assay. Disease severity was assessed by SLICC damage score, number of affected organs, number of severe flares and pharmacological history. SLE patients with the CT genotype of FokI polymorphism have a higher SLICC value (p = 0.031). The same result was observed for the group of patients with the TT genotype of TaqI polymorphism (p = 0.046). No differences were observed in VDR genotype between patients and controls. Also, we observed that the other clinical features analysed were not influenced by VDR polymorphisms. Our study confirms a possible role of VDR gene polymorphisms in SLE. A positive association was found between VDR polymorphisms and SLE severity (chronic damage). The presence of CT genotype of FokI and TT genotype of TaqI seems to confer a worse prognosis and may constitute a risk factor for higher long-term cumulative damage in SLE patients.

Background:Systemic lupus erythematosus (SLE) exhibits significant heterogeneity in clinical progression and treatment response, posing challenges in both diagnosis and therapeutic interventions.Objectives:To explore mechanisms underlying relevant clinical endotypes in SLE patients though the integrated analysis of the serum proteomic and metabolomic profiles, employing advanced machine learning approaches.Methods:Proteomic and metabolomic analyses assessed 184 proteins (Olink) and 250 metabolites (NMR, Nightingale) in 100 SLE patients and 27 healthy donors (HD). A comprehensive clinical profile complemented the analysis. Molecular profiles were established using clustering, differential protein expression, pathway enrichment (STRING and Metascape), univariate logistic regression, and advanced machine learning models integrated with clinical data. A validation SLE cohort (n=41) from the University College London Hospital (UCLH) was included.Results:Unsupervised hierarchical clustering of proteomic data identified two patient groups. Forty-seven proteins were elevated in patients within Cluster-1 vs Cluster-2, while 31 proteins were upregulated in Cluster-1 relative to HD. Cluster-1 was characterised by a heightened disease severity and prevalence of cardiovascular (CV) risk factors, including prolonged disease duration, high disease activity (SLEDAI >5), prevalence of lupus nephritis (LN), hypertension, abnormal lipid profile and obesity. Differentially regulated proteins were enriched in pathways associated with nephritis, CV-risk, and immune response.A univariate logistic regression (LR) analysis of metabolomic data between clusters identified a distinctive metabolite signature, which included elevated levels of Acetoacetate, Citrate, Creatinine, and various triglycerides. Moreover, a neural network machine learning model applied to metabolomic and clinical data classified patients into Cluster-1 and -2 with high accuracy (Area Under the Curve=0.77).Hierarchical clustering applied to proteins enriched in both CV and nephritis pathways confirmed the distinct SLE subgroups. Furthermore, correlation analysis between regulated proteins and metabolites identified a positive relationship between creatinine and proteins within the CV [Natriuretic peptide precursor C, Mevalonate kinase, Placenta growth factor, and CD40] and nephritis [CD40 and IL17C] pathways.Finally, comparison of patients with and without LN identified 40 upregulated metabolites, including several CV markers: low-density lipoprotein subsets, fatty acids and apolipoprotein-B. This signature was validated in an external SLE cohort of patients stratified for the presence/absence of LN (UCLH), where 35 out of 40 (87.5%) LN-associated metabolites were also detected, underscoring the robustness of our findings.Conclusion:The present study revealed a distinct molecular signature associated with novel SLE subgroups defined by high disease activity, elevated CV risk and incidence of LN. This integrative approach, harnessing proteomic and metabolomic methodologies, could enhance molecular characterization of novel SLE patient endotypes, refine the understanding of patient clinical profiles and potentially unveil novel disease biomarkers, paving the way for improved therapeutic interventions.Supported by the EU/EFPIA Innovative Medicines Initiative Joint Undertaking 3TR, Projects no. PI21/0591 & CD21/00187 funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union. Project no. RD21/0002/0033 funded by ISCIII and funded by the European Union-NextGeneration EU, via Plan de Recuperación, Transformacion y Resiliencia (PRTR) and MINECO (RYC2021-033828-I, and PID2022-141500OA-I00).REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:None declared.

A simple and straightforward synthesis of diporphyrins and pentaporphyrins is reported here. The supramolecular interactions of the new porphyrin derivatives with C60 and PyC60 (a pyridyl [60]fulleropyrrolidine) were evaluated by absorption and fluorescence titrations in toluene. While no measurable modifications of the absorption and fluorescence spectra were observed upon addition of C60 to the porphyrin derivatives, the addition of PyC60 to the corresponding mono-Zn(II) porphyrins resulted in the formation of Zn(porphyrin)–PyC60 coordination complexes and the binding constants were calculated. Results show that the four free-base porphyrin units in pentaporphyrin 6 have a significant contribution in the stabilization of the 6–PyC60 complex. The crystal and molecular features of the pentaporphyrin Zn5 were unveiled using single-crystal X-ray diffraction studies.

BackgroundAnti-SSA autoantibodies can be differentiated according to their antigenic target proteins as anti-Ro60 (60 kDa) or anti-Ro52 (52 kDa). Anti-SSA(Ro60) are clearly associated with Connective Tissue Diseases (CTD), but the clinical significance of anti-SSA(Ro52) remains unclear.ObjectivesTo analyze the disease phenotype of patients with anti-Ro52 and/or anti-Ro60.MethodsMulticenter, cross-sectional study of anti-Ro52 and/or Ro60 positive patients followed at 10 Rheumatology centers from January 2018 until December 2021. Patients were categorised into 3 groups: group 1 (Ro52+/Ro60-); group 2 (Ro52-/Ro60+); group 3 (Ro52+/Ro60+). Antinuclear antibodies were evaluated by indirect immunofluorescence assay and further screened for anti-extractable nuclear antigen (ENA) antibodies. Demographics and clinical data were compared between the 3 groups, by patients’ medical chart review. Univariate analysis was performed using chi-square, Fisher’s exact or Kruskall-Wallis test. Subsequently, the Bonferroni test was used to identify intergroup differences (level of significance: p<0.0167). Univariate logistic regression was used to calculate the odds ratio with a 95% confidence interval (CI).ResultsWe included 776 patients [female: 83.1%; median age: 59 (46-71) years]. Groups 1, 2 and 3 comprised 31.1%, 32.6%, and 36.3% of the patients, respectively. Characteristics of the groups are presented in Table 1. Anti-Ro52 alone is more frequently associated with non-rheumatic diseases, older age, and men (p<0.05). Among patients with CTD, the diagnosis of systemic lupus erythematosus is 3 and 2 times more prevalent in groups 2 and 3, respectively, than in group 1 [OR 2.8 (95% CI 1.60, 4.97),p=<0.001; OR 2.2 (95% CI 1.28, 3.86), p=0.007]. In group 2, the diagnosis of undifferentiated connective tissue disease is more frequent than in the other groups. The presence of isolated Ro52+ is more frequently associated with inflammatory myositis than in group 2 [OR 0.09 (95% CI 0.01, 0.33), p=<0.001] or group 3 [OR 0.08 (95% CI 0.01, 0.29), p=<0.001]. Group 1 was also more frequently associated with arthritis (p=0.006), interstitial lung disease (p=0.002), and myositis (p=0.009).Table 1.Characteristics of the study population according to the groups of anti-SSA(Ro) positivity.Group 1 (n=241)Group 2 (n=253)Group 3 (n=282)pAge, median (IQR)64 (52-76)56 (44-67)57 (44-69)<0.001Female, n (%)185 (76.8)214 (84.6)246 (87.2)0.005Other anti-ENA, n (%) Anti-La24 (10)50 (19.8)114 (40.4)<0.001 Anti-RNP11 (4.6)23 (9.1)17 (6.0)0.115 Anti-Scl703 (1.2)4 (1.6)6 (2.1)0.146 Anti-Jo17 (3)1 (0.4)3 (1.1)0.070 Anti-Sm1 (0.4)7 (2.8)6 (2.13)0.098Anti-dsDNA11 (4.6)39 (15.4)37 (13.1)<0.001Anti-centromere12 (5)3 (1.2)6 (2.1)0.026Lupus anticoagulant10 (4.2)32 (12.7)23 (8.2)0.008Anti-cardiolipin8 (3.3)10 (3.9)23 (8.2)0.024Anti-β2 glycoprotein 16 (2.5)10 (3.9)10 (3.6)0.736Rheumatoid Factor46 (19.1)44 (17.4)81 (28.7)0.001Anti-CCP11 (4.6)15 (5.9)19 (6.7)0.327Non-rheumatologic disease, n (%)77 (32)35 (13.8)30 (10.6)<0.001 Infections11 (14.3)2 (5.7)1 (3.3)0.192 Neoplasms22 (28.6)3 (8.6)6 (20.0)0.057 Interstitial lung disease5 (6.5)4 (11.4)00.168 Other diseases46 (59.7)25 (71.4)22 (73.3)-Immune-mediated rheumatologic disease, n (%)164 (68.1)218 (86.2)252 (89.4)<0.001 Sjögren syndrome92 (56.1)88 (40.3)150 (59.5)<0.001 Systemic lupus erythematosus20 (12.2)61 (28)59 (23.4)0.001 Systemic sclerosis11 (6.7)7 (3.2)8 (3.2)0.150 Inflammatory myositis15 (9.2)2 (0.9)2 (0.8)<0.001 Rheumatoid arthritis18 (11)17 (7.8)16 (6.4)0.234 Undifferentiated connective tissue disease11 (6.7)35 (16.1)21 (8.3)0.004 Mixed connective tissue disease6 (3.7)6 (2.8)4 (1.6)0.406 Other diseases9 (5.5)8 (3.7)10 (4.0)-ConclusionAnti-Ro52+ alone is frequently found in patients with non-rheumatic diseases. In addition, anti-Ro52+ is also prevalent in patients with CTD and associated with clinical phenotypes that are different from anti-Ro60+.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundAlthough the prognosis has improved in the last decades, Lupus patients still have a 3-fold increase in mortality, compared with the general population.1Lupus nephritis (LN) is one of the most severe manifestations of this complex systemic disease, occurring in up to 60% of patients.Objectives1) To obtain the overall and renal survival curves for a LN cohort; 2) To investigate factors affecting survival; 3) To identify the causes of death in this cohort.MethodsSingle-centre retrospective observational study, including all patients with biopsy-proven LN, followed at UCLH Rheumatology department from 1975 to 2017. Individual clinical files were reviewed to obtain demographic, clinical, laboratory and pathological data. We also recorded data on treatment with corticosteroids, immunosuppressants and antimalarials. We analysed overall survival and renal survival through the Kaplan-Meier method. COX regression analyses were conducted to investigate possible predictors of shorter survival. Significance level was defined at 0.05.Results209 patients were included (table 1). Cumulative survival at 5, 10, 15 and 20 years after the diagnosis of LN was 92%, 86%, 81% and 76%, respectively. Main causes of death were infection (29%), malignancy (21%) and cardiovascular (21%). Regarding progression to end-stage renal disease (ESRD), cumulative renal survival at 5, 10, 15 and 20 years was 94%, 86%, 79% and 72%, respectively. Table 2 shows the predictors of shorter survival identified for this cohort. Image 1 represents the Kaplan-Meier curves according to the factors affecting renal survival.Abstract SAT0419 – Table 1Characterisation of the UCLH cohort of Lupus Nephritis patientsISN/RNP 2003 classificationTotal IIIIIIIVVVIIII+V or IV+V Total, N218389738214209SexF, N (%)218358833211189 (90.4)M, N (%)003950320 (9.6)EthnicityCaucasian, N (%)181948121392 (44)Afro-Caribbean, N (%)17926181668 (32.5)Asian, N (%)03102380549 (23.4)ESRD, N (%)0082631240 (19)Deaths, N (%)0292141138 (18)Age LN diagnosis, mean±SD28.68±11.81Time FU since LN, mean±SD12.95±8.96ISN/RNP: International Society of Nephrology and Renal Pathology Society; F: females; M: males; ESRD: end-stage renal disease; LN: Lupus nephritis; FU: follow-up.Abstract SAT0419 – Table 2Final models for predictors of shorter survival.Multivariable COX regressionHR [95% CI] p Overall survivalESRD 3.002 [1.461–6.171] 0.003No antimalarials2.942 [1.430–6.052] 0.003Ethnicity (Afro-Caribbean)2.656 [1.250–5.642] 0.011Age at LN diagnosis1.039 [1.012–1.067] 0.004Renal survivalHistological class (III, IV or VI) 4.424 [1.542–12.695] 0.006Ethnicity (Afro-Caribbean)3.727 [1.691–8.218] 0.001No antimalarials2.482 [1.237–4.982] 0.011HR: hazard ratio; ESRD: end-stage renal disease; LN: Lupus nephritisConclusionsCumulative survival rates and causes of death for this cohort are comparable with other cohorts of LN. ESRD confers the higher risk for death; African or Caribbean ethnicities and not taking antimalarials predict shorter overall and renal survival among these patients.Reference[1] Yurkovich M, Vostretsova K, Chen W, Avina-Zubieta JA. Overall and cause-specific mortality in patients with systemic lupus erythematosus: a meta-analysis of observational studies. Arthritis Care Res (Hoboken)2014;66(4):608–16.Disclosure of InterestNone declared

BackgroundLupus nephritis (LN) is currently classified according to the 2003 International Society of Nephrology/Renal pathology Society (ISN/RPS) classification system, which is based on histology. Most patients have proliferative lupus nephritis (PLN), which has been the most studied type of LN. Membranous lupus nephritis (MLN) is less frequent, accounting for 10%–20% of the cases. In some patients there is a combination of the two types.ObjectivesTo compare MLN and PLN with respect to demographic, clinical and laboratory characteristics.MethodsSingle-centre retrospective observational study. All patients with biopsy-proven proliferative (class III and IV), membranous (class V) and mixed (class III or IV+V) LN (according to the 2003 ISN/RPS classification), followed at UCLH Rheumatology department from 1975 to 2017, were included. Individual clinical files were reviewed to obtain demographic, clinical, laboratory and pathological data. We also recorded data on treatment with corticosteroids, immunosuppressants and antimalarials. We compared groups using Pearson’s chi-squared test for qualitative variables and Mann-Whitney test for quantitative variables. Renal survival was analysed through the Kaplan-Meier method. Significance level was defined at 0.05.Results187 patients were included (table 1). Age at diagnosis was not significantly different between groups (p=0.474). The groups differ regarding ethnicity – higher proportion of Caucasians with PLN versus higher proportion of Afro-Caribbeans with MLN. Patients with MLN present with higher C3 levels and significantly lower anti-dsDNA levels than the ones with proliferative changes. Thirty-four patients with PLN, 3 with MLN and 2 with mixed nephritis, progressed to end-stage renal disease. Cumulative renal survival rates at 5, 10, 15 and 20 years were 91, 81, 75% and 66% for PLN and 100, 97, 92% and 84% for MLN, respectively (Image 1).Abstract SAT0432 – Table 1Comparison between the three groups of patientsClass III and IVClass VIII+V or IV+Vp Total, N1353814 SexF, N (%)M, N (%)123 (91)12 (9)33 (87)5 (13)11 (79)3 (21)0.303EthnicityCaucasian, N (%)67 (50)12 (32)3 (21)0.044Afro-Caribbean, N (%)35 (26)18 (47)6 (43)Asian, N (%)33 (24)8 (21)5 (36)uPCR at LN diagnosis, median; IQR261.5; 372254.0; 276143.0; 1950.663Creatinine at LN diagnosis, median; IQR73.5; 4054.5; 1773; 580.106Albumin at LN diagnosis, median; IQR32.5; 1331; 935; 40.624C3 at LN diagnosis, median; IQR0.61; 0.340.81; 0.570.64; 0.320.002Anti-dsDNA at LN diagnosis, median; IQR863.0; 1616.7580; 149.5296; 2420.000Ever Low C3, N (%)107 (80)35 (92)11 (79)0.203Ever anti-dsDNA positive, N (%)111 (83)32 (84)12 (86)0.950Ever anti-Sm positive, N (%)25 (19)16 (42)6 (43)0.004Ever anti-RNP positive, N (%)42 (31)19 (50)8 (57)0.030Ever anti-Ro positive, N (%)54 (40)16 (42)10 (71)0.081Ever anti-La positive, N (%)21 (16)3 (8)4 (29)0.168Use of antimalarials, N (%)82 (66)27 (73)9 (69)0.732Use of immunosuppressants, N (%)121 (95)35 (95)14 (100)0.669Use of corticosteroids, N (%)125 (97)36 (95)13 (93)0.668F: females; M: males; uPCR: urinary protein-creatinine ratio; LN: Lupus nephritis; FU: follow-upConclusionsIn spite of presenting in the context of the same autoimmune systemic disease, PLN and MLN appear to be very different entities, showing significant differences regarding serologic profiles and renal survival.Disclosure of InterestNone declared

Hemophagocytic syndrome is an unusual but fatal disorder characterized by pancytopenia and activation of macrophages. We describe one case of acute systemic lupus erythematosus with an unusual presentation of hemophagocytic syndrome not related to infection. The patient presented with pancytopenia related to increasing hemophagocytic activity of histiocytes in the bone marrow. Concomitant class IV World Health Organization lupus nephritis, serositis, high titer of antinuclear factor and positive test for anti-DNA antibody fitted the diagnostic criteria of systemic lupus erythematosus. She also presented with alveolar hemorrhage and lupus myocarditis. She underwent immunosuppressive therapy with recovery from the hemophagocytic syndrome. Therefore, diagnosis of acute lupus hemophagocytic syndrome was made. The clinical presentation, laboratory diagnosis, and management of the patient are discussed and the literature was reviewed and presented, with emphasis on a possible distinct lupus subset, which includes a more aggressive systemic disease with heart involvement.