Sulfate radical anion: Laser flash photolysis study and application in water disinfection and decontamination

[EN] Sulfate radicals (SO4 center dot-) reactivity against gram-negative (E. coli) and gram-positive (E. faecalis) bacteria and Contaminants of Emerging Concern (CECs) (Diclofenac-DCF, Sulfamethoxazole-SMX and Trimethoprim-TMP) was investigated through laser flash photolysis (LFP) technique. Analysis of the lifetime of SO4 center dot- in presence of cell-wall compounds of bacteria and CECs allowed determining reactivity of SO4 center dot- towards these compounds. Results showed that SO4 center dot- reacts with common cell-wall components through H-abstraction mechanism (kSO4 center dot ¿ 109 M-1s-1 were found using aromatic amino acids (AAA) only present in Porins of the gram-negative outer-membrane. The intermediates detected from the reaction of SO4 center dot- with the AAA confirmed the involvement of electron transfer processes. Moreover, kSO4 center dot ¿ values determined for DCF, TMP and SMX also agreed with an electron transfer mechanism. Interestingly, bacteria and CECs removal at pilot plant scale by UV-C/SO4 center dot- is in accordance with the kSO4 center dot ¿ obtained using the LFP: E. coli > E. faecalis and DCF > TMP approximately equal to SMX.This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie Grant Agreement No 765860 (AQUAlity) . Authors also acknowledge the Spanish Ministry of Science and Innovation (Projects PID2019-110441RB-C32 and PID2019-110441RB-C33) . PhD Scholarship from CONACYT for J. Flores-Garcia (709358) is acknowledged.Berruti, I.; Polo-López, MI.; Oller, I.; Flores, J.; Marín García, ML.; Bosca Mayans, F. (2022). Sulfate radical anion: Laser flash photolysis study and application in water disinfection and decontamination. Applied Catalysis B Environmental. 315:1-12. https://doi.org/10.1016/j.apcatb.2022.12151911231

Biradical vs singlet oxygen photogeneration in suprofen cholesterol systems

Cholesterol (Ch) is an important lipidic building block and a target for oxidative degradation, which can be induced via free radicals or singlet oxygen (1O2). Suprofen (SP) is a nonsteroidal anti-inflammatory drug that contains the 2-benzoylthiophene (BZT) chromophore and has a π,π* lowest triplet excited state. In the present work, dyads (S)- and (R)-SP-α-Ch (1 and 2), as well as (S)-SP-β-Ch (3) have been prepared from β- or α-Ch and SP to investigate the possible competition between photogeneration of biradicals and 1O2, the key mechanistic steps in Ch photooxidation. Steady-state irradiation of 1 and 2 was performed in dichloromethane, under nitrogen, through Pyrex, using a 400 W medium pressure mercury lamp. The spectral analysis of the separated fractions revealed formation of two photoproducts 4 and 5, respectively. By contrast, under the same conditions, 3 did not give rise to any isolable Ch-derived product. These results point to an intramolecular hydrogen abstraction in 1 and 2 from the C7 position of Ch and subsequent C C coupling of the generated biradicals. Interestingly, 2 was significantly more photoreactive than 1 indicating a clear stereodifferentiation in the photochemical behavior. Transient absorption spectra obtained for 1 3 were very similar and matched that described for the SP triplet excited state (typical bands with maxima at ca. 350 nm and 600 nm). Direct kinetic analysis of the decay traces at 620 nm led to determination of triplet lifetimes that were ca. 4.1 μs for 1 and 2 and 5.8 μs for 3. From these data, the intramolecular quenching rate constants in 1 and 2 were determined as 0.78 × 105 s−1. The capability of dyads 1 3 to photosensitize the production of singlet oxygen was assessed by time-resolved near infrared emission studies in dichloromethane using perinaphthenone as standard. The quantum yields (ΦΔ) were 0.52 for 1 and 2 and 0.56 for 3. In conclusion, SP-α-Ch dyads are unique in the sense that they can be used to photogenerate both biradicals and singlet oxygen, thus being able to initiate Ch oxidation from their triplet excited states following either of the two competing mechanistic pathways.Financial support from the Generalitat Valenciana (Prometeo Program), the Spanish Government (CTQ2014-54729-C2-2-P and FPU fellowship for F.P.) and the Carlos III Institute of Health (Grant RIRAAF, RETICS program and Miguel Servet Contract CP11/00154 for I. A.) is gratefully acknowledged.Palumbo, F.; Bosca Mayans, F.; Morera Bertomeu, IM.; Andreu Ros, MI.; Miranda Alonso, MÁ. (2016). Biradical vs singlet oxygen photogeneration in suprofen cholesterol systems. Beilstein Journal of Organic Chemistry. 12:1196-1202. https://doi.org/10.3762/bjoc.12.115S119612021

Revision of the risk of secondary leukaemia after mitoxantrone in multiple sclerosis populations is required

The objective in this paper is to compare the cumulative incidence and incidence density of therapy-related acute myeloid leukaemia in two cohorts of patients with multiple sclerosis treated with mitoxantrone, and with previously reported data in the literature. Six new cases of acute myeloid leukaemia were observed by prospectively following two Spanish series of 142 and 88 patients with worsening relapsing multiple sclerosis and secondary-progressive disease treated with mitoxantrone. A literature review shows 32 further cases of acute myeloid leukaemia reported, 65.6% of which are therapy-related acute promyelocytic leukaemia. Five cases in the cohorts fulfilled the diagnostic criteria for acute promyelocytic leukaemia, and one patient was diagnosed with pre-B-acute lymphoblastic leukaemia. Acute myeloid leukaemia latency after mitoxantrone discontinuation was 1 to 45 months. The accumulated incidence and incidence density was 2.82% and 0.62%, respectively, in the Valencian cohort, and 2.27% and 0.44% in the Catalonian cohort. In the only seven previously reported series, the accumulated incidence varied from 0.15% to 0.80%. The real incidence of acute myeloid leukaemia after mitoxantrone therapy in the multiple sclerosis population could be higher as evidenced by the growing number of cases reported. Haematological monitoring should continue for at least 5 years after the last dose of mitoxantrone. These data stress the necessity of re-evaluating this ris

Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

(1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case-control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March-July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3-5.9), occupational risk (OR: 2.9; 95%CI: 1.8-4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2-2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09-0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study

Background Large real-world-evidence studies are required to confirm the durability of response, effectiveness, and safety of ustekinumab in Crohn’s disease (CD) patients in real-world clinical practice. Methods A retrospective, multicentre study was conducted in Spain in patients with active CD who had received ≥1 intravenous dose of ustekinumab for ≥6 months. Primary outcome was ustekinumab retention rate; secondary outcomes were to identify predictive factors for drug retention, short-term remission (week 16), loss of response and predictive factors for short-term efficacy and loss of response, and ustekinumab safety. Results A total of 463 patients were included. Mean baseline Harvey-Bradshaw Index was 8.4. A total of 447 (96.5%) patients had received prior biologic therapy, 141 (30.5%) of whom had received ≥3 agents. In addition, 35.2% received concomitant immunosuppressants, and 47.1% had ≥1 abdominal surgery. At week 16, 56% had remission, 70% had response, and 26.1% required dose escalation or intensification; of these, 24.8% did not subsequently reduce dose. After a median follow-up of 15 months, 356 (77%) patients continued treatment. The incidence rate of ustekinumab discontinuation was 18% per patient-year of follow-up. Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation, while a maintenance schedule every 12 weeks had a lower risk; neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk. Fifty adverse events were reported in 39 (8.4%) patients; 4 of them were severe (2 infections, 1 malignancy, and 1 fever). Conclusions Ustekinumab is effective and safe as short- and long-term treatment in a refractory cohort of CD patients in real-world clinical practice

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements

Sulfate radical anion: Laser flash photolysis study and application in water disinfection and decontamination

Sulfate radicals (SO) reactivity against gram-negative (E. coli) and gram-positive (E. faecalis) bacteria and Contaminants of Emerging Concern (CECs) (Diclofenac-DCF, Sulfamethoxazole-SMX and Trimethoprim-TMP) was investigated through laser flash photolysis (LFP) technique. Analysis of the lifetime of SO in presence of cell-wall compounds of bacteria and CECs allowed determining reactivity of SO towards these compounds. Results showed that SO reacts with common cell-wall components through H-abstraction mechanism (k 10 Ms were found using aromatic amino acids (AAA) only present in Porins of the gram-negative outer-membrane. The intermediates detected from the reaction of SO with the AAA confirmed the involvement of electron transfer processes. Moreover, k values determined for DCF, TMP and SMX also agreed with an electron transfer mechanism. Interestingly, bacteria and CECs removal at pilot plant scale by UV-C/SO is in accordance with the k obtained using the LFP: E. coli > E. faecalis and DCF > TMP ≅ SMX.This work is part of a project that has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No 765860 (AQUAlity). Authors also acknowledge the Spanish Ministry of Science and Innovation (Projects PID2019–110441RB-C32 and PID2019–110441RB-C33). PhD Scholarship from CONACYT for J. Flores-Garcia (709358) is acknowledged

Solvent effects in hydrogen abstraction from cholesterol by benzophenone triplet excited state

[EN] Hydrogen abstraction from the C-7 position of cholesterol (Ch) by triplet excited benzophenone (BZP) exhibits remarkable solvent-dependence in product studies. Kinetic measurements on the intramolecular version of the process in dyads containing covalently linked Ch and BZP units reveal important solvent effects and significant stereodifferentiation.Financial support from the MICINN (Grants CTQ2009-13699 and CTQ2010-19909), from the Generalitat Valenciana (GV/2009/104) and from Carlos III Institute of Health (Grant RIRAAF, RETICS program) is gratefully acknowledged. Dedicated to Prof. Dr. Carmen Najera on the occasion of her 60th birthday.Andreu Ros, MI.; Palumbo, F.; Tilocca, F.; Morera Bertomeu, IM.; Bosca Mayans, F.; Miranda Alonso, MÁ. (2011). Solvent effects in hydrogen abstraction from cholesterol by benzophenone triplet excited state. Organic Letters. 13(15):4096-4099. https://doi.org/10.1021/ol2016059S40964099131