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Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.

The Imaging Magnetograph eXperiment (IMaX) is a spectropolarimeter built by four institutions in Spain that flew on board the Sunrise balloon-borne solar observatory in June 2009 for almost six days over the Arctic Circle. As a polarimeter, IMaX uses fast polarization modulation (based on the use of two liquid crystal retarders), real-time image accumulation, and dual-beam polarimetry to reach polarization sensitivities of 0.1%. As a spectrograph, the instrument uses a LiNbO 3 etalon in double pass and a narrow band pre-filter to achieve a spectral resolution of 85 mÅ. IMaX uses the high-Zeeman-sensitive line of Fe i at 5250.2 Å and observes all four Stokes parameters at various points inside the spectral line. This allows vector magnetograms, Dopplergrams, and intensity frames to be produced that, after reconstruction, reach spatial resolutions in the 0.15 – 0.18 arcsec range over a 50×50 arcsec field of view. Time cadences vary between 10 and 33 s, although the shortest one only includes longitudinal polarimetry. The spectral line is sampled in various ways depending on the applied observing mode, from just two points inside the line to 11 of them. All observing modes include one extra wavelength point in the nearby continuum. Gauss equivalent sensitivities are 4 G for longitudinal fields and 80 G for transverse fields per wavelength sample. The line-of-sight velocities are estimated with statistical errors of the order of 5 – 40 m s −1 . The design, calibration, and integration phases of the instrument, together with the implemented data reduction scheme, are described in some detail.

ABSTRACT The Rcs phosphorelay is a two-component signal transduction system that senses stressful environmental signals such as desiccation or low temperatures, which serve as natural inducers in bacteria. RcsA is an important coregulator in this system involved in some functions regulated by the Rcs system, including biofilm formation and capsule synthesis. In this sense, we previously showed that RcsA is necessary for colanic acid synthesis in Escherichia coli K92. Here, using an E. coli K92ΔrcsA mutant lacking rcsA gene we further characterize the implications of RcsA on E. coli K92 survival under osmotic and oxidative stressful conditions, and bacterial attachment and biofilm formation on both biotic and abiotic surfaces. Our results show that RcsA protects E. coli K92 against osmotic and, especially, oxidative stress at low temperatures. In addition, RcsA did not interfere in biofilm formation in any surface tested, including polystyrene, stainless steel, silicone, Teflon, aluminum and glass. By contrast, deletion of rcsA increased bacterial attachment to the caco-2 cells monolayer used as biotic surface. RcsA protects Escherichia coli K92 against osmotic and, especially, oxidative stress at low temperatures, and it has implications for bacterial attachments and biofilm formation

The present work was aimed at characterizing 12 strains of lactic acid bacteria (LAB) to obtain improved potential starter or probiotic cultures that could be used for making dairy products from ewe's milk and cow's milk. Eight strains with antimicrobial properties, isolated from ewe's milk and from cheese made from ewe's and/or cow's milk, were studied. They were identified as Enterococcus faecalis (five strains), Lactococcus lactis subsp. cremoris, Leuconostoc mesenteroides, and Lactobacillus paracasei subsp. paracasei (one strain of each species). Additionally, four strains were obtained from the American Type Culture Collection: Lactobacillus casei 393 (isolated from cheese), L. lactis subsp. lactis 11454 (origin nonspecified and a producer of nisin), and two strains isolated from human feces (L. paracasei subsp. paracasei 27092 and Lactobacillus rhamnosus 53103, antibacterial agent producer). All E. faecalis strains showed at least one virulence factor (either hemolysin or gelatinase), which emphasizes the importance of these studies in this species. Both L. lactis strains and most Lactobacillus spp. were good acidifiers in ewe's milk and cow's milk at 30°C. High β-galactosidase activity, as well as aminopeptidase activities that favor the development of desirable flavors in cheese, were detected in all Lactobacillus spp. strains. Furthermore, L. rhamnosus ATCC 53103 showed α-fucosidase activity (thought to help colonization of the intestine) and lack of α-glucosidase activity (a trait considered positive for diabetic and obese humans). This last enzymatic activity was also lacking in L. lactis ATCC 11454. L. mesenteroides was the only strain D(−)-lactic acid producer. The selection of any particular strain for probiotic or dairy cultures should be performed according to the technological and/or functional abilities needed.

This communication reports a four-step protocol to produce 3-allyl-2-(allyloxy)-5-bromoaniline 5 from commercially available 2-allylphenol. The synthetic steps used were nitration, selective bromination, allylation, and reduction of the nitro group.

The human gastrointestinal system has the capacity to metabolize dietary gluten. The capacity to degrade gliadin-derived peptide is present in humans from birth and increases during the first stages of life (up to 6–12 months of age). Fecal samples from 151 new-born and adult non-celiac disease (NCD) volunteers were collected, and glutenase and glianidase activities were evaluated. The capacity of total fecal proteins to metabolize 33-mer, 19-mer, and 13-mer gliadin peptides was also evaluated by high-performance liquid chromatography (HPLC). Feces from new-borns (meconium) showed glutenase and gliadinase activities, and peptidase activity against all three gliadin peptides. Maximal gluten degradative activity was observed in fecal samples from the youngest volunteers (0–12 months old). After the age of nine months, the gluten digestive capacity of gastrointestinal tract decreases and, from ±8 years old, individuals lose the ability to completely degrade toxic peptides. The gastrointestinal proteases involved in gluten digestion: elastase 2A, elastase 3B, and carboxipeptidase A1 are present from earlier stages of life. The human digestive tract contains the proteins capable of metabolizing gluten from birth, even before starting gluten intake. Humans are born with the ability to digest gluten and to completely degrade the potentially toxic gliadin-derived peptides (33-, 19-, and 13-mer).

Background and ImportanceRetractions in scientific literature can profoundly impact healthcare professionals, potentially misleading hospital pharmacists and affecting patient safety.Aim and ObjectivesThis study aimed to provide a focused examination of article retractions in pharmacological research.Material and MethodsA cross-sectional observational study was carried out using data from the recently released (10/09/2023) ‘Retraction Watch Database’* which compiles data from retracted scientific articles since the early 70s. We included data from retracted articles categorised as ‘Medicine-Pharmacology’ involving European researchers. We excluded data from article reinstatements.We studied variables such as: type of study, date of article publication, date of article retraction, and reasons for retraction.Time to retraction was calculated as date of article retraction – date of article publication. As most articles had several reasons for retraction, they were presented in a heat mat of pairwise combinations.ResultsA total of 516 articles were retracted within the study period. Retracted articles were original studies 61.2% (316), reviews 27.1% (140), Review and meta-analysis 3.9% (20) and others 7.8% (40).Abstract 6ER-015 Table 1 Year period Article publication N (%) Article retraction N (%) 1975–1999 63 (12.2) 6 (1.2) 2000–2004 94 (18.2) 12 (2.3) 2005–2009 116 (22.5) 22 (4.3) 2010–2014 138 (26.7) 174 (33.7) 2015–2019 66 (12.8) 138 (26.74) 2020–2023 39 (7.6) 164 (31.8) The median time to retraction was 2135 (IQR: 3680) days.Abstract 6ER-015 Figure 1Conclusion and RelevanceThis study revealed a significant number of retracted pharmacology articles, often with substantial time lags from publication to retraction for several significant reasons. Hospital pharmacists must be aware of this issue, as it influences clinical decision-making. Discernment in citing articles is imperative to minimise associated risks.References and/or Acknowledgements1. The Retraction Watch Database [Internet]. New York: The Center for Scientific Integrity. 2018. ISSN: 2692-465X. [Cited (20/09/2023)]. Available from: http://retractiondatabase.org/Conflict of InterestNo conflict of interest.

Abstract We studied growth temperature as a factor controlling the expression of genes involved in capsular polymers of Escherichia coli K92. These genes are shown to be regulated by growth temperature. Expression levels of genes belonging to the kps cluster, responsible for polysialic acid (PA) biosynthesis, were significantly increased at 37°C compared with at 19°C, being up to 500-fold increased for neuE and neuS genes. Similarly, the genes for the nan operon, responsible for PA catabolism, also reached higher expression levels at 37°C, although with slightly lower values (39–141-fold). In contrast, genes of the cps operon, which are implicated in colanic acid (CA) metabolism, were upregulated when the bacteria were grown at 19°C, albeit to a much lesser extent (around twofold). This different regulation of genes involved in the biosynthesis of polysialic and CAs correlates with the reported maximal production temperatures for the two polymers. The results suggest that the metabolism of PA is predominantly regulated by changes in gene expression, while CA production may be regulated mainly by post-transcriptional processes such as phosphorylation–dephosphorylation reactions.

Background and ImportanceCytomegalovirus (CMV) infection poses a significant threat to transplant recipients,1 often necessitating antiviral treatment. Ganciclovir and valganciclovir have been mainstays, but CMV resistance in over 20% of cases requires alternatives like foscarnet or cidofovir.2 Maribavir, a novel CMV UL97 protein kinase inhibitor, has emerged as an effective option.3 Here, we unveil a previously unreported adverse effect (AE) associated with maribavir.Aim and ObjectivesOur aim is to report a case of toxic epidermal necrolysis (TEN) linked to maribavir intake.Material and MethodsIn March 2021, a male liver-transplanted patient with CMV-related retinal necrosis developed severe pancytopenia during valganciclovir treatment, subsequently receiving foscarnet in multiple hospitalisations. In May 2023, maribavir was initiated, marking the first such case in our hospital. Within a month, the patient was readmitted with painful skin lesions and mucositis in oral and genital mucosa. TEN diagnose was assumed, evidenced by tense bullae, extensive epidermal detachment (60% of Body Surface Area), and a clearly positive Nikolsky sign. He was transferred to the ICU 3 days later and treated with a 5-day-course of 125 mg intravenous methylprednisolone and 2g/kg immunoglobulin.ResultsThe patient’s overall status improved, with reduced lesions and epidermal detachment. After 10 days, only scarring remained. This AE was classified as probable causality due to maribavir, with a score of 6 on the Naranjo Scale.4 The Spanish System for Pharmacovigilance of Human Drugs was informed of this event by the Pharmacy Service.Conclusion and RelevanceTEN, a life-threatening drug-associated AE, must be considered when prescribing. While antibiotics cause 25% of TEN cases, antivirals rarely induce it.5 This AE is especially noteworthy since maribavir, marketed in November 2022, has limited exposure to patients in Spain. Early-phase pharmacovigilance is crucial for detecting unreported AEs. Establishing multidisciplinary teams comprising physicians and pharmacists is essential to ensure drug safety, mitigating severe AEs.References and/or Acknowledgements1. Razonable RR. Clin Transplant. 2019;33:e13512. DOI: 10.1111/ctr.135122. Chemaly RF, et al. Clin Infect Dis. 2019;68(8):1420–1426. DOI: 10.1093/cid/ciy6963. Livtencity technical data sheet. EMA. 2022.4. Naranjo CA, et al. Clin Pharmacol Ther. 1981;30:239245. DOI: 10.1038/clpt.1981.1545. Lee EY, et al. JAMA Dermatol. 2023;4:384–392. DOI:10.1001/jamadermatol.2022.6378Conflict of InterestNo conflict of interest.