Nitrate increases the capacity of an aerobic moving-bed biofilm reactor (MBBR) for winery wastewater treatment.

We used bench-scale tests and mathematical modeling to explore chemical oxygen demand (COD) removal rates in a moving-bed biofilm reactor (MBBR) for winery wastewater treatment, using either urea or nitrate as a nitrogen source. With urea addition, the COD removal fluxes ranged from 34 to 45 gCOD/m2-d. However, when nitrate was added, fluxes increased up to 65 gCOD/m2-d, twice the amount reported for aerobic biofilms for winery wastewater treatment. A one-dimensional biofilm model, calibrated with data from respirometric tests, accurately captured the experimental results. Both experimental and modelling results suggest that nitrate significantly increased MBBR capacity by stimulating COD oxidation in the deeper, oxygen-limited regions of the biofilm. Our research suggests that the addition of nitrate, or other energetic and broadly used electron acceptors, may provide a cost-effective means of covering peak COD loads in biofilm processes for winery or another industrial wastewater treatment.

Diffuse colonic capillary hemangioma mimicking ulcerative colitis.

Inflammatory bowel disease (IBD) diagnosis requires clinical, laboratory, endoscopic and histologic findings, and sometimes it can become a challenge. An exhaustive differential diagnosis with infectious disease, immunodeficiencies, hematologic, neoplastic, or vascular diseases must be made1, since prognosis and treatment vary depending on etiology. We present the case of a 62-year-old man, with no personal history of interest, who undergoes a colonoscopy after a positive colorectal cancer screening test (fecal occult blood test). In the endoscopy, a continuous involvement was observed from the anal margin to the splenic flexure, with erythematous mucosa, loss of vascular pattern, and alternating scar areas with neovessels. Histopathological findings were compatible with diffuse capillary hemangioma. Since no symptoms of gastrointestinal (GI) bleeding nor anemia were referred, periodic surveillance was carried out.

Gastric lymphangioma. Diagnosis by endoscopic resection of a foreign entity.

The lymphangioma is a rare and very uncommon benign tumor at the gastric level. Its diagnosis typically involves imaging tests and endoscopy, and its treatment usually involves surgery. We present a case of an 82-year-old patient who presented with chronic anemia, with a large gastric polyp detected during the initial gastroscopy. Subsequently, an endoscopic resection was performed, confirming histologically that it was a lymphangioma.

Individual competence predominates over host nutritional status in Arabidopsis root exudate-mediated bacterial enrichment in a combination of four Burkholderiaceae species.

BACKGROUND: Rhizosphere microorganisms play a crucial role in plant health and development. Plant root exudates (PRE) are a complex mixture of organic molecules and provide nutritional and signaling information to rhizosphere microorganisms. Burkholderiaceae species are non-abundant in the rhizosphere but exhibit a wide range of plant-growth-promoting and plant-health-protection effects. Most of these plant-associated microorganisms have been studied in isolation under laboratory conditions, whereas in nature, they interact in competition or cooperation with each other. To improve our understanding of the factors driving growth dynamics of low-abundant bacterial species in the rhizosphere, we hypothesized that the growth and survival of four Burkholderiaceae strains (Paraburkholderia phytofirmans PsJN, Cupriavidus metallidurans CH34, C. pinatubonensis JMP134 and C. taiwanensis LMG19424) in Arabidopsis thaliana PRE is affected by the presence of each other. RESULTS: Differential growth abilities of each strain were found depending on plant age and whether PRE was obtained after growth on N limitation conditions. The best-adapted strain to grow in PRE was P. phytofirmans PsJN, with C. pinatubonensis JMP134 growing better than the other two Cupriavidus strains. Individual strain behavior changed when they succeeded in combinations. Clustering analysis showed that the 4-member co-culture grouped with one of the best-adapted strains, either P. phytofirmans PsJN or C. pinatubonensis JMP134, depending on the PRE used. Sequential transference experiments showed that the behavior of the 4-member co-culture relies on the type of PRE provided for growth. CONCLUSIONS: The results suggest that individual strain behavior changed when they grew in combinations of two, three, or four members, and those changes are determined first by the inherent characteristics of each strain and secondly by the environment.

Redox traits characterize the organization of global microbial communities.

The structure of biological communities is conventionally described as profiles of taxonomic units, whose ecological functions are assumed to be known or, at least, predictable. In environmental microbiology, however, the functions of a majority of microorganisms are unknown and expected to be highly dynamic and collectively redundant, obscuring the link between taxonomic structure and ecosystem functioning. Although genetic trait-based approaches at the community level might overcome this problem, no obvious choice of gene categories can be identified as appropriate descriptive units in a general ecological context. We used 247 microbial metagenomes from 18 biomes to determine which set of genes better characterizes the differences among biomes on the global scale. We show that profiles of oxidoreductase genes support the highest biome differentiation compared with profiles of other categories of enzymes, general protein-coding genes, transporter genes, and taxonomic gene markers. Based on oxidoreductases' description of microbial communities, the role of energetics in differentiation and particular ecosystem function of different biomes become readily apparent. We also show that taxonomic diversity is decoupled from functional diversity, e.g., grasslands and rhizospheres were the most diverse biomes in oxidoreductases but not in taxonomy. Considering that microbes underpin biogeochemical processes and nutrient recycling through oxidoreductases, this functional diversity should be relevant for a better understanding of the stability and conservation of biomes. Consequently, this approach might help to quantify the impact of environmental stressors on microbial ecosystems in the context of the global-scale biome crisis that our planet currently faces.

Reconstruction of a gene regulatory network of the induced systemic resistance defense response in Arabidopsis using boolean networks.

BACKGROUND: An important process for plant survival is the immune system. The induced systemic resistance (ISR) triggered by beneficial microbes is an important cost-effective defense mechanism by which plants are primed to an eventual pathogen attack. Defense mechanisms such as ISR depend on an accurate and context-specific regulation of gene expression. Interactions between genes and their products give rise to complex circuits known as gene regulatory networks (GRNs). Here, we explore the regulatory mechanism of the ISR defense response triggered by the beneficial bacterium Paraburkholderia phytofirmans PsJN in Arabidopsis thaliana plants infected with Pseudomonas syringae DC3000. To achieve this, a GRN underlying the ISR response was inferred using gene expression time-series data of certain defense-related genes, differential evolution, and threshold Boolean networks. RESULTS: One thousand threshold Boolean networks were inferred that met the restriction of the desired dynamics. From these networks, a consensus network was obtained that helped to find plausible interactions between the genes. A representative network was selected from the consensus network and biological restrictions were applied to it. The dynamics of the selected network showed that the largest attractor, a limit cycle of length 3, represents the final stage of the defense response (12, 18, and 24 h). Also, the structural robustness of the GRN was studied through the networks' attractors. CONCLUSIONS: A computational intelligence approach was designed to reconstruct a GRN underlying the ISR defense response in plants using gene expression time-series data of A. thaliana colonized by P. phytofirmans PsJN and subsequently infected with P. syringae DC3000. Using differential evolution, 1000 GRNs from time-series data were successfully inferred. Through the study of the network dynamics of the selected GRN, it can be concluded that it is structurally robust since three mutations were necessary to completely disarm the Boolean trajectory that represents the biological data. The proposed method to reconstruct GRNs is general and can be used to infer other biologically relevant networks to formulate new biological hypotheses.

Vermiproductivity, maturation and microbiological changes derived from the use of liquid anaerobic digestate during the vermicomposting of market waste.

Recently, it has been suggested that the liquid fraction of anaerobic digestate, derived from the treatment of wastewater and solid wastes, could be used in vermicomposting as a solution to its disposal, and even for its valorization. Nevertheless, the literature does not provide enough information about its impact on the process of vermicomposting itself and on the final quality of the end-product. In this study, the effect of different doses of digestate in the vermicomposting process treating market waste is assessed measuring earthworm population dynamics, the bacterial community succession present in the vermibeds, as well as maturation and the end-quality of the vermicompost. Our results show that the addition of liquid digestate to the vermibeds increased the earthworms biomass, i.e. 71%, 94% and 168% in control, and vermibeds with 30% and 60% digestate, respectively. Further, the increase in the amount of N in the vermicompost decreased as the digestate addition increased, i.e. 75%, 8%, 3%. The maturity achieved was high in all treatments as shown by the C/N ratio, 7.98, 7.40 and 10.20, and the high seed germination rate, above 90%. Finally, the succession of the microbial community was not disturbed and compositional stabilization was reached after 92 days.

Efficacy and safety of the SB Knife™ Jr. for the treatment of Zenker's diverticulum: a case series.

BACKGROUND AND AIMS: the stag-beetle knife is a new scissor-like endoscopic device that can be used for the treatment of Zenker's diverticulum, although experience is limited. The aim of this study was to evaluate the efficacy and safety of the SB Knife™ for the endoscopic treatment of Zenker's diverticulum. METHODS: a single-center prospective study of 16 patients was performed between May 2017 and April 2019. The rate of complications and symptom changes was evaluated. RESULTS: the median age was 78 years and 62.5% of the patients were male. All had dysphagia, 43.8% choking, 31.3% regurgitation and 6.3% respiratory symptoms. The median size of the diverticulum was 20 mm and the median follow-up was 281 days. There were no intra-procedure complications and only one major post-procedure complication was reported that was a microperforation. All patients had clinical improvement. Two patients had relapsing symptoms and were successfully treated with the same method. CONCLUSIONS: the SB Knife™ seems to be a safe and effective technique for the treatment of Zenker's diverticulum.

Collapsing Lesions and Focal Segmental Glomerulosclerosis in Pregnancy: A Report of 3 Cases.

The relationship between focal segmental glomerulosclerosis (FSGS) and pregnancy is complex and not completely elucidated. Pregnancy in patients with FSGS poses a high risk for complications, possibly due to hemodynamic factors, imbalance between angiogenic and antiangiogenic factors, and hormonal conditioning. Although poor clinical outcomes associated with collapsing FSGS are common outside of pregnancy, the prognosis during pregnancy is not well documented. We report 3 patients who developed collapsing FSGS during pregnancy, 2 of whom had presumed underlying FSGS. Two patients underwent biopsy during pregnancy, and 1, during the puerperium. None of the 3 patients improved spontaneously after delivery, and 1 experienced a rapid deterioration in kidney function and proteinuria after delivery. Aggressive immunosuppressive therapy led to a full response in 1 case (without chronic lesions) and to partial responses in the remaining 2 cases. These cases suggest that collapsing lesions should be considered in patients with FSGS who develop a rapid increase in serum creatinine level or proteinuria during pregnancy and that these lesions may at least partially respond to treatment.

Xenobiotics Formed during Food Processing: Their Relation with the Intestinal Microbiota and Colorectal Cancer.

The colonic epithelium is exposed to a mixture of compounds through diet, among which some are procarcinogens, whereas others have a protective effect. Therefore, the net impact of these compounds on human health depends on the overall balance between all factors involved. Strong scientific evidence has demonstrated the relationship between nitrosamines (NA), heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs), which are the major genotoxins derived from cooking and food processing, and cancer. The mechanisms of the relationship between dietary toxic xenobiotics and cancer risk are not yet well understood, but it has been suggested that differences in dietary habits affect the colonic environment by increasing or decreasing the exposure to mutagens directly and indirectly through changes in the composition and activity of the gut microbiota. Several changes in the proportions of specific microbial groups have been proposed as risk factors for the development of neoplastic lesions and the enrichment of enterotoxigenic microbial strains in stool. In addition, changes in the gut microbiota composition and activity promoted by diet may modify the faecal genotoxicity/cytotoxicity, which can be associated with a higher or lower risk of developing cancer. Therefore, the interaction between dietary components and intestinal bacteria may be a modifiable factor for the development of colorectal cancer in humans and deserves more attention in the near future.

Quorum-Sensing Systems in the Plant Growth-Promoting Bacterium Paraburkholderia phytofirmans PsJN Exhibit Cross-Regulation and Are Involved in Biofilm Formation.

Quorum-sensing systems play important roles in host colonization and host establishment of Burkholderiales species. Beneficial Paraburkholderia species share a conserved quorum-sensing (QS) system, designated BraI/R, that controls different phenotypes. In this context, the plant growth-promoting bacterium Paraburkholderia phytofirmans PsJN possesses two different homoserine lactone QS systems BpI.1/R.1 and BpI.2/R.2 (BraI/R-like QS system). The BpI.1/R.1 QS system was previously reported to be important to colonize and produce beneficial effects in Arabidopsis thaliana plants. Here, we analyzed the temporal variations of the QS gene transcript levels in the wild-type strain colonizing plant roots. The gene expression patterns showed relevant differences in both QS systems compared with the wild-type strain in the unplanted control treatment. The gene expression data were used to reconstruct a regulatory network model of QS systems in P. phytofirmans PsJN, using a Boolean network model. Also, we examined the phenotypic traits and transcript levels of genes involved in QS systems, using P. phytofirmans mutants in homoserine lactone synthases genes. We observed that the BpI.1/R.1 QS system regulates biofilm formation production in strain PsJN and this phenotype was associated with the lower expression of a specific extracytoplasmic function sigma factor ecf26.1 gene (implicated in biofilm formation) in the bpI.1 mutant strain.

Paraburkholderia phytofirmans PsJN Protects Arabidopsis thaliana Against a Virulent Strain of Pseudomonas syringae Through the Activation of Induced Resistance.

Paraburkholderia phytofirmans PsJN is a plant growth-promoting rhizobacterium (PGPR) that stimulates plant growth and improves tolerance to abiotic stresses. This study analyzed whether strain PsJN can reduce plant disease severity and proliferation of the virulent strain Pseudomonas syringae pv. tomato DC3000, in Arabidopsis plants, through the activation of induced resistance. Arabidopsis plants previously exposed to strain PsJN showed a reduction in disease severity and pathogen proliferation in leaves compared with noninoculated, infected plants. The plant defense-related genes WRKY54, PR1, ERF1, and PDF1.2 demonstrated increased and more rapid expression in strain PsJN-treated plants compared with noninoculated, infected plants. Transcriptional analyses and functional analysis using signaling mutant plants suggested that resistance to infection by DC3000 in plants treated with strain PsJN involves salicylic acid-, jasmonate-, and ethylene-signaling pathways to activate defense genes. Additionally, activation occurs through a specific PGPR-host recognition, being a necessary metabolically active state of the bacterium to trigger the resistance in Arabidopsis, with a strain PsJN-associated molecular pattern only partially involved in the resistance response. This study provides the first report on the mechanism used by the PGPR P. phytofirmans PsJN to protect A. thaliana against a widespread virulent pathogenic bacterium.

Transition boundaries for protistan species turnover in hypersaline waters of different biogeographic regions.

The identification of environmental barriers which govern species distribution is a fundamental concern in ecology. Even though salt was previously identified as a major transition boundary for micro- and macroorganisms alike, the salinities causing species turnover in protistan communities are unknown. We investigated 4.5 million high-quality protistan metabarcodes (V4 region of the SSU rDNA) obtained from 24 shallow salt ponds (salinities 4%-44%) from South America and Europe. Statistical analyses of protistan community profiles identified four salinity classes, which strongly selected for different protistan communities: 4-9%, 14-24%, 27-36% and 38-44%. The proportion of organisms unknown to science is highest in the 14-24% salinity class, showing that environments within this salinity range are an unappreciated reservoir of as yet undiscovered organisms. Distinct higher-rank taxon groups dominated in the four salinity classes in terms of diversity. As increasing salinities require different cellular responses to cope with salt, our results suggest that different evolutionary lineages of protists have evolved distinct haloadaptation strategies. Salinity appears to be a stronger selection factor for the structuring of protistan communities than geography. Yet, we find a higher degree of endemism in shallow salt ponds compared with less isolated ecosystems such as the open ocean. Thus, rules for biogeographic structuring of protistan communities are not universal, but depend on the ecosystem under consideration.

Biochemical and Genetic Bases of Indole-3-Acetic Acid (Auxin Phytohormone) Degradation by the Plant-Growth-Promoting Rhizobacterium Paraburkholderia phytofirmans PsJN.

Several bacteria use the plant hormone indole-3-acetic acid (IAA) as a sole carbon and energy source. A cluster of genes (named iac) encoding IAA degradation has been reported in Pseudomonas putida 1290, but the functions of these genes are not completely understood. The plant-growth-promoting rhizobacterium Paraburkholderia phytofirmans PsJN harbors iac gene homologues in its genome, but with a different gene organization and context than those of P. putida 1290. The iac gene functions enable P. phytofirmans to use IAA as a sole carbon and energy source. Employing a heterologous expression system approach, P. phytofirmans iac genes with previously undescribed functions were associated with specific biochemical steps. In addition, two uncharacterized genes, previously unreported in P. putida and found to be related to major facilitator and tautomerase superfamilies, are involved in removal of an IAA metabolite called dioxindole-3-acetate. Similar to the case in strain 1290, IAA degradation proceeds through catechol as intermediate, which is subsequently degraded by ortho-ring cleavage. A putative two-component regulatory system and a LysR-type regulator, which apparently respond to IAA and dioxindole-3-acetate, respectively, are involved in iac gene regulation in P. phytofirmans These results provide new insights about unknown gene functions and complex regulatory mechanisms in IAA bacterial catabolism. IMPORTANCE: This study describes indole-3-acetic acid (auxin phytohormone) degradation in the well-known betaproteobacterium P. phytofirmans PsJN and comprises a complete description of genes, some of them with previously unreported functions, and the general basis of their gene regulation. This work contributes to the understanding of how beneficial bacteria interact with plants, helping them to grow and/or to resist environmental stresses, through a complex set of molecular signals, in this case through degradation of a highly relevant plant hormone.

Response to erythropoietic-stimulating agents in patients with chronic myelomonocytic leukemia.

BACKGROUND: The efficacy of erythropoietic-stimulating agents (ESA) in chronic myelomonocytic leukemia (CMML) is unknown. Our objective was to analyze erythroid response (ER) and overall survival (OS) in a series of 94 patients with CMML treated with ESA. METHODS: We analyzed a series of 94 patients with CMML treated with ESA included in the Spanish and Düsseldorf-MDS registries. FINDINGS: ER was observed in 64% of patients and red blood cell (RBC) transfusion independence in 31%. The median duration of ER was 7 months (range, 0-88). CPSS and EPO level were significantly associated with ER in multivariate analysis (P = 0.003). Considering only patients with CPSS low- or intermediate-1-risk group, the absence of RBC transfusion dependence and erythropoietin (EPO) level predicted ER (P = 0.003 and P = 0.008, respectively). In multivariate analysis, only the EPO level retained its prognostic value (P = 0.029). Achievement of ER correlated with a better survival since ER evaluation (P = 0.016). INTERPRETATION: The CPSS and EPO levels are adequate tools to select CMML patients with symptomatic anemia who may benefit from treatment with ESA. A significant ER to ESA is expected in anemic patients with low/intermediate-1 CMML risk by the CPSS and a low endogenous serum EPO level.

Hierarchy of Carbon Source Utilization in Soil Bacteria: Hegemonic Preference for Benzoate in Complex Aromatic Compound Mixtures Degraded by Cupriavidus pinatubonensis Strain JMP134.

Cupriavidus pinatubonensis JMP134, like many other environmental bacteria, uses a range of aromatic compounds as carbon sources. Previous reports have shown a preference for benzoate when this bacterium grows on binary mixtures composed of this aromatic compound and 4-hydroxybenzoate or phenol. However, this observation has not been extended to other aromatic mixtures resembling a more archetypal context. We carried out a systematic study on the substrate preference of C. pinatubonensis JMP134 growing on representative aromatic compounds channeled through different catabolic pathways described in aerobic bacteria. Growth tests of nearly the entire set of binary combinations and in mixtures composed of 5 or 6 aromatic components showed that benzoate and phenol were always the preferred and deferred growth substrates, respectively. This pattern was supported by kinetic analyses that showed shorter times to initiate consumption of benzoate in aromatic compound mixtures. Gene expression analysis by real-time reverse transcription-PCR (RT-PCR) showed that, in all mixtures, the repression by benzoate over other catabolic pathways was exerted mainly at the transcriptional level. Additionally, inhibition of benzoate catabolism suggests that its multiple repressive actions are not mediated by a sole mechanism, as suggested by dissimilar requirements of benzoate degradation for effective repression in different aromatic compound mixtures. The hegemonic preference for benzoate over multiple aromatic carbon sources is not explained on the basis of growth rate and/or biomass yield on each single substrate or by obvious chemical or metabolic properties of these aromatic compounds.

Environmental conditions influence host-parasite interactions and host fitness in a migratory passerine.

The study of host-parasite co-evolution is a central topic in evolutionary ecology. However, research is still fragmented and the extent to which parasites influence host life history is debated. One reason for this incomplete picture is the frequent omission of environmental conditions in studies analyzing host-parasite dynamics, which may influence the exposure to or effects of parasitism. To contribute to elucidating the largely unresolved question of how environmental conditions are related to the prevalence and intensity of infestation and their impact on hosts, we took advantage of 25 years of monitoring of a breeding population of pied flycatchers, Ficedula hypoleuca, in a Mediterranean area of central Spain. We investigated the influence of temperature and precipitation during the nestling stage at a local scale on the intensity of blowfly (Protocalliphora azurea) parasitism during the nestling stage. In addition, we explored the mediating effect of extrinsic and intrinsic factors and blowfly parasitism on breeding success (production of fledglings) and offspring quality (nestling mass on day 13). The prevalence and intensity of blowfly parasitism were associated with different intrinsic (host breeding date, brood size) and extrinsic (breeding habitat, mean temperature) factors. Specifically, higher average temperatures during the nestling phase were associated with lower intensities of parasitism, which may be explained by changes in blowflies' activity or larval developmental success. In contrast, no relationship was found between the prevalence of parasitism and any of the environmental variables evaluated. Hosts that experienced high parasitism intensities in their broods produced more fledglings as temperature increased, suggesting that physiological responses to severe parasitism during nestling development might be enhanced in warmer conditions. The weight of fledglings was, however, unrelated to the interactive effect of parasitism intensity and environmental conditions. Overall, our results highlight the temperature dependence of parasite-host interactions and the importance of considering multiple fitness indicators and climate-mediated effects to understand their complex implications for avian fitness and population dynamics.

Celiac disease prevalence in patients with idiopathic inflammatory myopathies, a cross-sectional study.

Up to 30% of patients with celiac disease (CD) suffer from concurrent autoimmune disease, compared to 3% of the general population. The association between CD and the current clinical phenotypes of inflammatory myopathies (IIM) patients has not been thoroughly addressed. Assess the CD features among patients with IIM and their relationship with the clinical phenotype and the myositis specific (MSA) and associated antibodies (MAA). For this cross-sectional study, we recruited 99 adult patients classified as IIM from a tertiary center in Mexico. We assessed serum MSA, MAA, and CD-associated autoantibodies (IgA anti-tissue transglutaminase (tTG) and both IgA and IgG anti-deaminated gliadin peptide (DGP)). Patients with highly suggestive serology for CD were then tested for IgG anti-endomysium antibodies, and a duodenal biopsy was performed. 70.7% of patients were positive for at least one antibody. Nine duodenal biopsies were taken, revealing findings compatible with celiac disease in two cases. Subjects with anti-MDA5 antibodies were more likely to have positive anti-tTG IgA antibodies (OR 6.76, 95% CI 1.85-24.62, P = 0.013) and suggestive CD serology (OR 6.41, 95% CI 1.62-25.29, P = 0.009). Patients with anti-Mi2 antibodies were more likely to have positive anti-DGP IgG antibodies (OR 3.35, 95% CI 1.12-9.96, P = 0.039), while positivity for these autoantibodies was less frequent in patients with anti-NXP2 antibodies (OR 0.22, 95% CI 0.06-0.80, P = 0.035). There is a higher prevalence of serologic and definite CD in patients with IIM compared to the general population. Identifying this subgroup of patients may have prognostic and therapeutic implications. Key points • The study estimated a serological celiac disease (CD) prevalence of 70.7% in patients with idiopathic inflammatory myopathies (IIM) and a biopsy-confirmed prevalence of 2%, suggesting that IIM patients should be considered a high-risk population for CD. • We identified a significant association between serological CD and the presence of anti-MDA5 and anti-Mi2 antibodies, suggesting a potential justification for celiac disease screening in this specific subgroup of patients. • The impact of gluten-free diets on IIM patients with serological markers of CD remains untested and warrants further investigation through prospective, randomized studies.

Outcomes and effect of somatic mutations after erythropoiesis stimulating agents in patients with lower-risk myelodysplastic syndromes.

Background: Erythropoiesis stimulating agents (ESAs) are the first-line therapy in patients with lower-risk myelodysplastic syndromes (LR-MDS). Some predictive factors for ESAs response have been identified. Type and number of somatic mutations have been associated with prognosis and response to therapies in MDS patients. Objectives: The objective was to evaluate the outcomes after ESAs in patients with LR-MDS and to address the potential predictive value of somatic mutations in ESAs-treated patients. Design: Multi-center retrospective study of a cohort of 722 patients with LR-MDS included in the SPRESAS (Spanish Registry of Erythropoietic Stimulating Agents Study) study. Retrospective analysis of 65 patients with next generation sequencing (NGS) data from diagnosis. Methods: ESAs' efficacy and safety were evaluated in patients receiving ESAs and best supportive care (BSC). To assess the potential prognostic value of somatic mutations in erythroid response (ER) rate and outcome, NGS was performed in responders and non-responders. Results: ER rate for ESAs-treated patients was 65%. Serum erythropoietin (EPO) level <200 U/l was the only variable significantly associated with a higher ER rate (odds ratio, 2.45; p = 0.036). Median overall survival (OS) in patients treated with ESAs was 6.7 versus 3.1 years in patients receiving BSC (p < 0.001). From 65 patients with NGS data, 57 (87.7%) have at least one mutation. We observed a trend to a higher frequency of ER among patients with a lower number of mutated genes (40.4% in <3 mutated genes versus 22.2% in ⩾3; p = 0.170). The presence of ⩾3 mutated genes was also significantly associated with worse OS (hazard ratio, 2.8; p = 0.015), even in responders. A higher cumulative incidence of acute myeloid leukemia progression at 5 years was also observed in patients with ⩾3 mutated genes versus <3 (33.3% and 10.7%, respectively; p < 0.001). Conclusion: This large study confirms the beneficial effect of ESAs and the adverse effect of somatic mutations in patients with LR-MDS.

Plasma miR-150-5p in Renal Transplant Recipients with Acute Antibody-Mediated Rejection.

Background: Rejection continues to be the main cause of renal graft loss. Currently, the gold standard for diagnosis is an allograft biopsy; however, because it is time-consuming, costly, and invasive, the pursuit of novel biomarkers has gained interest. Variation in the expressions of miRNAs is currently considered a probable biomarker for the diagnosis of acute rejection. This study aimed to determine whether miR-150-5p in serum is related to microvascular damage in patients with acute antibody-mediated rejection (ABMR). Methods: A total of 27 patients who underwent renal transplantation (RT) with and without ABMR were included in the study. We performed the quantification of hsa-miR-150-5p, hsa-miR-155, hsa-miR-21, hsa-miR-126, and hsa-miR-1 in plasma by RT-qPCR. The expressions between the groups and their correlations with the histological characteristics of the patients with ABMR were also investigated. Results: miR-150-5p significantly increased in the plasma of patients with rejection (p < 0.05), and the changes in miR-150-5p were directly correlated with microvascular inflammation in the allograft biopsies. Clinical utility was determined by ROC analysis with an area under the curve of 0.873. Conclusions: Our results show that the patients with RT with ABMR exhibited increased expression of miR-150-5p compared to patients without rejection, which could have clinical consequences, as well as probable utility in the diagnosis of ABMR, and bioinformatics may help in unraveling the molecular mechanisms underlying ABMR conditions.