Gut Microbiota Composition Correlates with Disease Severity in Myelodysplastic Syndrome.

The myelodysplastic syndrome (MDS) is a heterogeneous group of clonal disorders of hematopoietic progenitor cells related to ineffective hematopoiesis and an increased risk of transformation to acute myelogenous leukemia. MDS is divided into categories, namely lineage dysplasia (MDS-SLD), MDS with ring sideroblasts (MDS-RS), MDS with multilineage dysplasia (MDS-MLD), MDS with excess blasts (MDS-EB). The International Prognostic Classification System (IPSS) ranks the patients as very low, low, intermediate, high, and very high based on disease evolution and survival rates. Evidence points to toll-like receptor (TLR) abnormal signaling as an underlying mechanism of this disease, providing a link between MDS and immune dysfunction. Microbial signals, such as lipopolysaccharides from gram-negative bacteria, can activate or suppress TLRs. Therefore, we hypothesized that MDS patients present gut microbiota alterations associated with disease subtypes and prognosis. To test this hypothesis, we sequenced the 16S rRNA gene from fecal samples of 30 MDS patients and 16 healthy elderly controls. We observed a negative correlation between Prevotella spp. and Akkermansia spp. in MDS patients compared with the control group. High-risk patients presented a significant increase in the genus Prevotella spp. compared to the other risk categories. There was a significant reduction in the abundance of the genus Akkermansia spp. in high-risk patients compared with low- and intermediate-risk. There was a significant decrease in the genus Ruminococcus spp. in MDS-EB patients compared with controls. Our findings show a new association between gut dysbiosis and higher-risk MDS, with a predominance of gram-negative bacteria.

Metabolic flexibility associated with flight time among combat pilots of the Brazilian air force.

INTRODUCTION: Fighter pilots must support the effects of many stressors, including physical and psychological exertion, circadian disturbance, jet lag, and environmental stress. Despite the rigorous selection of military pilots, those factors predispose to failures in physiological compensatory mechanisms and metabolic flexibility. OBJECTIVES: We compared through NMR-based metabolomics the metabolic profile of Brazilian F5 fighter pilots with different flight experiences vs. the control group of non-pilots. We hypothesized that combat pilots have metabolic flexibility associated with combat flight time. METHODS: We evaluated for the first time 34 Brazilian fighter pilots from Santa Cruz Air Base (Rio de Janeiro, RJ) allocated into three groups: pilots with lower total accumulated flight experience < 1,100 h (PC1, n = 7); pilots with higher total accumulated flight experience ≥ 1,100 h (PC2, n = 6); military non-pilots (CONT, n = 21). Data collection included anthropometric measurements, total blood count, lipidogram, markers of oxidative stress, and serum NMR-based metabolomics. RESULTS: In comparison with controls (p < 0.05), pilots exhibited decreased levels of white blood cells (-13%), neutrophils (-15%), lymphocytes (-20%), alfa-glucose (-13%), lactate (-26%), glutamine (-11%), histidine (-20%), and tyrosine (-11%), but higher isobutyrate (+ 10%) concentrations. Significant correlations were found between lactate vs. amino acids in CONT (r = 0.55-0.68, p < 0.001), and vs. glutamine in PC2 (r = 0.94, p = 0.01). CONCLUSION: Fighter pilots with lower experience showed a dysregulation in immune-metabolic function in comparison with controls, which seemed to be counteracted by the accumulation of flight hours. Those findings might have implications for the health preservation and operational training of fighter pilots.

Gene expression patterns of Sirtuin family members (SIRT1 TO SIRT7): Insights into pathogenesis and prognostic of Myelodysplastic neoplasm.

To assess and validate the gene expression profile of SIRTs (SIRT1, SIRT2, SIRT3, SIRT4, SIRT5, SIRT6, and SIRT7) in relation to the pathogenesis and prognostic progression of Myelodysplastic neoplasm (MDS). Eighty bone marrow samples of patients with de novo MDS were diagnosed according to WHO 2022 and IPSS-R criteria. Ten bone marrow samples were obtained from elderly healthy volunteers and used as control samples. Gene expression levels of all SIRTs were assessed using RT-qPCR assays. Downregulation of SIRT2 (p = 0.009), SIRT3 (p = 0.048), SIRT4 (p = 0.049), SIRT5 (p = 0.046), SIRT6 (p = 0.043), and SIRT7 (p = 0.047) was identified in MDS patients compared to control individuals. Also, we identified that while SIRT2-7 genes are typically down-regulated in MDS patients compared to normal controls, there are relative expression variations among MDS patient subgroups. Specifically, SIRT4 (p = 0.029) showed increased expression in patients aged 60 or above, and both SIRT2 (p = 0.016) and SIRT3 (p = 0.036) were upregulated in patients with hemoglobin levels below 8 g/dL. SIRT2 (p = 0.045) and SIRT3 (p = 0.033) were highly expressed in patients with chromosomal abnormalities. Different SIRTs exhibited altered expression patterns concerning specific MDS clinical and prognostic characteristics. The downregulation in SIRTs genes (e.g., SIRT2 to SIRT7) expression in Brazilian MDS patients highlights their role in the disease's development. The upregulation of SIRT2 and SIRT3 in severe anemia patients suggests a potential link to manage iron overload-related complications in transfusion-dependent patients. Moreover, the association of SIRT2/SIRT3 with genomic instability and their role in MDS progression signify promising areas for future research and therapeutic targets. These findings underscore the importance of SIRT family in understanding and addressing MDS, offering novel clinical, prognostic, and therapeutic insights for patients with this condition.

Role of the STING pathway in myeloid neoplasms: a prospero-registered systematic review of principal hurdles of STING on the road to the clinical practice.

Myeloid neoplasms are a group of bone marrow diseases distinguished by disruptions in the molecular pathways that regulate the balance between hematopoietic stem cell (HSC) self-renewal and the generation of specialized cells. Cytokines and chemokines, two important components of the inflammatory process, also influence hematological differentiation. In this scenario, immunological dysregulation plays a pivotal role in the pathogenesis of bone marrow neoplasms. The STING pathway recognizes DNA fragments in the cell cytoplasm and triggers an immune response by type I interferons. The role of STING in cancer has not yet been established; however, both actions, as an oncogene or tumor suppressor, have been documented in other types of cancer. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42023407512) to discuss the role of STING pathway in the advancement of pathogenesis and/or prognosis for different myeloid neoplasms. In brief, scientific evidence supports investigations that primarily use cell lines from myeloid neoplasms, such as leukemia. More high-quality research and clinical trials are needed to understand the role of the STING pathway in the pathology of hematological malignancies. Finally, the STING pathway suggests being a promising therapeutic molecular target, particularly when combined with current drug therapies.

High PD-L1 expression is associated with unfavorable clinical features in myelodysplastic neoplasms.

INTRODUCTION: Immune checkpoints are regulators of the immune system response that allow self-tolerance. Molecules such as Programmed Cell Death Protein 1 (PD-1) and its Ligand (PD-L1) participate in the immune checkpoint by signaling co-inhibition of lymphocyte responses. In cancers, PD-L1 expression is associated with the immune evasion mechanism, which favors tumor growth. The use of anti-PD-1/PD-L1 drugs is already well described in solid tumors, but still not fully understood in hematologic malignancies. Myelodysplastic neoplasms (MDSs) are heterogeneous bone marrow disorders with an increased risk of progression to Acute Myeloid Leukemia (AML). The MDS affects hematopoietic stem cells and its pathogenesis is linked to genetic and epigenetic defects, in addition to immune dysregulation. The influence of the PD-L1 on the MDS remains unknown. METHODS: In this study, we evaluated the mRNA expression of the PD-L1 in 53 patients with MDS, classified according to the WHO 2016 Classification. RESULTS: Patients with dyserythropoiesis presented significantly higher PD-L1 expression than patients without dyserythropoiesis (p = 0.050). Patients classified as having MDS with an excess of blasts 2 (MDS-EB2) presented a significant upregulation in the mRNA expression of the PD-L1 compared to the MDS with an excess of blasts 1 (MDS-EB1) (p = 0.050). Furthermore, we detected three patients with very high levels of PD-L1 expression, being statistically classified as outliers. CONCLUSION: We suggested that the high expression of the PD-L1 is associated with a worse prognosis in the MDS and functional studies are necessary to evaluate the possible use of anti-PD-L1 therapies for high-risk MDS, such as the MDS-EBs.

USP15-USP7 Axis and UBE2T Differential Expression May Predict Pathogenesis and Poor Prognosis in De Novo Myelodysplastic Neoplasm.

The aim of this study was to evaluate the expression of USP7, USP15, UBE2O, and UBE2T genes in Myelodysplastic neoplasm (MDS) to identify possible targets of ubiquitination and deubiquitination in MDS pathobiology. To achieve this, eight datasets from the Gene Expression Omnibus (GEO) database were integrated, and the expression relationship of these genes was analyzed in 1092 MDS patients and healthy controls. Our results showed that UBE2O, UBE2T, and USP7 were upregulated in MDS patients compared with healthy individuals, but only in mononucleated cells collected from bone marrow samples (p < 0.001). In contrast, only the USP15 gene showed a downregulated expression compared with healthy individuals (p = 0.03). Additionally, the upregulation of UBE2T expression was identified in MDS patients with chromosomal abnormalities compared with patients with normal karyotypes (p = 0.0321), and the downregulation of UBE2T expression was associated with MDS hypoplastic patients (p = 0.033). Finally, the USP7 and USP15 genes were strongly correlated with MDS (r = 0.82; r2 = 0.67; p < 0.0001). These findings suggest that the differential expression of the USP15-USP7 axis and UBE2T may play an important role in controlling genomic instability and the chromosomal abnormalities that are a striking characteristic of MDS.

Discrepancy in transcriptomic profiling between CD34 + stem cells and primary bone marrow cells in myelodysplastic neoplasm.

Differentially expressed genes (DEGs) biomarkers can be used to help diagnose and monitor the disease, as well as to determine which treatments are most effective. So, given the complexity of Myelodysplastic neoplasm (MDS), it is difficult to determine the impact and disparities of DEGs between CD34+ HSC (hematopoietic stem cells) or primary bone marrow cells (PBMC) in MDS pathogenesis, and therefore it remains largely unknown. Here, we performed an in-silico transcriptome analysis on CD34+ HSC and PBMC from 1092 MDS patients analyzing the divergences between differential gene expression patterns in these two cell types as potential pathogenic biomarkers for MDS. Initially, we observed a difference of 7117 expressed transcripts between PBMC (n = 40,165) and CD34 +HSC (n = 33,048). Also, we identified that CD34+ HSC and PBMC samples showed 240 and 2948 DEGs, respectively. In summary, we identified DEGs disparities in CD34+ HSC and PBMC cell types. However, there was a certain similarity of the activated pathways in both cellular samples based on Gene Ontology and KEGG pathways enrichment analyses. Our results provide novel insights into novel DEGs biomarkers to MDS pathogenesis with clinical significance. AVAILABILITY OF DATA AND MATERIALS: All microarray databases were obtained from Gene Expression Omnibus (https://www.ncbi.nlm.nih.gov/geo/). To evaluate the biological function of differentially expressed genes, the DAVID (Database for Annotation, Visualization and Integrated Discovery tool was used) (https://david.ncifcrf.gov/).

Clinical Evaluation of Bilateral Multiple Gingival Recession Treatment with Autogenous Connective Tissue Graft Associated with Low-Level Laser Therapy.

BACKGROUND: Gingival recession (GR) is described as an apical displacement of the gingival margin in relation to the cementoenamel junction, exposing the root surface to the oral cavity environment. This study aimed to evaluate the clinical results of a bilateral root coverage (RC) of GR associated with an autogenous connective tissue graft (aCTG) alone or combined with low-level laser therapy (aCTG + LLLT). METHODS: This cross-sectional, split-mouth, double-blind, clinical pilot study featured three individuals who attended a periodontics post-graduate program with the main complaint of GR and dental hypersensitivity (DHS). Of these, only one patient met the inclusion criteria and the parameters evaluated were: DHS, the keratinized tissue's thickness and width clinical attachment level (CAL), probing on depth (PD), and bilateral GR based on Cairo RT I. The patient was evaluated by a first clinical evaluator and the treatment was randomly divided into two groups, G1: aCTG only (control group, n = 3 teeth per side) and G2: aCTG + LLLT (test group, n = 3 teeth per side). LLLT used a diode laser (660 nm) with a dose of 3 J/cm2 per point and 4 s per point was applied in four different periods, preoperatively; transoperatively and immediately postoperatively, the application was performed in three points (eight applications) on alternate days for 7 days and a 90-day follow-up was performed for clinical evaluations of the periodontal parameters and the collected data were analyzed by Kruskal-Wallis and Dunn tests. RESULTS: the RC mean percentage was <95% in both groups after 90 days. Comparing treatment sides, G1 (n = 3/3, 100%) had a higher prevalence of RC than G2 had (n = 3/3, 95%). DHS significantly decreased after 90 days in both groups. Both groups showed an improvement in the other periodontal parameters evaluated during the short-term follow-up; mainly, PD had a statistically significant (p ˂ 0.05) increase after 90 days and a CAL decrease during this period; KTW and KTT also had a significant increase in both groups (p ˂ 0.05). CONCLUSIONS: the results indicated that aCTG + LLLT might have an additional benefit to GR root coverage within the evaluated time and this section also includes the within-study limitations.

A randomized clinical study of the performance of self-etching adhesives containing HEMA and 10-MDP on non-carious cervical lesions: A 2-year follow-up study.

OBJECTIVE: To evaluate the association of HEMA and 10-MDP in the clinical performance of self-etching adhesives in the restoration of NCCLs during 2-years. MATERIALS AND METHODS: 60 restorations were performed in 17 volunteers and randomized into three groups: G1 (n = 20) - Prime and Bond Universal (10-MDP); G2 (n = 20) - Optibond All-in-One (HEMA); and G3 (n = 20) - Clearfil SE (10-MDP and HEMA). No cavity preparation was performed. After 2 years, the restorations were evaluated using the modified USPHS criteria for retention, marginal adaptation/ staining, postoperative sensitivity and secondary caries. The results were analyzed using Fisher's exact test and Kruskal-Wallis test. RESULTS: All groups showed 100% retention rate, except G1, who lost two restorations (p > 0.05). Regarding marginal adaptation, G1 showed greater deficiency, as only eight restorations (40%) remained intact (p < 0.05). Regarding marginal staining, G1 and G2 showed higher rate, as only 12 restorations (65%) in each one were free of staining (p < 0.05). All groups showed similar results for postoperative sensitivity and secondary caries (p > 0.05). CONCLUSION: The association of HEMA and 10-MDP monomers in the self-etching adhesives did not influence the clinical performance of the NCCL restorations with respect to retention, postoperative sensitivity, and incidence of secondary caries. However, positively influenced the marginal adaptation and marginal staining at the 2-year follow-up. CLINICAL SIGNIFICANCE: The association of HEMA and 10-MDP monomers in the self-etching adhesives positively influence the clinical performance of the NCCL restorations with respect to marginal adaptation and marginal staining.

Positivity of dengue, chikungunya, and Zika infections in women in Northeast Brazil post-Zika epidemic.

The state of Ceará, in the Northeast Region of Brazil, presents the simultaneous circulation of Zika (ZIKV), dengue (DENV) and chikungunya (CHIKV) viruses. In 2017 there were a high number of cases of these three arboviruses, especially CHIKV. Here, we detected the presence of arboviruses ZIKV, DENV and CHIKV and their coinfections in women in endemic regions of the city of Fortaleza, Ceará in a post-Zika epidemic year. Sociodemographic and environmental characteristics associated with arbovirus positivity were also analyzed. Women (n = 1289) between 15 and 39 years old were included. RT-qPCR was performed for virus detection and IgM antibody positivity was also analyzed. One hundred and six (8.3%) participants were positive for one or more arboviruses. Monoinfections (76; 5.9%) were distributed between 22 (1.7%) for ZIKV, 39 (3.1%) for DENV and 15 (1.2%) for CHIKV. Co-infections were detected in 30 (2.3%) of the positive participants and one case with triple infection was found. IgM positivity was found in 2.4% of ZIKV RT-qPCR, 9.6% of DENV and 16.3% of CHIKV. RT-qPCR positivity for arboviruses was associated with low socioeconomic class and presence of a water box sealing in the household. A higher positivity to the three viruses occurred in the month with the lowest wind velocity, which was also preceded by the highest peak of rain and humidity. We identified the simultaneous circulation and co-infection of ZIKV, DENV and CHIKV in Fortaleza in a post-Zika epidemic year. We also highlight the need for continuous epidemiological surveillance combined with molecular diagnostic tools.

Role of Sirtuins in the Pathobiology of Onco-Hematological Diseases: A PROSPERO-Registered Study and In Silico Analysis.

The sirtuins (SIRT) gene family (SIRT1 to SIRT7) contains the targets implicated in cellular and organismal aging. The role of SIRTs expression in the pathogenesis and overall survival of patients diagnosed with solid tumors has been widely discussed. However, studies that seek to explain the role of these pathways in the hematopoietic aging process and the consequences of their instability in the pathogenesis of different onco-hematological diseases are still scarce. Therefore, we performed a systematic review (registered in PROSPERO database #CRD42022310079) and in silico analysis (based on GEPIA database) to discuss the role of SIRTs in the advancement of pathogenesis and/or prognosis for different hematological cancer types. In summary, given recent available scientific evidence and in silico gene expression analysis that supports the role of SIRTs in pathobiology of hematological malignances, such as leukemias, lymphomas and myeloma, it is clear the need for further high-quality research and clinical trials that expands the SIRT inhibition knowledge and its effect on controlling clonal progression caused by genomic instability characteristics of these diseases. Finally, SIRTs represent potential molecular targets in the control of the effects caused by aging on the failures of the hematopoietic system that can lead to the involvement of hematological neoplasms.

Evaluation of the Bond Strength of Self-Etching Adhesive Systems Containing HEMA and 10-MDP Monomers: Bond Strength of Adhesives Containing HEMA and 10-MDP.

The aim of this in vitro study was to assess the bond strength of self-etching adhesives containing HEMA and 10-MDP monomers. Twenty-four bovine teeth were divided into three groups. Two cylinders of composite resin were made in each tooth (n = 16): G1-Prime and Bond Universal (control); G2-OptiBond All-in-One (HEMA); and G3-Clearfil SE (10-MDP and HEMA). After 24-hour storage in distilled water, the specimens were fixed to a universal testing machine (Kratos Equipamentos Ltda.) for the microshear test at a speed of 0.5 mm/min. A qualitative analysis of the fracture pattern was also performed using scanning electron microscopy (500× magnification). The normality of sample data distribution was determined using the Shapiro-Wilk test. The results were assessed using the Kruskal-Wallis test, and α level of 5% was used for the analysis. The results indicated a statistical difference (p > 0.05) between G3 (15.6080 MPa) and G2 (11.2180 MPa). No statistical difference was observed when G1 (14,6325 MPa) was compared with the other two groups. It was also observed that a mixed fracture pattern was predominant in all groups. The self-etching adhesive containing HEMA and 10-MDP monomers showed to be promising in increasing the bond strength between the dental substrate and the composite resin, whereas the adhesive containing only HEMA exhibited lower bond strength to dentin.

The effect of photobiomodulation using low-level laser therapy on tooth sensitivity after dental bleaching: a systematic review.

The authors aimed to conduct a systematic review to assess data from the current literature on the effectiveness of low-level laser therapy (LLLT) in preventing tooth sensitivity (TS) after tooth whitening (DB). PRISMA guidelines for systematic reviews were followed. Clinical trials evaluating the treatment of LLLT in patients with sensitivity after tooth whitening were selected. A full bibliographic search was performed on May 4, 2021, in the following databases: Embase, MEDLINE via PubMed, SciELO, VHL Regional Portal, Web of Science, Gray Literature, Scopus, ClinicalTrials.gov and Cochrane Library. This study followed Cochrane's recommendations for analyzing risk of bias. A total of 1054 studies were found (255 studies were excluded because they were duplicates and 785 because of titles and abstracts). Only 14 articles were selected for analysis, of which eight were excluded because they had one or more exclusion criteria, resulting in six articles included in this systematic review, the vast majority being classified as low risk of bias. The studies reviewed indicated that LLLT showed promise in preventing TS after TB. However, evidence is limited and more clinical trials with low risk of bias are needed to reach a definitive conclusion on the action of LLLT in pain control after TB.

Tissue methylation and demethylation influence translesion synthesis DNA polymerases (TLS) contributing to the genesis of chromosomal abnormalities in myelodysplastic syndrome.

AIMS: DNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle. METHODS: We evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (POLH, POLL, REV3L, POLN, POLQ, POLI, POLK, IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF6, IRF-7, IRF-8,IRF-9, MAD2, CDC20, AURKA, AURKB and TPX2). RESULTS: The M-score (5mC) was significantly higher in patients with chromosomal abnormalities than patients with normal karyotype (95% CI -27.127779 to -2.368020; p=0.022). We observed a higher 5mC/5hmC ratio in patients classified as high-risk subtypes compared with low-risk subtypes (95% CI -72.922115 to -1.855662; p=0.040) as well as patients with hypercellular bone marrow compared with patients with normocellular/hypocellular bone marrow (95% CI -69.189259 to -0.511828; p=0.047) and with the presence of dyserythropoiesis (95% CI 17.077703 to 51.331388; p=0.001). DNA pols with translesion activity are significantly influenced by methylation. As 5mC immunoexpression increases, the expressions of POLH (r=-0.816; r2 =0.665; p=0.000), POLQ (r=-0.790; r2=0.624; p=0.001), PCNA (r=-0.635; r2=0.403; p=0.020), POLK (r=-0.633; r2=0.400; p=0.036 and REV1 (r=-0.578; r2=0.334; p=0.049) decrease. CONCLUSIONS: Our results confirm that there is an imbalance in the DNA methylation in MDS, influencing the development of chromosomal abnormalities which may be associated with the low expression of DNA polymerases with translesion synthesis polymerases activity.

Antimicrobial Potential of Metabolites in Fungal Strains Isolated from a Polluted Stream: Annulohypoxylon stygium WL1B5 Produces Metabolites against Extended-Spectrum Beta-Lactamase-Positive Escherichia coli.

The emergence of multidrug resistance in bacterial pathogens is a growing public health concern requiring solutions including the discovery of new antimicrobial drugs. Fungi have been used for decades as a source of antimicrobials. Ongoing screenings for newly characterized fungal strains producing antimicrobials include environments that are difficult to access like the deep sea, glaciers, wastewaters and environments polluted due to human activity. In the present study, fungal microorganisms were isolated from water samples taken from a polluted stream in the city of Manaus, AM, Brazil, and screened for antimicrobial effects against Escherichia coli. Using extracts from five isolates (Annulohypoxylon stygium WL1B5, Colletotrichum fructicola WL3B9, Clonostachys rosea WL5B18, Clonostachys rosea WL8B28 and Trichoderma harzianum WL9B49), antimicrobial activity against the reference strains Escherichia coli ATCC 25922 as well as E. coli NCTC 13353, an extended-spectrum beta-lactamase-positive strain, was observed. Inhibition zones ranged from 1 to 35.9 mm and a minimum inhibitory concentration of 400 µg/mL could be demonstrated. Assessments of the metabolites of Annulohypoxylon stygium WL1B5 allowed us to identify nodulisporone and daidzein, which have already been associated with antimicrobial activity. The findings confirm the feasibility of isolating fungal strains from polluted sites producing metabolites that can serve as potential future alternatives for the treatment of multidrug-resistant bacteria.

Chemical and technological attributes of sugarcane as functions of organomineral fertilizer based on filter cake or sewage sludge as organic matter sources.

Sugarcane is one of the main alternative sources of biomass for the biofuel sector, and its large-scale production has considerable environmental impact. Organomineral fertilizers formulated with potential environmental contaminants, such as filter cake and sewage sludge, positively influence plant growth and development. The objective of the present study was to evaluate the chemical and physical characteristics of sugarcane fertilized with pelletized organomineral fertilizers based on filter cake or sewage sludge. Eight field treatments were applied, based on three organomineral fertilizer compositions (50%, 100%, and 150%) associated with two organic matter (OM) sources (filter cake or sewage sludge), in addition to a control with 100% mineral fertilizer application, and a no-fertilization control (0%). Sugarcane attributes were evaluated during two consecutive harvests. The weights of stalks per hectare (ton ha-1), sugarcane productivity (ton ha-1), quantity of sugar per hectare (TSH, ton ha-1), and physicochemical properties of sugarcane juice (pol [%], Brix [%], purity [%], and fiber [%]) were evaluated. There were no significant differences in the attributes between OM sources or organomineral fertilization treatments and the exclusive mineral fertilization. The organomineral fertilizer application rate recommended for maximum quantitative and qualitative sugarcane in the first sugarcane harvest was between 2 and 9% above the regular recommendation for mineral fertilizer, regardless of the OM source. In the second harvest, the sewage sludge source increased total sugar and sugarcane per hectare by 4.68 and 4.19%, respectively, compared to the sugarcane filter cake source. Sewage sludge and sugarcane filter cake are viable alternatives for organomineral composition and could improve economic returns and minimize negative environmental impacts in sugarcane cultivation systems.

Production and composition of Lavender oil: nutritional management and cultivation systems / Producción y composición de aceite de lavanda: manejo nutricional y sistemas de cultivo

The objective was to evaluate the production and composition of lavender essential oil, simultaneously at open field and greenhouse, in spring-summer season, under different types of fertilization. Each cultivation system was considered an experiment (field and greenhouse), and in both, the experimental design used was randomized blocks, with five treatments, being fertilization with nutrient source -100% mineral (100%M), 100% organic (100%O), 100% organomineral (100%OM), 50% organomineral (50%OM), and without fertilization (control), and three repetitions. Better performance and productivity of Lavandula dentatais related to respectively 100% OM and 50% OM fertilization in the field and greenhouse. The essential oil content does not differ between cultivation systems and kind of fertilizers, and the majorities compounds were 1.8-cineol, fenchone and camphor.

El objetivo fue evaluar la producción y composición del aceite esencial de lavanda a campo abierto e invernadero simultáneamente, en la temporada primavera-verano, bajo diferentes tipos de fertilización. Cada sistema de cultivo fue considerado un experimento (campo e invernadero), y en ambos, el diseño experimental utilizado fue bloques al azar, con cinco tratamientos, siendo la fertilización con fuente de nutrientes 100% mineral (100% M), 100% orgánico (100% O), 100% organomineral (100% MO), 50% organomineral (50% MO), y sin fertilización (control), y tres repeticiones. Un mejor rendimiento y productividad de Lavandula dentata está relacionado con una fertilización de 100%OM y 50% OM en el campo y en invernadero, respectivamente. El contenido de aceite esencial no difiere entre sistemas de cultivo y tipo de fertilizante, y los compuestos mayoritarios fueron 1.8-cineol, fenchone y alcanfor.

Germline Compound Heterozygous Variants Identified in the STXBP2 Gene Leading to a Familial Hemophagocytic Lymphohistiocytosis Type 5: A Case Report.

Familial hemophagocytic lymphohistiocytosis (FHL) is a rare, potentially fatal autosomal-recessive immunodeficiency, and STXBP2 mutations have been associated with FHL type 5 (FHL-5). Here, we report a case of a 2-year-old boy who presented with recurrent fever, hepatosplenomegaly, pancytopenia, hyperferritinemia, and hypofibrinogenemia since 4 months of age. His genetic analysis revealed a compound heterozygosity of the STXBP2 gene with a described pathogenic mutation, c.1247-1G>C (splicing acceptor site), harbored by his father and a likely pathogenic variant of uncertain significance (VUS), c.704G>A (p.Arg235Gln), harbored by his mother. He was diagnosed as compound heterozygous for FHL-5 and was treated with the HLH-2004 protocol. Since treatment, this patient has been in remission, and he is being evaluated for a hematopoietic stem cell transplantation (HSCT).

Plasma IL-33 levels are decreased in patients with high-risk myelodysplastic syndrome and show no correlation with pro-inflammatory IL-6 levels.

Aberrant inflammatory signaling has been shown to be a key pathogenic driver in myelodysplastic syndromes (MDS). Abnormal IL-33 expression has been implicated in inflammatory, immune-related disorders and, some tumors. However, its role in MDS remains widely unknown. This study aimed to evaluate the relationship between plasma levels of IL-33, clinical and prognostic data and, IL-6 levels in 101 patients with MDS. A comparative group of 59 healthy individuals was also evaluated. Plasma levels of cytokines were determined by enzyme-linked immunosorbent assay. Lower levels of IL-33 were found in patients with MDS when compared to the control group (p = 0.001), mainly in patients with more advanced stages of the disease and worse prognosis. No significant correlation between the levels of IL-33 and IL-6 was observed (r = 0.175; p = 0.081). These results reinforce the close association between immunological disorders and the pathogenesis of MDS. A greater understanding of the role of inflammatory cytokines in the disease can potentially provide new diagnosis and prognosis markers and new therapeutic targets.

ERVs-TLR3-IRF axis is linked to myelodysplastic syndrome pathogenesis.

Toll-like receptors are mutated or overexpressed in up to 50% of patients with myelodysplastic syndrome (MDS). Endogenous retroviruses (ERV) trigger TLR3 leading to interferon regulatory genes (IRFs) activation. We evaluated if the ERVs-TLR3-IRF axis activation would be linked to MDS pathogenesis and we also conducted a detailed cancer analysis of the ERVs, TLR3 and IRFs gene expression in 30 cancer types using GEPIA database. Seventy-nine bone marrow samples from patients with MDS were evaluated for cytogenetics and quantitative real­time PCR of TLR3, ERVK6, ERVW-1, ERV3-1, IRF3 and IRF7. Patients with dyserythropoiesis showed higher TLR3 (p = 0.035), ERVK6 (p = 0.001), ERVW1 (p = 0.045) and ERV3-1 (p = 0.016) expression than patients without dyserythropoiesis. Upregulation of Interferon Regulatory Factors, IRF3 and IRF7, was associated with poor prognostic markers in MDS such as > 10% of blasts (p = 0.003-IRF3; p = 0.009-IRF7), low platelets count (< 50.000/mm3) (p = 0.001-IRF3; p = 0.021-IRF7), transfusion dependence (p = 0.014-IRF3) and chromosomal abnormalities (p = 0.036-IRF7). We found strong correlations between ERVK6-ERVW1 (r = 0.800; r2 = 0.640; p = 0.000), ERVW1-ERV3-1 (r = 0.715; r2 = 0.511; p = 0.000), and IRF7-IRF3 (r = 0.567; r2 = 0.321; p = 0.000) and moderate correlation between ERVK6-ERV3-1(r = 0.485; r2 = 0.235; p = 0.000), ERVW1-IRF7 (r = 0.389; r2 = 0.151; p = 0.001), ERVW1-IRF3 (r = 0.357; r2 = 0.127; p = 0.004), ERV3-1-IRF7 (r = 0.314; r2 = 0.098; p = 0.009), and ERV3-1-IRF3 (r = 0.324; r2 = 0.104; p = 0.007). Using GEPIA Database in 30 cancer types, we detected a typical pattern of upregulation as here presented in MDS. We suggest TLR3 activation by ERVs is linked to MDS pathogenesis leading to bone marrow failure. Abnormal double-stranded RNA (dsRNA) expression of Endogenous Retroviruses (ERV) triggers TLR3 hyperactivation. This induces IRF3, IRF7, and NF-kB to translocate to the nucleus and activate transcription of IFNα/ß which binds to the type I-IFN receptor promoting interferon response. Thus, just as TLR4 induces a crucial myeloid shift, the ERVs-TLR3 axis may play an important role in establishing one of the most striking characteristics in MDS, dyserythropoiesis.