Exploring Real-World HER2-Low Data in Early-Stage Triple-Negative Breast Cancer: Insights and Implications.

Purpose: This study aimed to compare the clinical behavior, clinicopathological and sociodemographic characteristics of patients with early-stage triple-negative breast cancer (TNBC) who belong to the HER2-low and HER2-zero subgroups. Patients and Methods: This study involved a thorough search in the internal database of a single Brazilian institution to identify women with TNBC who underwent neoadjuvant chemotherapy (NACT) followed by curative surgery within the period from January 2010 to December 2014. HER2 analysis through immunohistochemistry (IHC) and, if required, amplification by in situ hybridization, was conducted using core biopsy samples. The study assesses outcomes of residual cancer burden (RCB), event-free survival (EFS), and overall survival (OS). Results: A total of 170 cases were analyzed, with a mean age of 51.4 years (standard deviation, SD 11.2). The HER2 status was categorized as IHC 0, 1+, or 2+ in 80 (47.1%), 73 (42.9%), and 17 (10%) patients, respectively. No significant differences were observed in the prevalence of clinical pathological characteristics among the subgroups. The absence of significant results for clinicopathological and demographic features hindered the multivariate analysis of HER2 subgroups. Similarly, no significant differences were found in the RCB, EFS, and OS outcomes between HER2 subgroups. Conclusion: The findings of this study suggest that, in early-stage TNBC, the clinical behavior and survival outcomes of the HER2-low subgroup may not differ significantly from those of the HER2-zero subgroup.

Non-Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417).

PURPOSE: Despite the advances in the approach to non-small-cell lung cancer (NSCLC) with CNS metastasis, access to timely diagnosis and treatment may not be optimal in many instances. Our main objective was to describe a cohort of patients with NSCLC with brain metastases from public and private cancer centers, and the differences between patients' presentation, treatment, and outcomes. METHODS: GBOT-LACOG 0417 is a multi-institutional retrospective cohort study of patients diagnosed with NSCLC and CNS metastasis in Brazil. All patients had confirmed diagnosis of NSCLC between January 2010 and December 2015. CNS metastases were identified by imaging. RESULTS: A total of 273 patients were included. Patients treated at public institutions were more often Black or Brown (38.8% v 15.4%), current or former smoker (88.6% v 60.0%), of squamous cell histology (25.0% v 9.1%), EGFR- and ALK-negative (95.9% v 74.9%), and were less frequently assessed by using brain magnetic resonance imaging (38.8% v 83.6%). At public institutions, patients were more often symptomatic (78.1% v 44.6%) and had worse performance status (Eastern Cooperative Oncology Group 2 or higher 61.5% v 10.3%). CNS metastases were larger (median size 25 v 15 mm) and more often surrounded by edema (67.7% v 55.2%) at public institutions. Patients at public institutions were more frequently treated with whole-brain radiation therapy (72.9% v 45.4%) and less frequently with radiosurgery (6.3% v 24.1%). Among patients from private care, median overall survival was 24.2 months (95% CI, 20.0 to 30.6), significantly higher than in public care (median 12.1 months; 95% CI, 6.7 to 13.6; P < .001). CONCLUSION: Our results demonstrate the discrepancy between public and private health care system in the critical setting of patients with CNS metastasis from NSCLC.

Complete Chromosome-Scale Genome Sequence Resource for Sporisorium panici-leucophaei, the Causal Agent of Sourgrass Smut Disease.

Here, we present the first complete chromosome-level genome assembly of the smut fungus strain Sporisorium panici-leucophaei SPL10A, the causal agent of the sourgrass (Digitaria insularis) smut disease. Combining Illumina paired-end and Nanopore long reads, we generated a final assembly composed of 23 chromosomes (22 nuclear and one mitochondrial) with 18,915,934 bp. Gene prediction accomplished using extrinsic evidence from the sugarcane smut fungus Sporisorium scitamineum originated a total of 6,402 protein-encoding genes. The secretome (388 proteins) and the effectorome repertoires (68 candidates) were also predicted, given their crucial roles in plant-pathogen interactions. The complete telomere-to-telomere chromosome sequences of this poorly studied fungus will provide a valuable resource for future comparative genomic studies among smuts to unravel their underlying pathogenicity mechanisms.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Wheat blast: from its origins in South America to its emergence as a global threat.

Wheat blast was first reported in Brazil in 1985. It spread rapidly across the wheat cropping areas of Brazil to become the most important biotic constraint on wheat production in the region. The alarming appearance of wheat blast in Bangladesh in 2016 greatly increased the urgency to understand this disease, including its causes and consequences. Here, we summarize the current state of knowledge of wheat blast and aim to identify the most important gaps in our understanding of the disease. We also propose a research agenda that aims to improve the management of wheat blast and limit its threat to global wheat production.

Novel Insights Into the Early Stages of Ratoon Stunting Disease of Sugarcane Inferred from Transcript and Protein Analysis.

Despite of the importance of ratoon stunting disease, little is known on the responses of sugarcane to its causal agent, the vascular bacterial endophyte Leifsonia xyli subsp. xyli. The transcriptome and proteome of young plants of a susceptible cultivar with no symptoms of stunting but with relative low and high bacterial titers were compared at 30 and 60 days after inoculation. Increased bacterial titers were associated with alterations in the expression of 267 cDNAs and in the abundance of 150 proteins involved in plant growth, hormone metabolism, signal transduction and defense responses. Some alterations are predicted to benefit the pathogen, such as the up-regulation of genes involved in the synthesis of methionine. Also, genes and proteins of the cell division cycle were all down-regulated in plants with higher titers at both times. It is hypothesized that the negative effects on cell division related to increased bacterial titers is cumulative over time and its modulation by other host and environmental factors results in the stunting symptom.

Novel insights into the early stages of ratoon stunting disease of sugarcane inferred from transcript and protein analysis

Despite of the importance of ratoon stunting disease, little is known on the responses of sugarcane to its causal agent, the vascular bacterial endophyte Leifsonia xyli subsp. xyli. The transcriptome and proteome of young plants of a susceptible cultivar with no symptoms of stunting but with relative low and high bacterial titers were compared at 30 and 60 days after inoculation. Increased bacterial titers were associated with alterations in the expression of 267 cDNAs and in the abundance of 150 proteins involved in plant growth, hormone metabolism, signal transduction and defense responses. Some alterations are predicted to benefit the pathogen, such as the up-regulation of genes involved in the synthesis of methionine. Also, genes and proteins of the cell division cycle were all down-regulated in plants with higher titers at both times. It is hypothesized that the negative effects on cell division related to increased bacterial titers is cumulative over time and its modulation by other host and environmental factors results in the stunting symptom.

Novel insights into the early stages of ratoon stunting disease of sugarcane inferred from transcript and protein analysis

Despite of the importance of ratoon stunting disease, little is known on the responses of sugarcane to its causal agent, the vascular bacterial endophyte Leifsonia xyli subsp. xyli. The transcriptome and proteome of young plants of a susceptible cultivar with no symptoms of stunting but with relative low and high bacterial titers were compared at 30 and 60 days after inoculation. Increased bacterial titers were associated with alterations in the expression of 267 cDNAs and in the abundance of 150 proteins involved in plant growth, hormone metabolism, signal transduction and defense responses. Some alterations are predicted to benefit the pathogen, such as the up-regulation of genes involved in the synthesis of methionine. Also, genes and proteins of the cell division cycle were all down-regulated in plants with higher titers at both times. It is hypothesized that the negative effects on cell division related to increased bacterial titers is cumulative over time and its modulation by other host and environmental factors results in the stunting symptom.

Functional analysis of oxidative burst in sugarcane smut-resistant and -susceptible genotypes.

MAIN CONCLUSION: Smut pathogen induced an early modulation of the production and scavenging of reactive oxygen species during defence responses in resistant sugarcane that coincided with the developmental stages of fungal growth. Sporisorium scitamineum is the causal agent of sugarcane smut disease. In this study, we characterized sugarcane reactive oxygen species (ROS) metabolism in response to the pathogen in smut-resistant and -susceptible genotypes. Sporisorium scitamineum teliospore germination and appressorium formation coincided with H2O2 accumulation in resistant plants. The superoxide dismutase (SOD) activity was not responsive in any of the genotypes; however, a higher number of isoenzymes were detected in resistant plants. In addition, related to resistance were lipid peroxidation, a decrease in catalase (CAT), and an increase in glutathione S-transferase (GST) activities and an earlier transcript accumulation of ROS marker genes (CAT3, CATA, CATB, GST31, GSTt3, and peroxidase 5-like). Furthermore, based on proteomic data, we suggested that the source of the increased hydrogen peroxide (H2O2) may be due to a protein of the class III peroxidase, which was inhibited in the susceptible genotype. H2O2 is sensed and probably transduced through overlapping systems related to ascorbate-glutathione and thioredoxin to influence signalling pathways, as revealed by the presence of thioredoxin h-type, ascorbate peroxidase, and guanine nucleotide-binding proteins in the infected resistant plants. Altogether, our data depicted the balance of the oxidative burst and antioxidant enzyme activity in the outcome of this interaction.

Molecular variability and genetic relationship among Brazilian strains of the sugarcane smut fungus.

Sporisorium scitamineum is the fungus that causes sugarcane smut disease. Despite of the importance of sugarcane for Brazilian agribusiness and the persistence of the pathogen in most cropping areas, genetic variation studies are still missing for Brazilian isolates. In this study, sets of isolates were analyzed using two molecular markers (AFLP and telRFLP) and ITS sequencing. Twenty-two whips were collected from symptomatic plants in cultivated sugarcane fields of Brazil. A total of 41 haploid strains of compatible mating types were selected from individual teliospores and used for molecular genetic analyses. telRFLP and ITS analyses were expanded to six Argentine isolates, where the sugarcane smut was first recorded in America. Genetic relationship among strains suggests the human-mediated dispersal of S. scitamineum within the Brazilian territory and between the two neighboring countries. Two genetically distinct groups were defined by the combined analysis of AFLP and telRFLP. The opposite mating-type strains derived from single teliospores were clustered together into these main groups, but had not always identical haplotypes. telRFLP markers analyzed over two generations of selfing and controlled outcrossing confirmed the potential for emergence of new variants and occurrence of recombination, which are relevant events for evolution of virulence and environmental adaptation.

GST activity and membrane lipid saturation prevents mesotrione-induced cellular damage in Pantoea ananatis.

Callisto(®), containing the active ingredient mesotrione (2-[4-methylsulfonyl-2-nitrobenzoyl]1,3-cyclohenanedione), is a selective herbicide that controls weeds in corn crops and is a potential environmental contaminant. The objective of this work was to evaluate enzymatic and structural changes in Pantoea ananatis, a strain isolated from water, in response to exposure to this herbicide. Despite degradation of mesotrione, probably due a glutathione-S-transferase (GST) pathway in Pantoea ananatis, this herbicide induced oxidative stress by increasing hydrogen peroxide production. Thiol fragments, eventually produced after mesotrione degradation, could be involved in increased GST activity. Nevertheless, there was no peroxidation damage related to this production, as malondialdehyde (MDA) synthesis, which is due to lipid peroxidation, was highest in the controls, followed by the mesotrione- and Callisto(®)-treated cultures at log growth phase. Therefore, P. ananatis can tolerate and grow in the presence of the herbicide, probably due an efficient control of oxidative stress by a polymorphic catalase system. MDA rates depend on lipid saturation due to a pattern change to a higher level of saturation. These changes are likely related to the formation of GST-mesotrione conjugates and mesotrione degradation-specific metabolites and to the presence of cytotoxic adjuvants. These features may shift lipid membrane saturation, possibly providing a protective effect to bacteria through an increase in membrane impermeability. This response system in P. ananatis provides a novel model for bacterial herbicide tolerance and adaptation in the environment.

Evaluation of protein extraction methods for enhanced proteomic analysis of tomato leaves and roots.

Proteomics is an outstanding area in science whose increasing application has advanced to distinct purposes. A crucial aspect to achieve a good proteome resolution is the establishment of a methodology that results in the best quality and wide range representation of total proteins. Another important aspect is that in many studies, limited amounts of tissue and total protein in the tissue to be studied are found, making difficult the analysis. In order to test different parameters, combinations using minimum amount of tissue with 4 protocols for protein extraction from tomato (Solanum lycopersicum L.) leaves and roots were evaluated with special attention to their capacity for removing interferents and achieving suitable resolution in bidimensional gel electrophoresis, as well as satisfactory protein yield. Evaluation of the extraction protocols revealed large protein yield differences obtained for each one. TCA/acetone was shown to be the most efficient protocol, which allowed detection of 211 spots for leaves and 336 for roots using 500 µg of leaf protein and 800 µg of root protein per gel.

Complete Genome Sequence of Sporisorium scitamineum and Biotrophic Interaction Transcriptome with Sugarcane.

Sporisorium scitamineum is a biotrophic fungus responsible for the sugarcane smut, a worldwide spread disease. This study provides the complete sequence of individual chromosomes of S. scitamineum from telomere to telomere achieved by a combination of PacBio long reads and Illumina short reads sequence data, as well as a draft sequence of a second fungal strain. Comparative analysis to previous available sequences of another strain detected few polymorphisms among the three genomes. The novel complete sequence described herein allowed us to identify and annotate extended subtelomeric regions, repetitive elements and the mitochondrial DNA sequence. The genome comprises 19,979,571 bases, 6,677 genes encoding proteins, 111 tRNAs and 3 assembled copies of rDNA, out of our estimated number of copies as 130. Chromosomal reorganizations were detected when comparing to sequences of S. reilianum, the closest smut relative, potentially influenced by repeats of transposable elements. Repetitive elements may have also directed the linkage of the two mating-type loci. The fungal transcriptome profiling from in vitro and from interaction with sugarcane at two time points (early infection and whip emergence) revealed that 13.5% of the genes were differentially expressed in planta and particular to each developmental stage. Among them are plant cell wall degrading enzymes, proteases, lipases, chitin modification and lignin degradation enzymes, sugar transporters and transcriptional factors. The fungus also modulates transcription of genes related to surviving against reactive oxygen species and other toxic metabolites produced by the plant. Previously described effectors in smut/plant interactions were detected but some new candidates are proposed. Ten genomic islands harboring some of the candidate genes unique to S. scitamineum were expressed only in planta. RNAseq data was also used to reassure gene predictions.

Differential responses of the antioxidant system of ametryn and clomazone tolerant bacteria.

The herbicides ametryn and clomazone are widely used in sugarcane cultivation, and following microbial degradation are considered as soil and water contaminants. The exposure of microorganisms to pesticides can result in oxidative damage due to an increase in the production of reactive oxygen species (ROS). This study investigated the response of the antioxidant systems of two bacterial strains tolerant to the herbicides ametryn and clomazone. Bacteria were isolated from soil with a long history of ametryn and clomazone application. Comparative analyses based on 16S rRNA gene sequences revealed that strain CC07 is phylogenetically related to Pseudomonas aeruginosa and strain 4C07 to P. fulva. The two bacterial strains were grown for 14 h in the presence of separate and combined herbicides. Lipid peroxidation, reduced glutathione content (GSH) and antioxidant enzymes activities were evaluated. The overall results indicated that strain 4C07 formed an efficient mechanism to maintain the cellular redox balance by producing reactive oxygen species (ROS) and subsequently scavenging ROS in the presence of the herbicides. The growth of bacterium strain 4C07 was inhibited in the presence of clomazone alone, or in combination with ametryn, but increased glutathione reductase (GR) and glutathione S-transferase (GST) activities, and a higher GSH concentration were detected. Meanwhile, reduced superoxide dismutase (SOD), catalase (CAT) and GST activities and a lower concentration of GSH were detected in the bacterium strain CC07, which was able to achieve better growth in the presence of the herbicides. The results suggest that the two bacterial strains tolerate the ametryn and clomazone herbicides with distinctly different responses of the antioxidant systems.

Water stress reveals differential antioxidant responses of tolerant and non-tolerant sugarcane genotypes.

The biochemical responses of the enzymatic antioxidant system of a drought-tolerant cultivar (IACSP 94-2094) and a commercial cultivar in Brazil (IACSP 95-5000) grown under two levels of soil water restriction (70% and 30% Soil Available Water Content) were investigated. IACSP 94-2094 exhibited one additional active superoxide dismutase (Cu/Zn-SOD VI) isoenzyme in comparison to IACSP 95-5000, possibly contributing to the heightened response of IACSP 94-2094 to the induced stress. The total glutathione reductase (GR) activity increased substantially in IACSP 94-2094 under conditions of severe water stress; however, the appearance of a new GR isoenzyme and the disappearance of another isoenzyme were found not to be related to the stress response because the cultivars from both treatment groups (control and water restrictions) exhibited identical changes. Catalase (CAT) activity seems to have a more direct role in H2O2 detoxification under water stress condition and the shift in isoenzymes in the tolerant cultivar might have contributed to this response, which may be dependent upon the location where the excessive H2O2 is being produced under stress. The improved performance of IACSP 94-2094 under drought stress was associated with a more efficient antioxidant system response, particularly under conditions of mild stress.

Atividade in vitro da tigeciclina frente aos isolados de Acinetobacter baumannii no Hospital Júlia Kubitschek da Fundação Hospitalar de Minas Gerais / In vitro activity of tigecycline against Acinetobacter baumannii isolates in Hospital Júlia Kubitschek of Minas Gerais Hospital Foundation

Acinetobacter baumannii, importante patógeno nosocomial, pode ser difícil de ser tratado devido à resistência a váriasclasses de antimicrobianos, evidenciando a necessidade do uso de drogas de novas classes terapêuticas para estes microorganismos. A tigeciclina, uma nova glicilciclina, tem um amplo espectro de ação, incluindo Acinetobacter baumannii. O objetivo deste estudo foi verificar a atividade da tigeciclina contra cepas de Acinetobacter baumannii isoladas entre setembro de 2008 a maio de 2009 de pacientes internados no Hospital Júlia Kubitschek. Os testes de sensibilidade pelo método de disco difusão foram realizados de acordo com metodologia padronizada pelo CLSI. Com relação ao perfil de resistência, foi observado que a maioria das cepas de Acinetobacter baumannii eram multirresistentes e a tigeciclina apresentou atividade in vitro contra todas estas cepas.

Acinetobacter baumannii, a nosocomial pathogen, can be problematic to treat due to resistance to multiple classes ofantibiotics, further highlighting the need for new therapeutic agents effective against this organism. Tigecycline, a novel glycylcycline, has a broad spectrum of activity which includes Acinetobacter baumannii. The aim of this study was to verify the tigecycline activity profile against A. baumannii isolated between September 2008- May 2009 from patients interned in Hospital Júlia Kubitschek. To perform the assay, disk diffusion susceptibility testing was performed according to the CLSI guidelines. Regarding the profile ofresistance, it was observed that the majority of the strains of Acinetobacter baumannii were multiresistant and tigecycline were active in vitro against all of this strains.

Atendimento odontológico ao paciente diabético tipo 1: [revisão] / Dental care for type 1 diabetic patients: [review]

Diabetes mellitus (DM) é uma desordem metabólica caracterizada por uma alteração nos níveis de insulina. Há dois tipos principais de DM: tipo 1, onde há deficiência total de secreção de insulina, e tipo 2, onde há uma inadequada secreção compensatória. Dentre as alterações bucais destes pacientes estão: baixo fluxo salivar e aumento de seu pH e viscosidade, que são fatores de risco para cárie. A presente revisão da literatura tem por objetivo fornecer maiores informações sobre esta síndrome, assim, como orientar o clínico como proceder com estes pacientes.

Diabetes mellitus (DM) is a metabolic disorder characterized by deficient management of insulin. Two main types of DM exist: type 1, a total deficiency in insulin secretion, and type 2, a combination of resistance to insulin action and inadequate compensatory insulin secretion. Amongst the buccal alterations of these patients, there are reduction of the flow and increase of the saliva's acidity and viscosity, risk factors for caries. This review intends to provide not only general information about this syndrome, but also orientations how to preceed with these patients.

Selection of microorganisms degrading S-Metolachlor herbicide

The aim of this work was to study herbicide degradation through selected microorganisms from humus and soil subjected to different plantation systems. The following bacterial species were identified: Klebsiella pneumoniae pneumoniae GC s.B strain 1, Pseudomonas alcaligenes, Enterobacter aerogenes GC s.A and Klebsiella pneumoniae pneumoniae GC s.B strain 2. Growth studies yet suggested the possibility of a very long lag phase. Although, culture with the herbicide presented biofilm formation and there were color changes in the herbicide that could have interfered with the espectrophotometry readings. After 5 days of incubation at 35°C, the difference in the concentration of herbicide was 14.42 percent on average and after 10 days, 35.01 percent.

Os herbicidas representam 65 por cento do consumo geral, sendo que o S-Metolachlor é um dos mais utilizados e está trazendo preocupações ambientais. Objetivamos detectar a degradação do S-Metolachlor por microorganismos de solos sob plantio. Foram identificadas as espécies bacterianas: Klebsiella pneumoniae pneumoniae GC s.B linhagem 1, Pseudomonas alcaligenes, Enterobacter aerogenes GC s.A e Klebsiella pneumoniae pneumoniae GC s.B linhagem 2. Resultados da curva de crescimento por espectrofotometria não permitiram definir diferentes fases, levando a pensar em uma fase Lag longa. Frascos de cultura demonstraram a formação de biofilme, provocando mudança na cor do herbicida, interferindo na leitura do crescimento. É possível a existência de fase Log, mas não detectável pelo método. Após 5 dias de incubação a 35°C, a diferença média de concentração do S-Metolachlor foi de 14.42 por cento, e em 10 dias, 35.01 por cento. Observou-se o aparecimento de um halo em volta das colônias, o que corrobora a hipótese de degradação microbiana do herbicida.