The detection of KPC-2, NDM-1, and VIM-2 carbapenemases in international clones isolated from fresh vegetables highlights an emerging food safety issue.

Resistance to carbapenems emerged in clinical settings and has rapidly spread to other sectors, such as food and the environment, representing a One Health problem. In this regard, vegetables contaminated by critical priority pathogens have raised global concerns. Here, we have performed a whole-genome sequence-based analysis of extensively drug-resistant Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa strains isolated from cabbage, spinach, and lettuce, respectively. Genomic analysis revealed the emergence of international and high-risk clones belonging to ST340, ST155, and ST233, harboring a broad resistome to clinically important antimicrobials. In this context, K. pneumoniae, E. coli, and P. aeruginosa strains carried blaKPC-2, blaNDM-1, and blaVIM-2, respectively. The blaKPC-2 gene with a non-Tn4401 element (NTEKPC-Ic) was located on an IncX3-IncU plasmid, while the blaVIM-2 gene was associated with a Tn402-like class 1 integron, In559, on the chromosome. Curiously, the blaNDM-1 gene coexisted with the blaPER-2 gene on an IncC plasmid and the regions harboring both genes contained sequences of Tn3-like element ISKox2-like family transposase. Comparative genomic analysis showed interspecies and clonal transmission of carbapenemase-encoding genes at the human-animal-environmental interface. These findings raise a food safety alert about hospital-associated carbapenemase producers, supporting that fresh vegetables can act as a vehicle for the spread of high-risk clones.

A Randomized Controlled Clinical Trial Testing Effects of Lademirsen on Kidney Function Decline in Adults with Alport Syndrome.

BACKGROUND: Preclinical models of disease have suggested that targeting microRNA-21 may slow the decline in kidney function in individuals with Alport syndrome. The objective of this study was to investigate the effects of the anti-microRNA-21 oligonucleotide, lademirsen, on rate of estimated glomerular filtration rate (eGFR) decline in adults with Alport syndrome at risk of rapid disease progression. METHODS: This study was a phase 2 trial of lademirsen, with a randomized, double-blind, placebo-controlled period followed by an open-label period. Adults with Alport syndrome, eGFR >35 to <90 mL/min/1.73 m2, and evidence of rapidly progressive kidney dysfunction were randomized 2:1 to lademirsen 110 mg subcutaneously once weekly or placebo for 48 weeks. Following a planned interim analysis (after 24 of 43 randomized participants completed the Week 48 study visit or discontinued prior to Week 48), the trial was terminated for futility. RESULTS: Forty-three adults with Alport syndrome (26 men, 17 women) participated (mean age 34 years) and 28 (lademirsen: n=19; placebo: n=9) completed 48 weeks of double-blind treatment. All participants in both groups developed treatment-emergent adverse events (TEAEs), mainly respiratory tract infections, headache, dizziness, metabolic/electrolyte disturbances, and anemia. Treatment was discontinued in three lademirsen-treated participants in the double-blind period, and one participant in the open-label period, owing to TEAEs. The least-squares mean eGFR slope (95% confidence interval) over 48 weeks in the lademirsen and placebo groups was -5 (-8.7, -1.1) and -5 (-10.2, 0.8) mL/min/1.73 m2/year, respectively. No significant differences between groups were identified in eGFR at any timepoint or in proportion of participants with prespecified reductions in eGFR at Weeks 24 or 48. CONCLUSION: While anti-microRNA-21 therapy with lademirsen was generally well-tolerated with an acceptable safety profile, no meaningful improvement in rate of kidney function decline in adults with Alport syndrome at risk of rapidly progressive disease was observed.

Laryngotracheomalacia in a Patient with Mosaic Trisomy 8.

Mosaic trisomy 8 is a condition characterized by a great phenotypic and cytogenetic variability whose incidence ranges around 1 in 25,000 to 50,000 live births. Here, we report a mosaic trisomy 8 patient presenting laryngotracheomalacia, an uncommon finding, analyzing its possible role over morbidity, and mortality. The patient was a boy who, after birth, had tachypnea and paleness. He presented periods of respiratory dysfunction with need of ventilatory support. Respiratory syncytial virus test was positive. Naso fibrobronchoscopy showed moderate laryngotracheomalacia. He also had recurrent episodes of pneumonia and difficulty in withdrawing continuous positive airway pressure. The patient also presented leucoma, abnormal and low-set ears, pectus excavatum, clenched fists with overlapping fingers, cryptorchidism, clubfeet, and deep longitudinal plantar creases. G-bands by Trypsin using giemsa (GTG-banding) karyotype from a peripheral blood sample revealed a mosaic trisomy 8: mos 47,XY, + 8[15]/46,XY[7]. At 4 months, the patient developed respiratory failure, and a chest computed tomography scan showed areas of atelectasis and gross fibroatelectatic striae. He ended up presenting clinical worsening and died at 4 months and 8 days. In our literature review, we found some reports describing patients with mosaic trisomy 8 and laryngotracheomalacia. However, we cannot rule out the possibility that this association could be casual, since laryngotracheomalacia is a relatively common finding in children. Therefore, more studies are still necessary to understand the possible relation between both conditions and the role of laryngotracheomalacia over morbidity and prognosis of mosaic trisomy 8 patients.

Perspectives of FTIR as Promising Tool for Pathogen Diagnosis, Sanitary and Welfare Monitoring in Animal Experimentation Models: A Review Based on Pertinent Literature.

Currently, there is a wide application in the literature of the use of the Fourier Transform Infrared Spectroscopy (FTIR) technique. This basic tool has also proven to be efficient for detecting molecules associated with hosts and pathogens in infections, as well as other molecules present in humans and animals' biological samples. However, there is a crisis in science data reproducibility. This crisis can also be observed in data from experimental animal models (EAMs). When it comes to rodents, a major challenge is to carry out sanitary monitoring, which is currently expensive and requires a large volume of biological samples, generating ethical, legal, and psychological conflicts for professionals and researchers. We carried out a survey of data from the relevant literature on the use of this technique in different diagnostic protocols and combined the data with the aim of presenting the technique as a promising tool for use in EAM. Since FTIR can detect molecules associated with different diseases and has advantages such as the low volume of samples required, low cost, sustainability, and provides diagnostic tests with high specificity and sensitivity, we believe that the technique is highly promising for the sanitary and stress and the detection of molecules of interest of infectious or non-infectious origin.

Emergence of carbapenem-resistant Klebsiella pneumoniae species complex from agrifood systems: detection of ST6326 co-producing KPC-2 and NDM-1.

BACKGROUND: Klebsiella pneumoniae species complex (KpSC) is an important disseminator of carbapenemase-encoding genes, mainly blaKPC-2 and blaNDM-1, from hospitals to the environment. Consequently, carbapenem-resistant strains can be spread through the agrifood system, raising concerns about food safety. This study therefore aimed to isolate carbapenem-resistant KpSC strains from the agricultural and environmental sectors and characterize them using phenotypic, molecular, and genomic analyses. RESULTS: Klebsiella pneumoniae and Klebsiella quasipneumoniae strains isolated from soils used for lemon, guava, and fig cultivation, and from surface waters, displayed an extensive drug-resistance profile and carried blaKPC-2, blaNDM-1, or both. In addition to carbapenemase-encoding genes, KpSC strains harbor a broad resistome (antimicrobial resistance and metal tolerance) and present putative hypervirulence. Soil-derived K. pneumoniae strains were assigned as high-risk clones (ST11 and ST307) and harbored the blaKPC-2 gene associated with Tn4401b and Tn3-like elements on IncN-pST15 and IncX5 plasmids. In surface waters, the coexistence of blaKPC-2 and blaNDM-1 genes was identified in K. pneumoniae ST6326, a new carbapenem-resistant regional Brazilian clone. In this case, blaKPC-2 with Tn4401a isoform and blaNDM-1 associated with a Tn125-like transposon were located on different plasmids. Klebsiella quasipneumoniae ST526 also presented the blaNDM-1 gene associated with a Tn3000 transposon on an IncX3 plasmid. CONCLUSION: These findings provide a warning regarding the transmission of carbapenemase-positive KpSC across the agricultural and environmental sectors, raising critical food safety and environmental issues. © 2024 Society of Chemical Industry.

Genetic diversity of KPC-2-producing Klebsiella pneumoniae complex from aquatic ecosystems.

During the COVID-19 pandemic, the occurrence of carbapenem-resistant Klebsiella pneumoniae increased in human clinical settings worldwide. Impacted by this increase, international high-risk clones harboring carbapenemase-encoding genes have been circulating in different sources, including the environment. The blaKPC gene is the most commonly disseminated carbapenemase-encoding gene worldwide, whose transmission is carried out by different mobile genetic elements. In this study, blaKPC-2-positive Klebsiella pneumoniae complex strains were isolated from different anthropogenically affected aquatic ecosystems and characterized using phenotypic, molecular, and genomic methods. K. pneumoniae complex strains exhibited multidrug-resistant and extensively drug-resistant profiles, spotlighting the resistance to carbapenems, ceftazidime-avibactam, colistin, and tigecycline, which are recognized as last-line antimicrobial treatment options. Molecular analysis showed the presence of several antimicrobial resistance, virulence, and metal tolerance genes. In-depth analysis showed that the blaKPC-2 gene was associated with three different Tn4401 isoforms (i.e., Tn4401a, Tn4401b, and Tn4401i) and NTEKPC elements. Different plasmid replicons were detected and a conjugative IncN-pST15 plasmid harboring the blaKPC-2 gene associated with Tn4401i was highlighted. K. pneumoniae complex strains belonging to international high-risk (e.g., ST11 and ST340) and unusual clones (e.g., ST323, ST526, and ST4216) previously linked to clinical settings. In this context, some clones were reported for the first time in the environmental sector. Therefore, these findings evidence the occurrence of carbapenemase-producing K. pneumoniae complex strains in aquatic ecosystems and contribute to the monitoring of carbapenem resistance worldwide.

Alcohol consumption during pregnancy by women from southern Brazil: a cross-sectional study.

BACKGROUND: Some maternal characteristics are related to alcohol intake during pregnancy, which irreversibly compromises the maternal-fetal binomial integrity. OBJECTIVES: To identify the frequency, impact, and factors associated with alcohol consumption during pregnancy. DESIGN AND SETTING: A cross-sectional study was performed at the Hospital Materno Infantil Presidente Vargas (HMIPV) in Porto Alegre/RS between March and December 2016. METHODS: A structured questionnaire was administered along with a medical records review. They refer to the maternal sociodemographic and gestational status, alcohol consumption patterns, and characteristics of the fetus/newborn. In the statistical analysis, P values < 0.05 were considered significant. RESULTS: The frequency of alcohol intake was 37.3%; this was characterized by the consumption of fermented beverages (89.3%), especially during the first trimester (79.6%). Risky consumption (high and/or early) occurred for 30.2% of participants. Risk factors associated with maternal alcohol consumption during pregnancy were tobacco use (P < 0.001) and abortion attempt (P = 0.023). Living with a partner (P = 0.002) and planning pregnancy (P = 0.009) were protective factors. Risky consumption was related to all of the aforementioned variables as well as threatened abortion (P = 0.023). CONCLUSIONS: Alcohol intake during pregnancy is common and affects nearly one-third of pregnant women. Knowledge of the population at risk and protective factors is essential for the development of campaigns that seek to reduce consumption and, therefore, its consequences for the mother and fetus.

Clinical Utility of Genetic Testing with Geographical Locations in ADPKD: Describing New Variants.

Background: Our study aims to comment on all ADPKD variants identified in our health area and explain how they are distributed geographically, to identify new variants, and relate the more frequent variants with their renal phenotype in terms of kidney survival. Materials and Methods: We identified patients suffering from ADPKD in a specialized consultation unit; genealogical trees were constructed from the proband. According to the ultrasound-defined modified Ravine-Pei criteria, relatives classified as at risk were offered participation in the genetic study. Socio-demographic, clinical, and genetic factors related to the impact of the variant on the survival of the kidney and the patient, such as age at RRT beginning and age of death, were recorded. Results: In 37 families, 33 new variants of the PKD1 gene were identified, which probably produce a truncated protein. These variants included 2 large deletions, 19 frameshifts, and 12 stop-codons, all of which had not been previously described in the databases. In 10 families, six new probably pathogenic variants in the PKD2 gene were identified. These included three substitutions; two deletions, one of which was intronic and not associated with any family; and one duplication. A total of 11 missense variants in the PKD1 gene were grouped in 14 families and classified as probably pathogenic. We found that 33 VUS were grouped into 18 families and were not described in the databases, while another 15 were without grouping, and there was only 1 in the PKD2 gene. Some of these variants were present in patients with a different pathogenic variant (described or not), and the variant was probably benign. Renal survival curves were compared to nonsense versus missense variants on the PKD1 gene to check if there were any differences. A group of 328 patients with a nonsense variant was compared with a group of 264 with a missense variant; mean renal survival for truncated variants was lower (53.1 ± 0.46 years versus non-truncated variant 59.1 ± 1.36 years; Log Rank, Breslow, and Tarone Ware, p < 0.05). Conclusions: To learn more about ADPKD, it is necessary to understand genetics. By describing new genetic variants, we are approaching creation of an accurate genetic map of the disease in our country, which could have prognostic and therapeutic implications in the future.

Patients' prognosis with congenital heart disease followed by ten years: survival and associated factors.

OBJECTIVE: To evaluate the prognosis and influence of associated factors in patients with congenital heart disease admitted for the first time to the Intensive Care Unit of the Hospital da Criança Santo Antônio/Irmandade da Santa Casa de Misericórdia de Porto Alegre, especially those factors associated with death. METHODS: Patients were prospectively and consecutively allocated over a period of one year (August 2005 to July 2006). Now, 15 years after the initial selection, we collected data from these patients in the database of the Cytogenetics Laboratory of the Universidade Federal de Ciências da Saúde de Porto Alegre and in the medical records of the hospital. RESULTS: Of the 96 patients, 11 died and 85 were alive until 20 years old. Four patients died in the Intensive Care Unit. The survival probability up to 365 days of life was 95.8%. The survival assessment identified that the deaths occurred mainly before the patients completed one thousand days of life. We found that complex heart disease was independently associated with an odds ratio of 5.19 (95% confidence interval - CI:1.09-24.71; p=0.038) for death. CONCLUSIONS: Knowledge about the factors that interfere with the prognosis can be crucial in care practice planning, especially considering that congenital heart disease is an important cause of mortality in the first year of life.

Monensin poisoning outbreak in free-ranging and captive birds.

Monensin poisoning is uncommon and has been rarely reported in birds. This work aimed to described clinical-pathological aspects of an outbreak of monensin poisoning in captive and free-ranging birds. Thirty-seven of 600 captive birds fed a diet containing 893.19 mg/kg of monensin died within 10 days (mortality 6.17%). There was no ionophore antibiotics on the feed label supplied to captive birds, which established an error in feed production. Necropsies were performed on twelve animals: Muscovy duck (Cairina moschata) (2/12), greater rhea (Rhea americana) (2/12), black-necked swan (Cygnus melancoryphus) (2/12), garganey (Anas querquedula) (1/12), ostrich (Struthio camelus) (1/12), and common pigeon (Columbus livia) (4/12). These four common pigeons were free-ranging birds and died after eating the same contaminated feed. Birds were mainly found dead, however in animals which clinical signs were observed (Columba livia, Rhea americana, Cairina moschata, Anas querquedula, and Struthio camelus), they included incoordination, inability to stand, and intense prostration, that ranged from 24 to 72 h until death. Grossly, five birds had focally extensive pale firm areas in the myocardium and two had in the skeletal muscles, one being concomitant lesions. Histologically, muscle necrosis and degeneration were observed in striated musculature (skeletal and/or heart) in all birds analyzed. Monensin poisoning outbreaks can affect free-ranging birds that are fed on external feeders, as well as captive birds, due to an error in the feed formulation.

Risk factors and characteristics of the birth of patients with craniofacial microsomia, a case-control study.

BACKGROUND: Craniofacial microsomia (CM) is characterized by changes in the first and second branchial arches. It is a clinical condition whose etiology is still uncertain, but studies have shown that genetic, nutritional, and environmental factors can result in disorders of blastogenesis of the branchial arches. This study evaluates gestational aspects, focusing on possible risk factors associated with CM. METHODS: This is a case-control study conducted with patients monitored at a medical genetics service and compared to a control group of patients without evidence of malformations, born in a mother and child hospital, both located in Porto Alegre, Southern Brazil. Mothers' data were obtained using questionnaires and by reviewing medical records. The sample consisted of 43 patients with CM (cases) and 129 patients without evidence of malformations (controls), paired by sex, totaling three controls for each case. Data analysis was performed using the two-tailed Fisher's exact test, Pearson's chi-square test, and the t-test. RESULTS: We identified several factors associated with the development of CM, including the use of abortion methods by the mothers of these babies (p = .001), maternal diabetes (p = .009), advanced maternal age (p = .035), and a history of vaginal bleeding (p < .001). Furthermore, these patients exhibited a tendency to be born prematurely (p = .027), with low birth weight (p = .007), and lower Apgar scores (p = .003) when compared to healthy infants. Using a multivariate model, the use of abortion methods (p = .003) and vaginal bleeding (p = .032) remained independently associated with craniofacial microsomia. CONCLUSIONS: We have identified several risk factors for the development of CM, including a propensity for premature birth, low birth weight, and respiratory difficulties. Additionally, women of advanced maternal age and/or those who used abortion methods and/or have diabetes have a higher risk of giving birth to a baby with CM. This information can be valuable in clinical practice, especially for the prevention of future cases.

Patients' prognosis with congenital heart disease followed by ten years: survival and associated factors / Prognóstico de pacientes com cardiopatia congênita seguidos por dez anos: sobrevida e fatores associados

ABSTRACT Objective: To evaluate the prognosis and influence of associated factors in patients with congenital heart disease admitted for the first time to the Intensive Care Unit of the Hospital da Criança Santo Antônio/Irmandade da Santa Casa de Misericórdia de Porto Alegre, especially those factors associated with death. Methods: Patients were prospectively and consecutively allocated over a period of one year (August 2005 to July 2006). Now, 15 years after the initial selection, we collected data from these patients in the database of the Cytogenetics Laboratory of the Universidade Federal de Ciências da Saúde de Porto Alegre and in the medical records of the hospital. Results: Of the 96 patients, 11 died and 85 were alive until 20 years old. Four patients died in the Intensive Care Unit. The survival probability up to 365 days of life was 95.8%. The survival assessment identified that the deaths occurred mainly before the patients completed one thousand days of life. We found that complex heart disease was independently associated with an odds ratio of 5.19 (95% confidence interval — CI:1.09-24.71; p=0.038) for death. Conclusions: Knowledge about the factors that interfere with the prognosis can be crucial in care practice planning, especially considering that congenital heart disease is an important cause of mortality in the first year of life.

RESUMO Objetivo: Avaliar o prognóstico e a influência de fatores associados em pacientes com cardiopatia congênita internados pela primeira vez na Unidade de Terapia Intensiva do Hospital da Criança Santo Antônio/Irmandade da Santa Casa de Misericórdia de Porto Alegre, principalmente aqueles fatores associados ao óbito. Métodos: Os pacientes foram alocados prospectiva e consecutivamente por um período de um ano (agosto de 2005 a julho de 2006). Agora, 15 anos após a seleção inicial, coletamos dados desses pacientes no banco de dados do Laboratório de Citogenética da Universidade Federal de Ciências da Saúde de Porto Alegre e nos prontuários do hospital. Resultados: Dos 96 pacientes, 11 faleceram e 85 permaneceram vivos até completar 20 anos. Quatro pacientes morreram na Unidade de Terapia Intensiva. A probabilidade de sobrevida até 365 dias de vida foi de 95,8%. A avaliação da sobrevida identificou que os óbitos ocorreram principalmente antes de os pacientes completarem mil dias de vida. Verificamos que a doença cardíaca complexa foi independentemente associada a um odds ratio de 5,19 (intervalo de confiança — IC95% 1,09-24,71; p=0,038) para morte. Conclusões: O conhecimento dos fatores que interferem no prognóstico pode ser fundamental no planejamento da prática assistencial, principalmente considerando-se que as cardiopatias congênitas são importante causa de mortalidade no primeiro ano de vida.

Anatomopathological characterization of branchial cysts in slaughtered pigs.

Branchial cysts are a congenital anomaly in humans and other animal species. In this study, twenty commercially bred slaughtered pigs ranging from 120 to 150 days of age, sourced from different farms and lots, were found to have cysts in the oropharyngeal region at meat inspection despite the absence of clinical signs. Two cysts were selected for histopathological examination. The first cyst was surrounded by fibrous connective tissue and lined by a simple single cell layer of epithelium. The second cyst comprised a squamous pseudostratified to simple stratified epithelium, accompanied by a mild inflammatory infiltrate. This cyst was also surrounded by fibrous connective tissue and glands. The pathological diagnosis of branchial cysts in slaughtered pigs was established on the basis of their anatomical location and gross and microscopic findings.

Genomic features of an extensively drug-resistant and NDM-1-positive Klebsiella pneumoniae ST340 isolated from river water.

The environmental contamination plays a significant role in the emergence of antimicrobial resistance. In this study, we report a genomic analysis of an extensively drug-resistant and blaNDM-1-producing Klebsiella pneumoniae (EW807) strain recovered from a surface water sample. Strain EW807 belonged to sequence type (ST) 340 and serotype O4:KL15, a high-risk clone of the clonal group 258. This strain carried a broad resistome, including blaNDM-1 and blaCTX-M-15. The core genome multilocus sequence typing phylogenetic analysis revealed that the EW807 strain was most related to strains from Brazil and the USA. An IncX3 plasmid was identified harboring the blaNDM-1 gene, while an IncFIB(K) plasmid was detected carrying the blaCTX-M-15 in addition to multidrug resistance and multimetal tolerance regions. IncX3 and IncFIB(K) plasmids shared high similarity with plasmids from a human in China and a dog in Brazil, respectively. The regions harboring the blaNDM-1 and blaCTX-M-15 genes contained sequences from the Tn3 family. These findings suggest that IncX3 plasmid could play a role in the spread of NDM-1 in a post-pandemic scenario. To the best of our knowledge, this is the first report of blaNDM-1-producing K. pneumoniae ST340 O4:KL15 strain in the environment. Therefore, the presence of high-risk clones of K. pneumoniae carrying carbapenemases in the environment requires strict surveillance.

Mouse Models of Mayaro Virus.

Mayaro virus (MAYV), the etiologic agent of Mayaro fever, leads patients to severe myalgia and arthralgia, which can have a major impact on public health in all the countries where the virus circulates. The emergence and dissemination of new viruses have led the scientific community to develop new in vivo models that can help in the fight against new diseases. So far, mice have been the most used animal model in studies with MAYV and have proved to be an adequate model for recapitulating several aspects of the disease observed in humans. Mice are widely used in in vivo research and, therefore, are well known in the scientific community, which has allowed for different strains to be investigated in the study of MAYV. In this review, we summarize the main studies with MAYV using mice as an experimental model and discuss how they can contribute to the advancement of the understanding of its pathogenesis and the development of new drugs and vaccines.

Drosophila melanogaster as a model for studies related to the toxicity of lavender, ginger and copaiba essential oils.

This study addresses the current trend of essential oils in alternative medicine using the non-chordate model Drosophila melanogaster. Following the three R's principles, it proposes non-chordate models to fill knowledge gaps on essential oil toxicity. Copaiba, lavender, and ginger essential oils are evaluated for effects on D. melanogaster lifespan, climbing ability, and brain structure, while their anti-inflammatory properties are also analyzed. Results show dose-related differences: higher concentrations (0.25% v/v) cause brain deterioration and impaired climbing, while lower concentrations (0.0625% v/v for copaiba and ginger; 0.125% for lavender) have no effect on climbing or brain structure. Lavender oil significantly extends lifespan and maintains anti-inflammatory activity when ingested, underscoring its therapeutic potential. These findings highlight the importance of D. melanogaster as a model for studying essential oil properties, potentially replacing chordate models. In addition, this research advances alternative remedies for currently incurable diseases, with lavender oil emerging as a promising candidate for drug discovery.

PDGFRA, KIT, and KDR Gene Amplification in Glioblastoma: Heterogeneity and Clinical Significance.

Glioblastoma (GBM) is the most frequent tumor of the central nervous system, and its heterogeneity is a challenge in treatment. This study examined tumoral heterogeneity involving PDGFRA, KIT, and KDR gene amplification (GA) in 4q12 and its association with clinical parameters. Specimens from 22 GBM cases with GA for the 4q12 amplicon detected by FISH were investigated for homogeneous or heterogeneous coamplification patterns, diffuse or focal distribution of cells harboring GA throughout tumor sections, and pattern of clustering of fluorescence signals. Sixteen cases had homogenously amplification for all three genes (45.5%), for PDGFRA and KDR (22.7%), or only for PDGFRA (4.6%); six cases had heterogeneous GA patterns, with subpopulations including GA for all three genes and for two genes - PDGFRA and KDR (13.6%), or GA for all three and for only one gene - PDGFRA (9.1%) or KIT (4.6%). In 6 tumors (27.3%), GA was observed in focal tumor areas, while in the remaining 16 tumors (72.7%) it was diffusely distributed throughout the pathological specimen. Amplification was universally expressed as double minutes and homogenously stained regions. Coamplification of all three genes PDGFRA, KIT, and KDR, age ≥ 60 years, and total tumor resection were statistically associated with poor prognosis. FISH proved effective for detailed interpretation of molecular heterogeneity. The study uncovered an even more diverse range of amplification patterns involving the 4q12 oncogenes in GBM than previously described, thus highlighting a complex tumoral heterogeneity to be considered when devising more effective therapies.

Klebsiella quasipneumoniae subsp. similipneumoniae ST1859 O5:KL35 from Soil: First Report of qnrE1 in the Environment.

A Klebsiella quasipneumoniae subsp. similipneumoniae strain, named S915, belonging to the ST1859 O5:KL35, and harboring the plasmid-mediated quinolone resistance qnrE1 gene, was isolated from a soil sample cultivated with lettuce in Brazil. The core genome multilocus sequence typing analysis revealed that S915 strain was most related to a clinical strain of Brazil. Comparative genomic analysis showed that ST1859 O5:KL35 strains have been circulating in clinical settings and are closely related to multidrug resistance and multimetal tolerance. Strain S915 presented a plasmid contig co-harboring the qnrE1 gene and tellurite tolerance operon. The region harboring the qnrE1 gene (ISEcp1-qnrE1-araJ-ahp) shared high similarity with others from infected humans, ready-to-eat dish, and food-producing animals in Brazil. This is the first report of the plasmid-mediated qnrE1 gene in the environment. Our findings evidence the initial dissemination of the qnrE1 gene in the environment by the introduction of a clinical strain, which may be spread to different sectors, representing a One Health challenge.