RESUMEN
Grapes are globally popular with wine production being one of the most well-known uses of grapes worldwide. Brazil has a growing wine industry, and the Serra Gaúcha region is a significant contributor to the country's wine production. Nonetheless, other states are increasing their relevance in this segment. Environmental factors and the soil microbiome (bacteria and fungi) heavily influence grape quality, shaping the crucial "terroir" for wines. Here, soil quality was assessed through nutrient analysis and bacteria microbial diversity, which could significantly impact grape health and final wine attributes. Soil samples from São Paulo's vineyards, focusing on Syrah, Malbec, and Cabernet Sauvignon, underwent chemical and microbial analysis via 16S rRNA metabarcoding and highlighted significant differences in soil composition between vineyards. Statistical analyses including PCA and CAP showcased region-based separation and intricate associations between microbiota, region, and grape variety. Correlation analysis pinpointed microbial genera linked to specific soil nutrients. Random Forest analysis identified abundant bacterial genera per grape variety and the Network analysis revealed varied co-occurrence patterns, with Cabernet Sauvignon exhibiting complex microbial interactions. This study unveils complex relationships between soil microbiota, nutrients, and diverse grape varieties in distinct vineyard regions. Understanding how these specific microorganisms are associated with grapes can improve vineyard management, grape quality, and wine production. It can also potentially optimize soil health, bolster grapevine resilience against pests and diseases, and contribute to the unique character of wines known as terroir.
RESUMEN
Primary thoracic cancers affect a large number of patients, mainly those with lung cancer and to a lesser extent those with pleural mesothelioma and thymic tumours. Given their frequency and associated comorbidities, in patients whose mean age is high, these diseases are associated with multiple complications. This article, the last of a series dedicated to emergencies in onco-haematological patients, aims to present a clinical picture of the severe complications (side effects, immune-related adverse events) associated with systemic treatments, excluding infections and respiratory emergencies, with which general practitioners and specialists can be confronted. New toxicities are to be expected with the implementation of innovative therapeutic approaches, such as CAR-T cells, along with immunomodulators and antibody-drug conjugates.
Asunto(s)
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , Neoplasias Pleurales , Timoma , Humanos , Urgencias Médicas , Mesotelioma/tratamiento farmacológico , Timoma/patología , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pleurales/tratamiento farmacológicoRESUMEN
The concept of oligometastatic disease was first introduced in the late 1990s to describe an situation more or less midway between locally advanced tumours and multifocal metastatic cancer. Four concepts are currently used: synchronous oligometastatic disease, metachronous oligometastatic disease (or oligo-recurrence), oligo-persistence and oligo-progression. Some phase II studies, randomised or not, have validated this concept in non-small cell lung cancer (NSCLC) and suggest the interest of adding local ablative therapy to systemic treatment. That said, numerous questions remain, and the impact of this therapeutic approach in the framework of immunotherapies and targeted therapies has yet to be assessed. Which of these new treatments offer hope of significantly improved long-term survival in stage IV NSCLC? This article appraises current knowledge and therapeutic regarding oligometastatic NSCLC.
RESUMEN
OBJECTIVE: Patients with rheumatoid arthritis (RA) have different presentations and prognoses. Cluster analysis based on proteomic signatures creates independent phenogroups of patients with different pathophysiological backgrounds. We aimed to identify distinct pathophysiological clusters of RA patients based on circulating proteomic biomarkers. METHOD: This was a cohort study including 399 RA patients. Clustering was performed on 94 circulating proteins (92 CVDII Olink®, high-sensitivity troponin T, and C-reactive protein). Unsupervised clustering was performed using a partitioning cluster algorithm. RESULTS: The clustering algorithm identified two distinct clusters: cluster 1 (n = 223) and cluster 2 (n = 176). Compared with cluster 1, cluster 2 included older patients with a higher burden of comorbidities (cardiovascular and RA related), more erosive and longer RA duration, more dyspnoea and fatigue, walking a shorter distance in the Six-Minute Walk Test, with more severe diastolic dysfunction, and a 4.5-fold higher risk of death or hospitalization for cardiovascular reasons. Tumour necrosis factor (TNF) receptor superfamily-related pathways were mainly responsible for the model's discriminative ability. CONCLUSION: Using unsupervised cluster analysis based on proteomic phenotypes, we identified two clusters of RA patients with distinct biomarkers profiles, clinical characteristics, and different outcomes that could reflect different pathophysiological backgrounds. TNF receptor superfamily-related proteins may be used to distinguish subgroups.
Asunto(s)
Artritis Reumatoide , Proteómica , Humanos , Estudios de Cohortes , Artritis Reumatoide/diagnóstico , Biomarcadores/metabolismo , Análisis por ConglomeradosRESUMEN
The production of ethanol from lignocellulosic sources presents increasingly difficult issues for the global biofuel scenario, leading to increased production costs of current second-generation (2G) ethanol when compared to first-generation (1G) plants. Among the setbacks encountered in industrial processes, the presence of chemical inhibitors from pre-treatment processes severely hinders the potential of yeasts in producing ethanol at peak efficiency. However, some industrial yeast strains have, either naturally or artificially, higher tolerance levels to these compounds. Such is the case of S. cerevisiae SA-1, a Brazilian fuel ethanol industrial strain that has shown high resistance to inhibitors produced by the pre-treatment of cellulosic complexes. Our study focuses on the characterization of the transcriptomic and physiological impact of an inhibitor of this type, p-coumaric acid (pCA), on this strain under chemostat cultivation via RNAseq and quantitative physiological data. It was found that strain SA-1 tend to increase ethanol yield and production rate while decreasing biomass yield when exposed to pCA, in contrast to pCA-susceptible strains, which tend to decrease their ethanol yield and fermentation efficiency when exposed to this substance. This suggests increased metabolic activity linked to mitochondrial and peroxisomal processes. The transcriptomic analysis also revealed a plethora of differentially expressed genes located in co-expressed clusters that are associated with changes in biological pathways linked to biosynthetic and energetical processes. Furthermore, it was also identified 20 genes that act as interaction hubs for these clusters, while also having association with altered pathways and changes in metabolic outputs, potentially leading to the discovery of novel targets for metabolic engineering toward a more robust industrial yeast strain.
Asunto(s)
Multiómica , Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Ácidos Cumáricos/metabolismo , Fermentación , Etanol/metabolismo , Microbiología IndustrialRESUMEN
BACKGROUND: Solid cancer is an independent prognostic factor for poor outcome with COVID-19. As guidelines for patient management in that setting depend on retrospective efforts, we here present the first analyses of a nationwide database of patients with cancer hospitalized with COVID-19 in Belgium, with a focus on changes in anticancer treatment plans at the time of SARS-CoV-2 infection. METHODS: Nineteen Belgian hospitals identified all patients with a history of solid cancer hospitalized with COVID-19 between March 2020 and February 2021. Demographic, cancer-specific and COVID-specific data were pseudonymously entered into a central Belgian Society of Medical Oncology (BSMO)-COVID database. The association between survival and primary cancer type was analyzed through multivariate multinomial logistic regression. Group comparisons for categorical variables were carried out through a Chi-square test. RESULTS: A total of 928 patients were registered in the database; most of them were aged ≥70 years (61.0%) and with poor performance scores [57.2% Eastern Cooperative Oncology Group (ECOG) ≥2]. Thirty-day COVID-related mortality was 19.8%. In multivariate analysis, a trend was seen for higher mortality in patients with lung cancer (27.6% versus 20.8%, P = 0.062) and lower mortality for patients with breast cancer (13.0% versus 23.3%, P = 0.052) compared with other tumour types. Non-curative treatment was associated with higher 30-day COVID-related mortality rates compared with curative or no active treatment (25.8% versus 14.3% versus 21.9%, respectively, P < 0.001). In 33% of patients under active treatment, the therapeutic plan was changed due to COVID-19 diagnosis, most frequently involving delays/interruptions in systemic treatments (18.6%). Thirty-day COVID-related mortality was not significantly different between patients with and without treatment modifications (21.4% versus 20.5%). CONCLUSION: Interruption in anticancer treatments at the time of SARS-CoV-2 infection was not associated with a reduction in COVID-related mortality in our cohort of patients with solid cancer, highlighting that treatment continuation should be strived for, especially in the curative setting.
Asunto(s)
COVID-19 , Neoplasias Pulmonares , Humanos , Bélgica/epidemiología , SARS-CoV-2 , Estudios Retrospectivos , Prueba de COVID-19 , Neoplasias Pulmonares/tratamiento farmacológico , Oncología Médica , Sistema de RegistrosRESUMEN
This study aimed to evaluate the performance of accelerated hydrogen peroxide® wipes (HPW) for decontamination of the chimpanzee adenovirus AZD1222 vaccine strain used in the production of recombinant COVID-19 vaccine in a pharmaceutical industry. Two matrices were tested on stainless-steel (SS) and low-density-polyethylene (LDP) surfaces: formulated recombinant COVID-19 vaccine (FCV) and active pharmaceutical ingredient (API). The samples were spiked, dried and the initial inoculum, possible residue effect (RE) and titre reduction after disinfection with HPW were determined. No RE was observed. The disinfection procedure with HPW resulted in complete decontamination the of AZD1222 adenovirus strain in FCV (≥7·46 and ≥7·49 log10 infectious unit [IFU] ml-1 for SS and LDP carriers respectively) and API (≥8·79 and ≥8·78 log10 IFU ml-1 for SS and LDP carriers respectively). In conclusion, virucidal activity of HPW was satisfactory against the AZD1222 adenovirus strain and can be a good option for disinfection processes of SS and LPD surfaces in pharmaceutical industry facilities during recombinant COVID-19 vaccine production. This procedure is simple and can be also applied on safety unit cabins and sampling bags made of LDP as well.
Asunto(s)
COVID-19 , Desinfectantes , Humanos , Peróxido de Hidrógeno/farmacología , Desinfectantes/farmacología , ChAdOx1 nCoV-19 , Vacunas contra la COVID-19 , Adenoviridae/genética , Descontaminación/métodos , COVID-19/prevención & control , Desinfección/métodos , Acero Inoxidable , Industria FarmacéuticaRESUMEN
The Curtobacterium genus is a member of the family Microbacteriaceae, and Curtobacterium species are recognized as plant pathogens. The aim of this study was to investigate a dubious result of species identification for an infection located on a catheter tip of a patient with Covid-19. A strain isolated from a catheter tip sample, identified by VITEK® 2 as Cronobacter spp., was submitted to polyphasic analysis: Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) using VITEK® MS, real-time polymerase chain reaction targeting dnaG gene, and 16S rRNA full gene Sanger sequencing analysis for confirmation. The strain presented negative result using qPCR and could not identified by MALDI-TOF MS. 16S rRNA full gene Sanger sequencing analysis identified the strain as Curtobacterium spp. The Gram-variable characteristic (Gram-negative instead of Gram-positive) of the isolated strain was the responsible for the misidentification by VITEK® 2 and VITEK® MS did not identify the strain. 16S rRNA full gene sequencing analysis identified the strain as Curtobacterium genus, but other complementary techniques are necessary to identify at species level.
Asunto(s)
Actinomycetales , COVID-19 , Cronobacter , Actinomycetales/genética , Técnicas de Tipificación Bacteriana/métodos , Catéteres , Humanos , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodosRESUMEN
Para medir el éxito de un deportista y su ejecución deportiva, se requiere cuantificar el máximo rendimiento que desempeñe durante los entrenamientos y campeonatos, a partir de un instrumento válido, fiable y adaptado al contexto peruano. Sin embargo, hasta el momento no existen evidencias psicométricas que respalden el uso de alguno para deportistas calificados. El objetivo principal del presente estudio consiste en evaluar las propiedades psicométricas del Inventario de Ejecución Deportiva (IPED) en la población mencionada. Método:Participaron 255 deportistas con edades entre 14 y 38 años (N: 23; DT: 4.29), pertenecientes a modalidades afiliadas al Instituto Peruano del Deporte (IPD), y que representan al país de manera activa. Para el recojo de información se utilizó una ficha sociodemográfica, el Inventario de Ejecución Deportiva (IPED y el Cuestionario de Fortaleza Mental (FM). Resultados: El modelo IPED, presentó un buen ajuste de datos (SBχ2= 2243.096 / df= 798; CFI= .955; SRMR= .095; RMSEA= .084 [IC90%: .080-.069] y una consistencia interna adecuada para sus 7 dimensiones, que oscila entre ω = .841 y el menor valor ω = .754. Asimismo, se observaron correlaciones positivas y estadísticamente significativas al vincularlo con las dos dimensiones del Cuestionario FM: Confianza (AC=.678; CAN= .557; CAT= .457; CVI= .328; NM= .425; CAP= .641; CAC= .662) y Control (AC= .558; CAN= .733; CAT= .682; CVI= .171; NM= .272; CAP= .432; CAC= .563). Conclusión: El IPED brinda evidencia de validez y confiabilidad adecuadas para medir el desempeño deportivo. (AU)
To measure athletes success and his sports performance, it is required to quantify the maximum performance developedduring seasons of trainings and championships; using a valid, reliable,and adapted to peruvian context instrument. However, caution is urged when considering there is no psychometric evidence to support the use of any scale related to peruvian high performance athletessample. The current study was designed to evaluate the psychometric properties of the Sports Performance Psychological Inventory (IPED) in the mentioned sample. Method: Participated 255 peruvian athletes with ages between 14 and 38 years (N:23; SD: 4.29); who actively represents the country and in sports modalities affiliated with the Peruvian Sports Institute (IPD). For the collection of information, a sociodemographic record, Sports Performance Psychological Inventory (IPED)and the Mental Toughness Questionnaire (MTQ) were used. Results: IPED model demonstrated, that the seven-dimensional model had an acceptable fit (SBχ2 = 2243.096 / df = 798; CFI= .955; SRMR= .095; RMSEA= .084 [IC90%: .080 -.069] and reliability analyses revealed high internal consistency (ω= .841 > ω= .754). In addition, scores correlated positively between IPP and MTQ dimensions (AC= .678; CAN= .557; CAT= .457 ; CVI= .328; NM= .425; CAP= .641; CAC= .662 ) and Control (AC= .558; CAN= .733; CAT= .682 ; CVI= .171; NM= .272; CAP= .432; CAC= .563) Conclusion: The IPED provides adequate evidence of validity and reliability to measuresports performance. (AU)
Para medir o sucesso de um atleta e seu desempenho esportivo é necessário quantificar o desempenho máximo que ele realiza durante os treinos e campeonatos a partir de um instrumento válido e confiável adaptado ao contexto eduardo.manzanares@upc.pe peruano.No entanto, até o momento não há evidências psicométricas para apoiar o uso de qualquer instrumento por atletas qualificados. Nesse sentido, o objetivo principal deste estudo é avaliar as propriedades psicométricas do Inventário de Performance Psicológicapara o Esporte(IPED) na referida população. Método:participaram 255 atletas que representam ativamente o país nas modalidades esportivas filiadas ao Instituto Peruano de Esportes (IPD). As idades variaram de 14 a 38 anos (N: 23; DT: 4,29). Para a coletadas informações foi utilizado um inventáriosociodemográfico, o Sports Performance Inventory e o Mental Strength Questionnaire. Resultados:O modelo sete-dimensional IPED apresentou um bom ajuste dos dados (SBχ2 = 2243,096 / df= 798; CFI= ,955; SRMR= ,095; RMSEA= ,084 [IC90%: 0,080-0,069] e consistência interna adequada para as dimensões que variam entre ω= 0,841 e o menor valor ω= 0,754. Da mesma forma, foram observadas correlações positivas e estatisticamente significativas entre as 7 dimensões do IPEDcom as dimensões de confiança (AC = 0,678; CAN = .557; CAT = .457; CVI = .328; NM = .425; CAP = .641; CAC = .662) e Controle (AC = .558; CAN = .733; CAT = .682; CVI = .171; NM = .272; CAP = .432; CAC = .563) do Questionário FM.Conclusão:Conclui-se que oIPED apresenta evidências de confiabilidade e validade adequadas para medir o desempenho esportivo. (AU)
Asunto(s)
Humanos , Adolescente , Adulto Joven , Adulto , Deportes , Psicología del Deporte , Psicometría , Atletas , Rendimiento Atlético , Perú , Encuestas y CuestionariosRESUMEN
This study aimed to evaluate the performance of hydrogen peroxide vapour (HPV) to inactivate the chimpanzee adenovirus AZD1222 vaccine strain used in the production of recombinant COVID-19 vaccine for application in cleaning validation in pharmaceutical industries production areas. Two matrixes were tested: formulated recombinant COVID-19 vaccine (FCV) and active pharmaceutical ingredient (API). The samples were dried on stainless steel and exposed to HPV in an isolator. One biological indicator with population >106 Geobacillus stearothermophilus spores was used to validate the HPV decontamination cycle as standard. HPV exposure resulted in complete virus inactivation in FVC (≥5·03 log10 ) and API (≥6·40 log10 ), showing HPV efficacy for reducing chimpanzee adenovirus AZD1222 vaccine strain. However, the optimum concentration and contact time will vary depending on the type of application. Future decontamination studies scaling up the process to the recombinant COVID-19 vaccine manufacturing areas are necessary to evaluate if the HPV will have the same or better virucidal effectivity in each specific production area. In conclusion, HPV showed efficacy for reducing AZD1222 chimpanzee adenovirus strain and can be a good choice for pharmaceutical industries facilities disinfection during recombinant COVID-19 vaccine production.
Asunto(s)
COVID-19 , Desinfectantes , Adenoviridae , Animales , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Industria Farmacéutica , Humanos , Peróxido de Hidrógeno/farmacología , Industria Manufacturera , Pan troglodytes , Preparaciones FarmacéuticasRESUMEN
Listeria monocytogenes is an opportunistic pathogen with the ability to adapt to different environmental conditions, resulting in safety issues for food producers. Foods contaminated by L. monocytogenes can represent a risk if consumed by susceptible individuals such as elderly, pregnant women and the immunocompromised. The aim of this study was to evaluate the genetic diversity of a collection of L. monocytogenes isolated from different matrices in Brazil during the period of 1979-2015. A total of 51 L. monocytogenes serotype 1/2a strains isolated from clinical samples (n = 3) and food samples (n = 48) were characterized by Multi-Virulence-Locus Sequence Typing (MVLST). The strains were assigned to nine virulence types (VT): VT-11 (n = 3, 5·9%), VT-45 (n = 27, 52·9%), VT-59 (n = 11, 21·6%), VT-68 (n = 3, 5·9%), VT-94 (n = 2, 3·9%), VT-107 (n = 2, 3·9%), VT-184 (n = 1, 1·9%), VT-185 (n = 1, 1·9%) and VT-186 (n = 1, 1·9%); and four of them (VT-11, VT-45, VT-59 and VT-68) have already been associated with cases of listeriosis worldwide. The VT-11, VT-59 (Epidemic Clone V) and VT-186 were identified in blood culture samples, as well as in different classes of foods. It is recommended that the epidemiological surveillance agencies evaluate the risk that foods contaminated with L. monocytogenes VTs pose to susceptible populations.
Asunto(s)
Adaptación Fisiológica/genética , Variación Genética/genética , Listeria monocytogenes/genética , Listeriosis/epidemiología , Factores de Virulencia/genética , Anciano , Brasil/epidemiología , Femenino , Microbiología de Alimentos , Humanos , Listeria monocytogenes/patogenicidad , Listeriosis/microbiología , Tipificación de Secuencias Multilocus , Embarazo , Serogrupo , Virulencia/genéticaRESUMEN
AIMS: The objective of this study was to evaluate the cytotoxic activity of Cronobacter strains isolated from foods (n = 50) and clinical samples (n = 6) in Brazil and genotype selected strains (n = 18) using multi-locus sequence typing (MLST) METHODS AND RESULTS: The cytotoxic activity of C. sakazakii (n = 29), C. dublinensis (n = 13), C. malonaticus (n = 6), C. turicensis (n = 6) and C. muytjensii (n = 2) was screened using Vero, RK13, Hep2c, NCTC clone 929 and BHK-21 cell lines. Selected Cronobacter strains were assigned to C. sakazakii ST 21, C. turicensis ST 252, C. sakazakii ST 647, and three newly assigned STs: C. turicensis STs 738-740. The maximum death caused by non-heat-treated filtrates was 20·4, 86·2, 47·0 and 84·0%, in Vero, RK13, Hep2c and NCTC clone 929 cells, respectively. These were caused by C. sakazakii strains C291 and C292 (ST 494) which had been isolated during neonatal Cronobacter meningitis infection, and C110 (ST 395) isolated from flaxseed flour. Thermal treatment (100°C/20 min) significantly reduced the cytotoxicity activity in NCTC clone 929 and Vero cells (P ≤ 2 × 10-6 ), but not in RK13 (P = 0·12) and Hep2c (P = 0·85), indicating the cytotoxin(s) were probably proteinaceous. Electron microscopy revealed that cytotoxic compounds from C. sakazakii induced several cell death characteristics, including loss of cell-cell contact, microvilli reduction and cellular lysis. Autophagic vacuoles and mitochondrial damage were the most common ultrastructural features observed. CONCLUSIONS: It was concluded that Cronobacter strains, especially C. sakazakii, could produce heat-labile cytotoxic compounds in cell filtrates. SIGNIFICANCE AND IMPACT OF THE STUDY: This study providing insights into the pathogenesis of the Cronobacter genus. Cytotoxins were identified in excreted filtrates of C. sakazakii strains isolated from food and clinical specimens. The presence of Cronobacter strains that can produce cytotoxins in foods can be a potential threat to human health and highlight the need for high levels of hygiene.
Asunto(s)
Cronobacter/clasificación , Cronobacter/patogenicidad , Microbiología de Alimentos , Meningitis Bacterianas/microbiología , Virulencia , Animales , Brasil , Línea Celular , Supervivencia Celular , Chlorocebus aethiops , Cronobacter/genética , ADN Bacteriano , Infecciones por Enterobacteriaceae/microbiología , Genotipo , Interacciones Huésped-Patógeno , Humanos , Tipificación de Secuencias Multilocus , Células VeroRESUMEN
A proximidade dos primatas não humanos (PNH) com o ser humano pode ser considerada um fator de risco para transmissão de bactérias entre essas duas populações. Neste estudo, foi investigada a microbiota anfibiôntica aeróbica oral e retal de calitriquídeos em um fragmento de Mata Atlântica localizado no Rio de Janeiro, Brasil, e foram realizados testes fenotípicos para detecção de bactérias multirresistentes nos isolados encontrados. Foram capturados 14 calitriquídeos e coletadas 21 amostras (14 de cavidade oral e sete de cavidade retal) em dois pontos da mata próximos às habitações humanas. As espécies mais frequentes, na cavidade oral, foram Klebsiella oxytoca (50,0%), K. pneumoniae (28,6%), Kluyvera ascorbata (21,4%) e Stenotrophomonas maltophilia (21,4%) e, na cavidade retal, K. pneumoniae (85,7%), Escherichia coli (28,6%) e Enterobacter spp. (42,9%). Todos os 48 isolados da família Enterobacteriaceae foram negativos para ESBL (betalactamase de espectro ampliado), mostrando-se não produtores da enzima nos dois métodos utilizados: disco-aproximação e método de detecção automatizado. Na pesquisa de ERC (enterobactérias resistentes a carbapenêmicos), esses mesmos isolados não apresentaram resistência aos antibióticos imipenem, meropenem e ertapenem. Todas as bactérias isoladas apresentam um potencial zoonótico, o que representa um risco à saúde pública e à conservação das espécies.(AU)
Proximity of nonhuman primates (NHP) to humans can be considered a risk factor for transmission of pathogens between these two populations. This study investigated the oral and rectal aerobic bacterial microbiota of marmosets in an anthropized area of the Atlantic Forest located in Rio de Janeiro, Brazil, and performed phenotypic tests for detection of multidrug-resistant bacteria. Twenty-one samples (14 from the oral cavity and seven from the rectum) were collected from 14 Callithrix sp. captured in two sites of the forest near human dwellings. The most frequent species identified from the oral cavity swabs were Klebsiella oxytoca (50.0%), K. pneumoniae (28.6%), Kluyvera ascorbata (21.4%) and Stenotrophomonas maltophilia (21.4%), whereas the species most commonly identified from the rectum swabs were K. pneumoniae (85.7%), Enterobacter spp. (42.9%) and Escherichia coli (28.6%). All isolates of family Enterobacteriaceae showed no extended spectrum ß-lactamase production by disk-diffusion and automated detection tests. In the search for carbapenem-resistant enterobacteriaceae these isolates presented no resistance to the imipenem, meropenem and ertapenem antibiotics. The isolate of Staphylococcus aureus was susceptible to oxacillin and the isolate of Enterococcus was susceptible to vancomycin. All isolated bacteria showed zoonotic potential, thus posing a risk to species conservation and public health.(AU)
Asunto(s)
Humanos , Animales , Recto/microbiología , Callithrix/microbiología , Microbiota , Boca/microbiología , Staphylococcus aureus , Brasil , Transmisión de Enfermedad Infecciosa , Stenotrophomonas maltophilia , Riesgo a la Salud , Klebsiella oxytoca , Escherichia coliRESUMEN
In this review, we discuss biomarkers of response and resistance to PI3K inhibitors (PI3Ki) in estrogen receptor-positive breast cancer, both in the early and advanced settings. We analyse data regarding PIK3CA mutations, PI3K pathway activation, PTEN expression loss, Akt signalling, insulin levels, 18FFDG-PET/CT imaging, FGFR1/2 amplification, KRAS and TP53 mutations. Most of the discussed data comprise retrospective and exploratory studies, hence many results are not conclusive. Therefore, among all of these biomarkers, only PIK3CA mutations have proved to have a predictive value for treatment with the α-selective PI3Ki alpelisib (SOLAR-1 trial) and the ß-sparing PI3Ki taselisib (SANDPIPER trial) in the advanced setting. Since the accuracy of current individual biomarkers is not optimal, a composite biomarker, including DNA, RNA and protein expression data, to more precisely assess the PI3K/AKT/mTOR pathway activation status, may arise as a promising approach. Finally, we describe the rational for new combination therapies involving PI3Ki and anti-HER2 agents, chemotherapy, CDK4/6 inhibitors, mTOR inhibitors or new endocrine treatments and discuss the ongoing trials in this field.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/enzimología , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Resistencia a Antineoplásicos , Femenino , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Cronobacter infections of infants are commonly regarded as due to the ingestion of contaminated feed. The aim of this study was to determine the occurrence of Cronobacter, total coliforms and Escherichia coli in different brands of natural mineral waters as sold in 20 l returnable bottles in Rio de Janeiro, Brazil. The quantification of total coliforms and E. coli was performed by Most Probable Number. The detection of Cronobacter was as according to the ISO 22964:2017 and Bacteriological Analytical Manual/FDA. Molecular characterization of Cronobacter isolates was performed by real-time PCR and by multi-locus sequence typing. The antibiotic susceptibility profile was determined and biofilm production was evaluated in polystyrene microplates. Total coliforms and E. coli were detected in 13 (39·4%) and 2 (6·1%) of the 33 lots analysed respectively, and were considered unsatisfactory for human consumption according to Brazilian law. One (3·0%) lot showed contamination by C. malonaticus ST440 (Cronobacter MLST Databases accession no. ID 2646). The strain was susceptible to all (n = 13) antibiotics tested and only formed a weak biofilm. Since there is a high consumption of natural mineral waters by elderly and immunosuppressed persons, epidemiological surveillance agencies should be aware of the risk that these waters may represent for these groups. SIGNIFICANCE AND IMPACT OF THE STUDY: Cronobacter malonaticus ST440 was isolated from 20 l bottled drinking natural mineral waters sold in markets in Rio de Janeiro State, Brazil, and can be a potential threat to human health, particularly for neonates. Thirteen lots (39·4%) were unsatisfactory for human consumption due to the presence of total coliforms and/or Escherichia coli.
Asunto(s)
Cronobacter/aislamiento & purificación , Agua Potable/microbiología , Escherichia coli/aislamiento & purificación , Aguas Minerales/microbiología , Anciano , Antibacterianos/farmacología , Biopelículas , Brasil , Cronobacter/clasificación , Cronobacter/efectos de los fármacos , Infecciones por Enterobacteriaceae/prevención & control , Escherichia coli/efectos de los fármacos , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
In susceptible individuals, exposure to intensely traumatic life events can lead to the development of posttraumatic stress disorder (PTSD), including long-term dysregulation of the contextual processing of aversive stimuli, the overgeneralization of learned fear, and impairments in the ability to learn or respond to safety signals. The neuropathophysiological changes that underlie PTSD remain incompletely understood. Attention has focused on forebrain structures associated with fear processing. Here we consider evidence from human and animal studies that long-lasting changes in functional connectivity between the midbrain periaqueductal gray (dPAG) and amygdala may be one of the precipitating events that contribute to PTSD. Long-lasting neuroplastic changes in the dPAG can persist after a single aversive stimulation and are pharmacologically labile. The early stage (at least up to 24 h post-stimulation) involves neurokinin-1 receptor-mediated events in the PAG and amygdala and is also regulated by dopamine, both of which are mainly involved in transferring ascending aversive information from the dPAG to higher brain structures, mainly the amygdala. Changes in the functional connectivity within the dPAG-amygdala circuit have been reported in PTSD patients. We suggest that further investigations of plasticity and pharmacology of the PAG-amygdala network provide a promising target for understanding pathophysiological circuitry that underlies PTSD in humans and that dopaminergic and neurokininergic drugs may have a potential for the treatment of psychiatric disorders that are associated with a dysfunctional dPAG.
Asunto(s)
Dopamina/metabolismo , Sustancia Gris Periacueductal/metabolismo , Trastornos por Estrés Postraumático/metabolismo , Taquicininas/metabolismo , Animales , HumanosRESUMEN
OBJECTIVE: Organic silicon has been linked to positive effects on the skin rejuvenation, mainly by the oral route. Thus, the main objective of the present study was to assess whether monomethylsilanetriol (MMST, a source of organic silicon) can deliver silicon to the epidermis and dermis, when applied topically in a cream. Once the hypothesis was confirmed, the present study also evaluated whether the product was toxic to keratinocytes; additionally, its possible antioxidant activity was assessed. METHODS: The ex vivo skin permeation profile was determined using human skin in Franz-cells equipment; cytotoxicity was assessed using HaCaT keratinocytes. Antioxidant capacity was determined as scavenging activity, measured according to the 1,1-diphenyl-2-picrylhydrazil free radical method. RESULTS: The permeation percentage was almost 60% of the applied MMST, with a large quantity of drug found in the viable epidermis and dermis. The cell viability assay showed no significant difference in the percentage of viable keratinocytes among the treated groups at the doses used. In terms of antioxidant activity, the IC50 value obtained was 2400 µg mL-1 . Low antioxidant activity, negligible toxicity for keratinocytes and a significant percentage of permeation were observed. CONCLUSION: We provide evidence that MMST applied topically can deliver silicon to the skin in biorelevant levels for cosmetic purposes.
OBJECTIF: Le silicium organique a été associé à des effets positifs sur le rajeunissement de la peau, principalement par voie orale. Ainsi, l'objectif principal de la présente étude était d'évaluer si le monométhylsilanetriol (MMST, une source de silicium organique) pouvait livrer du silicium à l'épiderme et au derme, lorsqu'il était appliqué localement dans une crème. Une fois l'hypothèse confirmée, la présente étude a également évalué si le produit était toxique pour les kératinocytes; de plus, son éventuelle activité antioxydante a été évaluée. MÉTHODES: Le profil de permeation cutanée ex vivo a été déterminé en utilisant de la peau humaine dans un équipement à cellules Franz; la cytotoxicité a été évaluée à l'aide de kératinocytes HaCaT. La capacité d'antioxydant a été déterminée en tant qu'activité de piégeage, mesurée selon la méthode des radicaux libres au 1,1-diphényl-2-picrylhydrazil. RÉSULTATS: Le pourcentage de perméation était proche de 60% du MMST appliqué, une grande quantité de médicament se trouvant dans l'épiderme et le derme viables. Le test de viabilité cellulaire n'a montré aucune différence significative dans le pourcentage de kératinocytes viables parmi les groupes traités aux doses utilisées. En termes d'activité antioxydante, la valeur de la CI50 obtenue était de 2400 µg mL−1 . Une faible activité antioxydante, une toxicité négligeable pour les kératinocytes et un pourcentage important de perméation ont été observés. CONCLUSION: Nous apportons la preuve que le MMST appliqué localement peut délivrer du silicium sur la peau à des niveaux biologiquement pertinents à des fins esthétiques.
Asunto(s)
Silanos/administración & dosificación , Silicio/administración & dosificación , Piel/efectos de los fármacos , Animales , Antioxidantes/farmacología , Células Cultivadas , Cosméticos/farmacología , Humanos , Queratinocitos/efectos de los fármacos , Ratones , Ratas , Ratas Sprague-Dawley , Piel/citologíaRESUMEN
Upper airways (UA) include the nasal cavities, pharynx, and larynx, and its main function is to warm and filter the inspired air. UA dysfunction is in the pathogenesis of various disorders, such as obstructive sleep apnea syndrome (OSAS) and vocal cord dysfunction. In addition, in some neurodegenerative diseases (e.g. Amyotrophic Lateral Sclerosis - ALS), UA dysfunction may also compromise the effective use of ventilatory support (VS). In this context, the endoscopic evaluation of UA may be useful in understanding the OSAS mechanisms, in determining the causes for treatment-induced airway obstruction and even in helping to titrate noninvasive ventilation (NIV) in ALS patients with bulbar or pseudo-bulbar (spastic) dysfunction. Specifically, in OSAS patients, when residual obstructive events persist, although an optimal ventilatory mode has been apparently achieved, along with interface and equipment, the endoscopic evaluation of UA seems to be a valuable tool in understanding its mechanisms, even assisting adjustments to NIV parameters. In addition, it has also been described as being useful in laryngeal response to mechanical in-exsufflation (MI-E) and Exercise-Induced Laryngeal Obstruction (EILO). However, no protocol has yet been published or validated for this. For this reason, a literature review was conducted on UA function and its response to positive pressure and MI-E. Special emphasis has also been given to the current indication for video endoscopy in chronically ventilated patients.