RESUMO
BACKGROUND: The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. METHODS: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34). CONCLUSIONS: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.
Assuntos
Adenocarcinoma , Neoplasias Esofágicas , Neoplasias Gástricas , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Gástricas/patologia , Anticorpos Monoclonais/efeitos adversos , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Junção Esofagogástrica/patologia , ClaudinasRESUMO
This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.
Assuntos
Fogachos , Menopausa , Humanos , Feminino , Fogachos/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Pessoa de Meia-Idade , Resultado do Tratamento , Sistema Vasomotor/efeitos dos fármacos , Qualidade de VidaRESUMO
Geopropolis resins are produced by stingless bees (Meliponinae), developed from the collection of resinous materials, waxes and exudates, from the flora of the region where stingless bees are present, in addition to the addition of clay or earth in its composition. Several biological activities are attributed to Ethanol Extracts of Geopropolis (EEGP). The bioactive properties are associated with the complex chemical composition that the samples have. This work aims to evaluate the biological activities of the EEGP, in order to contribute with a natural therapeutic alternative, to face infections, mainly those caused by resistant strains of Staphylococcus aureus. The EEGP MIC tests showed antibacterial activity against two strains of S. aureus, both at concentrations of 550â µg/mL. The MBC performed with the inhibition values showed that the EEGP has bacteriostatic activity in both strains. Biofilm inhibition rates exhibited an average value greater than 65 % at the highest concentration. The EEGP antioxidant potential test showed good antioxidant activity (IC50) of 11.05±1.55â µg/mL. In the cytotoxicity test against HaCat cells, after 24â hours, EEGP induced cell viability at the three tested concentrations (550â µg/mL: 81.68±3.79 %; 1100â µg/mL: 67.10±3.76 %; 2200â µg/mL: 67.40±1.86 %). In view of the above, the safe use of EEGP from the brazilian northeast could be proven by the cytotoxicity test, and its use as an antioxidant and antibacterial agent has proven to be effective, as an alternative in combating oxidative stress and microorganisms such as S.â aureus, which, through the spread and ongoing evolution of drug resistance, generates an active search for effective solutions.
Assuntos
Antibacterianos , Biofilmes , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Staphylococcus aureus/efeitos dos fármacos , Animais , Abelhas , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Humanos , Biofilmes/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Própole/química , Própole/farmacologia , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a DrogaRESUMO
OBJECTIVES: To provide an update on the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on stroke in patients with type 2 diabetes (T2D). METHODS: PubMed, Embase, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) comparing SGLT2 inhibitors versus placebo or other therapies in patients with T2D and reporting stroke endpoint. We computed the risk ratios (RRs) to binary endpoints, with 95â¯% confidence intervals (CIs). RESULTS: A total of 71 RCTs and 105,914 patients were included, of whom 62,488 (59â¯%) were randomized to the SGLT2 inhibitors group. The follow-up ranged from 12 weeks to 4.2 years. There were no significant differences between groups in all types of stroke (RR 0.96; 95â¯% CI 0.89-1.04), ischemic stroke (RR 0.89; 95â¯% CI 0.76-1.04), and transient ischemic attack (RR 0.96; 95â¯% CI 0.79-1.16). Patients on SGLT2 inhibitors experienced lower rates of hemorrhagic stroke (RR 0.62; 95â¯% CI 0.39-0.98). In the subgroup analysis of the type of drug, sotagliflozin significantly reduced all types of stroke (RR 0.74; 95â¯% CI 0.56-0.97). CONCLUSION: In this meta-analysis of 71 RCTs comprising 105,914 patients with T2D, SGLT2 inhibitors were not associated with a reduced risk of stroke and transient ischemic attack compared to placebo or other therapies; however, there was a trend toward reduced risk of hemorrhagic stroke. Among all SGLT2 inhibitors, sotagliflozin significantly reduced the risk of stroke.
Assuntos
Diabetes Mellitus Tipo 2 , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose , Acidente Vascular Cerebral , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/tratamento farmacológico , Resultado do Tratamento , Fatores de Risco , Medição de Risco , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral Hemorrágico/diagnóstico , Fatores de Tempo , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Transportador 2 de Glucose-SódioRESUMO
Syagrus coronata, a native palm tree in the Caatinga domain, produces fixed oil (ScFO) used therapeutically and dietary by Northeast Brazilian communities. This study evaluated its anti-inflammatory potential of CFA-induced arthritis and its effect on behavioral parameters. In the acute model, ScFO at 25, 50, and 100 mg/kg showed edematogenic effects similar to indomethacin at 4 mg/kg (p > 0.05). In the arthritis model, 100 mg/kg ScFO treatment was comparable to indomethacin (4 mg/kg) (p > 0.05). TNF-α and IL-1ß levels were significantly reduced in ScFO-treated groups at 25, 50, and 100 mg/kg, and the indomethacin group (4 mg/kg) versus the positive control (p > 0.05). Radiographs showed severe soft-tissue swelling and bone deformities in the control group, while the 100 mg/kg ScFO group had few alterations, similar to the indomethacin group. Histopathological analysis revealed intense lymphocytic infiltration in the control group, mild diffuse lymphocytic infiltration in the indomethacin group, and mild lymphoplasmacytic infiltration with focal polymorphonuclear infiltrates in the 100 mg/kg ScFO group. Behavioral analysis showed improved exploratory stimuli in ScFO and indomethacin-treated mice compared to the positive control (p > 0.05). ScFO demonstrated anti-inflammatory effects in both acute and chronic arthritis models, reducing edema and pro-inflammatory cytokines, and improved exploratory behavior due to its analgesic properties.
RESUMO
Two large barriers are impeding the wide implementation of electric vehicles, namely driving-range and cost, primarily due to the low specific energy and high cost of mono-valence cathodes used in lithium-ion batteries. Iron is the ideal element for cathode materials considering its abundance, low cost and toxicity. However, the poor reversibility of (de)lithiation and low electronic conductivity prevent iron-based high specific energy multi-valence conversion cathodes from practical applications. In this work, a sustainable FeOF nanocomposite is developed with extraordinary performance. The specific capacity and energy reach 621 mAh g-1 and 1124 Wh kg-1 with more than 100 cycles, which triples the specific capacity, and doubles the specific energy of current mono-valence intercalation LiCoO2 . This is the result of an effective approach, combing the nanostructured FeOF with graphene, realized by making the (de)lithiation reversible by immobilizing FeOF nanoparticles and the discharge products over the graphene surface and providing the interparticle electric conduction. Importantly, it demonstrates that introducing small amount of graphene can create new materials with desired properties, opening a new avenue for altering the (de)lithiation process. Such extraordinary performance represents a significant breakthrough in developing sustainable conversion materials, eventually overcoming the driving range and cost barriers.
RESUMO
Mephedrone (MEP) is an illicit stimulant drug that belongs to the synthetic cathinone (SC) class, which has been widely used for recreational purposes and reported in forensic analysis. The preliminary identification of MEP and other SCs in seized samples is of great interest for forensic investigation and a fast and simple screening test for these drugs would be useful for on-site and in-house analyses. In this study, we present the electrochemical detection of MEP in forensic samples using, for the first time, independent redox processes of SCs on a graphene screen-printed electrode (SPE-GP). The proposed method for MEP detection on the SPE-GP was optimized in Britton-Robinson buffer solution (0.1 mol L-1) at pH 10.0 with adsorptive stripping differential pulse voltammetry (AdSDPV). The use of the SPE-GP with AdSDPV provides a wide linear range for MEP determination (2.6 to 112 µmol L-1) with a low limit of detection (LOD) (0.3 µmol L-1). The real surface area available for adsorption on the SPE-GP was estimated to be between 3.80 and 5.70 cm2, which provided high sensitivity for the proposed method. Furthermore, good stability of MEP electrochemical responses on the SPE-GP was obtained using the same or different electrodes (N = 3), with relative standard deviation (RSD) < 5.0% for both redox processes. Interference studies for a common adulterant (caffeine) and twelve other illicit drugs (phenethylamines, amphetamines, and other SCs) were performed with a highly selective response for MEP detection. Therefore, the SPE-GP with AdSDPV is demonstrated to be a selective and sensitive screening method to detect MEP and other SCs in forensic analysis, providing a fast and simple preliminary identification of these drugs in seized samples.
Assuntos
Grafite , Metanfetamina , Catinona Sintética , Eletrodos , Técnicas Eletroquímicas/métodosRESUMO
In this study, eight naphthoquinone derivatives were synthesized in yields ranging from 52 to 96% using easy, fast, and low-cost methodologies. All naphthoquinone derivatives were screened for their inâ vitro anti-proliferative activities against OVCA A2780 cancer cell lines. Amongst all analysed compounds, derivatives 3-5 presented the most prominent cytotoxic potential. Naphthoquinones 3 and 4, bearing sulfur-containing groups, were identified as having high potential for ROS production, in particular the superoxide anion. Furthermore, 3 and 4 compounds caused a decrease in the cell population in G0/G1 and induced more than 90% of the cell population to apoptosis. Compound 5 did not act in any of these processes. Finally, compounds 3-5 were tested for their inhibitory ability against PI3K and MAPK. Compounds 3 and 4 do not inhibit the PI3K enzyme. On the other hand, the naphthoquinone-polyphenol 5 was only able to inhibit the percentage of cells expressing pERK.
Assuntos
Antineoplásicos , Naftoquinonas , Neoplasias Ovarianas , Humanos , Feminino , Linhagem Celular Tumoral , Naftoquinonas/farmacologia , Antineoplásicos/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células , Relação Estrutura-AtividadeRESUMO
INTRODUCTION: Success-related factors of microimplant-assisted rapid palatal expansion (MARPE) were evaluated, including age, palatal depth, suture, and parassutural bone thickness, suture density and maturation, and the relation to corticopuncture (CP) technique, as well as skeletal and dental effects. METHODS: Sixty-six cone-beam computed tomography scans were analyzed before and after rapid maxillary expansion procedures in 33 patients aged 18-52 years for both sexes. The scans were generated in digital imaging and communications in medicine file format and analyzed in the multiplanar reconstruction of the regions of interest. Palatal depth, suture thickness, density and maturation, age, and CP were assessed. To evaluate dental and skeletal effects, the sample was divided into 4 groups: successful MARPE (SM), SM + CP technique (SMCP), failure MARPE (FM), and FM + CP (FMCP). RESULTS: Successful groups presented more skeletal expansion and dental tipping than failure groups (P <0.05). The mean age of the FMCP group was significantly higher than the SM groups; suture and parassutural thickness significantly related to the success, and patients who received CP showed a success rate of 81.2% compared with 33.3% in the no CP group (P <0.05). Suture density and palatal depth did not show a difference between the success and failure groups. Suture maturation was higher in SMCP and FM groups (P <0.05). CONCLUSIONS: Older age, thin palatal bone, and higher stage of maturation can influence the success of MARPE. CP technique in these patients appears to have a positive impact, increasing the chance of treatment success.
Assuntos
Maxila , Técnica de Expansão Palatina , Masculino , Feminino , Humanos , Tomografia Computadorizada de Feixe Cônico , Palato/diagnóstico por imagem , SuturasRESUMO
MicroRNAs (miRNAs) are important regulators of eukaryotic gene expression and their dysfunction is often associated with cancer. Alongside the canonical miRNA biogenesis pathway involving stepwise processing and export of pri- and pre-miRNA transcripts by the microprocessor complex, Exportin 5 and Dicer, several alternative mechanisms of miRNA production have been described. Here, we reveal that the atypical box C/D snoRNA U3, which functions as a scaffold during early ribosome assembly, is a miRNA source. We show that a unique stem-loop structure in the 5' domain of U3 is processed to form short RNA fragments that associate with Argonaute. miR-U3 production is independent of Drosha, and an increased amount of U3 in the cytoplasm in the absence of Dicer suggests that a portion of the full length snoRNA is exported to the cytoplasm where it is efficiently processed into miRNAs. Using reporter assays, we demonstrate that miR-U3 can act as a low proficiency miRNA in vivo and our data support the 3' UTR of the sortin nexin SNX27 mRNA as an endogenous U3-derived miRNA target. We further reveal that perturbation of U3 snoRNP assembly induces miR-U3 production, highlighting potential cross-regulation of target mRNA expression and ribosome production.
Assuntos
RNA Nucleolar Pequeno/metabolismo , Nexinas de Classificação/genética , Células HCT116 , Células HEK293 , Humanos , RNA Nucleolar Pequeno/genética , Ribonucleoproteínas Nucleares Pequenas/metabolismo , Nexinas de Classificação/metabolismoRESUMO
Humans' balance recovery responses to gait perturbations are negatively impacted with ageing. Slip and trip events, the main causes preceding falls during walking, are likely to produce severe injuries in older adults. While traditional exercise-based interventions produce inconsistent results in reducing patients' fall rates, perturbation-based balance training (PBT) emerges as a promising task-specific solution towards fall prevention. PBT improves patients' reactive stability and fall-resisting skills through the delivery of unexpected balance perturbations. The adopted perturbation conditions play an important role towards PBT's effectiveness and the acquisition of meaningful sensor data for studying human biomechanical reactions to loss of balance (LOB) events. Hence, this narrative review aims to survey the different methods employed in the scientific literature to provoke artificial slips and trips in healthy adults during treadmill and overground walking. For each type of perturbation, a comprehensive analysis was conducted to identify trends regarding the most adopted perturbation methods, gait phase perturbed, gait speed, perturbed leg, and sensor systems used for data collection. The reliable application of artificial perturbations to mimic real-life LOB events may reduce the gap between laboratory and real-life falls and potentially lead to fall-rate reduction among the elderly community.
Assuntos
Marcha , Equilíbrio Postural , Humanos , Idoso , Equilíbrio Postural/fisiologia , Marcha/fisiologia , Acidentes por Quedas/prevenção & controle , Caminhada/fisiologia , Velocidade de CaminhadaRESUMO
Recently, fall risk assessment has been a main focus in fall-related research. Wearable sensors have been used to increase the objectivity of this assessment, building on the traditional use of oversimplified questionnaires. However, it is necessary to define standard procedures that will us enable to acknowledge the multifactorial causes behind fall events while tackling the heterogeneity of the currently developed systems. Thus, it is necessary to identify the different specifications and demands of each fall risk assessment method. Hence, this manuscript provides a narrative review on the fall risk assessment methods performed in the scientific literature using wearable sensors. For each identified method, a comprehensive analysis has been carried out in order to find trends regarding the most used sensors and its characteristics, activities performed in the experimental protocol, and algorithms used to classify the fall risk. We also verified how studies performed the validation process of the developed fall risk assessment systems. The identification of trends for each fall risk assessment method would help researchers in the design of standard innovative solutions and enhance the reliability of this assessment towards a homogeneous benchmark solution.
Assuntos
Dispositivos Eletrônicos Vestíveis , Acidentes por Quedas/prevenção & controle , Algoritmos , Reprodutibilidade dos Testes , Medição de RiscoRESUMO
Breast cancer (BC) has a high mortality rate, which is attributed to the absence of effective treatment markers. Doxorubicin (DOX) was evaluated by molecular docking in vitro in cultured BC spheroids and its association with genes involved in the PI3K/AKT/PTEN signaling pathway. Spheroids were obtained from a primary BC. The selected compound was used for molecular docking experiments. Spheroids were treated with DOX for 1 (D1) and 9 (D9) days. qPCR was used to evaluate PIK3CA, HIF-1α, VEGF-A, PTEN expression. Treatment with DOX (1 µM) significantly increased the number of spheroids (D1), whereas exposure to chemotherapy at 2 µM on D9 was more effective. DOX treatment resulted in significantly higher expression of VEGF-A, HIF-1α and PIK3CA by D1 and HIF-1α and PTEN were upregulated by D9. Compared to treatment on D1 with D9 (1 µM) had significantly higher PTEN and lower PIK3CA gene expression. The genes HIF-1α and PTEN were more expressed with 2 µM of DOX while VEGF-A was downregulated. D1 vs. D9 exhibited reduced VEGF-A, HIF-1α, and PIK3CA expression and upregulation of PTEN expression. DOX effects at the molecular mechanisms can be involved the modulation of genes related to angiogenesis cell proliferation and tumor growth in BC tissue spheroids.
Assuntos
Neoplasias da Mama , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Doxorrubicina/farmacologia , Feminino , Humanos , Simulação de Acoplamento Molecular , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Projetos Piloto , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Esferoides Celulares , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
In this study, we use differential phase contrast images obtained by scanning transmission electron microscopy combined with computer simulations to map the atomic electrostatic fields of MoS2 monolayers and investigate the effect of sulfur monovacancies and divancancies on the atomic electric field and total charge distribution. A significant redistribution of the electric field in the regions containing defects is observed, with a progressive decrease in the strength of the projected electric field for each sulfur atom removed from its position. The electric field strength at the sulfur monovacancy sites is reduced by approximately 50% and nearly vanishes at the divacancy sites, where it drops to around 15% of the original value, demonstrating the tendency of these defects to attract positively charged ions or particles. In addition, the absence of the sulfur atoms leads to an inversion in the polarity of the total charge distribution in these regions.
RESUMO
Predicting the geographic distribution of plants that provide ecosystem services is essential to understand the adaptation of communities and conserve that group toward climate change. Predictions can be more accurate if changes in physiological characteristics of species due to those changes are included. Thus, we aimed to evaluate the impacts of climate change on the different hierarchical levels of Apuleia leiocarpa (Vogel) J. F. Macbr. (Fabaceae). Therefore, we experimentally evaluate the effect of different temperatures on the initial development (vigor) and estimate the impact of climate change on the potential geographic distribution of the species, using ecological niche approaches. For the experiment, we used 11 temperature intervals of 2 °C ranging from 21 to 41 °C. We used ecological niche modeling techniques (ENM) to predict the species' environmental suitability in future climate scenarios. The association between the experiment and niche models was obtained by testing the relationships of temperature increase on the species vigor and geographic distribution. This conceptual model to determine the direct and indirect effects of temperature was generated using the methodological framework of structural equation models. The experiment showed that the seeds had the highest growth at 31 °C. ENMs indicated that due to climate change, there is a tendency for the plant to migrate to regions with milder temperatures. However, such regions may be unsuitable for the plant since they do not have ideal temperatures to germinate, which may cause a drastic reduction in their availability in a future climate change scenario. The inclusion of seed germination through experimental research allowed us to detect an area that is less suitable for germination despite being climatically suitable for the species. Thus, research that integrates the effect of climate on the different stages of the organism's development is essential to understand the impact of climate change on biodiversity.
Assuntos
Mudança Climática , Ecossistema , Animais , Espécies em Perigo de Extinção , Monitoramento Ambiental , Germinação , SementesRESUMO
Rutin is an important flavonoid consumed in the daily diet. It is also known as vitamin P and has been extensively investigated due to its pharmacological properties. On the other hand, neuronal death induced by glutamate excitotoxicity is present in several diseases including neurodegenerative diseases. The neuroprotective properties of rutin have been under investigation, although its mechanism of action is still poorly understood. We hypothesized that the mechanisms of neuroprotection of rutin are associated with the increase in glutamate metabolism in astrocytes. This study aimed to evaluate the protective effects of rutin with a focus on the modulation of glutamate detoxification. We used brain organotypic cultures from post-natal Wistar rats (P7-P9) treated with rutin to evaluate neural cell protection and levels of proteins involved in the glutamate metabolism. Moreover, we used cerebral cortex slices from adult Wistar rats to evaluate glutamate uptake. We showed that rutin inhibited the cell death and loss of glutamine synthetase (GS) induced by glutamate that was associated with an increase in glutamate-aspartate transporter (GLAST) in brain organotypic cultures from post-natal Wistar rats. Additionally, it was observed that rutin increased the glutamate uptake in cerebral cortex slices from adult Wistar rats. We conclude that rutin is a neuroprotective agent that prevents glutamate excitotoxicity and thereof suggest that this effect involves the regulation of astrocytic metabolism.
Assuntos
Morte Celular/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Neurônios/efeitos dos fármacos , Rutina/farmacologia , Animais , Astrócitos/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Transportador 1 de Aminoácido Excitatório , Glutamato-Amônia Ligase/genética , Ácido Glutâmico/toxicidade , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Neurotoxinas/metabolismo , Neurotoxinas/toxicidade , Ratos , Ratos WistarRESUMO
Mycoplasma is the smallest self-replicating bacteria, figuring as common contaminant of eukaryotic cell cultures. Production inputs and operator's manipulation seem to be the main sources of such contamination. Many analytical approaches have been applied for mycoplasma detection in cell cultures and also in biological products. However, unless they were validated, only indicator cell culture and bacteriological culture are considered as compendial methods for quality control of biological products. Nano-flow cytometry has been pointed out as an alternative technique for addressing prokaryotic and eukaryotic cell viability being a substantial tool for reference material production. In this study, a viability-flow-cytometry assay was standardized for M. gallisepticum and then applied to other cell-culture-contaminant mycoplasmas. For this, M. galliseticum's growth rate was observed and different treatments were evaluated to establish low viability cultures (cell death-induced control). Distinct viability markers and their ideal concentrations (titration) were appraised. Ethanol treatment showed to be the best death-inducing control. CFDA and TOPRO markers revealed to be the best choice for detecting live and dead mycoplasma frequencies, respectively. The standardized methodology was applied to Mycoplasma arginini, M. hyorhinis, M. orale, Spiroplasma citri and Acholeplasma laidlawii. Significant statistical difference was observed in the percentage of viable cells in comparison to ethanol treatment for A. laidlawii in CFDA and in both markers for M. gallisepticum, M. hyorhinis and S. citri. In summary, we standardized a flow cytometry assay for assessing M. gallisepticum - and potentially other species - viability and ultimately applied for reference material production improving the quality control of biological products.
Assuntos
Mycoplasma gallisepticum , Tenericutes , Técnicas de Cultura de Células , Citometria de Fluxo , MycoplasmaRESUMO
Urine and struvite are organic fertilizers that have all nutritional requirements for the growth of a plant. However, these fertilizers may contain some emerging organic contaminants, such as ethinylestradiol, which is one of the most common hormones found in aquatic environments and can cause several changes in living organisms. Thus, the present study developed a fast, sensitive, inexpensive, and portable method for determining ethinylestradiol in urine and struvite, using square wave voltammetry (SWV) and screen-printed carbon electrodes modified with electrodeposited nickel film (SPCE-Ni). The electrodeposition of the nickel film on the screen-printed electrode was performed by cyclic voltammetry and optimized using complete factorial design 23 and central composite design. The parameters optimized for SPCE-Ni were: number of cycles (1000); scan rate (5 V s-1) and Ni2+ concentration (9.4 mmol L-1). The operational parameters of the SWV for ethinylestradiol analysis were also optimized by experimental designs and obtained the following optimal values: step potential (10 mV), modulation amplitude (40 mV), and frequency (20 Hz). The method used 0.1 mol L-1 BR buffer (pH 8.0) as support electrolyte and presented a limit of detection of 0.052 µmol L-1 (R2 = 0.996). Ethinylestradiol recovery test in struvite, human urine, synthetic urine, and pharmaceutical tablets ranged from 93.9% to 107.5%, indicating that there is no matrix effect. Furthermore, an interference test was performed with several drugs did not show any significant changes in the ethinylestradiol analytical signal, guaranteeing a greater precision of the method. These results reinforce the possibility of applying the proposed method in loco with a practical and fast way, without the need to use significant amounts of sample.
Assuntos
Monitoramento Ambiental/métodos , Etinilestradiol/análise , Fertilizantes/análise , Níquel/química , Carbono/química , Eletrodos , Humanos , Projetos de Pesquisa , EstruvitaRESUMO
BACKGROUND: Among the processes to be experienced by any organization during its establishment is the formation of an organizational identity. This process can be understood as the activity and event through which an organization becomes unique in the mind of its members. An organizational identity leads to an identification and both are directly associated with the success of an institution. This study is about a public higher education institution in health in its early years, with distinctive characteristics in the country where it is situated. In spite of having been successful in the graduation of its students it has fragile institutional bases, lack of autonomy and internal problems common to other institutions of this type. Thus, this study was conducted to understand how this institution defined itself among its own members, the elements of its identity and what justified its relative success despite its weaknesses. METHODS: A mixed-method approach was used to evaluate how a representative portion of this organization identifies with it. For the qualitative study two focus groups were conducted with transcripts submitted to content analysis proposed by Bardin, culminating in results from which a Likert scale-based questionnaire was elaborated and applied to 297 subjects. RESULTS: There were six central elements of the organizational identity made evident by the focus groups: political / ideological conflict; active teaching and learning methodologies; location / separation of campuses; time of existence; teaching career; political-administrative transformations. The quantitative analysis revealed in more detail the general impressions raised in the focus groups. Most results were able to demonstrate distinct identifications of the same identity with its exposed weaknesses. CONCLUSIONS: Lack of autonomy, administrative and structural shortcomings and ideological or political conflicts presented themselves as problems capable of destabilizing the identity of a public higher education institution. On the other hand, one way to combat such problems is through the development of the institution itself, particularly by becoming more active and useful to the community and seeking in a common interest to the higher administration agencies.
Assuntos
Aprendizagem , Universidades , Grupos Focais , Humanos , Pesquisa QualitativaRESUMO
It is essential to predict areas of losses or exchanges of ecosystem services to adapt communities to the impacts caused by climate change. Particularly for provisioning ecosystem services provided by economically important plant species, understanding the association between climate change impacts and deforestation of native vegetation increases the accuracy of those predictions. Thus, we aim to (i) map the richness of provisioning ecosystem services from economically important native plants; (ii) use forecasts (present and future) of the distribution of ecosystem services to assess areas of changes in the number and type of provisioning ecosystems services. We evaluated provisioning ecosystem services from 110 Cerrado native species of economic importance for the local population. We determined the potential distribution of these plants using ecological niche modeling techniques, which were grouped according to the 21 different services provided. The forecasts for variation in richness and type of service used four future climate change scenarios (RCPs 4.5 and 8.5 in 2050 and 2070). The service losses detected in our models were associated with variables representing the progress of native vegetation deforestation in the biome due to agricultural expansion. Currently, ecosystem services can be found simultaneously in practically the entire biome. However, changes in the global climate will impact the potential geographic distribution of those plants, causing many areas in the biome to have reduced availability of potential ecosystem services. Moreover, due to the association between exposure to climate change and deforestation of native vegetation, the northern region of the biome will likely have the distribution of ecosystem services severely affected.