Recent findings show that many human pathogenic bacteria can use multiple host organisms. For example, Salmonella Typhimurium can use plants as alternative hosts to humans and other animals. These ...bacteria are able to adhere to plant surfaces and actively infect the interior of plants. Similarly to the infection of animal cells, S. Typhimurium suppresses plant defense responses by a type III secretion mechanism, indicating that these bacteria possess a dedicated multi-kingdom infection strategy, raising the question of host specificity. In addition, evidence is accumulating that the interaction of Salmonella with plants is an active process with different levels of specificity, because different Salmonella serovars show variations in pathogenicity, and different plant species reveal various levels of resistance towards these bacteria.
This study was aimed at developing a nanoparticle strategy to overcome acquired resistance against erlotinib in non-small cell lung cancer (NSCLC). To load erlotinib on biodegradable PLGA ...nanoparticles, erlotinib-cyclodextrin (Erlo-CD) complex was prepared using β-cyclodextrin sulfobutyl ether, which was in turn loaded in the core of PLGA nanoparticles using multiple emulsion solvent evaporation. Nanoparticles were characterized for size distribution, entrapment and loading efficiency, in-vitro release, and therapeutic efficacy against different lung cancer cells. Effect of formulation on cell cycle, apoptosis, and other markers was evaluated using flow cytometry and western blotting studies. The efficacy of optimized nanoformulation was evaluated using a clinically relevant in-vitro 3D-spheroid model. Results showed that Erlo-CD loaded nanoparticles (210 ± 8 nm in size) demonstrated 3-fold higher entrapment (61.5 ± 3.2% vs 21.9 ± 3.7% of plain erlotinib loaded nanoparticles) with ~5% loading efficiency and sustained release characteristics. Developed nanoparticles demonstrated significantly improved therapeutic efficacy against NSCLC cells in terms of low IC50 values and suppressed colony forming ability of cancer cells, increased apoptosis, and autophagy inhibition. Interestingly, 3D spheroid study demonstrated better anticancer activity of Erlo-CD nanoparticles compared to plain erlotinib. Present study has shown a premise to improve therapeutic efficacy against erlotinib-resistant lung cancer using modified nanoErlo formulations.
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Osmotic treatment (OT) was applied to infuse grape phenolic compounds into plant tissue. The stability of the grape phenolics after a post-treatment, such as convective air drying, was evaluated. A ...model food made of agar gel and three plant commodities (two fruits, apple and banana, and one vegetable, potato) were osmo-treated and subsequently air-dried (55
°C). In the osmotic solution, sodium chloride (10%, w/w) and sucrose (50%, w/w) were used when treating vegetables and fruits, respectively, while a commercial grape seed extract was the source of phenolics (0.63%, w/w). During OT, total phenolic content and antiradical scavenging capacity of plant foods were significantly increased. The extent of grape phenolic impregnation was controlled by food structure and the kind of osmo-active solute: plant tissue showed a lower grape phenolic infusion than that of the model food. OT, as a pre-treatment, protected against grape phenolic degradation during further convective air drying, even though the mechanisms controlling the phenolic degradation process require further research.
Pulmonary arteriovenous malformations (PAVM) present with a variety of clinical manifestations, including hemoptysis. The usual management strategy relies upon interventional techniques, with surgery ...reserved for cases which are recalcitrant to less invasive measures.
A 14-year-old female presented with massive and refractory hemoptysis. CTA and bronchoscopy did not identify a targetable lesion, but given her clinical instability she underwent percutaneous angiography which identified a right-sided PAVM with bronchial artery to pulmonary artery communication coursing near the right mainstem bronchus. Embolization procedures were initially successful to control bleeding, but recurrences of hemoptysis prompted surgical evaluation. Approximately two years after initial presentation, we performed robotic ligation of her PAVM which resulted in definitive control of the lesion with no additional bleeding episodes. She recovered well from surgery with a one-night hospital stay, and has experienced no surgical complications or recurrent bleeding to date.
Rarely, pediatric PAVMs may require surgical intervention if interventional methods do not achieve definitive therapy. A variety of surgical techniques may be employed as dictated by the lesion's characteristics. Robotic approaches, including ligation, should be considered for patients with failure of conservative measures as it provides minimally invasive, precise technical management of PAVM.
•What is currently known about this topic?•Pulmonary arteriovenous malformations (PAVM) are rare lesions that cause bleeding, embolism, and pathologic shunting. Interventional techniques are the mainstay of therapy, but surgery is required complex or recurrent cases; the role of robotic approaches to PAVM management is relatively unexplored.•What new information is contained in this article?•We report a robotic surgical technique to manage recrruent bleeding due to a PAVM. This technique can be used when other interventional measures fail.
Mental stress-induced myocardial ischemia (MSIMI) is frequent in patients with coronary artery disease and is associated with worse prognosis. Young women with a previous myocardial infarction (MI), ...a group with unexplained higher mortality than men of comparable age, have shown elevated rates of MSIMI, but the mechanisms are unknown.
We studied 306 patients (150 women and 156 men) ≤61 years of age who were hospitalized for MI in the previous 8 months and 112 community controls (58 women and 54 men) frequency matched for sex and age to the patients with MI. Endothelium-dependent flow-mediated dilation and microvascular reactivity (reactive hyperemia index) were measured at rest and 30 minutes after mental stress. The digital vasomotor response to mental stress was assessed using peripheral arterial tonometry. Patients received
Tc-sestamibi myocardial perfusion imaging at rest, with mental (speech task) and conventional (exercise/pharmacological) stress.
The mean age of the sample was 50 years (range, 22-61). In the MI group but not among controls, women had a more adverse socioeconomic and psychosocial profile than men. There were no sex differences in cardiovascular risk factors, and among patients with MI, clinical severity tended to be lower in women. Women in both groups showed a higher peripheral arterial tonometry ratio during mental stress but a lower reactive hyperemia index after mental stress, indicating enhanced microvascular dysfunction after stress. There were no sex differences in flow-mediated dilation changes with mental stress. The rate of MSIMI was twice as high in women as in men (22% versus 11%,
=0.009), and ischemia with conventional stress was similarly elevated (31% versus 16%,
=0.002). Psychosocial and clinical risk factors did not explain sex differences in inducible ischemia. Although vascular responses to mental stress (peripheral arterial tonometry ratio and reactive hyperemia index) also did not explain sex differences in MSIMI, they were predictive of MSIMI in women only.
Young women after MI have a 2-fold likelihood of developing MSIMI compared with men and a similar increase in conventional stress ischemia. Microvascular dysfunction and peripheral vasoconstriction with mental stress are implicated in MSIMI among women but not among men, perhaps reflecting women's proclivity toward ischemia because of microcirculatory abnormalities.
Abstract
The dynamical approach represents a new branch in the understanding of functional brain networks. Using simple indices to represent time connectivity and topological stability, we evaluated ...the hypothesis of increased brain stability during the meditative state in comparison to the relaxation state. We used a new way to consider the time evolution of synchronization patterns in electroencephalography (EEG) data. The time-varying graph approach and the motif synchronization method were combined to build a set of graphs representing time evolution for the synchronization of 29 EEG electrodes. We analysed these graphs during meditation and relaxation states in 17 experienced meditators. As result, we found significant increasing of time connectivity (t(15) $= -2.50$, p $= 0.023$) and topological stability (t(15) $= 1.23$, p $= 0.020$) in the meditation state when compared to the relaxation state. These findings suggest that dynamical properties of the synchronization network may revel aspects of brain activity in altered states of consciousness not possible to measure using a static approach. We concluded that the topological patterns evolution in the functional networks of experienced meditators are more stable in the meditative state than in the relaxation state.
We determined the feasibility and diagnostic performance of segmental 18F-flurpiridaz myocardial blood flow (MBF) measurement by positron emission tomography (PET) compared with the standard ...territory method, and assessed whether flow metrics provide incremental diagnostic value beyond relative perfusion quantitation (PQ).
All evaluable pharmacological stress patients from the Phase III trial of 18F-flurpiridaz were included (n = 245) and blinded flow metrics obtained. For each coronary territory, the segmental flow metric was defined as the lowest 17-segment stress MBF (SMBF), myocardial flow reserve (MFR), or relative flow reserve (RFR) value. Diagnostic performances of segmental and territory MBF metrics were compared by receiver operating characteristic (ROC) areas under the curve (AUC). A multiple logistic model was used to evaluate whether flow metrics provided incremental diagnostic value beyond PQ alone. The diagnostic performances of segmental flow metrics were higher than their territory counterparts; SMBF AUC = 0.761 vs. 0.737; MFR AUC = 0.699 vs. 0.676; and RFR AUC = 0.716 vs. 0.635, respectively (P < 0.001 for all). Similar results were obtained for per-vessel coronary artery disease (CAD) ≥70% stenosis categorization and per-patient analyses. Combinatorial analyses revealed that only SMBF significantly improved the diagnostic performance of PQ in CAD ≥50% stenoses, with PQ AUC = 0.730, PQ + segmental SMBF AUC = 0.782 (P < 0.01), and PQ + territory SMBF AUC = 0.771 (P < 0.05). No flow metric improved diagnostic performance when combined with PQ in CAD ≥70% stenoses.
Assessment of segmental MBF metrics with 18F-flurpiridaz is feasible and improves flow-based epicardial CAD detection. When combined with PQ, only SMBF provides additive diagnostic performance in moderate CAD.
Abstract Facklamia hominis is a Gram-positive bacterium that was first isolated from various human samples, excluding abscesses of the scapula. We here report the first scapular abscess infection due ...to F. hominis , found in Marseille, France. We also reviewed all cases published in the literature.
Emerging powers have increasingly been vocal about reforming the structures of global governance. Brazil has asserted itself both as a player to be reckoned with in multilateral organizations and as ...a candidate for permanent membership at the United Nations Security Council. This article aims at investigating the circumstances surrounding Brazil’s efforts at three historical moments: the failed attempt to gain a permanent seat on the Council of the League of Nations, the short-lived campaign to become the “sixth permanent member” of the Security Council in 1945, and the candidacy in the 1990s and after. Although some studies focus on each candidature separately, there is not a comprehensive comparison to put them into perspective. By comparing how foreign policy was conducted by different administrations, the article sheds light on the future behavior that could be expected from Brazil on this issue, regardless of the government in charge.
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•Three types of graphene oxide were produced with different degree of oxidation.•Structural and compositional changes affect graphene oxide-As(III) adsorption.•A higher As(III) ...adsorption capacity is reached with a higher degree of oxidation.•Interaction energies of graphene oxide-arsenic were calculated by computer modeling.•The cytotoxicity of graphene oxide is not dependent on its degree of oxidation.
The study of the interaction between graphene oxide (GO) and arsenic is of great relevance not only in the design of adsorbent materials to remove this contaminant but also in the understanding of its combined nanotoxicity. In this work, we show that As(III) adsorption, primarily H3AsO3, by graphene oxide is affected by its degree of oxidation. Three types of GO with C/O ratios between 1.35 and 1.98 were produced, resulting in important variations in the concentration of COH and COC functional groups. The less oxidized material reached a maximum As(III) adsorption capacity of 123 mg/g, whereas the GO with the highest degree of oxidation reached a value of 288 mg/g at pH 7, the highest reported in the literature. We also show that sulfates and carbonates present in water strongly inhibit As(III) adsorption. The interaction between graphene oxide and As(III) was also studied by Density Functional Theory (DFT) computer models showing that graphene oxide interacts with As(III) primarily through hydrogen bonds, having interaction energies with the hydroxyl and epoxide groups of 1508.6 and 1583.6 kJ/mol, respectively. Finally, cytotoxicity tests showed that the graphene oxide maintained cellular viability of 57% with 50 μg/ml, regardless of its degree of oxidation.
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