Calcium-doped manganese ferrite nanoparticles (NPs) are gaining special interest in the biomedical field due to their lower cytotoxicity compared with other ferrites, and the fact that they have ...improved magnetic properties. Magnetic hyperthermia (MH) is an alternative cancer treatment, in which magnetic nanoparticles promote local heating that can lead to the apoptosis of cancer cells. In this work, manganese/calcium ferrite NPs coated with citrate (Ca
Mn
Fe
O
(
= 0, 0.2, 1), were synthesized by the sol-gel method, followed by calcination, and then characterized regarding their crystalline structure (by X-ray diffraction, XRD), size and shape (by Transmission Electron Microscopy, TEM), hydrodynamic size and zeta potential (by Dynamic Light Scattering, DLS), and heating efficiency (measuring the Specific Absorption Rate, SAR, and Intrinsic Loss Power, ILP) under an alternating magnetic field. The obtained NPs showed a particle size within the range of 10 nm to 20 nm (by TEM) with a spherical or cubic shape. Ca
Mn
Fe
O
NPs exhibited the highest SAR value of 36.3 W/g at the lowest field frequency tested, and achieved a temperature variation of ~7 °C in 120 s, meaning that these NPs are suitable magnetic hyperthermia agents. In vitro cellular internalization and cytotoxicity experiments, performed using the human cell line HEK 293T, confirmed cytocompatibility over 0-250 µg/mL range and successful internalization after 24 h. Based on these studies, our data suggest that these manganese-calcium ferrite NPs have potential for MH application and further use in in vivo systems.
Adalimumab, etanercept and infliximab are effective TNF inhibitors (TNFis) in the treatment of RA, but no randomized clinical trials have compared the three agents. Prior observational data are not ...consistent. We compared their effectiveness over 1 year in a prospective cohort.
Analyses were performed on subjects' first episode of TNFi use in the Rheumatic Diseases Portuguese Register, Reuma.pt. The primary outcome was the proportion of patients with European League Against Rheumatism good response sustained at two consecutive observations separated by 3 months during the first year of TNFi use. Comparisons were performed using conventional adjusted logistic regression, as well as matching subjects across the three agents using a propensity score. In addition, baseline predictors of treatment response to TNFi were identified.
The study cohort included 617 RA patients, 250 starting etanercept, 206 infliximab and 161 adalimumab. Good response was achieved by 59.6% for adalimumab, 59.2% for etanercept and 51.9% for infliximab (P = 0.21). The modelled probability of good response did not significantly differ across agents (etanercept vs adalimumab OR = 0.97, 95% CI 0.55, 1.71; etanercept vs infliximab OR = 1.25, 95% CI 0.74, 2.12; infliximab vs adalimumab OR = 0.80, 95% CI 0.47, 1.36). Matched propensity score analyses also showed no significant treatment response differences. Greater educational attainment was a predictor of better response, while smoking, presence of ACPA, glucocorticoid use and worse physician assessment of disease activity at baseline each predicted a reduced likelihood of treatment response.
Over 1 year, we found no difference in effectiveness between adalimumab, etanercept and infliximab.
Different positive pharmacological effects have been attributed to the natural product resveratrol (RSV), including antioxidant, antiaging, and cancer chemopreventive properties. However, its low ...bioavailability and rapid metabolic degradation has led to the suspicion that many of the biological activities of this compound observed in vitro may not be attainable in humans. To improve its bioavailability and pharmacokinetic profile, attempts have been made to encapsulate RSV into lipid-based nanocarrier systems. Here, the dioctadecyldimethylammonium bromide (DODAB):monoolein (MO) liposomal system (1:2) loaded with RSV revealed appropriate characteristics for drug release purposes: reduced size for cellular uptake (157 ± 23 nm), stability up to 80 days, positive surface charge (ζ ≈ +40 mV), and a controlled biphasic release of RSV from the lipid nanocarriers over a period of almost 50 h at pH 5.0 and 7.4. Moreover, the encapsulation efficiency of the nanocarrier ranged from 70% to 92% and its RSV loading capacity from 9% to 14%, when RSV was between 100 and 200 μM. The partition coefficient (K p) of RSV between lipid and aqueous phase was log K p = 3.37 ± 0.10, suggesting moderate to high lipophilicity of this natural compound and reinforcing the lipid nanocarriers’ suitability for RSV incorporation. The thermodynamic parameters of RSV partitioning in the lipid nanocarriers at 37 °C (ΔH = 43.76 ± 5.68 kJ mol–1; ΔS = 0.20 ± 0.005 kJ mol–1; and ΔG = −18.46 ± 3.48 kJ mol–1) reflected the spontaneity of the process and the establishment of hydrophobic interactions. The cellular uptake mechanism of the RSV-loaded nanocarriers labeled with the lipophilic fluorescent probe 1,6-diphenyl-1,3,5-hexatriene (DPH) was studied in the eukaryotic model system Saccharomyces cerevisiae. Thirty minutes after incubation, yeast cells readily internalized nanocarriers and the spots of blue fluorescence of DPH clustered around the central vacuole in lipid droplets colocalized with the green fluorescence of the lipophilic endocytosis probe FM1-43. Subsequent studies with the endocytosis defective yeast deletion mutant (end3Δ) and with the endocytosis inhibitor methyl-β-cyclodextrin supported the involvement of an endocytic pathway. This novel nanotechnology approach opens good perspectives for medical applications.
Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information ...on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard.
The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level.
There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49.
The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.
Worldwide, foodborne diseases are a growing public health problem. Among the infectious bacteria, non-typhoidal
serovars (NTS) are the major cause of hospitalization and death, and the emergence and ...spread of their antibiotic-resistance is becoming a worldwide health issue. This, coupled with the restrictions of antibiotics use in agriculture and animal production, calls for alternative approaches to solve this problem. Plant-derived aqueous extracts compounds could provide novel straightforward approaches to control pathogenic bacteria. This review discusses the antimicrobial activity of aqueous plant extracts against
serovars, the possible mechanisms of action involved, which components/structures might be responsible for such activity, and the current challenges for the use of these extracts/components in
infection management and their application perspectives.
Background and Objective
The improvement in the appearance of the skin with dermal striae (DS) is currently eval‐uated by invasive methods, such as biopsy. This study evaluates whether ...high‐resolution ultrasound (HRUS) could be used to identify skin lesions in vivo caused by DS, using 2D images and measuring the thickness of the dermal layer.
Methods
High‐resolution ultrasound at frequencies of 20 and 30 MHz was used in this study in ten volunteers with DS. The thickness of the skin layers was estimated by tracing five vertical lines from epidermis (EP) to dermis (DE) and DE to hypodermis (H) surface.
Results
The dermal lesions caused by striae appeared in ultrasonic images as poor echo areas. The average normal DE thickness varied from 1.07 to 1.65 mm, while the DE thickness with DS varied between 0.35 and 1.33 mm. A statistically significant reduction in the DE thickness was found (P‐value < .05) in the presence of DS. The mean values of the EP thickness without and with DS were 0.12 ± 0.03 mm and 0.11 ± 0.02 mm, respec‐tively. A total of 90.00% of the EP‐related groups did not present the normal distribu‐tion (P‐value < .05).
Conclusions
High‐resolution ultrasound permitted the visualization of the three skin layers and the dermal lesions caused by striae. The dermal layer thicknesses with striae were thinner than those without. Therefore, ultrasound 2D imaging has shown to be a promising and financially feasible tool to be used as a noninvasive diagnostic method for evaluating therapeutic protocols used in the treatment of these dermal conditions.
First examples of 8π + 2π cycloaddition of 16-dehydropregnenolone (16-DPA) acetate with diazafulvenium methides leading to chiral 4,5,6,7-tetrahydropyrazolo1,5-apyridine-fused steroids are reported. ...These hexacyclic steroids were obtained exclusively or selectively with the approach of the 1,7-dipole by the less hindered α-face of 16-DPA. Quantum chemical calculations at the DFT level were carried out, using the cycloaddition of 1-methyl- and 1-benzyl-diazafulvenium methides with N-phenylmaleimide as model reactions, in order to rationalize the stereochemistry outcome. The results indicate that endo cycloadditions of the more stable dipole conformation, having the 1-substituent pointing outward, are significantly more favorable than the alternative exo cycloaddition.
Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term ...potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.
A new specialist group for Brazilian fungi Drechsler-Santos, Elisandro Ricardo; Calaça, Francisco J. Simões; Martins-Cunha, Kelmer ...
Oryx,
07/2023, Volume:
57, Issue:
4
Journal Article
At this time the effectiveness of the COVID-19 vaccines has been proven, and it is crucial to carry out the complete vaccination of the population. Therefore, it is imperative to optimize the vaccine ...distribution fleets. This paper discusses the optimization of distribution routes for the Pfizer vaccine in Portugal in terms of transportation time, total costs, and CO2 emissions. To this end, the Vehicle Routing Problem with Time Windows (VRPTW) model with a vehicle capacity restriction was used. The VRPTW model was tested for two scenarios. The first scenario allowed the driver to work overtime (585 min). The second scenario considered that the driver works 8 h (480 min). The results are presented to compare and justify the proposed method with large significance placed in terms of safety concerns, economic savings, environmental protection, and energy consumption. This paper aims to contribute to the healthcare system by optimizing the COVID-19 vaccine distribution routes and minimizing this process’s carbon footprint.
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