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Metallic prostheses are the most used for the partial or total recovery of damaged organs and tissues, with titanium being the most applied material. Aiming to enhance the device to be implanted, the application of polymeric and ceramic coatings has been studied. The use of polycaprolactone (PCL) has shown promising characteristics, given its biodegradability, and the addition of hydroxyapatite (HA) has favored osseointegration. Nevertheless, complications related to infectious processes are recurrent to surgical procedures. In this context, the present study proposes the manufacture of a functional hybrid material for prosthetic application. As a strategy to minimize postsurgical bacterial contamination, this work proposes the incorporation of Melaleuca alternifolia essential oil (TTO) as a natural bactericide, in polycaprolactone and hydroxyapatite coatings in a titanium substrate. The samples were characterized to demonstrate that the coatings were performed on the whole surface of the titanium and that the incorporation of the essential oil did not alter the morphology of the polymeric film. The surface morphological evaluation performed after the corrosion assays in simulated body fluid indicated there was PCL degradation, being more intense for the samples containing HA, deriving from the alteration in the polymeric coating hydrophilicity combined with the bioceramic and the increase in surface porosity. Simultaneously to the process of polymeric layer degradation, it is suggested that there will be a release of the TTO incorporated in PCL and the formation of overlapping apatitic layers. Therefore, the results demonstrated that the proposed coatings may contribute to biocompatibility and the osseointegrative process, indicating the potentiality for application in orthopedic medical devices. [ABSTRACT FROM AUTHOR]

Purpose: New generation of receptor tyrosine kinase inhibitors (RTKIs) have shown to improve survival in many solid tumors. However, an imaging biomarker is needed for patient selection and prediction of treatment response. This study evaluates the use of quantitative changes of HER3 on 68 Ga-NOTA-HER3P1 PET/MRI for prediction of early response to pan-RTKIs in gastric cancer (GCa).Procedures: GCa cell lines were evaluated for expression of RTKs, and downstream signaling pathways (AKT and MAPK). Cell viability was assessed following 24-72 h of treatment with 0.01-1 µmol/L of afatinib, a pan-RTKI. HER3-expressing afatinib-sensitive (NCI-N87) and resistant cells (SNU16) were selected for evaluation of changes in RTKs expression and downstream pathways, with 24-72 h of 0.1 µmol/L afatinib treatment. 68 Ga-NOTA-HER3P1 PET/MRI was performed in subcutaneous NCI-N87 and SNU16 xenografts (nu:nu, n = 12/group) at baseline and 4 days after afatinib treatment (10 mg/kg, PO, daily). Temporal changes in PET measures were correlated to HER3 expression in tumors, tumor growth rate, and treatment response.Results: With afatinib therapy, NCI-N87 cells showed increased total HER3 expression, and reduction of other RTKs and downstream nodes within 72 h, while SNU16 cells showed no significant change in total HER3 and downstream nodes. 68 Ga-HER3P1 PET/MRI showed increased uptake in NCI-N87 and no significant change in SNU16 tumors (day 4 vs. baseline SUVmean: 3.8 ± 0.7 vs. 1.6 ± 0.6, p < 0.05 in NCI-N87, and 1.5 ± 0.7 vs. 1.7 ± 0.7, p > 0.05 in SNU16). These findings were in concordance with HER3 expression in histopathological analyses and tumor growth over 3 weeks of treatment (mean tumor volume in treated vs. control: 11 ± 17 mm3 vs. 293 ± 79 mm3, p < 0.001 in NCI-N87, and 238 ± 91 mm3 vs. 282 ± 35 mm3, p > 0.05 in SNU16).Conclusions: Quantitative changes in HER3 PET could be used to predict response to pan-RTKI within few days after initiation of treatment and can help with personalizing GCa management. [ABSTRACT FROM AUTHOR]

Purpose: The lack of effective molecular biomarkers to monitor idiopathic pulmonary fibrosis (IPF) activity or treatment response remains an unmet clinical need. Herein, we determined the utility of fibroblast activation protein inhibitor for positron emission tomography (FAPI PET) imaging in a mouse model of pulmonary fibrosis. Methods: Pulmonary fibrosis was induced by intratracheal administration of bleomycin (1 U/kg) while intratracheal saline was administered to control mice. Subgroups from each cohort (n = 3–5) underwent dynamic 1 h PET/CT after intravenously injecting FAPI-46 radiolabeled with gallium-68 ([68 Ga]Ga-FAPI-46) at 7 days and 14 days following disease induction. Animals were sacrificed following imaging for ex vivo gamma counting and histologic correlation. [68 Ga]Ga-FAPI-46 uptake was quantified and reported as percent injected activity per cc (%IA/cc) or percent injected activity (%IA). Lung CT density in Hounsfield units (HU) was also correlated with histologic examinations of lung fibrosis. Results: CT only detected differences in the fibrotic response at 14 days post-bleomycin administration. [68 Ga]Ga-FAPI-46 lung uptake was significantly higher in the bleomycin group than in control subjects at 7 days and 14 days. Significantly (P = 0.0012) increased [68 Ga]Ga-FAPI-46 lung uptake in the bleomycin groups at 14 days (1.01 ± 0.12%IA/cc) vs. 7 days (0.33 ± 0.09%IA/cc) at 60 min post-injection of the tracer was observed. These findings were consistent with an increase in both fibrinogenesis and FAP expression as seen in histology. Conclusion: CT was unable to assess disease activity in a murine model of IPF. Conversely, FAPI PET detected both the presence and activity of lung fibrogenesis, making it a promising tool for assessing early disease activity and evaluating the efficacy of therapeutic interventions in lung fibrosis patients. [ABSTRACT FROM AUTHOR]

Purpose: Evaluating the potential of gross Linum usitatissimum L. seed mucilage to be used as a drug release retardant. In order to do so, seeds were subjected to a simple and scalable extractive process comprising few stages, without alcohol-based precipitation. Matrix tablets based on hydrophilic polymers are one of the simplest forms of developing modified release systems. Methods: Flaxseeds were added to distilled water at a flaxseed:water ratio of 1:13; the suspension was continuously stirred at room temperature, for 24 h. Flaxseeds were sieved and the gross linseed mucilage was freeze-dried. Subsequently, the sample was analyzed through Fourier transform infrared spectroscopy (IV-TF) at wavelength ranging from 650 to 4000 cm−1. Results: Infrared (IR) spectroscopy analysis has suggested the presence of flaxseed mucilage polymers in the extracted product. Tablets presenting mucilage or HPMC (hydroxypropyl methylcellulose) and tablets without polymer were prepared based on the wet granulation technique. Matrix tablets presenting mucilage or HPMC have shown similar dissolution profiles, as well as similar potential in drug release control. Conclusion: The product extracted from flaxseed under simple conditions, even without undergoing purification process, can have high technological value in the pharmaceutical industry because it has excellent potential to be used as excipient for matrix tablet manufacturing. [ABSTRACT FROM AUTHOR]

Background: The assessment of adherence to warfarin therapy is useful in clinical practice due to its wide variability in dose–response and risks of complications. The aim of this study was to investigate validated instruments used to assess adherence to warfarin therapy. Methods: Information was collected from the MEDLINE (PubMed), LILACS, EMBASE, and Cochrane Library databases. Search strategies were applied for each database, with no time limit or language restriction. Inclusion criteria consisted of study participants of ≥ 18 years of age, from both sexes, on chronic anticoagulation with warfarin for any indication and the use of validated instruments to assess adherence to warfarin therapy. Exclusion criteria consisted of duplicate articles, narrative or systematic reviews, and meta-analyses, as well as case reports/series and experimental studies involving animals. Two independent reviewers performed the following steps: evaluation of titles/abstracts, selection of studies after full reading, data extraction, and evaluation of potential bias. Discrepancies were resolved by a third reviewer. Results: Overall, 19 articles were selected for this systematic review, including 17 cross-sectional studies, one cohort study, and one quasi-experimental study, published from 2009 to 2019. The validated instruments identified in this review were Morisky Medication Adherence Scale (MMAS), the eight-item Morisky Medication Adherence Scale (MMAS-8), Measurement of Treatment Adherence (MTA), and Brief Medication Questionnaire (BMQ). Only MMAS-8 was tested for reliability, using the internal consistency assessment, with Cronbach's α range 0.56–0.71. Conclusions: This review highlighted a gap in knowledge regarding the scarcity of validated instruments to assess adherence to warfarin therapy. Limitations were found in instruments that comprised the assessment of the isolated use of medication and the lack of analysis of other relevant therapeutic aspects. Future studies are needed to develop and validate more comprehensive instruments in an attempt to assess adherence to warfarin therapy. PROSPERO: Registration number CRD42019128324 [ABSTRACT FROM AUTHOR]

The antimicrobial peptides Ocellatin-LB1, -LB2 and -F1, isolated from frogs, are identical from residue 1 to 22, which correspond to the -LB1 sequence, whereas -LB2 carries an extra N and -F1 additional NKL residues at their C-termini. Despite the similar sequences, previous investigations showed different spectra of activities and biophysical investigations indicated a direct correlation between both membrane-disruptive properties and activities, i.e., ocellatin-F1 > ocellatin-LB1 > ocellatin-LB2. This study presents experimental evidence as well as results from theoretical studies that contribute to a deeper understanding on how these peptides exert their antimicrobial activities and how small differences in the amino acid composition and their secondary structure can be correlated to these activity gaps. Solid-state NMR experiments allied to the simulation of anisotropic NMR parameters allowed the determination of the membrane topologies of these ocellatins. Interestingly, the extra Asn residue at the Ocellatin-LB2 C-terminus results in increased topological flexibility, which is mainly related to wobbling of the helix main axis as noticed by molecular dynamics simulations. Binding kinetics and thermodynamics of the interactions have also been assessed by Surface Plasmon Resonance and Isothermal Titration Calorimetry. Therefore, these investigations allowed to understand in atomic detail the relationships between peptide structure and membrane topology, which are in tune within the series -F1 > > -LB1 ≥ -LB2, as well as how peptide dynamics can affect membrane topology, insertion and binding. [ABSTRACT FROM AUTHOR]

Silver tungstate nanoparticles have been presenting attractive characteristics that could allow its usage in the biomedical sciences. In this study, Ag2WO4 nanoparticles with an average size of 242 nm were obtained and radiolabeled with technetium-99m with high labeling-yield as well as high stability. Biodistribution studies were carried out in healthy and tumor-bearing mice to determine the nanoparticle's in vivo behavior. The results revealed an important tumor-to-muscle ratio, reaching values above than 1.5, demonstrated the ability of this nanomaterial in accumulating preferentially in tumor tissue. All results together, converge to consider the Ag2WO4 nanoparticles as a potential system against cancer and a potential new radiolabeled probe for tumor identification and uptake. [ABSTRACT FROM AUTHOR]

In vivo vagus nerve stimulation holds great promise in regulating food intake for obesity treatment. Here we present an implanted vagus nerve stimulation system that is battery-free and spontaneously responsive to stomach movement. The vagus nerve stimulation system comprises a flexible and biocompatible nanogenerator that is attached on the surface of stomach. It generates biphasic electric pulses in responsive to the peristalsis of stomach. The electric signals generated by this device can stimulate the vagal afferent fibers to reduce food intake and achieve weight control. This strategy is successfully demonstrated on rat models. Within 100 days, the average body weight is controlled at 350 g, 38% less than the control groups. This work correlates nerve stimulation with targeted organ functionality through a smart, self-responsive system, and demonstrated highly effective weight control. This work also provides a concept in therapeutic technology using artificial nerve signal generated from coordinated body activities. [ABSTRACT FROM AUTHOR]

Reactive oxygen and nitrogen species (RONS) are essential for normal physiological processes and play important roles in cell signaling, immunity, and tissue homeostasis. However, excess radical species are implicated in the development and augmented pathogenesis of various diseases. Several antioxidants may restore the chemical balance, but their use is limited by disappointing results of clinical trials. Nanoparticles are an attractive therapeutic alternative because they can change the biodistribution profile of antioxidants, and possess intrinsic ability to scavenge RONS. Herein, we review the types of RONS, how they are implicated in several diseases, and the types of nanoparticles with inherent antioxidant capability, their mechanisms of action, and their biological applications. [ABSTRACT FROM AUTHOR]

Purpose: Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. Methods: The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with Lu ( t 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: Lu only, TRC105 only, Lu-DTPA-IgG (a nonspecific antibody), Lu-DTPA-TRC105 low-dose, and Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose Lu-DTPA-TRC105. Results: Biodistribution studies indicated steady uptake of Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival ( p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. Conclusion: Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a significant survival benefit without off-target toxicity. Thus, this targeted agent could be used in combination with other treatment options to slow tumor growth allowing the other agents to be more effective. [ABSTRACT FROM AUTHOR]

In Brazil, there are approximately 9.7 million inhabitants who are deaf or hard of hearing. Moreover, about 30% of the Brazilian deaf community is illiterate in Brazilian Portuguese due to difficulties to offer deaf children an inclusive environment based on bilingual education. Currently, the prevailing teaching practice depends heavily on verbal language and on written material, making the inclusion of the deaf a challenging task. This paper presents the author's approach for tackling this problem and improving deaf students' accessibility to written material in order to help them master Brazilian Portuguese as a second language. We describe an ongoing project aimed at developing an automatic Brazilian Portuguese-to-Libras translation system that presents the translated content via an animated virtual human, or avatar. The paper describes the methodology adopted to compile a source language corpus having the deaf student needs in central focus. It also describes the construction of a parallel Brazilian Portuguese/Brazilian Sign Language (Libras) corpus based on motion capture technology. The envisioned translation architecture includes the definition of an Intermediate Language to drive the signing avatar. The results of a preliminary assessment of signs intelligibility highlight the application potential. [ABSTRACT FROM AUTHOR]

Generalization prevails in flower–animal interactions, and although animal visitors are not equally effective pollinators, most interactions likely represent an important energy intake for the animal visitor. Hummingbirds are nectar-feeding specialists, and many tropical plants are specialized toward hummingbird-pollination. In spite of this, especially in dry and seasonal tropical habitats, hummingbirds may often rely on non-ornithophilous plants to meet their energy requirements. However, quantitative studies evaluating the relative importance of ornithophilous vs. non-ornithophilous plants for hummingbirds in these areas are scarce. We here studied the availability and use of floral resources by hummingbirds in two different areas of the Cerrado, the seasonal savannas in Central Brazil. Roughly half the hummingbird visited plant species were non-ornithophilous, and these contributed greatly to increase the overall nectar availability. We showed that mean nectar offer, at the transect scale, was the only parameter related to hummingbird visitation frequency, more so than nectar offer at single flowers and at the plant scale, or pollination syndrome. Centrality indices, calculated using hummingbird–plant networks, showed that ornithophilous and non-ornithophilous plants have similar importance for network cohesion. How this foraging behaviour affects reproduction of non-ornithophilous plants remains largely unexplored and is probably case specific, however, we suggest that the additional energy provided by non-ornithophilous plants may facilitate reproduction of truly ornithophilous flowers by attracting and maintaining hummingbirds in the area. This may promote asymmetric hummingbird–plant associations, i.e., pollination depends on floral traits adapted to hummingbird morphology, but hummingbird visitation is determined more by the energetic "reward" than by pollination syndromes. [ABSTRACT FROM AUTHOR]

Bombesin is a tetradecapeptide that binds specifically to gastrin releasing peptide receptors in humans. Several forms of cancer, including lung, prostate, breast, and colon express receptors for bombesin-like peptides. Radiolabeled bombesin analogs with a high affinity for these receptors might therefore be used for scintigraphic imaging of these tumor types. A truncated bombesin derivative (HYNIC-βAla-Bombesin) was radiolabeled with technetium-99m using EDDA and tricine as coligands. In vitro stability was evaluated in presence of plasma and excess of cysteine. The receptor-binding affinity assays was evaluated in MDA-MB-231 cancer cell line. In addition, in vivo biodistribution was performed in nude mice bearing breast tumor. In vitro assay showed a good affinity for the MDA-MB-231 cell line, showing 20.0 % of internalization at 4 h post-administration. Tc-HYNIC-βAla-Bombesin biodistribution revealed a rapid clearance and a significant renal excretion. In addition, tumor uptake was higher than non-excretory organs, such as the spleen, the liver, and muscles. Tumor-to-muscle and tumor-to-blood ratios for Tc-HYNIC-βAla-Bombesin showed high values at 4 h post-injection (5.34 and 4.55, respectively). Furthermore, blocked studies using cold bombesin peptide were performed, which demonstrated an important decrease in tumor uptake, indicating a tumor specificity for Tc-HYNIC-βAla-Bombesin. The Tc-HYNIC-βAla-Bombesin displayed suitable radiochemical characteristics, and adequate affinity to breast tumor cells (MDA-MB-231). Therefore, this analog can be considered as a candidate for the identification of bombesin-positive tumors. [ABSTRACT FROM AUTHOR]