Use of Zebrafish (Danio rerio) for Biosafety Evaluation of Strontium Nanostructured Hydroxyapatite.

Despite the numerous studies on biocompatibility with nano-biomaterials, the biological effects of strontium-substituted HA nanoparticles (nSrHA) need to be better understood. So, we conducted an embryotoxicity test using zebrafish (Danio rerio) according to the OECD 236 guideline, a model that represents a viable alternative that bridges the gap between in vitro and mammalian models. Zebrafish embryos were exposed for 120 h to microspheres containing nSrHA nanoparticles with low and high crystallinity, synthesized at temperatures of 5°C (nSrHA5) and 90°C (nSrHA90). We evaluated lethality, developmental parameters, and reactive oxygen species (ROS) production. The larval behavior was assessed at 168 hpf to determine if the biomaterials affected motor responses and anxiety-like behavior. The results showed that the survival rate decreased significantly for the nSrHA5 group (low crystalline particles), and an increase in ROS was also observed in this group. However, none of the biomaterials caused morphological changes indicative of toxicity during larval development. Additionally, the behavioral tests did not reveal any alterations in all experimental groups, indicating the absence of neurotoxic effects from exposure to the tested biomaterials. These findings provide valuable insights into the biosafety of modified HA-based nanostructured biomaterials, making them a promising strategy for bone tissue repair. As the use of hydroxyapatite-based biomaterials continues to grow, it is crucial to ensure rigorous control over the quality, reliability, and traceability of these materials.

Effects of the oral administration of glycosaminoglycans with or without native type II collagen on the articular cartilage transcriptome in an osteoarthritic-induced rabbit model.

BACKGROUND: In a previous study, the 84-day administration of glycosaminoglycans (GAGs), with or without native collagen type II (NC), in an osteoarthritis (OA)-induced rabbit model slowed down OA progression, improved several micro- and macroscopic parameters and magnetic resonance imaging (MRI) biomarkers in cartilage, and increased hyaluronic acid levels in synovial fluid. To elucidate the potential underlying mechanisms, a transcriptomics approach was conducted using medial femoral condyle and trochlea samples. RESULTS: The administration of chondroitin sulfate (CS), glucosamine hydrochloride (GlHCl), and hyaluronic acid (HA), with (CGH-NC) or without (CGH) NC, strongly modulated several genes involved in chondrocyte extracellular matrix (ECM) remodeling and homeostasis when compared to non-treated rabbits (CTR group). Notably, both treatments shared the main mechanism of action, which was related to ECM modulation through the down-regulation of genes encoding proteolytic enzymes, such as ADAM metallopeptidase with thrombospondin type 1 motif, 9 (Adamts9), and the overexpression of genes with a relevant role in the synthesis of ECM components, such as aggrecan (Acan) in both CGH-NC and CGH groups, and fibronectin 1 (Fn1) and collagen type II, alpha 1 (Col2A1) in the CGH group. Furthermore, there was a significant modulation at the gene expression level of the mTOR signaling pathway, which is associated with the regulation of the synthesis of ECM proteolytic enzymes, only in CGH-NC-supplemented rabbits. This modulation could account for the better outcomes concerning the microscopic and macroscopic evaluations reported in these animals. CONCLUSIONS: In conclusion, the expression of key genes involved in chondrocyte ECM remodeling and homeostasis was significantly modulated in rabbits in response to both CGH and CGH-NC treatments, which would partly explain the mechanisms by which these therapies exert beneficial effects against OA.

High Spatial Resolution Detector System Based on Reconfigurable Dual-FPGA Approach for Coincidence Measurements.

Time-resolved spectroscopic and electron-ion coincidence techniques are essential to study dynamic processes in materials or chemical compounds. For this type of analysis, it is necessary to have detectors capable of providing, in addition to image-related information, the time of arrival for each individual detected particle ("x, y, time"). The electronics capable of handling such sensors must meet requirements achievable only with time-to-digital converters (TDC) with a resolution on the order of tens of picoseconds and the use of a field-programmable gate array (FPGA) to manage data acquisition and transmission. This study introduces the design and implementation of an innovative TDC based on two FPGAs working symbiotically with different tasks: the first (AMD/Xilinx Artix® 7) directly implements a TDC, aiming for a temporal precision of 12 picoseconds, while the second (Intel Cyclone® 10) manages the acquisition and connectivity with the external world. The TDC has been optimized to operate on eight channels (+ sync) simultaneously but is potentially extendable to a greater number of channels, making it particularly suitable for coincidence measurements where it is necessary to temporally correlate multiple pieces of information from various measurement systems.

Physical activity levels during COVID-19 pandemic and its associated factors in patients with Chagas disease.

Background: A better understanding of the consequences of the Coronavirus Disease 2019 (COVID-19) pandemic on lifestyle of patients with Chagas disease (ChD) is of paramount importance to facilitate the implementation of intervention strategies tailored to this specific population. Objective: The present study aimed to evaluate the level of physical activity (PA) in Chagas disease (ChD) patients during the Coronavirus Disease 2019 (COVID-19) pandemic and its main associated factors. Methods: This is a cross-sectional study with 187 patients of both sexes, aged ≥18 years, followed in a national infectious disease center (Rio de Janeiro, Brazil). The level of PA was determined by the International Physical Activity Questionnaire short version and expressed in terms of total volume of physical activity (PA) (MET-minutes per week). Individuals were classified as physically active following the 2020 World Health Organization PA guideline. The exposure variables were age, sex, race, marital status, schooling, income per capita, number of rooms per domicile, number of residents per domicile, body mass index, clinical form of ChD, COVID-19 antibodies, comorbidities, self-reported anxiety, self-reported depression, self-reported fear, and self-reported sadness. The association between the exposure variables with total PA (as a continuous variable) was determined using univariate and multivariate linear regression models. Results: Mean age was 61.1 ± 11.6 years. Most (62%) were women and self-declared their race as mixed (50.8%). The percentage of physically active individuals according to was 52%. The variables independently associated with total PA levels were non-white race (Exp ß = 1.39; 95% CI 1.02 to 1.90), dyslipidemia (Exp ß = 0.73; 95% CI 0.56 to 0.95) and self-reported depression during quarantine (Exp ß = 0.71; 95% CI 0.52 to 0.96). Conclusion: Non-white race was positively associated with total levels of PA, while dyslipidemia, and self-reported depression during quarantine were negatively associated with total levels of PA. The identification of associated factors can facilitate the development of tailored strategies to increase PA levels ChD patients.

Towards Sustainable Packaging Using Microbial Cellulose and Sugarcane (Saccharum officinarum L.) Bagasse.

The high consumption of packaging has led to a massive production of waste, especially in the form of nonbiodegradable polymers that are difficult to recycle. Microbial cellulose is considered a biodegradable, low-cost, useful, ecologically correct polymer that may be joined with other biomaterials to obtain novel characteristics and can, therefore, be used as a raw material to produce packaging. Bagasse, a waste rich in plant cellulose, can be reprocessed and used to produce and reinforce other materials. Based on these concepts, the aim of the current research was to design sustainable packaging material composed of bacterial cellulose (BC) and sugarcane bagasse (SCB), employing an innovative shredding and reconstitution method able to avoid biomass waste. This method enabled creating a uniform structure with a 0.10-cm constant thickness, classified as having high grammage. The developed materials, particularly the 0.7 BC/0.3 SCB [70% (w/w) BC plus 30% (w/w) SCB] composite, had considerable tensile strength (up to 46.22 MPa), which was nearly thrice that of SCB alone (17.43 MPa). Additionally, the sorption index of the 0.7 BC/0.3 SCB composite (235.85 ± 31.29 s) was approximately 300-times higher than that of SCB (0.78 ± 0.09 s). The packaging material was also submitted to other analytical tests to determine its physical and chemical characteristics, which indicated that it has excellent flexibility and can be folded 100 times without tearing. Its surface was explored via scanning electron microscopy, which revealed the presence of fibers measuring 83.18 nm in diameter (BC). Greater adherence after the reconstitution process and even a uniform distribution of SCB fibers in the BC matrix were observed, resulting in greater tear resistance than SCB in its pure form. The results demonstrated that the composite formed by BC and SCB is promising as a raw material for sustainable packaging, due to its resistance and uniformity.

A Review of the Literature on Episodes of Acute Fentanyl Intoxication in Pediatric Age and Toxicological Applications.

Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms "fentanyl" AND "overdose" AND "children". The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures.

Older adults, perceived ageism, civic participation and mental health: a qualitative study.

OBJECTIVES: This study has three objectives: A) To investigate the relationship of ageism on older adults' civic activities; B) To analyze the influence of ageism on mental health; and C) To explore the impact of civic participation on older adults' mental health. METHOD: This qualitative study included 782 older people from three different nationalities (Portuguese, Brazilian, and English) ranging in age from 65 to 88. All the interviews went through the process of content analysis. RESULTS: For the first objective, the findings encompass one high-level theme (Social and individual incompetence), which included social rejection (86%), reduced competence (84%), expectations of failure (83%), and not being able to contribute (77%). For the second objective, findings indicated two overarching categories: Perceived inability, including frustration and impotence (89%), incompetence (77%) and irrelevance (71%); and Perceived distress, including anger (81%), feelings of anxiety (68%); and emotional bursts (63%). For the third objective, the following two high-level themes emerged: Ego-oriented resources, which comprised the development of a sense of purpose (81%), learning cognitive skills (71%), and (A3) practising sense of agency (67%); and Social-oriented resources, encompassing feeling socially integrated (80%); and expressing emotionally (54%). Findings indicated that the most verbalized themes for the three objectives were the same across the three nationalities. CONCLUSIONS: Ageism made it difficult for people to participate in civic life, which has been linked to better mental health. These findings emphasize the need to encourage inclusive civic involvement to improve older individuals' mental health.

Inspiratory muscle endurance is similarly reduced in the early and late stages of chronic Chagas heart disease.

OBJECTIVE: Inspiratory muscle strength (IMS) appears to be reduced in subjects with chronic Chagas heart disease (CHD), especially in the presence of heart failure (HF). However, only one study about IMS and inspiratory muscle endurance (IME) in those with CHD without heart failure is available. This study aimed to compare IMS and IME in subjects with CHD in the presence and absence of HF. METHODS: This is a cross-sectional study in which 30 CHD adult patients were divided into CHD-CC group (initial phase of CHD, without HF; n = 15) and CHD-HF group (advanced phase of CHD, with HF; n = 15). We assessed IMS by maximum inspiratory pressure (MIP) and IME by incremental (Pthmax) and constant load (TLim) tests. Reduced IMS and IME were considered by predicted MIP values <70% and Pthmax/MIP <75%, respectively. RESULTS: Inspiratory muscle weakness (IMW) was more frequent in CHD-HF than in CHD-CC (46.7% vs. 13.3%; p = 0.05), and both groups had high frequencies of reduced IME (93.3% CHD-CC vs. 100.0% CHD-HF; p = 0.95). Age-adjusted logistic regression analysis using HF as a dependent variable showed that HF was associated with an increased chance of IMW compared with the CHD-CC group (OR = 7.47; p = 0.03; 95% CI 1.20-46.19). CONCLUSION: This study suggests that, in patients with CHD, HF is associated with IMW, and that reduction of IME is already present in the initial phase, similar to the advanced phase with HF.

First report of coexistence of blaKPC-2 and blaNDM-1 in carbapenem-resistant clinical isolates of Klebsiella aerogenes in Brazil.

Klebsiella aerogenes is an important opportunistic pathogen with the potential to develop resistance against last-line antibiotics, such as carbapenems, limiting the treatment options. Here, we investigated the antibiotic resistance profiles of 10 K. aerogenes strains isolated from patient samples in the intensive-care unit of a Brazilian tertiary hospital using conventional PCR and a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. All isolates were completely resistant to ß-lactam antibiotics, including ertapenem, imipenem, and meropenem with differencing levels of resistance to aminoglycosides, quinolones, and tigecycline also observed. Half of the strains studied were classified as multidrug-resistant. The carbapenemase-producing isolates carried many genes of interest including: ß-lactams (blaNDM-1, blaKPC-2, blaTEM-1, blaCTX-M-1 group, blaOXA-1 group and blaSHVvariants in 20-80% of the strains), aminoglycoside resistance genes [aac(6')-Ib and aph(3')-VI, 70 and 80%], a fluoroquinolone resistance gene (qnrS, 80%), a sulfonamide resistance gene (sul-2, 80%) and a multidrug efflux system transporter (mdtK, 70%) while all strains carried the efflux pumps Acr (subunit A) and tolC. Moreover, we performed a comprehensive genomic characterization of a specific K. aerogenes strain (CRK317) carrying both the blaKPC-2 and blaNDM-1 genes simultaneously. The draft genome assembly of the CRK317 had a total length of 5,462,831 bp and a GC content of 54.8%. The chromosome was found to contain many essential genes. In silico analysis identified many genes associated with resistance phenotypes, including ß-lactamases (blaOXA-9, blaTEM-1, blaNDM-1, blaCTX-M-15, blaAmpC-1, blaAmpC-2), the bleomycin resistance gene (bleMBL), an erythromycin resistance methylase (ermC), aminoglycoside-modifying enzymes [aac(6')-Ib, aadA/ant(3")-Ia, aph(3')-VI], a sulfonamide resistance enzyme (sul-2), a chloramphenicol acetyltransferase (catA-like), a plasmid-mediated quinolone resistance protein (qnrS1), a glutathione transferase (fosA), PEtN transferases (eptA, eptB) and a glycosyltransferase (arnT). We also detected 22 genomic islands, eight families of insertion sequences, two putative integrative and conjugative elements with a type IV secretion system, and eight prophage regions. This suggests the significant involvement of these genetic structures in the dissemination of antibiotic resistance. The results of our study show that the emergence of carbapenemase-producing K. aerogenes, co-harboring blaKPC-2 and blaNDM-1, is a worrying phenomenon which highlights the importance of developing strategies to detect, prevent, and control the spread of these microorganisms.