Local Antibiotic Delivery Ceramic Bone Substitutes for the Treatment of Infected Bone Cavities and Bone Regeneration: A Systematic Review on What We Have Learned from Animal Models

Aims: the focus of this study is to evaluate if the combination of an antibiotic with a ceramic biomaterial is effective in treating osteomyelitis in an infected animal model and to define which model and protocol are best suited for in vivo experiments of local bone infection treatment. Methods: a systematic review was carried out based on PRISMA statement guidelines. A PubMed search was conducted to find original papers on animal models of bone infections using local antibiotic delivery systems with the characteristics of bone substitutes. Articles without a control group, differing from the experimental group only by the addition of antibiotics to the bone substitute, were excluded. Results: a total of 1185 records were retrieved, and after a three-step selection, 34 papers were included. Six manuscripts studied the effect of antibiotic-loaded biomaterials on bone infection prevention. Five articles studied infection in the presence of foreign bodies. In all but one, the combination of an antibiotic with bioceramic bone substitutes tended to prevent or cure bone infection while promoting biomaterial osteointegration. Conclusions: this systematic review shows that the combination of antibiotics with bioceramic bone substitutes may be appropriate to treat bone infection when applied locally. The variability of the animal models, time to develop an infection, antibiotic used, way of carrying and releasing antibiotics, type of ceramic material, and endpoints limits the conclusions on the ideal therapy, enhancing the need for consistent models and guidelines to develop an adequate combination of material and antimicrobial agent leading to an effective human application.The authors would like to thank Fluidinova, S.A., and CaixaImpulse (laCaixa Foundation) for supporting Biocomposites research group, at i3S, Universidade do Porto

Underlying Dimensions of the Physical Educators\u27 Judgments about Inclusion Instrument: Brazilian-Version

Background/Objective: The available information pertaining to the attitudes of Brazilian physical education teachers about teaching students with disabilities is limited in the extant literature base. Rationally, however, scholars argue that determining, analyzing, and theorizing about the attitudes of physical education teachers is important in the preparation and professional development of these teachers. It is therefore important to extend the research base using valid and reliable measures regarding teachers’ attitudes about inclusion and teaching students with various disabilities. Purpose: The purpose of this study was to examine the underlying dimensions of the Physical Educators’ Judgments about Inclusion (PEJI) scale following translation procedures that converted the existing measure to Portuguese. The PEJI was designed to analyze teachers’ attitudes about inclusion and teaching students with various disabilities. Method: Using a descriptive survey research design, data were collected from 147 participants (women = 57.1%, men = 42.9%) on the PEJI survey instrument. Results: Principal component analysis resulted in salient loadings on three dimensions consistent with prior study using the PEJI and explained 57% of the variance for measuring judgments about: Inclusion versus Exclusion, Acceptance of Students with Disabilities, and Perceived Training Needs. Conclusions: The overall results confirm validity of the PEJI survey consistent with prior study on this measure. The strong magnitude of values indicates that each of the subscales measures separate dimensions of judgments (attitudes). Implications for future use, we recommend reporting individual scale scores rather than a total PEJI score

Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model

The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model.This work was financed by FEDER-Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; by Portuguese funds through FCT/MCTES in the framework of the project institute for Research and Innovation in Health Sciences (POCI-01-0145-FEDER-007274); by the Project Biotherapies (NORTE-01-0145-FEDER-000012); and by the project HEPHAPC Program RESOLVE, Norte 2020 (NORTE-01-0246-FEDER-000018). The authors would also like to acknowledge the technical support for histology and histochemical studies of Rui Fernandes and Rossana Correia and all the staff from HEMS/i3S, as well as the support of all the staff and students at the Hospital Veterinario-Universidade de Evora

A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionine β -Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5′-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood. Here we found that the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral properties and markedly increased affinity for CO, making the protein much more prone than wild type (WT) CBS to inactivation at physiological CO levels. The higher CO affinity could result from the slightly higher flexibility in the heme surroundings revealed by solving at 2.80-Å resolution the crystallographic structure of a truncated p.P49L. Additionally, we report that p.P49L displays impaired H2S-generating activity, fully rescued by PLP supplementation along the purification, despite a minor responsiveness to AdoMet. Altogether, the results highlight how increased propensity to CO inactivation of an otherwise WT-like variant may represent a novel pathogenic mechanism in classical homocystinuria

Encefalopatía necrotizante aguda (ENA): reporte de casos

La encefalitis necrotizante aguda (ENA) es una rara enfermedad del SNC de curso fulminante con necrosis tisular, de carácter parainfeccioso. Presenta secuelas neurológicas graves. Se presenta de manera aguda con depresión del sensorio y convulsiones. El mismo es precedido por un cuadro infeccioso. El diagnóstico se basa en lesiones características del SNC. Afecta principalmente a niños pequeños y jóvenes, requiriéndose su reconocimiento precoz y tratamiento apropiado. Nuestro objetivo es reportar 3 casos de encefalopatía necrotizante aguda que ingresaron a nuestro hospital, mostrar su presentación clínica y hallazgos neurorradiológicos que orientaron al diagnóstico. Todos los casos presentaban criterios sugestivos de ENA.Acute necrotizing encephalitis (ENA) is a rare CNS condition of fulminating parainfectious course with tissue necrosis during the course of viral infection. It presents severe neurological sequelae. It associates acute encephalopathy with sensory depression and seizures, which is preceded by an infectious disease. The diagnosis is based on characteristic lesions of the CNS. It mainly affects kids and young children, requiring early recognition and appropriate treatment. Our objective is to report 3 cases of acute necrotizing encephalopathy that entered our hospital. Show your clinical presentation and neuroradiological findings that guided the diagnosis. All the cases presented criteria suggestive of ENA

Southern Brazilian native fruit shows neurochemical, metabolic and behavioral benefits in an animal model of metabolic syndrome.

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Reliability and Comparison of Some GEANT4-DNA Processes and Models for Proton Transportation: An Ultra-Thin Layer Study

This chapter presents a specific reliability study of some GEANT4-DNA (version 10.02.p01) processes and models for proton transportation considering ultra-thin layers (UTL). The Monte Carlo radiation transport validation is fundamental to guarantee the simulation results accuracy. However, sometimes this is impossible due to the lack of experimental data and, it is then that the reliability evaluation takes an important role. Geant4-DNA runs in an energy range that makes impossible, nowadays, to perform a proper microscopic validation (cross-sections and dynamic diffusion parameters) and allows very limited macroscopic reliability. The chemical damage cross-sections reliability (experiment versus simulation) is a way to verify the consistency of the simulation results which is presented for 2 MeV incident protons beam on PMMA and PVC UTL. A comparison among different Geant4-DNA physics lists for incident protons beams from 2 to 20 MeV, interacting with homogeneous water UTL (2 to 200 nm) was performed. This comparison was evaluated for standard and five other optional physics lists considering radial and depth profiles of deposited energy as well as number of interactions and stopping power of the incident particle

Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer's type

Aims The aim of this study was to analyze if the pre-administration of anthocyanin on memory and anxiety prevented the effects caused by intracerebroventricular streptozotocin (icv-STZ) administration-induced sporadic dementia of Alzheimer's type (SDAT) in rats. Moreover, we evaluated whether the levels of nitrite/nitrate (NOx), Na+,K+-ATPase, Ca2 +-ATPase and acethylcholinesterase (AChE) activities in the cerebral cortex (CC) and hippocampus (HC) are altered in this experimental SDAT. Main methods Male Wistar rats were divided in 4 different groups: control (CTRL), anthocyanin (ANT), streptozotocin (STZ) and streptozotocin + anthocyanin (STZ + ANT). After seven days of treatment with ANT (200 mg/kg; oral), the rats were icv-STZ injected (3 mg/kg), and four days later the behavior parameters were performed and the animals submitted to euthanasia. Key findings A memory deficit was found in the STZ group, but ANT treatment showed that it prevents this impairment of memory (P < 0.05). Our results showed a higher anxiety in the icv-STZ group, but treatment with ANT showed a per se effect and prevented the anxiogenic behavior induced by STZ. Our results reveal that the ANT treatment (100 μM) tested displaces the specific binding of [3H] flunitrazepam to the benzodiazepinic site of GABAA receptors. AChE, Ca+-ATPase activities and NOx levels were found to be increased in HC and CC in the STZ group, which was attenuated by ANT (P < 0.05). STZ decreased Na+,K+-ATPase activity and ANT was able to prevent these effects (P < 0.05). Significance In conclusion, these findings demonstrated that ANT is able to regulate ion pump activity and cholinergic neurotransmission, as well as being able to enhance memory and act as an anxiolytic compound in animals with SDAT

Biological evaluation of alginate-based hydrogels, with antimicrobial features by Ce(III) incorporation, as vehicles for a bone substitute

In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HA. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca2+ ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 hours at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HA, particularly the hydrogel Alg/HA.The authors would like to acknowledge the financial support from FCT (Fundacao para a Ciencia e a Tecnologia) through the grant SFRH/BD/76237/2011 and project ENMED/0002/2010, from FEDER funds through the program COMPETE-Programa Operacional Factores de Competitividade-under the project PEst-C/EME/UI0285/2011, as well as to the project I&DT BIOMAT&CELL n. 1372