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Periodontal health and biofilm control are primordial to success in orthodontic treatment. This study aimed to evaluate the effect of chlorhexidine (CHX) mouthwashes on periodontal status and extrinsic tooth staining in orthodontic patients. Thirty-three patients of both sexes, aged 11-33 years, under orthodontic treatment with fixed appliances at <16 months, were randomly distributed into 2 groups. In the control group, patients received mechanical hygiene instruction, and in the experimental group, patients also used CHX wash twice a week for 60 days. The effectivity of the protocols was evaluated using the plaque, gingival, gingival bleeding, and discoloration indexes before the hygiene protocol was applied, 15, 30, and 60 days after protocol implementation. In the experimental group, there was a decrease in the plaque, gingival, and gingival bleeding indexes at the different evaluation periods (P <0.05). In addition, there was a significant difference in the discoloration index at 60 days compared with initial time points after implementing hygiene protocols in the experimental group (P <0.05). In contrast, there were no significant differences in plaque, gingival, gingival bleeding, and discoloration indexes in the control group at any time (P >0.05). CHX mouthwash administered 30 days, twice a week, significantly improved the periodontal status with mild brown staining. After this period, expressive extrinsic tooth staining was observed. • Chlorhexidine (CHX) mouthwash is the first choice because of its antigingivitis effect. • CHX has antibacterial effects. • CHX mouthwash (0.12%) decreased microbial levels and periodontal index. • The most favorable period to maintain with CHX mouthwash was 30 days. [ABSTRACT FROM AUTHOR]

Perform a systematic review of the literature and present the results of randomized clinical trials (RCTs) pointing out under which conditions and forms of administration menthol is really capable of improving performance in endurance exercise. Thirteen studies met the eligibility criteria. The sample size ranged from 6 to 12 athletes and the studies were evaluated between 5 and 9 on the PEDro scale. Six studies evaluated menthol mouth rinse, of which three demonstrated an increase in time to exhaustion between 6% and 9% and two demonstrated a decrease in time trial (2.7% and 3.5%). Five studies evaluated the topical application but without modification of physical performance variables. Two studies assessed the oral intake, of which in one of them there was a decrease in the time trial between 5.2% and 8.2%. Current data point to a good perspective on the determination of menthol as an ergogenic resource, provided that further studies form a body of evidence on each of the forms of administration. The available evidence suggests that physical exercise practitioners who use menthol orally seem to be able to promoter sport advantage, but these results need to be weighed due to the evidence level is considered to be of low quality due to small sample size, heterogeneous supplementation and exercise protocols and low volume of studies. [ABSTRACT FROM AUTHOR]

This clinical, crossover, double-blind trial evaluated the microbial contamination of removable orthodontic appliances used by children and the efficacy of 0.12% chlorhexidine gluconate spray use for disinfection. Twenty children aged 7-11 years were instructed to wear removable orthodontic appliances for 1 week. They were instructed to use a placebo solution (control) or 0.12% chlorhexidine gluconate (experimental) to clean the appliances on days 4 and 7 after installation. After this period, the microbial contamination on the surfaces of the appliance was analyzed using checkerboard DNA-DNA hybridization for 40 bacterial species. Data were analyzed by Fisher exact, t , and Wilcoxon tests (α = 0.05). Removable orthodontic appliances were heavily contaminated by the target microorganisms. Streptococcus sanguinis, Streptococcus oralis, Streptococcus gordonii, and Eikenella corrodens were found in 100% of the appliances. Among cariogenic microorganisms, Streptococcus mutans and Streptococcus sobrinus were more abundant than Lactobacillus acidophilus and Lactobacillus casei. Red complex pathogens were more abundant than orange complex species. Purple complex bacteria were the most prevalent among bacterial complexes not associated with specific pathologies, detected in 34% of the samples. After the use of chlorhexidine, the number of cariogenic microorganisms (S. mutans, S. sobrinus, and L. casei) decreased significantly (P <0.05), and the numbers of periodontal pathogenic species from the orange and red complex also decreased significantly (P <0.05). There was no reduction for Treponema socranskii. Removable orthodontic appliances were densely contaminated by several bacterial species. Twice-a-week application of chlorhexidine spray effectively reduced cariogenic and orange and red complex periodontal pathogens. • Chlorhexidine (CHX) has antibacterial effects that are sustained for longer periods. • 0.12% CHX mouthwash decreased microbial levels. • Twice-a-week application of CHX spray reduced cariogenic pathogens. • Twice-a-week application of CHX spray reduced orange complex periodontal pathogens. • Twice-a-week application of CHX spray reduced red complex periodontal pathogens. [ABSTRACT FROM AUTHOR]

• Plasma epinephrine is decreased in priming models of fibromyalgia-like pain. • Clenbuterol attenuates hyperalgesia in an acid saline-induced fibromyalgia-like pain model. • Clenbuterol mitigates muscle atrophy in fibromyalgia priming model. Fibromyalgia (FM) is characterized by chronic widespread musculoskeletal pain accompanied by fatigue and muscle atrophy. Although its etiology is not known, studies have shown that FM patients exhibit altered function of the sympathetic nervous system (SNS), which regulates nociception and muscle plasticity. Nevertheless, the precise SNS-mediated mechanisms governing hyperalgesia and skeletal muscle atrophy in FM remain unclear. Thus, we employed two distinct FM-like pain models, involving intramuscular injections of acidic saline (pH 4.0) or carrageenan in prepubertal female rats, and evaluated the catecholamine content, adrenergic signaling and overall muscle proteolysis. Subsequently, we assessed the contribution of the SNS to the development of hyperalgesia and muscle atrophy in acidic saline-injected rats treated with clenbuterol (a selective β2-adrenergic receptor agonist) and in animals maintained under baseline conditions and subjected to epinephrine depletion through adrenodemedullation (ADM). Seven days after inducing an FM-like model with acidic saline or carrageenan, we observed widespread mechanical hyperalgesia along with loss of strength and/or muscle mass. These changes were associated with reduced catecholamine content, suggesting a common underlying mechanism. Notably, treatment with a β2-agonist alleviated hyperalgesia and prevented muscle atrophy in acidic saline-induced FM-like pain, while epinephrine depletion induced mechanical hyperalgesia and increased muscle proteolysis in animals under baseline conditions. Together, the results suggest that reduced sympathetic activity is involved in the development of pain and muscle atrophy in the murine model of FM analyzed. [ABSTRACT FROM AUTHOR]

Intellectual developmental disorder with dysmorphic facies and behavioral abnormalities (IDDFBA) is a recently described autosomal dominant entity caused by pathogenic variants, mostly de novo, in the FBXO11 gene. It presents in the first years of life with highly variable clinical manifestations. The main features of IDDFBA include borderline-to-severe intellectual disability, behavioral problems, hypotonia, facial dysmorphisms, minor skeletal abnormalities, and recurrent infections. Although eye problems, such as refractive errors, eye misalignment and minor visual changes, have been described in about 48% of patients, a major ocular defect, namely, bilateral optic nerve hypoplasia, has been reported in the literature only once. We report an 8-year-old boy with a novel de novo pathogenic variant in FBXO11 gene (NM_001190274.1: c.1166dup, p.Cys390Metfs∗3) and a complex ophthalmological phenotype, consisting of right microphthalmia, very shallow anterior chamber, and persistent pupillary membrane, right dense nuclear cataract, bilateral optic nerve hypoplasia, and bilateral horizontal manifest nystagmus. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to evaluate in vitro and in vivo bacterial endotoxin (LPS) adhesion in polyurethane and silicone esthetic elastomeric orthodontic ligatures. The null hypotheses tested were: (1) there is no LPS adhesion in esthetic elastomeric orthodontic ligatures; and (2) there is no difference in the LPS adhesion between different brands of these ligatures.Methods: For the in vitro study, 4 types of esthetic elastomeric ligatures were used (Sani-Ties and Sili-Ties [Dentsply GAC, Islandia, NY;] and Mini Single Case Ligature Stick and Synergy low-friction ligatures [Rocky Mountain Orthodontics, Denver, Colo]), contaminated or not with endotoxin solution. Replicas of twisted wire and cast stainless steel ligatures were used as control. For the in vivo study, 10 male and 10 female patients, aged 15-30 years, received the same 4 types of ligatures, 1 of each inserted in the maxillary and mandibular canines, randomly. Twenty-one days later, the ligatures were removed, and endotoxin quantification was performed using the Limulus amebocyte lysate test. Data were analyzed (α = 0.05) using the Kruskal-Wallis test and Dunn's posttest or analysis of variance and Tukey's posttest.Results: GAC silicone group had the lowest median contamination (1.15 endotoxin units/mL; P <0.0001) in vitro. In the in vivo study, the GAC silicone group had the lowest mean contamination (0.577 endotoxin units/mL; P <0.001). In both studies, the other groups did not present a significant difference when compared with each other (P >0.05).Conclusions: LPS exhibited an affinity for all the tested polyurethane and silicone elastomeric ligatures. GAC silicone ligatures presented with lower amounts of LPS attached to their surfaces. Thus, both null hypotheses were rejected. [ABSTRACT FROM AUTHOR]

Ecological Urbanism and Water Sensitive Urban Design have a central contribution to make in protecting and caring for people, nature and water in cities but readings of Urban Political Ecology evidence how ecological metaphors in urban design can easily translate into discriminatory urban development processes. This paper posits that for UPE to become meaningful for urban design practice, it is necessary to move beyond a critique. Instead, the insights of UPE should be pro-actively mobilized to develop a new vision of water sensitivity. The paper therefore identifies ways in which the key learnings of the critical social sciences, namely UPE, can be mobilized to support Water Sensitive Urban Design practice. How can ecological urbanists imagine new, more politically astute, forms of water sensitive living, charting design processes that not just recognize but also actively question and challenge uneven socio-ecological dynamics? In answering this question, the goal of this article is to make use of critique from UPE to influence Ecological Urbanists' goals and activate their political alignment with agendas that prioritize social equity. In imagining a new form of WSUD, we tried as much as possible not to over-instrumentalize UPE by rejecting the suggestion that some UPE 'lessons' or 'insights' could simply be inserted into ecological urbanism. On a different direction, we argue for a different emphasis in WSUD that does not deny the causes of current environmental degradation, pollution and depletion but, on the contrary, actively takes issue with and challenges the extractive and exploitative roots of contemporary urbanization processes. • Re-composition of Ecological Urbanism and WSUD is needed. • WSUD needs to actively challenge the extractive and exploitative roots of urbanization. • Critical designs will become more controversial and contested. • Designers are/should be mediators and activists. [ABSTRACT FROM AUTHOR]

Periapical radiography (PR) is a diagnostic tool to be used by professionals in clinical practice. The method presents limitations, and doubts still exist about its value to evaluate furcation perforation and the reparative process of hard or soft tissues after treatment. Thus, the aim of this study was to evaluate the accuracy of PR as a diagnostic method to detect both resorption of the furcation area after induced experimental perforation and repair after perforation treatment using histopathological findings as a gold standard. Thirty teeth of beagle dogs with furcation perforation were filled with Biodentine (Septodont, Saint-Maur-des-Fossés, France), ProRoot White mineral trioxide aggregate (Dentsply Tulsa Dental Specialties, Tulsa, OK), or gutta-percha and examined using PR and histology. Sensitivity, specificity, predictive values, and accuracy were calculated. PR detected repair and reabsorption of furcation perforation in 55% and 48% of the teeth, respectively. Histologic analysis showed furcation perforation in 66% and 21% of the teeth, respectively. Sensitivity and specificity of PR for the detection of repair were 0.84 and 1, respectively, whereas for resorption detection, the values were 0.43 and 0.65, respectively. Diagnostic accuracy for PR was 0.89 and 0.72 for repair and resorption of furcation perforation, respectively. PR showed more accurate diagnostic (true positives + true negatives/total) in repair detection compared with resorption of furcation perforation. We conclude that PR is not adequate in detecting resorption progress after the treatment of furcation perforation, and we encourage the use of digital imaging when suspicious of a possible unsuccessful result after furcation perforation treatment. [ABSTRACT FROM AUTHOR]

• CBD presents anticonvulsant behavioral effects in animal models of epilepsy. • CBD induces neuroprotection in animal models of epileptic seizures. • Multiple mechanisms of action are associated to CBD anticonvulsant effects. • Animal models support CBD therapeutic use for epilepsies treatment. • Detailed behavioral analysis are crucial for a better basic-clinical translation. Epilepsy is a neurological disorder characterized by the presence of seizures and neuropsychiatric comorbidities. Despite the number of antiepileptic drugs, one-third of patients did not have their seizures under control, leading to pharmacoresistance epilepsy. Cannabis sativa has been used since ancient times in Medicine for the treatment of many diseases, including convulsive seizures. In this context, Cannabidiol (CBD), a non-psychoactive phytocannabinoid present in Cannabis , has been a promising compound for treating epilepsies due to its anticonvulsant properties in animal models and humans, especially in pharmacoresistant patients. In this review, we summarize evidence of the CBD anticonvulsant activities present in a great diversity of animal models. Special attention was given to behavioral CBD effects and its translation to human epilepsies. CBD anticonvulsant effects are associated with a great variety of mechanisms of action such as endocannabinoid and calcium signaling. CBD has shown effectiveness in the clinical scenario for epilepsies, but its effects on epilepsy-related comorbidities are scarce even in basic research. More detailed and complex behavioral evaluation about CBD effects on seizures and epilepsy-related comorbidities are required. [ABSTRACT FROM AUTHOR]

Polyurethane (PUF) foam market has grown rapidly in recent years due to its wide variety of applications. Their environmental impact is a matter of significant concern as so far, the production of PUF is essentially dependent on fossil raw materials, namely isocyanates and polyols. With the purpose of reducing climate change and decoupling economic growth from resource use, the use of renewable polyols is already a reality in the PUF industry, namely vegetable oils, recycled polyols, and CO 2 -based polyols. However, this only contributes in part to the total polyol used in some formulations in various industrial-scale applications. Even though there are other potential renewable polyol counterparts (e.g. lignin, as well as alternative synthetic routes to produce PUF including variations of the so-called via Non-Isocyanate Polyurethane (NIPU)), there are still several limitations compared to the conventional manufacturing processes involving petroleum-derived raw materials, which hampers the availability of these alternatives. The possible benefits of these potentially greener alternatives need to be quantified and compared with the environmental performance of well-established conventional processes. This review work encompasses the results from a systematic literature analysis regarding Life Cycle Assessment (LCA) studies on PUF produced using a variety of raw materials, classified as four different feedstocks in this work. This timely work identifies the main trends in methodological choices, including functional unit, system boundaries, multifunctionality, impact assessment methods, and sensitivity analysis, and enables the understanding of their effect on the environmental sustainability of PUF, namely in the most evaluated impact category-the climate change (CC). A wide range of CC variation was observed, ranging from 2.95 kgCO 2 eq/FU for a fossil-based to 7.67 kgCO 2 eq/FU for a recovered fossil polyol. The main issues for this high variability are addressed, highlighting the need for further harmonization and consistency in data collection and methodological choices used in LCA studies. [Display omitted] • Bio-based polyols are the most studied type of feedstock for polyurethane foams (PUF). • Isocyanates are the main hotspot for climate change of polyurethane foams. • Harmonization of the functional unit is critical for comparing impact assessment results. • More consistent data and consensus are necessary for the harmonization of all impact categories in the literature. [ABSTRACT FROM AUTHOR]

Leading causes of vision loss include neovascular age-related macular degeneration (NVAMD) and macular edema (ME), which both require frequent intravitreal injections for treatment. A safe, poly(lactic-co-glycolic acid) (PLGA)-based biodegradable polymeric microparticle (MP) delivery system was developed that encapsulates and protects a biomimetic peptide from degradation, allows sustained intraocular release through polymer hydrolysis, and demonstrates a prolonged anti-angiogenic effect in vivo in three different NVAMD animal models (a laser-induced choroidal neovascularization mouse model, a rho VEGF transgenic mouse model, and a Tet/opsin/VEGF transgenic mouse model) following intravitreal administration. The role of copolymer composition and microparticle shape was explored and 85:15 lactide-to-glycolide PLGA formed into ellipsoidal microparticles was found to be effective at inhibiting neovascularization for at least 16 weeks in vivo. Treatments were found to not only inhibit the growth of neovascularization, but also to cause regression of the neovasculature, reduce vascular leakage, and prevent exudative retinal detachment. These particulate devices are promising for the sustained release of biologics in the eye and may be useful for treating retinal diseases. Devastating retinal diseases cause blindness in millions of people around the world. Current protein-based treatments have insufficient efficacy for many patients and also necessitate frequent intravitreal injections. Here, we demonstrate a new treatment consisting of a peptide encapsulated in biodegradable microparticles. We explore the effects of copolymer composition and physical shape of polymeric microparticles and find that both modulate peptide release. Efficacy of the treatment was validated in three different mouse models and the lead formulation was determined to be effective long-term, for at least 16 weeks in vivo , following a single injection. Treatments inhibited and regressed neovascularization as well as reduced vascular leakage. Anisotropic polymeric microparticles are promising for the sustained release of biologics in the eye. [ABSTRACT FROM AUTHOR]

• Offshore carbon dioxide rich Gas-To-Wire with carbon capture is proven viable. • Supersonic separator used in gas processing, decarbonation and fluid dehydration. • No decarbonation prior to gas-turbine firing for better economic performance. • Gas-To-Wire with carbon capture generates 612 MW and 38% return-on-investment. • Addressed pioneering use of supersonic separator for carbon dioxide dehydration. Gas-To-Wire is a solution for remote offshore oil-gas fields with high gas-oil ratio and high carbon dioxide content, as it requires minimum natural gas upgrade and is feasible for long-distance transportation. Additionally, combining offshore Gas-To-Wire with carbon capture enables abatement of emissions while providing revenues from enhanced oil recovery. This work investigated offshore Gas-To-Wire comprising processing of natural gas with high carbon dioxide content, power generation, post-combustion carbon capture and enhanced oil recovery. Supersonic separator is proposed for three applications: fuel-gas conditioning, fuel-gas decarbonation and pioneering dehydration of supercritical carbon dioxide. Economic analysis, including offshore rig and electricity transmission, results in positive Net Present Value with 20% of return-on-investment, besides a Levelized Cost of Energy comparable to onshore power plants with carbon capture and storage. Sensitivity analysis shows high impact of electricity-price and oil recovery yield on profitability, as well as better economic performance when carbon dioxide is not removed from fuel-gas; i.e., all carbon capture should be post-combustion capture. Thus, despite effectiveness of supersonic separator for fuel-gas decarbonation, the 612 MW optimized Gas-To-Wire with carbon capture plant should have 100% of carbon removal via post-combustion, resulting in 38.3% return-on-investment and even better Levelized Cost of Energy similar to onshore power plants without carbon capture. [ABSTRACT FROM AUTHOR]

Existing models of deradicalisation, countering violent extremism (CVE), and counter-terrorism (CT) have lacked a clear theory of change, as well as robust empirical methodologies. This paper proposes an empirically-based systematic and transparent methodology – the Innovative Moments Coding System (IMCS) – which is empirically sensitive, ethically defensible, and can be of use in the context of research to inform practitioner contexts. Through a case study of former violent militants, we explore the adaptation and usage of this instrument to identify and track self-narrative change in the processes of engagement and disengagement, as well as radicalisation and deradicalisation in the context of violent extremism and terrorism. We illustrate how this methodology has the potential to bring benefits to the work of researchers involved in producing guidelines for disengagement, deradicalisation or risk-reduction interventions. [ABSTRACT FROM AUTHOR]

Abstract The present work addresses the detailed structural elucidation by high resolution techniques of both liquid pyrolysis products from slow pyrolysis of crambe seeds. Bio-oil and aqueous phase were obtained at 400 °C with 32% and 15.8% (w/w) yield and were separated by density difference. Lyophilization was applied to concentrate the organic compounds present in aqueous phase (OCAP). Bio-oil and the OCAP were analyzed by comprehensive bidimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC-TOFMS) and positive and negative-ion electrospray (ESI) high resolution Orbitrap mass spectrometry (HRMS). For the bio-oil, 1,400 analytes were identified by GC×GC-TOFMS and the most abundant classes were hydrocarbons (448.6 mg g−1) and N-containing compounds (172.2 mg g−1). In the bio-oil ESI-(+) Orbitrap HRMS data, the N2 class was the most abundant (79.9%). In the negative mode, ca. 87.6% of assigned peaks corresponded to O2 class for bio-oil. The major compounds identified by GC×GC-TOFMS in the OCAP were oxygenated (49.8%) and NO containing compounds (45.9%). ESI (−) Orbitrap HRMS analysis for OCAP presented high percentage of O2 (57.2%) and NO (28.3%) classes, while ESI (+) Orbitrap MS of N2 (51.8%) and NO (28.8%) classes. The aqueous fraction composition profile indicates a potential biological activity due to the presence of N-heterocyclic compounds and the bio-oil (38.9 MJ kg−1; 5.4% H 2 O) has the potential to be used as a second generation (ASTM D7544) or hydrotreated to improve fuel quality. Graphical abstract Image 1 Highlights • Crambe is an interesting non-food biomass with a low production cost. • The liquid products of slow pyrolysis from crambe seeds were analyzed. • The bio-oil consists mainly of compounds with apolar characteristics. • The organic compounds present in the aqueous phase (OCAP) have a more polar profile. • Bio-oil is rich in hydrocarbons while OCAP is rich in N- and O-containing compounds. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Oxidized alginate hydrogels are appealing alternatives to natural alginate due to their favourable biodegradability profiles and capacity to self-crosslink with amine containing molecules facilitating functionalization with extracellular matrix cues, which enable modulation of stem cell fate, achieve highly viable 3-D cultures, and promote cell growth. Stem cell metabolism is at the core of cellular fate (proliferation, differentiation, death) and metabolomics provides global metabolic signatures representative of cellular status, being able to accurately identify the quality of stem cell differentiation. Herein, umbilical cord blood mesenchymal stem cells (UCB MSCs) were encapsulated in novel oxidized alginate hydrogels functionalized with the glycine-histidine-lysine (GHK) peptide and differentiated towards the osteoblastic lineage. The ADA-GHK hydrogels significantly improved osteogenic differentiation compared to gelatin-containing control hydrogels, as demonstrated by gene expression, alkaline phosphatase activity and bone extracellular matrix deposition. Metabolomics revealed the high degree of metabolic heterogeneity in the gelatin-containing control hydrogels, captured the enhanced osteogenic differentiation in the ADA-GHK hydrogels, confirmed the similar metabolism between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. Our results suggest a novel paradigm for metabolomics-guided biomaterial design and robust stem cell bioprocessing. Statement of Significance Producing high quality engineered bone grafts is important for the treatment of critical sized bone defects. Robust and sensitive techniques are required for quality assessment of tissue-engineered constructs, which result to the selection of optimal biomaterials for bone graft development. Herein, we present a new use of metabolomics signatures in guiding the development of novel oxidised alginate-based hydrogels with umbilical cord blood mesenchymal stem cells and the glycine-histidine-lysine peptide, demonstrating that GHK induces stem cell osteogenic differentiation. Metabolomics signatures captured the enhanced osteogenesis in GHK hydrogels, confirmed the metabolic similarity between differentiated cells and primary osteoblasts, and elucidated the metabolic mechanism responsible for the function of GHK. In conclusion, our results suggest a new paradigm of metabolomics-driven design of biomaterials. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the role of the proinflammatory axis TNF-α–TNFR1 in experimentally induced periapical inflammation and bone resorption in mice. After receiving Ethics Committee Approval (2019.1.139.58.0), experimental apical periodontitis was induced by means of inoculating oral microorganisms into the root canals of molars of mice. Genetically deficient tumor necrosis factor-α receptor-1 mice (TNFR1-/-; n = 50) response was compared with that of C57Bl6 wild-type mice (wild-type; n = 50) after 7, 14, 28, and 42 days. The analyses performed were micro–computed tomographic, histopathologic, histomicrobiological, and histometric evaluation, tartrate-resistant acid phosphatase staining, immunohistochemistry, and quantitative reverse transcriptase polymerase chain reaction. Data were analyzed by using one-way analysis of variance, followed by Tukey or Bonferroni tests (α = 5%). TNFR1-/- mice exhibited lower recruitment of neutrophils at 14, 28, and 42 days (P <.05), which resulted in reduced area and volume of apical periodontitis at 42 days (P <.05). The number of osteoclasts was also lower in TNFR1-/- animals at 14 and 42 days (P <.01), along with reduced synthesis of CTSK, MMP-9, and COX-2. Expression of RANKL, but not OPG, was reduced at 14 and 42 days (P <.001). The highest RANKL expression over OPG (ratio > 1) was found in wild-type animals at 7 (P <.0001) and 42 days (P <.001). Periapical inflammation and bone resorption were exacerbated in wild-type animals compared with TNFR1-/- mice, demonstrating that the TNF-α–TNFR1 signaling pathway mediated catabolic events in bone after root canal contamination. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate bone mineral density (BMD) and microarchitecture in femurs and maxillary bones of ovariectomized (OVX) rats treated or not treated with alendronate (ALD) or odanacatib (ODN).Study Design: Twenty rats were divided into groups: SHAM, OVX, OVX/ALD, and OVX/ODN. After 12 weeks, the femurs and maxillae were removed and subjected to 3-dimensional analysis by micro-computed tomography. Results were analyzed with 1-way analysis of variance and Tukey's post hoc test (α = 0.05).Results: OVX decreased maxillary and femoral BMD and altered femoral microarchitecture (P < .05). The drugs increased BMD of both types of bones, but only ALD maintained the phenotype similar to the SHAM group. The action of ALD was limited to the femoral trabecular separation (Tb.Sp). OVX and the drugs had no effect on the microarchitecture of the maxilla (P > .05).Conclusions: ALD and ODN therapy increased BMD in both bones after ovariectomy. ALD was more successful than ODN in preserving the morphology of bone similar to the SHAM group. ALD maintained the phenotype for Tb.Sp in the femur, but ODN did not. In the maxillae, neither ovariectomy nor the 2 antiresorptive drugs had significant effects on microarchitecture. [ABSTRACT FROM AUTHOR]

Hydrogels from natural polymers are widely used in tissue engineering due to their unique properties, especially when regarding the cell environment and their morphological similarity to the extracellular matrix (ECM) of native tissues. In this study, we describe the production and characterization of novel hybrid hydrogels composed of alginate blended with elastin from bovine neck ligament. The properties of elastin as a component of the native ECM were combined with the excellent chemical and mechanical stability as well as biocompatibility of alginate to produce two hybrid hydrogels geometries, namely 2D films obtained using sonication treatment and 3D microcapsules produced by pressure-driven extrusion. The resulting blend hydrogels were submitted to an extensive physico-chemical characterization. Furthermore, the biological compatibility of these materials was assessed using normal human dermal fibroblasts, indicating the suitability of this blend for soft tissue engineering. [ABSTRACT FROM AUTHOR]

Phthalocyanines bearing four or eight sulfonamide units were synthesized and their efficiency in the photodynamic inactivation of Gram-negative ( Escherichia coli ) and Gram-positive ( Staphylococcus aureus ) bacteria was evaluated. Conjugates with simpler sulfonamide units ( N , N -diethylbenzenesulfonamide, N -isopropylbenzenesulfonamide and N -(4-methoxyphenyl)benzenesulfonamide) caused stronger inactivation than those with heterocyclic groups ( N -(thiazol-2-yl)benzenesulfonamide) or long alkyl chains ( N -dodecylbenzenesulfonamide) in both bacteria. Furthermore, the encapsulation of the phthalocyanine–sulfonamide conjugates within polyvinylpyrrolidone micelles, used as drug delivery vehicles, in general showed to enhance the inactivation efficiency. The results show that encapsulated phthalocyanine–sulfonamide conjugates are a promising class of photosensitizers to be used in photodynamic antimicrobial therapy. [ABSTRACT FROM AUTHOR]

Introduction The aim of this study was to evaluate the gene expression of proinflammatory cytokines, matrix metalloproteinases (MMPs), and cathepsin K in apical periodontitis (AP) and the volume of lesions in ovariectomized and sham-operated rats. Methods Twenty 12-week-old female Wistar rats were subjected to ovariectomy (OVX) or sham surgery. After 9 weeks, access cavities were prepared in the maxillary and mandibular first molars, pulp tissue was removed, and canals were exposed to the oral environment during 21 days for the induction of AP. The groups were as follows: sham, OVX, sham+AP, and OVX+AP. Animals were euthanized, and blocks containing the maxillary first molar and the surrounding bone were removed for quantification of proinflammatory cytokines cathepsin K and MMP genes by real-time polymerase chain reaction. The hemimandibles containing the mandibular first molars were used for analysis of the AP lesion volume by micro–computed tomographic imaging. Results AP in OVX rats showed an increased expression of interleukin 1 beta, tumor necrosis factor alpha, interleukin 6, MMP-8, and MMP-13 ( P < .05). OVX alone, without AP induction, did not affect the expression of the evaluated genes. Additionally, AP induced an increase in cathepsin K expression, without significant differences between AP in the sham and OVX groups ( P > .05). Micro–computed tomographic imaging showed a significantly greater AP lesion mean volume in OVX compared with sham animals ( P < .05). Conclusions AP lesions in ovariectomized rats are larger and have an increased expression of proinflammatory cytokines and MMPs, indicating that the infection combined with ovariectomy has an important role in the regulation of these signaling molecules and enzymes during the development of AP. Based on that, it may be assumed that the hypoestrogenic condition aggravates inflammation and degradation of extracellular matrix components in AP, which may provide insight into understanding the development of AP in female postmenopausal patients. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most prevalent type of cancer in men around the world. Due to its high incidence, new therapies have been evaluated, including drugs capable of inhibiting the FGF/VEGF pathways, as Nintedanib. The aim herein was to evaluate the Nintedanib therapeutic effects on morphology and COX-2 and IL-17 levels in the prostate anterior lobe in different grades of the tumor progression in TRAMP mice. Animals were treated with Nintedanib at a dose of 10 mg/kg/day in initial and intermediate grades of tumor development. At the end of treatment, the prostate anterior lobe was collected and submitted to morphological, immunohistochemical and Western Blotting analyses. The results showed that Nintedanib delayed the prostate carcinogenesis progression, with over 20% of reduction in frequency of tissue injuries, particularly in the group treated from 12 to 16 weeks of age. Also, decreased COX-2 and IL-17 levels were observed in both groups treated with Nintedanib in the prostate anterior lobe. Thus, we concluded that Nintedanib was effective in delaying tumor progression and, despite not directly acting on inflammation, Nintedanib may adversely affect inflammatory pathways, favoring prostate cancer delay. [ABSTRACT FROM AUTHOR]

Purpose Assessing bidirectional longitudinal associations between early sexual behaviors (≤16.0 years) and psychological well-being (global self-esteem, physical self-esteem, depression) among 716 adolescents, and the direct and buffering effect of parent–adolescent relationship quality. Methods We used data from Project STARS (Studies on Trajectories of Adolescent Relationships and Sexuality), a longitudinal study on adolescent sexual development in the Netherlands. Participants were 11.0–16.0 years old (mean age at T1 = 13.3 years). Self-reports from four waves of online questionnaires were used. Bidirectional longitudinal associations were assessed by linear mixed-effects models. Results At most waves, boys had significantly higher levels of psychological well-being than girls, but genders did not differ in experience with sexual behaviors. Engagement in early sexual behaviors did not predict lower levels of psychological well-being over time, and lower levels of psychological well-being did not predict more engagement in early sexual behaviors over time. Parent–adolescent relationship quality did not moderate these associations in either direction, although we found a significant direct effect, in which a higher-quality parent–adolescent relationship predicted more optimal levels of the three indicators of adolescents' psychological well-being (but not lower levels of early sexual activity) over time. Conclusions Our results show that, among Dutch adolescents, early sexual behaviors and psychological well-being were not interrelated. This may be explained by socio-cultural aspects of the Dutch society, such as more normalization of sexual behaviors during adolescence. As a result, early sexual activity in and of itself was not related to lower psychological well-being over time. Yet, cross-cultural differences in links between adolescents' sexuality and well-being should be further investigated. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to evaluate a protocol for systemic administration of rosiglitazone in mice in order to stimulate apoptosis of osteocytes in the jaws and to evaluate the effect of osteocyte apoptosis induced by rosiglitazone in the progression of periapical lesions in mice at 7, 21, and 42 days. Methods C57BL/6 mice at 4–5 weeks of age were used. In phase 1, mice ( n = 24) were treated with rosiglitazone (gavage, 10 mg/kg dose) or without (phosphate-buffered saline + 10% dimethyl sulfoxide) for 1, 2, or 3 weeks. We used the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling and 4′-6-diamidino-2-phenylindole methods for quantification of apoptotic cells. In phase 2, mice ( n = 30) received rosiglitazone for 2 weeks or just vehicle for 1 week ( n = 30), and periapical lesions were induced for 7, 21, or 42 days. We performed the measurement of periapical lesions, tartrate-resistant acid phosphatase staining, dual-energy x-ray absorptiometry for the evaluation of bone mineral density (BMD) in long bone, and gene evaluation using real time quantitative polymerase chain reaction of osteocyte markers ( Sost , Hyou1 , and Dmp1 ) and receptor activator of nuclear factor kappa-B ligand (RANKL) ( Tnfsf11 ). Results It was observed that systemic administration of rosiglitazone for 2 weeks showed apoptosis of osteocytes in a more expressive manner. In phase 2, in the groups that received rosiglitazone, a trend toward larger periapical lesions was observed ( P > .05). Rosiglitazone also induced a greater number of osteoclasts and a greater expression of Sost and Hyou1 at 21 days of lesions. Moreover, there were no statistically significant differences in RANKL and Dmp1 expression or in the BMD of femurs. Conclusions Rosiglitazone stimulated apoptosis of osteocytes, interfering in the progression of periapical lesions in mice. [ABSTRACT FROM AUTHOR]

Several neuropeptidergic systems act as modulators of cognitive performances. Among them, nociceptin, an opioid-like peptide also known as orphanin FQ (N/OFQ), has recently gained attention. Stimulation of its receptor, the N/OFQ opioid receptor (NOP), which is expressed in brain regions involved in emotion, memory and stress response, has inhibitory effects on the acquisition and/or consolidation of spatial and emotional memory in rodents. Recently, N/OFQ was also proposed to be linked to the pathogenesis of Post-Traumatic Stress Disorder in humans. However, until now the effect of the activation of the N/OFQ-NOP system on already consolidated memory, such as during retrieval and reconsolidation phases, has never been explored. In the present study, we investigated the consequences of systemic injection of NOP agonists or i.c.v. injection of the N/OFQ peptide on the retrieval and the reconsolidation of contextual fear memory in mice. We demonstrate that the activation of the N/OFQ system impairs the reconsolidation of context-dependent but not cue-dependent aversive memories. We also show that this amnestic effect is associated with decreased c-Fos expression in the hippocampus and amygdala. Our data thus provide the first evidence that the NOP receptor could be targeted during the reconsolidation process to weaken maladaptive memories. The N/OFQ-NOP system might constitute in the future an interesting pharmacological target for interfering with so-called “pathological memories”, in particular those involving maladaptive contextual memories. [ABSTRACT FROM AUTHOR]

Introduction The purpose of this study was to evaluate the in vivo response of periradicular tissues after sealing of furcation perforations with Biodentine, mineral trioxide aggregate (MTA), and gutta-percha by means of histopathologic and indirect immunofluorescence analyses. Methods Thirty teeth of 3 dogs were divided into 3 groups: Biodentine ( n = 14 teeth), MTA (negative control, n = 10 teeth), and gutta-percha (positive control, n = 6 teeth). After endodontic treatment, perforations were made on the center of the pulp chamber floor and filled with the materials. After 120 days, the animals were killed, and blocks containing the teeth and periradicular tissues were processed histotechnically for histopathologic semiquantitative (new mineralized tissue formation and bone resorption at the perforation site) and quantitative (thickness and area of newly formed mineralized tissue and number of inflammatory cells) analyses and RUNX2 immunofluorescence assay. Data were analyzed by χ 2 , Fisher exact test, Mann-Whitney test, one-way analysis of variance, Kruskal-Wallis test, and Dunn posttest (α = 0.05). Results MTA and Biodentine induced the formation of significantly more new mineralized tissue ( P < .0001) than gutta-percha, which did not induce the formation of mineralized tissue in any case. Complete sealing of the perforations was more frequent with MTA, which formed mineralized tissue with greater thickness and area. Biodentine and MTA exhibited no bone resorption in the furcation region, fewer inflammatory cells, and greater RUNX2 immunostaining intensity than gutta-percha. Conclusions Although MTA presented higher frequency of complete sealing and greater thickness and area of newly formed mineralized tissue, Biodentine also had good histopathologic results and can be considered as an adequate furcation perforation repair material. [ABSTRACT FROM AUTHOR]

Soft tissue regeneration requires the use of matrices that exhibit adequate mechanical properties as well as the ability to supply nutrients and oxygen, and to remove metabolic bio-products. In this work, we describe the development of hydrogels based on the blend between alginate (Alg) and silk fibroin (SF). Herein, we report two main strategies to combine cells with biomaterials: cells are either seeded onto prefabricated hydrogels films (2D), or encapsulated during hydrogel microcapsules formation (3D). Both geometries were successfully produced and characterized. FTIR results indicated a change of conformation of SF from random coil to β-sheet after hydrogel formation. The thermal degradation behavior of films and microcapsules fabricated from Alg, and Alg/SF was dependent on the hydrogel composition and on the geometry of the samples. The presence of SF caused decreased water uptake ability and affected the degradation behavior. Mechanical tests showed that addition of SF promotes an increase in storage modulus, leading to a stiffer material as compared with pure Alg (6 times higher stiffness). Moreover, the in vitro cell-material interaction on Alg/SF hydrogels of different geometries was investigated using human umbilical vein endothelial cells (HUVECs). Viability, attachment, spreading and proliferation of HUVECs were significantly increased on Alg/SF hydrogels compared to neat Alg. These findings indicate that Alg/SF hydrogel is a promising material for the biomedical applications in tissue-engineering and regeneration. [ABSTRACT FROM AUTHOR]

Mesangial cells are modified smooth muscle cells with the ability to modulate glomerular filtration rate (GFR) – a marker of ischemic renal injury. We aimed to determine the role of intracellular O-GlcNAc levels and ER stress in mesangial cells subjected to ATP depletion. Immortalized mouse mesangial cells culture was incubated for 30, 45 and 60 min, or not (control group) with a buffer containing antimycin A and 2-deoxy- d -glucose, inhibitors of ATP synthesis. Mesangial cells subjected to ATPdepletion for 45 min followed by 24 h reperfusion (H 45 /R 24 mesangial cells) promoted 30 % of cell death mainly by necrosis. ATP depletion was sustained throughout reperfusion until 24 h. Resistant H 45 /R 24 mesangial cells presented: (i) low protein content of GFAT, OGT and OGA, however no modification of total O-GlcNAcylation and (ii) attenuation of protein synthesis related to a UPR response mediated by GRP78/PERK/p-eIF2α and a decrease in the protein content of ATF4. The lower activation of apoptosis was related to no alterations in the levels of CHOP and activated caspase 3. We also detected activation of intracellular mediators of necroptosis: IRE1, ATF6, GADD34, ERO1, Mdm2 and P53. The resistant H 45 /R 24 mesangial cells can replenish the cell culture dish indicating that the UPR adaptative response permitted cell survival. Successive ATP depletion induced lower levels O-GlcNAcylation leading to a 30 % cell death in every H/R process. We concluded that lower levels of O-GlcNAcylation and the GRP78/PERK/p-eIF2α UPR response are the molecular mechanisms involved in H 45 /R 24 mesangial cell survival. • Mesangial cells are involved in the glomerular alterations induced by ischemia-reperfusion injury. • Mesangial cells subjected to ATP depletion for 45 min and 24 h reperfusion caused 30% cell death. • The 70% resistant mesangial cells presented decreased levels GlcNAcylation and the enzymes of the hexosamine biosynthetic pathway. • The resistance mechanism involves the protective arm of the unfolding protein response: PERK/phosphoEIF2a. • The mesangial cells, resistant to successive ATP depletion-reperfusion, presented decreased levels of O-GlcNAcylation. [ABSTRACT FROM AUTHOR]

Preconditioning can induce a cascade of cellular events leading to neuroprotection against subsequent brain insults. In this study, we investigated the chronic effects of hypoxic preconditioning on spontaneous recurrent seizures (SRS), neuronal death, and spatial memory performance in rats subjected to pilocarpine (Pilo)-induced status epilepticus (SE). Rats underwent a short hypoxic episode (7% O 2 + 93% N 2 ; 30 min on two consecutive days) preceding a 4-h SE (HSE group). Control groups were rats submitted to SE only (SE), rats subjected to hypoxia only (H) or normoxia-saline (C). Animals were monitored for the occurrence of SRS, and spatial memory performance was evaluated in the radial-arm maze. Hippocampal sections were analyzed for cell death and mossy fiber sprouting at 1 or 60 days after SE. Compared to SE group, HSE had increased SE latency, reduced number of rats with SRS, reduced mossy fiber sprouting at 60 days, and reduced cell death in the hilus and the CA3 region 1 and 60 days after SE. Additionally, HSE rats had better spatial memory performance than SE rats. Our findings indicated that short hypoxic preconditioning preceding SE promotes long-lasting protective effects on neuron survival and spatial memory. [ABSTRACT FROM AUTHOR]