Changes in public attitude toward epilepsy in Hungary since 1994. A multicriteria weighting analysis.

OBJECTIVE: To assess the adult Hungarian population's knowledge about and attitude toward epilepsy and compare the present findings with previous ones in 1994 and 2000. METHODS: We performed a cross-sectional survey of the Hungarian adult population from 28th February to 8th March 2023. A non-probability quota sampling with a random walk method was used. We applied the computer-assisted personal interviewing (CAPI) method and used a multicriteria weighting procedure to correct for bias along the main sociodemographic variables. To detect changes over time, we used chi-squared tests, and to analyze the effect of sociodemographic characteristics, we applied multivariate logistic regression. RESULTS: One thousand participants (53.1% women, mean age 48.1 ± 16.75 years) representing Hungary's population were interviewed yielding a response rate of 80.3%. 26.3% knew someone with epilepsy (55.9% in 1994 and 51.9% in 2000), and 30.8% saw an epileptic seizure (58% in 1994 and 55.3% in 2000). Compared to the young, fewer adults and elderly people knew someone with epilepsy or had seen a seizure. Like in 1994 and 2000, 16.6% reported objection to their children's interaction with people with epilepsy; however, in the present study, significantly fewer people opposed their children marrying or working together with epileptic people, indicating a change in attitude (p < 0.0001). Rural residents had less objection to their children's interaction with people with epilepsy (p < 0.05). People with secondary education objected significantly more often than those with primary education to their children's interaction (p = 0.037), marriage to people with epilepsy (p = 0.043), or their having equal employment (p = 0.008). Higher education people were as "permissive" as those with primary education. SIGNIFICANCE: Certain parameters of familiarity and attitude markers of the Hungarian population toward epilepsy have improved. These tendencies are promising, but work is still needed; our results will hopefully evoke educational programs and campaigns against negative attitudes. PLAIN LANGUAGE SUMMARY: The knowledge of the Hungarian population about epilepsy and their attitude toward people with epilepsy has been improved since 1994. People from rural areas have shown more acceptance for people with epilepsy. Those people who completed secondary education were significantly more prone to stigmatization than those with primary education.

Parasomnias manifest different phenotypes of sleep-related behaviors in age and sex groups. A YouTube-based video research highlighting the age slope of sleepwalking.

STUDY OBJECTIVE: Finding typical patterns - phenotypes - of sleep behaviors characterizing parasomnias in different age and sex groups. METHODS: We analyzed YouTube videos on sleep-related behaviors likely representing parasomnias. We applied the search terms "sleepwalking", "somnambulism", "sleep eating" "sleep sex", "sleep talking" and "aggression in sleep" in six languages. We classified those persons shown on the videos into estimated biological sex and age (child, adult, elderly) groups. We scored the activity types by a self-made scale and applied binary logistic regression to analyze the association between sleep behaviors versus sex and age groups by the STATA package, providing a 95 % confidence interval and the probability of statistical significance. RESULTS: 224 videos (102 women; 68 children, 116 adults, and 40 elderly people) were scored. Elderly people had significantly (P < 0.012) less odds of ambulation in sleep likely consistent with somnambulism compared to adults and children. Adult females performed complex manual activities during sleepwalking more often, than males (P < 0.012). Elderly males had 40-fold odds compared to adults and children, to perform aggressive movements and 70-fold odds of complex movements in bed, compared to adults. Elderly people presented emotional behaviors less frequently than adults (P < 0.004), and females showed them twice as often as males. Adults sleep-talked full sentences more often than children and elderly people (P < 0.001). CONCLUSION: Our results support the existence of age- and sex-specific parasomnia phenotypes, denoting possible safety measures. The remarkably low odds of sleepwalking in the elderly highlight the possibility of different pathomechanisms in higher age groups compared to children.

Parasomnias manifest different phenotypes of sleep-related behaviors in age and sex groups. A YouTube-based video research highlighting the age slope of sleepwalking.

STUDY OBJECTIVE: Finding typical patterns - phenotypes - of sleep behaviors characterizing parasomnias in different age and sex groups. METHODS: We analyzed YouTube videos on sleep-related behaviors likely representing parasomnias. We applied the search terms "sleepwalking", "somnambulism", "sleep eating", "sleep sex", "sleep talking", and "aggression in sleep" in six languages. We classified those persons shown on the videos into estimated biological sex and age (child, adult, elderly) groups. We scored the activity types by a self-made scale and applied binary logistic regression to analyze the association between sleep behaviors versus sex and age groups by the STATA package, providing a 95% confidence interval and the probability of statistical significance. RESULTS: 224 videos (102 women, 68 children, 16 adults, and 40 elderly people) were scored. Elderly people had significantly (P < 0.012) lower odds of sleepwalking compared to adults and children. Adult females performed complex manual activities during sleepwalking more often than males (P < 0.012). Elderly males had 40-fold odds compared to adults and children, to perform aggressive movements and 70-fold odds of complex movements in bed, compared to adults. Elderly people presented emotional behaviors less frequently than adults (P < 0.004), and females showed them twice as often as males. Adults sleep-talked full sentences more often than children and elderly people (P < 0.001). CONCLUSION: Our results support the existence of age- and sex-specific parasomnia phenotypes, denoting possible safety measures. The remarkably low odds of sleepwalking in the elderly highlight the possibility of different pathomechanisms in higher age groups compared to children. BRIEF SUMMARY AND STUDY IMPACT: Parasomnias present highly variable clinical forms and often cause injuries. Identifying typical phenotypes may help risk management and imply theoretical conclusions. Our study supports the existence of age-specific parasomnia phenotypes. We found that adult women have a high risk of performing dangerous activities during sleep, and elderly males often move violently in bed, likely representing dream enactment behaviors. Elderly people of both sexes have low odds of sleep ambulation- likely representing somnambulism; compared to adults and children, constituting a descending "age slope" of somnambulism that might reflect different underlying pathomechanisms in children versus adults and the elderly.

Apical Sealing and Bioactivity of an Experimental Gutta-Percha Containing Niobium Phosphate Bioglass.

This study evaluated the apical sealing ability and bioactivity of an experimental gutta-percha containing niobium phosphate bioglass. Thirty-six human premolars were endodontically prepared and divided into three groups: GPC-filling with conventional gutta-percha; GBC-filling with bioceramic gutta-percha (EndoSequence BC); GNB-filling with experimental gutta-percha containing niobophosphate. Teeth were stored in tubes containing 2 mL of simulated body fluid (SBF) solution in an oven for 30 days. Then, the samples were immersed in lanthanum nitrate solution and analyzed for apical nanoleakage (NI) with a scanning electron microscope (SEM/EDS) and transmission electron microscope (TEM). Gutta-percha specimens were immersed for 28 days (SBF) and analyzed in SEM/EDS and X-ray diffraction (XRD) to assess bioactivity. NI data originated from the SEM/EDS were analyzed using the Kruskal-Wallis test (α = 5%). NI data originated from TEM and bioactivity were descriptively reported. Statistical analysis did not detect a significant difference between groups (p = 0.13) for NI. In the bioactivity analysis, an abundant layer of hydroxyapatite was identified only in the surface of the GNB group samples. The gutta-percha containing niobophosphate bioglass promoted an apical sealing similar to EndoSequence BC, in addition to demonstrating bioactivity through the deposition of hydroxyapatite on the surface of the material after immersion in SBF.

Cholinergic control of Th17 cell pathogenicity in experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis (MS) in which Th17 cells have a crucial but unclear function. Here we show that choline acetyltransferase (ChAT), which synthesizes acetylcholine (ACh), is a critical driver of pathogenicity in EAE. Mice with ChAT-deficient Th17 cells resist disease progression and show reduced brain-infiltrating immune cells. ChAT expression in Th17 cells is linked to strong TCR signaling, expression of the transcription factor Bhlhe40, and increased Il2, Il17, Il22, and Il23r mRNA levels. ChAT expression in Th17 cells is independent of IL21r signaling but dampened by TGFß, implicating ChAT in controlling the dichotomous nature of Th17 cells. Our study establishes a cholinergic program in which ACh signaling primes chronic activation of Th17 cells, and thereby constitutes a pathogenic determinant of EAE. Our work may point to novel targets for therapeutic immunomodulation in MS.

Clinical Effect of Selective Serotonin Reuptake Inhibitors (SSRIs) on Fracture Healing.

PURPOSE: Chronic use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression has been linked to an imbalance in bone metabolism leading to osteoporosis. More recently, the use of SSRIs in murine models has been shown to delay bone healing both in vivo and in vitro by decreasing the osteoblastic differentiation and mineralization. The purpose of this study was to evaluate whether or not chronic use of SSRI's in nonunion patients increases their time to union after surgical intervention. METHODS: We retrospectively analyzed 343 patients in a nonunion database to determine which patients were on SSRI medication. Of these patients, 139 could be contacted and of those 102 were not taking SSRIs and 37 were taking SSRIs. Patient's time to union from nonunion surgical intervention between each cohort at our institution was recorded as the primary outcome. Patient's medical comorbidities that could affect union rates such as diabetes and smoking status were also noted. Baseline Short Musculoskeletal Function Assessment (SMFA) index for bother and function were recorded from the time of nonunion surgery as well as last follow-up. RESULTS: Compared to recent census data, we found significantly more patients in the nonunion cohort using SSRIs (26.6%) than patients in the general population using any type of antidepressant (11%). There was no significant difference in the patients' baseline characteristics other than patients on SSRI treatment had a higher body mass index (BMI) and age (p = 0.048 and p = 0.043, respectively). There was no significant difference noted in the fracture types (p = 0.2063). Patients on SSRIs had a higher SMFA bother index and function index on follow-up (p = 0.0103, p = 0.0147). Patients in the SSRI group had a mean time to union from nonunion surgery of 6.1 months compared to 6.0 in patients without SSRI usage (p = 0.74). These did not reach statistical significance when subcohort analysis for long bone fractures was performed for the femur, tibia, and humerus. CONCLUSION: To our knowledge, this is the first clinical study to investigate the effects of SSRIs on fracture healing. While in vivo and in vitro murine models have shown that SSRIs can have a deleterious effect on osteoblastic activity, our retrospective analysis did not show a significant difference in time to union between patients with chronic SSRI use and patients who have not been on SSRIs. However, this investigation did show a higher incidence of SSRI use in the nonunion cohort when compared to the general population. In the context of the recent animal model study, this may point to a negative effect of SSRI use on the acute fracture healing process.

Inhibition of osteoclastogenesis after bisphosphonate therapy discontinuation: an in vitro approach.

Osteoclasts are specialized cells that degrade and resorb bone. Bisphosphonates (BPs) are drugs with well-known capacity to inhibit the resorption of mineralized tissues. Nitrogen-containing BPs, like alendronate (ALN) and zoledronic acid (ZA), inactivate osteoclast activity mostly by alterations on the cytoskeleton architecture of the cell. In this study, we used an in vitro model to test the hypothesis that bisphosphonates may have inhibitory effects on the osteoclastogenesis and osteoclast activity after the therapy was discontinued. Primary osteoclasts were generated from mouse bone marrow in media supplemented with 1,25-dihydroxyvitamin D3 and cultivated over bones pre-treated with ALN and ZA. The pre-saturation of the bone slices with bisphosphonates did not affect cell viability. We found, however, that by disrupting the gene expression of RANKL and OPG the osteoclastogenesis and resorption activity of osteoclasts was significantly disturbed. These inhibitory effects were confirmed by scanning electron microscopy resorption assay, assessment of osteoclast ultrastructure, and by gene expression analysis of TRAP and Cathepsin K. In conclusion, ALN and ZA adhered to the bone matrix reduced the osteoclast activity in vitro.

Narrativas, afetos e saberes coletivos: caminhos do PET-Saúde Interprofissionalidade do Campus-UFRJ Macaé / Narratives, affections and collective knowledge: paths of PET-Saúde Interprofessionalidade at Campus-UFRJ Macaé

O livro, "Narrativas, afetos e saberes coletivos: caminhos do PET-Saúde/Interprofissionalidade do Campus UFRJ ­ Macaé", é fruto do pensamento coletivo do corpo social da Universidade Federal do Rio de Janeiro ­ Campus Macaé e dos trabalhadores de saúde de Macaé, cidade do Norte Fluminense. Todos, co-participantes do Projeto PET-Saúde/Interprofissionalidade. Assim, evidenciamos ser este um marco histórico local, onde a academia, a gestão e os trabalhadores do Sistema Único de Saúde (SUS) se unem para transformar e inovar numa perspectiva ímpar e complementar às práticas formativas e de cuidados, em prol dos usuários e voltadas para a potência de vida em cada encontro. Ainda neste sentido, a edição 2018/2019 do PET-Saúde, trouxe o desafio da implementação curricular da Educação Interprofissional (EIP), este tema, por sua vez, propõe de maneira enfática uma maior aproximação entre a academia, profissionais da saúde e a comunidade, cujos objetivos são ampliar, promover, articular e apoiar ações interprofissionais voltadas, tanto para as mudanças na formação acadêmica em saúde, quanto para a integração da tríade "ensino-serviço-comunidade", articuladas à Educação Permanente em Saúde (EPS). Destarte, nossa obra traduz a confecção de um leque de experiências e relatos multidisciplinares e interprofissionais, a partir de narrativas, saberes e afetos singulares e coletivos, que são desvelados em cada capítulo. O prisma interprofissional do PET-Saúde, reflete uma formação colaborativa e participativa, que é apreendida em todo manuscrito. Pois, "aprendemos juntos, para trabalhar juntos".

Author Correction: Hox gene expression determines cell fate of adult periosteal stem/progenitor cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Spontaneous Bisphosphonate-related Osteonecrosis Associated with a Tooth that Had a Necrotic Pulp: A Case Report.

This study reports the endodontic treatment performed in a patient who presented with spontaneous bone exposure in the mandible while using intravenous bisphosphonate medication (Zometa , Novartis Pharmaceuticals Co., Basel, Switzerland). A 63-year-old female patient was referred to a private dental clinic at Fortaleza, Brazil. The patient reported that one year before, she had undergone chemotherapy for the treatment of lung cancer and associated bone metastasis. Among the medications administered was the zolendronic acid, with dosage of 4 mg every 21 days. In the oral exam, the presence of extensive bone exposure was observed in the lingual region near tooth 37. The patient reported severe pain on palpation in the region; in the pulpal sensitivity test with cold stimulus, there was an absence of pain, characteristic of pulp necrosis. Radiographically, no periapical lesion was observed. Thus, endodontic treatment was performed, and instrumentation with Reciproc R25 files in the mesial root canals and R40 in the distal canal was done, alongside with abundant 2.5% sodium hypochlorite irrigation. Interappointment medication with calcium hydroxide was maintained for 15 days. In the second session, there was the spontaneous detachment of the exposed cortical bone fragment. The root canals were filled with gutta-percha and Endosequence BC Sealer cement. After two years, complete tissue repair was observed, and the patient presented with normal periapical tissues and the tooth in masticatory function. It may be concluded that a possible relationship between pulp and periapical infections and osteonecrosis exists in patients who use bisphosphonates.

Prediction of birth weight in twin pregnancies using fractional limb volumes by three-dimensional ultrasonography.

Objective: To predict birth weight using fetal fractional limb volumes (FLVs) by three-dimensional (3D) ultrasonography in twin pregnancies.Method: This prospective observational cohort study evaluated 51 twin pregnancies, including 28 dichorionic and 23 monochorionic pregnancies. Ultrasound examinations were performed up to 5 d before delivery. Birth weight prediction models were developed using the fractional arm volume (FAV), fractional thigh volume (FTV), and Hadlock's formula and were compared with the actual birth weight.Results: The mean gestational age at the time of ultrasound examination was 35.3 weeks. The mean birth weight was slightly higher in dichorionic than in monochorionic pregnancies 2391.2 versus 2352.4 g. The measurements using FTV were the closest to actual birth weights. For the total group, the Hadlock formula had mean percentage change of 7.18% while the FTV model presented mean percentage change of 6.62% in relation to birth weight. However, no significant difference was noted between Hadlock's formula and FTV p = .363 and .678 for dichorionic and monochorionic pregnancies, respectively.Conclusions: FTV accurately predicted birth weight in twin monochorionic and dichorionic pregnancies. However, Hadlock's formula should still be used.

Propranolol Reverses Impaired Fracture Healing Response Observed With Selective Serotonin Reuptake Inhibitor Treatment.

Selective serotonin reuptake inhibitors (SSRIs) are one of the most commonly prescribed antidepressants worldwide and recent data show significant impairment of fracture healing after treatment with the SSRI fluoxetine in mice. Here, we provide evidence that the negative effects of SSRIs can be overcome by administration of the beta-blocker propranolol at the time of fracture. First, in vitro experiments established that propranolol does not affect osteogenic differentiation. We then used a murine model of intramembranous ossification to study the potential rescue effect of propranolol on SSRI-induced impaired fracture healing. Micro-CT analysis revealed that fluoxetine treatment resulted in a smaller bony regenerate and that this decrease in bone formation can be overcome by co-treatment with propranolol. We then tested this in a clinically relevant model of endochondral ossification. Fluoxetine-treated mice with a femur fracture were treated with propranolol initiated at the time of fracture, and a battery of analyses demonstrated a reversal of the detrimental effect of fluoxetine on fracture healing in response to propranolol treatment. These experiments show for the first time to our knowledge that the negative effects of SSRIs on fracture healing can be overcome by co-treatment with a beta-blocker. © 2019 American Society for Bone and Mineral Research.

Infrared Light-Emitting Diode (LED) Effects on Orthodontic Tooth Movement.

The present study aimed to analyze the effect of LED phototherapy on the presence of hyalinization and root resorption during orthodontic tooth movement (OTM) in rats and to measure the amount of tooth movement. Eighty rats were allocated into two groups: LED and control (CON), where the LED rats were irradiated with infrared LED (850 nm, 30 mW) for 5 min during the first five days of OTM and where controls were not irradiated. Both groups were subdivided into four subgroups (n=10) according to the date of euthanasia (4, 7, 14 and 21 days). Five out of ten LED21 and five of ten CON21 rats were submitted to micro-computed tomography (µCT); µCT scans were taken on days 0, 7, 14 and 21. For histological study, maxillae were processed to light microscopy using Hematoxylin-Eosin (HE) and Tartrate-Resistant Acid Phosphatase (TRAP) histochemistry. The amount of tooth movement did not differ between LED and CON. Hyalinization was observed at the pressure areas in both groups, and it did not show a statistically significant difference between the groups. Root resorption was also observed in both groups after 7 days and it did not represent any differences between the two groups. LED phototherapy was not able to increase the amount of OTM. Similar characteristics of hyalinization and root resorption were observed in both groups.

Infrared light-emitting diode (led) effects on orthodontic tooth movement

Abstract The present study aimed to analyze the effect of LED phototherapy on the presence of hyalinization and root resorption during orthodontic tooth movement (OTM) in rats and to measure the amount of tooth movement. Eighty rats were allocated into two groups: LED and control (CON), where the LED rats were irradiated with infrared LED (850 nm, 30 mW) for 5 min during the first five days of OTM and where controls were not irradiated. Both groups were subdivided into four subgroups (n=10) according to the date of euthanasia (4, 7, 14 and 21 days). Five out of ten LED21 and five of ten CON21 rats were submitted to micro-computed tomography (μCT); μCT scans were taken on days 0, 7, 14 and 21. For histological study, maxillae were processed to light microscopy using Hematoxylin-Eosin (HE) and Tartrate-Resistant Acid Phosphatase (TRAP) histochemistry. The amount of tooth movement did not differ between LED and CON. Hyalinization was observed at the pressure areas in both groups, and it did not show a statistically significant difference between the groups. Root resorption was also observed in both groups after 7 days and it did not represent any differences between the two groups. LED phototherapy was not able to increase the amount of OTM. Similar characteristics of hyalinization and root resorption were observed in both groups.

Resumo O presente estudo tem como objetivo analisar o efeito da fototerapia LED na presença da hialinização e reabsorção radicular durante o movimento dentário ortodôntico (MDO) em ratos, e a mensuração da quantidade de movimento dentário. Oitenta ratos foram alocados em dois grupos: LED e Controle (CON), os ratos foram irradiados com um LED infravermelho (850nm, 30mW) por 5 minutos durante os cinco primeiros dias da MDO; e o grupo controle não foi irradiado. Ambos os grupos foram subdivididos em 4 subgrupos (n=10) de acordo com a data da eutanásia (4, 7, 14 e 21 dias). Cinco dos dez ratos LED21 e cinco dos dez ratos CON21foram submetidos a microtomografia computadorizada (μCT); As μCT foram realizadas nos dias 0, 7, 14 e 21. Para o estudo histológico, as maxilas foram processadas para microscopia de luz, usando hematoxilina-eosina (HE) e Fosfatase ácido Tartrate-Resistente (TRAP) para histoquímica. A quantidade de movimento dentário não diferiu entre o LED e o CON. A hialinização foi observada nas áreas de pressão em ambos os grupos e não mostrou diferença estatisticamente significante. Reabsorção radicular também foi observada em ambos os grupos depois de 7 dias e não houve diferença entre os grupos. A fototerapia LED não aumentou a quantidade de MDO. Características similares de hialinização e reabsorção radicular foram observadas em ambos os grupos

KLF4 as a rheostat of osteolysis and osteogenesis in prostate tumors in the bone.

We previously showed that KLF4, a gene highly expressed in murine prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. Here, we show that the anti-tumorigenic effect of KLF4 extends to PC3 human prostate cancer cells growing in the bone. We compared KLF4 null cells with cells transduced with a DOX-inducible KLF4 expression system, and find KLF4 function inhibits PC3 growth in monolayer and soft agar cultures. Furthermore, KLF4 null cells proliferate rapidly, forming large, invasive, and osteolytic tumors when injected into mouse femurs, whereas KLF4 re-expression immediately after their intra-femoral inoculation blocks tumor development and preserves a normal bone architecture. KLF4 re-expression in established KLF4 null bone tumors inhibits their osteolytic effects, preventing bone fractures and inducing an osteogenic response with new bone formation. In addition to these profound biological changes, KLF4 also induces a transcriptional shift from an osteolytic program in KLF4 null cells to an osteogenic program. Importantly, bioinformatic analysis shows that genes regulated by KLF4 overlap significantly with those expressed in metastatic prostate cancer patients and in three individual cohorts with bone metastases, strengthening the clinical relevance of the findings in our xenograft model.

Promovendo a saúde auditiva no programa saúde na escola de Macaé / Promoting hearing health in the health school programe of Macaé

Objetivos: descrever as experiências de graduandos dos cursos de Medicina, Enfermagem e Nutrição, integrantes de um projeto de extensão da Universidade Federal do Rio de Janeiro, Campus UFRJ/Macaé, Brasil, em uma ação de promoção à saúde auditiva no espaço escolar da rede pública de ensino de Macaé. Métodos: Realizouse um relato de experiências a partir da abordagem de educadores (cinco bolsistas e dois voluntários, graduandos de três cursos da área da saúde) de um projeto extensionista, que organizaram e executaram uma ação educativa intitulada "Os cinco sentidos e os cuidados com a audição", em 2017; voltada aos préescolares e escolares (educandos) de uma escola da rede pública de ensino. Foram realizadas duas reuniões, utilizando-se a roda de conversa como estratégia para a construção da prática dialógia nas quais os educadores apresentaram suas experiências vivenciadas na ação realizada. Resultados: Ao analisar os relatos, observaram-se cinco palavras chaves, com suas respectivas ideias centrais: expectativas e interação [quanto ao tipo de estratégia de educação em saúde (roda de conversa, dramatização, ludicidade) e receptividade dos educandos]; relevância (importância do tema abordado); formação/capacitação profissional (aquisição de experiências tanto no âmbito pessoal como profissional); assimilação (entendimento do tema pelos educandos); avaliação das atividades (quanto aos objetivos alcançados). Conclusões: As experiências vivenciadas pelos educadores do projeto proporcionaram interação, a aproximação do tema com os educandos, o que permitiu aos educadores um novo olhar sobre o tema abordado devido a forma como foi bem recebida pelos educandos

Objectives: To describe the experiences of undergraduate students of Medicine, Nursing and Nutrition courses, members of an extension project of the Federal University of Rio de Janeiro, Campus UFRJ - Macaé, Brazil, in an action to promote the hearing health in school space of public - school system of Macaé. Methods: An experiment was carried out based on the approach of educators (five fellows and two volunteers graduating from three health courses) of an extension project, who organized and carried out an educational action entitled "The five senses and the hearing care ", in 2017; directed to preschoolers and schoolchildren (learners) of a school in the public -school system. Two meetings were held, using the talk wheel as a strategy for the construction of the dialogical practice, in which the educators presented their lived experiences in the accomplished action. Results: When analyzing the reports, five key words were observed, with their respective central ideas: expectations and interaction [about the type of health education strategy (talk wheel, dramatization, playfulness) and receptivity of learners]; relevance (importance of the topic addressed); professional training (acquisition of experience in both the personal and professional spheres); assimilation (understanding of the subject by learners); evaluation of the activities (regarding the objectives reached). Conclusions: The experiences of the project educators provided the interaction, the approach of the subject with the learners, which allowed the educators a new look on the topic addressed due to the way it was well received by the learners.

Age-related inflammation triggers skeletal stem/progenitor cell dysfunction.

Aging is associated with impaired tissue regeneration. Stem cell number and function have been identified as potential culprits. We first demonstrate a direct correlation between stem cell number and time to bone fracture union in a human patient cohort. We then devised an animal model recapitulating this age-associated decline in bone healing and identified increased cellular senescence caused by a systemic and local proinflammatory environment as the major contributor to the decline in skeletal stem/progenitor cell (SSPC) number and function. Decoupling age-associated systemic inflammation from chronological aging by using transgenic Nfkb1KO mice, we determined that the elevated inflammatory environment, and not chronological age, was responsible for the decrease in SSPC number and function. By using a pharmacological approach inhibiting NF-κB activation, we demonstrate a functional rejuvenation of aged SSPCs with decreased senescence, increased SSPC number, and increased osteogenic function. Unbiased, whole-genome RNA sequencing confirmed the reversal of the aging phenotype. Finally, in an ectopic model of bone healing, we demonstrate a functional restoration of regenerative potential in aged SSPCs. These data identify aging-associated inflammation as the cause of SSPC dysfunction and provide mechanistic insights into its reversal.

Hox gene expression determines cell fate of adult periosteal stem/progenitor cells.

Hox genes are evolutionarily conserved transcription factors that during embryonic development function as master regulators of positional identity. In postnatal life, the function of Hox proteins is less clear: Hox genes are expressed during tissue repair, but in this context their function(s) are largely unknown. Here we show that Hox genes are expressed in periosteal stem/progenitor cells in a distribution similar to that during embryonic development. Using unbiased sequencing, we established that periosteal stem/progenitor cells from distinct anatomic sites within the skeleton significantly differ in their transcriptome, and that Hox expression status best defines these differences. Lastly, we provide evidence that Hox gene expression is one potential mechanism that maintains periosteal stem/progenitor cells in a more primitive, tripotent state, while suppression of Hox genes leads to fate changes with loss of tripotency. Together, our data describe an adult role of Hox genes other than positional identity, and the modulatory role of Hox genes in fate decisions may offer potential druggable targets for the treatment of fractures, non-unions and bone defects.

Ecto-5'-nucleotidase (CD73) regulates bone formation and remodeling during intramembranous bone repair in aging mice.

Ecto-5'-nucleotidase (CD73) generates adenosine, an osteoblast activator and key regulator of skeletal growth. It is unknown, however, if CD73 regulates osteogenic differentiation during fracture healing in adulthood, and in particular how CD73 activity regulates intramembranous bone repair in the elderly. Monocortical tibial defects were created in 46-52-week-old wild type (WT) and CD73 knock-out mice (CD73-/-) mice. Injury repair was analyzed at post-operative days 5, 7, 14 and 21 by micro-computed tomography (micro-CT), histomorphometry, proliferating cell nuclear antigen (PCNA) immunostaining, alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) histochemistry. Middle-aged CD73 knock-out mice exhibited delayed bone regeneration and significantly reduced bone matrix deposition detected by histomorphometry and micro-CT. Cell proliferation, ALP activity and osteoclast number were reduced in the CD73-/- mice, suggesting a combined defect in bone formation and resorption due the absence of CD73 activity in this model of intramembranous bone repair. Results from this study demonstrate that osteoblast activation through CD73 activity is essential during bone repair in aging mice, and it may present a drugable target for future biomimetic therapeutic approaches that aim at enhancing bone formation in the elderly patients.

Effects of bisphosphonates on osteogenesis and osteoclastogenesis signaling during the endochondral ossification of growing rats.

Osteoclasts and chondroclasts are necessary, during endochondral ossification, for the resorption of primary bone and calcified cartilage septa, respectively. The bisphosphonates inhibit mineralized tissue resorption by various mechanisms according to the different types of this drug, which can affect bone remodeling during skeletal growth. The objective of the present study is to analyze the way that alendronate (ALN) and etidronate (ETN) can affect osteoclastogenesis and bone formation during endochondral ossification of the long bones of growing rats. Newborn Wistar rats were treated daily with ETN, ALN, or sterile saline solution (control) for 21 days. Their femur and tibiae epiphyses were radiographed and analyzed by light, scanning and transmission electron microscopy. The expression of genes related to osteogenesis and to osteoclast differentiation and activity were analyzed by real-time quantitative polymerase chain reaction. The ETN group presented reduced body weight, disorganized growth plate and an extended area of cartilage in the ossification zone with little bone matrix; in the ALN group, this area was not altered. The ALN presented latent TRAP-positive cells, whereas in the ETN group, they were activated. The expression of NFκB1 and 2, OPG, Spp1 and Runx2 in the ossification zone was reduced by both bisphosphonates. RANKL expression was reduced by ETN, whereas ALN decreased the expression of RANK. The results also indicated that, in addition to the anti-resorptive effect of the drugs, disturbances in bone deposition occurred concomitantly with the reduced expression of osteogenesis-related genes.