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The exact role of inflammatory immune response in bone healing process is still unclear, but the success of the alveolar bone healing process seems to be associated with a moderate and transitory inflammatory response, while insufficient or exacerbated responses seems to have a detrimental influence in the healing outcome. In this context, we performed a comparative analysis of mice strains genetically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response to address the influence of inflammation genes in alveolar bone healing outcome. Experimental groups comprised 8-week-old male or female AIRmax and AIRmin submitted to extraction of upper right incisor, and evaluated at 0, 3, 7, 14 and 21 days after upper incision extraction by micro-computed tomography (μCT), histomorphometry, birefringence, immunohistochemistry and molecular (PCRArray) analysis. Overall, the results demonstrate a similar successful bone healing outcome at the endpoint was evidenced in both AIRmin and AIRmax strains. The histormophometric analysis reveal a slight but significant decrease in blood clot and inflammatory cells density, as well a delay in the bone formation in AIRmax strain in the early times, associated with a decreased expression of BMP2, BMP4, BMP7, TGFb1, RUNX2, and ALP. The evaluation of inflammatory cells nature reveals increased GR1+ cells counts in AIRmax strain at 3d, associated with increased levels of neutrophil chemoattractants such as CXCL1 and CXCL2, and its receptor CXCR1, while F4/80+ cell prevails in AIRmin strain at 7d. Also, our results demonstrate a relative predominance of M2 macrophages in AIRmin strain, associated with an increased expression of ARG1, IL10, TGFb, while M1 macrophages prevail in AIRmax, which parallel with increased IL-1B, IL-6 and TNF expression. At late repair stage, AIRmax presents evidences of increased bone remodeling, characterized by increased density of blood vessels and osteoclasts in parallel with decreased bone matrix density, as well increased levels of MMPs, osteoclastogenic and osteocyte markers. In the view of contrasting inflammatory and healing phenotypes of AIRmin and AIRmax strains in other models, the unpredicted phenotype observed suggests the existence of specific QTLs (Quantitative trait loci) responsible for the regulation ‘sterile’ inflammation and bone healing events. Despite the similar endpoint healing, AIRmax strain delayed repair was associated with increased presence of neutrophils and M1 macrophages, supporting the association of M2 cells with faster bone healing. Further studies are required to clarify the elements responsible for the regulation of inflammatory events at bone healing sites, as well the determinants of bone healing outcome.

Background and purpose Auriculotherapy is a therapeutic technique used for a wide variety of conditions. Nevertheless, similarly to any health related intervention, the clinical use of this therapy requires scientific evidence of effectiveness in order to support its rational use. The main goal of this article is to critically analyze published literature on auriculotherapy and to provide an overview of the effectiveness of this technique in the management of health disorders. Methods The inventory of published reviews on this subject was carried out in November 2017, by assessing the following computerized databases: PubMed, MEDLINE, PsycINFO, EBMR, Cochrane Database of Systematic Reviews, CINAHL Plus NRC and Science Direct. Were only considered the systematic reviews based on meta-analysis with high methodological quality described according to AMSTAR (Assessment of Multiple Systematic Reviews). The eligible articles were systematically reviewed to find out in which health conditions auriculotherapy can be used with effectiveness. Results A total of 14 reviews were eligible according to the inclusion and exclusion criterions. Those reviews were focused on the management of insomnia, smoking cessation and pain, within the clinical scope of Neurology, Orthopaedics and Rheumatology. Conclusions Auriculotherapy has shown to have positive effects while associated to conventional treatments of insomnia, chronic and acute pain. Further well designed studies are required to evaluate the effectiveness of this technique in the treatment of other health conditions.

Introduction The side effects associated with standard anxiety medications can limit their use. Therefore, a non-pharmacological approach such as auriculotherapy could play an important role in anxiety management. The main aim of this protocol for a systematic review will be to examine the effectiveness and safety of auriculotherapy for anxiety disorders (AD). Methods The authors will conduct searches on the following databases: Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Stephens Company, PubMed, Latin American and Caribbean Health Sciences Literature Database, British Library's table of contents, World Health Organization, Clinical Trials. We will conduct a systematic review for randomized controlled trials (RCTs) evaluating the effectiveness and safety of auriculotherapy compared with placebo, waitlist treatment, routine care, or alternative treatment. To assess the evidence's quality, we plan to use the Grading of Recommendations Assessment, Development and Evaluation tool while, for risk assessments, we will use the statistical software RevMan V 5.4. Data collection and analysis will be performed by two reviewers independently. Discussion If effective and safe, then auriculotherapy may be an appropriate alternative to pharmacological treatment. Registration number: PROSPERO ID: CRD42021254503.

Introduction Students are exposed to various challenges that trigger anxiety in relation to their academic requirements. Some studies suggest that auricular acupuncture, may improve anxiety. This study aimed to evaluate the clinical effect of Auricular Acupuncture (AA) on the anxiety-levels of university students. Methods An experimental, prospective, randomized, controlled and single-blinded study was conducted. The sample included university students (N = 69), unfamiliar to acupuncture, under no psychotropic medication, with no known psychiatric or thyroid disorders. Individuals were randomly allocated to the Experimental Group (EG, n = 25): verum AA points; Placebo Group (PG, n = 22): sham AA points in neurological segments distinct from the verum AA and the Control group (CG, n = 22): without any AA treatment. One week prior to the examination period at the University, subjects were treated with AA using semi-permanent needles placed for 48 h. Anxiety assessments were conducted using the State Anxiety Inventory (STAI), the Visual Analogue (VAS) for anxiety, and a scale on the neurovegetative status based on a scored analysis of the tongue according to the principles of Traditional Chinese Medicine (SN-TCM) Results 69 students (49 women; 20 men) participated in this study, 15,5% showing moderate to severe states of anxiety, and 12% some trace of anxiety. We found a significant reduction of the anxiety levels in the experimental group, according to STAI-form Y1 (p = 0,031), VAS (p = Conclusion AA seems effective in reducing exam-related anxiety in university-level students, as corroborated by an SN-TCM and VAS for anxiety tests.

The chronic inflammatory immune response triggered by the infection of the tooth root canal system results in the local upregulation of RANKL, resulting in periapical bone loss. While RANKL has a well-characterized role in the control of bone homeostasis/pathology, it can play important roles in the regulation of the immune system, although its possible immunoregulatory role in infectious inflammatory osteolytic conditions remains largely unknown. Here, we used a mouse model of infectious inflammatory periapical lesions subjected to continuous or transitory anti-RANKL inhibition, followed by the analysis of lesion outcome and multiple host response parameters. Anti-RANKL administration resulted in arrest of bone loss but interfered in the natural immunoregulation of the lesions observed in the untreated group. RANKL inhibition resulted in an unremitting proinflammatory response, persistent high proinflammatory and effector CD4 response, decreased regulatory T-cell (Treg) migration, and lower levels of Treg-related cytokines IL-10 and TGFb. Anti-RANKL blockade impaired the immunoregulatory process only in early disease stages, while the late administration of anti-RANKL did not interfere with the stablished immunoregulation. The impaired immunoregulation due to RANKL inhibition is characterized by increased delayed-type hypersensitivity in vivo and T-cell proliferation in vitro to the infecting bacteria, which mimic the effects of Treg inhibition, reinforcing a possible influence of RANKL on Treg-mediated suppressive response. The adoptive transfer of CD4+FOXp3+ Tregs to mice receiving anti-RANKL therapy restored the immunoregulatory capacity, attenuating the inflammatory response in the lesions, reestablishing normal T-cell response in vivo and in vitro, and preventing lesion relapse upon anti-RANKL therapy cessation. Therefore, while RANKL inhibition efficiently limited the periapical bone loss, it promoted an unremitting host inflammatory response by interfering with Treg activity, suggesting that this classic osteoclastogenic mediator plays a role in immunoregulation.

Inflammatory bone resorption is a hallmark of periodontitis, and Tregs and Th2 cells are independently associated with disease progression attenuation. In this study, we employed an infection-triggered inflammatory osteolysis model to investigate the mechanisms underlying Treg and Th2 cell migration and the impact on disease outcome. Aggregatibacter actinomycetemcomitans-infected C57Bl/6 (wild-type [WT]) mice develop an intense inflammatory reaction and alveolar bone resorption, and Treg and Th2 cell migration is temporally associated with disease progression attenuation. Tregs extracted from the lesions preferentially express CCR4 and CCR8, whereas Th2 cells express CCR3, CCR4, and CCR8. The absence of CCR5 and CCR8 did not significantly impact the migration of Tregs and Th2 cells or affect the disease outcome. CCR4KO mice presented a minor reduction in Th2 cells in parallel with major impairment of Treg migration, which was associated with increased inflammatory bone loss and higher proinflammatory and osteoclastogenic cytokine levels. The blockade of the CCR4 ligand CCL22 in WT mice resulted in an increased inflammatory bone loss phenotype similar to that in the CCR4KO strain. Adoptive transfer of CCR4(+) Tregs to the CCR4KO strain revert the increased disease phenotype to WT mice-like levels; also, the in situ production of CCL22 in the lesions is mandatory for Tregs migration and the consequent bone loss arrest. The local release of exogenous CCL22 provided by poly(lactic-co-glycolic acid) (PLGA) microparticles promotes migration of Tregs and disease arrest in the absence of endogenous CCL22 in the IL-4KO strain, characterized by the lack of endogenous CCL22 production, defective migration of Tregs, and exacerbated bone loss. In summary, our results show that the IL-4/CCL22/CCR4 axis is involved in the migration of Tregs to osteolytic lesion sites, and attenuates development of lesions by inhibiting inflammatory migration and the production of proinflammatory and osteoclastogenic mediators.

Nitric oxide has an important effect on host immune response. However, little has been studied in relation to its potential as a possible diagnostic tool in peri-implant disease. The present study analyzed nitrite levels in the peri-implant sulcular fluid (PISF) of implants with mucositis and the correlation of these nitrite levels with clinical parameters using a simplified fluid collection methodology. Twenty-five partially edentulous patients showing peri-implant mucositis were evaluated, and the peri-implant status was determined based on current clinical parameters: probing depth (PD) and bleeding on probing (BOP). The sulcular fluid (SF) around teeth (control) and implants were collected, and the nitrite levels were evaluated using the Griess method. The mean probing depth (mm) was significantly higher (P < .0001) in implants (2.852 ± 0.6484) than in control teeth (1.585 ± 0.3636). The mean total nitrite level (μM) was statistically higher (P = .0069) in implants with mucositis (14.34 ± 11.83) than in control teeth (9.316 ± 5.534). No correlation was observed between the total nitrite levels and the PD mean in the control group (P = .2558, r = −0.2361) or in the implant group (P = .1160, r = −0.3224), as well as the number of faces showing bleeding on probing (P = .8747, r = 0.0332). These results demonstrated that the nitrite levels were higher in inflamed areas. According to the methodology applied and results obtained, the higher nitrite levels in inflamed areas suggest that, in the future, nitrite could be used as a marker of peri-implant mucositis associated with clinical data to monitor the cure or evolution of the disease.

El hemangioendotelioma hepático infantil (HHI) es una enfermedad grave y con elevada mortalidad. A pesar de ello, estas lesiones vasculares pueden evolucionar espontáneamente para su resolución completa entre 12 y 18 meses. La decisión de intentar un tratamiento específico y la elección entre las varias opciones terapéuticas continúa siendo polémica, especialmente en los casos asintomáticos de afectación multifocal o bilobular.Describimos un caso de HHI, multifocal y bilobular, asintomático, no sometido a ningún tipo de terapia y con regresión de las lesiones antes de los 2 años de edad. : Infantile hepatic hemangioendothelioma is a severe disease with a high mortality rate. Nevertheless these vascular lesions may experience spontaneous regression within 12 to 18 months. The decision of trying a specific treatment and the choice among the several therapeutic options remains controversial, particularly in those asymptomatic cases of multifocal, bilobular involvement.We describe a case of multifocal, bilobular and asymptomatic infantile hepatic hemangioendothelioma, untreated, and with spontaneous regression before 2 years of age.

The hallmark of periodontal disease is the progressive destruction of gingival soft tissue and alveolar bone, which is initiated by inflammation in response to an invasive and persistent bacterial insult. In recent years, it has become apparent that this tissue destruction is associated with a decrease in local regulatory processes, including a decrease of forkhead box P3-expressing regulatory lymphocytes. Accordingly, we developed a controlled release system capable of generating a steady release of a known chemoattractant for regulatory lymphocytes, C-C motif chemokine ligand 22 (CCL22), composed of a degradable polymer with a proven track record of clinical translation, poly(lactic-co-glycolic) acid. We have previously shown that this sustained presentation of CCL22 from a point source effectively recruits regulatory T cells (Tregs) to the site of injection. Following administration of the Treg-recruiting formulation to the gingivae in murine experimental periodontitis, we observed increases in hallmark Treg-associated anti-inflammatory molecules, a decrease of proinflammatory cytokines, and a marked reduction in alveolar bone resorption. Furthermore, application of the Treg-recruiting formulation (fabricated with human CCL22) in ligature-induced periodontitis in beagle dogs leads to reduced clinical measures of inflammation and less alveolar bone loss under severe inflammatory conditions in the presence of a diverse periodontopathogen milieu.

There are no studies evaluating the possible use of immunoglobulin A1 (IgA1) as an early marker for peri-implant inflammation. The aim of this study was to evaluate the IgA1 levels in peri-implant sulcular fluid (PISF) and saliva of partially edentulous patients as an indicator of mucositis. Twenty-seven patients were examined to determine the peri-implant status based on probing depth and bleeding on probing. Saliva and PISF around dental implants were collected and the IgA1 levels were evaluated by Elisa assay. IgA1 in saliva and PISF of these patients were compared and their correlations with clinical parameters were evaluated. Differences in IgA1 levels in saliva (821.1 ± 290.6; 779.8 ± 401.5) and PISF (26.6 ± 20.7; 25.1 ± 20.5) of healthy and mucositis groups, respectively were not observed (p>0.05). Correlation between clinical parameters and IgA1 in saliva or PISF was not observed in healthy or mucositis groups (p=0.607; p=0.826, respectively). These results suggest that IgA1 cannot be used as an immunological marker of mucositis. Não existem estudos que avaliem a utilização de imunoglobulina A1 (IgA1) como marcador precoce da inflamação peri-implantar. O objetivo deste estudo foi avaliar os níveis de IgA1 do fluido sulcular peri-implantar (PISF) e saliva de pacientes parcialmente desdentados como indicador da mucosite. Vinte e sete pacientes foram examinados para determinar a condição peri-implantar com base na profundidade de sondagem e sangramento à sondagem. Saliva e PISF ao redor de implantes dentários foram coletados e os níveis IgA1 foram avaliados pelo teste Elisa. IgA1 na saliva e PISF destes pacientes foram comparados e suas correlações com parâmetros clínicos foram avaliados. Não foram observadas diferenças nos níveis de IgA1 (821,1 ± 290,6; 779,8 ± 401,5) na saliva e PISF (26,6 ± 20,7; 25,1 ± 20,5) de grupos saudáveis e mucosite, respectivamente (p>0,05). Correlação entre os parâmetros clínicos e IgA1 na saliva ou PISF não foi observada em grupos saudáveis ou mucosite (p=0,607; p=0,826, respectivamente). Estes resultados demonstraram que IgA1 não pode ser utilizada como marcador imunológico da mucosite.

The oral cavity is a complex environment that may harbor more than 750 bacterial species. Proper oral hygiene is essential to maintain the equilibrium of microbial community and oral health. The ecological balance can be compromised in inadequate microbial control situations and an oral infection can be evoked. The bacteria can aid in the formation of dental plaque and caries, leading to periodontal disease (PD) and periapical lesion (PL). PD is the most common chronic inflammatory disorder of microbial origin that affects toothsupporting tissues including the periodontal ligament and the alveolar bone. Dental caries is characterized by demineralization of enamel and dentine produced by microorganisms’ acids. This process can cause pulp necrosis and root canal infection and the progression through the root apex can induce PL. PD and PLs constitute inflammatory and immune response against oral pathogens. Both processes encompass pathogenic mechanisms of inflammation-mediated soft tissue destruction and bone resorption. The etiopathogenesis of these diseases have been extensively investigated over the last decades and the role of several cell types, cytokines and pathways has been described (Graves, 2008, Graves et al., 2011a, Nair, 1997). Last decades research have documented the importance and commitment of immune system to protect the host from pathogen and also the paradoxical effect accounting for the bone resorption observed in these diseases. More recently, the pattern of immune cell response involved in the lesions progression (i.e. Th1, Th2, Th17, Th9 or T regulatory) has received particular attention (Cardoso et al., 2009, Colic et al., 2009a, Gaffen & Hajishengallis, 2008, Ohlrich et al., 2009, Queiroz-Junior et al, 2011). Although chemokines and cytokines are pivotal to determine these Th patterns, not much is known regarding the expression of these markers in the regulation of bone resorption in sites of PD and PL. This

Osseointegrated dental implants are inserted into the alveolar ridge, and for them to function as tooth replacements, the surrounding tissues need to adapt to them. Just as with teeth, dental implants traverse the oral mucosa and have access to the contaminated environment of the oral cavity. Therefore, periodontal and peri-implant tissues are important for establishing a protective barrier. The aim of the present study was to perform a histologic analysis of the mucosa surrounding osseointegrated implant cover screws. For this study, 17 mucosal specimens were obtained from 12 patients during the second surgical session for implant exposure to the oral environment. After histologic preparation, specimens were sectioned perpendicularly to the mucosal surface to a thickness of about 3 µm, stained with 1% toluidine blue, and examined under light microscopy. All specimens showed a keratinized, stratified, squamous epithelium with well-defined strata. In the lamina propria, unorganized dense connective tissue was noted in the reticular layer, and in 4 samples, a chronic inflammatory infiltrate was seen in this region. The papillary layer presented tall connective papillae consisting of loose connective tissue. The results of this study confirm the hypothesis that the mucosa that conceals osseointegrated implant cover screws has the same morphologic characteristics as the alveolar masticatory mucosa. Furthermore, clinical conditions of normality in peri-implant tissues may not coincide with situations of histologic normality.