Dynamics of chikungunya virus transmission in the first year after its introduction in Brazil: A cohort study in an urban community.

BACKGROUND: The first chikungunya virus (CHIKV) outbreaks during the modern scientific era were identified in the Americas in 2013, reaching high attack rates in Caribbean countries. However, few cohort studies have been performed to characterize the initial dynamics of CHIKV transmission in the New World. METHODOLOGY/PRINCIPAL FINDINGS: To describe the dynamics of CHIKV transmission shortly after its introduction in Brazil, we performed semi-annual serosurveys in a long-term community-based cohort of 652 participants aged ≥5 years in Salvador, Brazil, between Feb-Apr/2014 and Nov/2016-Feb/2017. CHIKV infections were detected using an IgG ELISA. Cumulative seroprevalence and seroincidence were estimated and spatial aggregation of cases was investigated. The first CHIKV infections were identified between Feb-Apr/2015 and Aug-Nov/2015 (incidence: 10.7%) and continued to be detected at low incidence in subsequent surveys (1.7% from Aug-Nov/2015 to Mar-May/2016 and 1.2% from Mar-May/2016 to Nov/206-Feb/2017). The cumulative seroprevalence in the last survey reached 13.3%. It was higher among those aged 30-44 and 45-59 years (16.1% and 15.6%, respectively), compared to younger (12.4% and 11.7% in <15 and 15-29 years, respectively) or older (10.3% in ≥60 years) age groups, but the differences were not statistically significant. The cumulative seroprevalence was similar between men (14.7%) and women (12.5%). Yet, among those aged 15-29 years, men were more often infected than women (18.1% vs. 7.4%, respectively, P = 0.01), while for those aged 30-44, a non-significant opposite trend was observed (9.3% vs. 19.0%, respectively, P = 0.12). Three spatial clusters of cases were detected in the study site and an increased likelihood of CHIKV infection was detected among participants who resided with someone with CHIKV IgG antibodies. CONCLUSIONS/SIGNIFICANCE: Unlike observations in other settings, the initial spread of CHIKV in this large urban center was limited and focal in certain areas, leaving a high proportion of the population susceptible to further outbreaks. Additional investigations are needed to elucidate the factors driving CHIKV spread dynamics, including understanding differences with respect to dengue and Zika viruses, in order to guide prevention and control strategies for coping with future outbreaks.

New Immunological Markers in Chromoblastomycosis-The Importance of PD-1 and PD-L1 Molecules in Human Infection.

The pathogenesis of chromoblastomycosis (CBM) is associated with Th2 and/or T regulatory immune responses, while resistance is associated with a Th1 response. However, even in the presence of IFN-γ, fungi persist in the lesions, and the reason for this persistence is unknown. To clarify the factors associated with pathogenesis, this study aimed to determine the polarization of the cellular immune response and the densities of cells that express markers of exhaustion in the skin of CBM patients. In the skin of patients with CBM, a moderate inflammatory infiltrate was observed, characterized primarily by the occurrence of histiocytes. Analysis of fungal density allowed us to divide patients into groups that exhibited low and high fungal densities; however, the intensity of the inflammatory response was not related to mycotic loads. Furthermore, patients with CBM exhibited a significant increase in the number of CD4+ and CD8+ cells associated with a high density of IL-10-, IL-17-, and IFN-γ-producing cells, indicating the presence of a chronic and mixed cellular immune response, which was also independent of fungal load. A significant increase in the number of PD-1+ and PD-L1+ cells was observed, which may be associated with the maintenance of the fungus in the skin and the progression of the disease.

Chromoblastomycosis: New Perspective on Adjuvant Treatment with Acitretin.

Chromoblastomycosis (CBM) is a neglected human disease, caused by different species of pigmented dematiaceous fungi that cause granulomatous and suppurative dermatosis. This infection is difficult to treat and there are limited therapeutic options, including terbinafine, itraconazole, and tioconazole. Classic treatment is administered for a long period of time, but some patients do not respond properly, and therefore, such therapeutic approaches possess low cure rates. Therefore, it is vital to develop new strategies for the treatment of CBM. In this regard, it has been observed that the association of immunomodulatory molecules such as glucan with therapy carried out with antifungal drugs improves cutaneous lesions in comparison to treatment with antifungal drugs alone, suggesting that drug association may be an interesting and significant approach to incorporate into CBM therapy. Thus, the aim of this work was to associate classical antifungal therapy with the adjuvants imiquimod and acitretin. In the present case, we reported a patient with extensive CBM caused by Fonsaecae pedrosoi, that affected an extensive area of the right leg, that was left without treatment for 11 years. He was treated with a classical combination of itraconazole and terbinafine via the oral route plus topical imiquimod and oral acitretin, as an adjuvant therapy. After five months of treatment, a significant regression of verrucous plaques was observed, suggesting that the use of these adjuvants combined with the classical antifungal drugs, intraconazole plus terbinafine, can reduce treatment time and rapidly improve the patient's quality of life. This result confirms that the use of coadjuvant drugs may be effective in the treatment of this infectious disease.

Assessment of depression, stress, anxiety and oral health-related quality of life in individuals with sjögren's syndrome: case control pilot study / Evaluación de la depresión, el estrés, la ansiedad y la calidad de vida relacionada con la salud bucal en personas con síndrome de Sjögren: estudio piloto de casos y controles

Objective: Sjögren's syndrome (SS) is a chronic auto-immune inflammatory systemic disease, in which the infiltration of mo-nonuclear cells in the exocrine glands leads to physiological and morphological changes. This pilot case-control study aims to describe the profile, evaluate the oral condition, quality of life (QoL) and psychological condition, through complete clinical examination, OHIP-14 and DASS-21 questionnaires. Materials and Methods: The study was conducted with seven individuals with a final diagnosis of SS (case group [CG]), and seven individuals with symptoms of dry mouth (control group [GCO]), consulting at the institution from January to November 2021. participants were selected by free demand and those previously seen at the institution with a diagnosis of SS between 19 and 70 years of age. The questionnaire OHIP-14 was applied to assess the patient's quality of life, where seven dimensions are assessed, subdivided into 14 questions through the Lickert scale (0 to 4) assigned by the individual and which quantifies the impact of oral health on QoL. The questionnaire DASS-21 assessed the psychological condition of the patient, which presents seven questions for each emotional state (depression, anxiety, and stress), totaling 21 questions. The general clinical condition, evolution of SS, oral clinical condition, and the profile of this population were related to QoL factors and psychological conditions, using these assessment instruments. Results: There was no statistically significant difference between the groups regarding stimulated salivary flow. The only symptom with a statistically significant difference in the CG was difficulty in phonation (p< 0.001). The dimensions related to functional limitation and physical pain showed the most expressive results (p=0.004) (p=0.025), showing a strong negative impact on the QoL of the CG individuals, and the dimension related to disability was the least affected (p=0.684). The analysis of depression, anxiety, and stress did not show statistically significant results between the groups; however, in the CG, 5 (71.42%) individuals showed a severe degree of depression, anxiety, and stress. Conclusions: Individuals in the case group showed some changes, with a strong negative impact on QoL compared to the control group.

Objetivo: El síndrome de Sjögren (SS) es una enfermedad inflamatoria sistémica crónica autoinmune, en la que la infiltración de células mononucleares en las glándulas exocrinas provoca cambios fisiológicos y morfológicos. Este estudio piloto de casos y controles tiene como objetivo describir el perfil, evaluar la condición bucal, calidad de vida (CdV) y condición psicológica, mediante examen clínico completo, cuestionarios OHIP-14 y DASS-21. Materiales y Métodos: El estudio se realizó con 7 individuos con diagnóstico final de SS, grupo de casos (CG) y 7 individuos con síntomas de sequedad bucal, grupo control (GCO) atendidos en la institución de enero a noviembre de 2021. Los participantes fueron seleccionados por libre demanda y entre los atendidos previamente en la institución con diagnóstico de SS entre 19 y 70 años de edad. Para evaluar la calidad de vida del paciente se aplicó el cuestionario OHIP-14, donde se evalúan siete dimensiones, sub-divididas en 14 preguntas a través de la escala de Likert (0 a 4) asignada por el individuo y que cuantifica el impacto de la salud bucal en la calidad de vida. El cuestionario DASS-21 evaluó la condición psicológica del paciente, el cual presenta siete preguntas para cada estado emocional (depresión, ansiedad y estrés), totalizando 21 preguntas. El estado clínico general, la evolución del SS, el estado clínico bucal y el perfil de esta población se relacionaron con factores de calidad de vida y condiciones psicológicas, mediante estos instrumentos de evaluación. Resultados: En cuanto al flujo salival estimulado, no hubo diferencias estadísticamente significativas entre los grupos. El único síntoma que mostró diferencia estadísticamente significativa en el CG fue la dificultad en la fonación (p< 0,001). Las dimensiones relacionadas con limitación funcional y dolor físico mostraron los resultados más expresivos (p=0,004) (p=0,025), mostrando un fuerte impacto negativo en la CdV de los individuos del GC, y la dimensión relacionada con discapacidad fue la menos afectada (p=0,684). El análisis de depresión, ansiedad y estrés no mostró resultados estadísticamente significativos entre los grupos; sin embargo, en el GC, 5 (71,42%) individuos presentaron un grado severo de depresión, ansiedad y estrés. Conclusión: Se puede concluir que los individuos del grupo de casos mostraron algunos cambios, con un fuerte impacto negativo en la calidad de vida en comparación con el grupo de control.

Mass spectrometry molecular fingerprinting of mineral and synthetic lubricant oils.

The molecular composition of lubricating oils has a strong impact on how automotive engines function, but the techniques used to monitor the quality parameters of these oils only inspect their gross physical-chemical properties such as viscosity, color, and bulk spectroscopy profiles; hence, bad-quality, adulterated, or counterfeit oils are hard to detect. Herein, we investigated the ability of direct infusion electrospray ionization mass spectrometry (ESI-MS) to provide simple, rapid but characteristic fingerprint profiles for such oils of the mineral and synthetic types. After a simple aqueous extraction, ESI-MS analyses, particularly in the positive ion mode, did indeed show characteristic molecular markers with unique profiles, which were confirmed and more clearly visualized by partial least squares-discriminant analysis (PLS-DA). Nuclear magnetic resonance and Fourier transform infrared-attenuated total reflection spectroscopy were also tested for the bulk samples but showed nearly identical spectra, thus failing to reveal their distinct molecular composition and to differentiate the oil samples. To simulate adulteration, mixtures of mineral and synthetic oils were also analyzed by ESI(+)-MS, and additions as low as 1% of mineral oil to synthetic oil could be detected. The technique therefore offers a simple and fast but powerful tool to monitor the molecular composition of lubricant oils, particularly vias their more polar constituents.

Mast cell-mediated inflammation relies on insulin-regulated aminopeptidase controlling cytokine export from the Golgi.

BACKGROUND: On activation, mast cells rapidly release preformed inflammatory mediators from large cytoplasmic granules via regulated exocytosis. This acute degranulation is followed by a late activation phase involving synthesis and secretion of cytokines, growth factors, and other inflammatory molecules via the constitutive pathway that remains ill defined. OBJECTIVE: We investigated the role for an insulin-responsive vesicle-like endosomal compartment, marked by insulin-regulated aminopeptidase (IRAP), in the secretion of TNF-α and IL-6 in mast cells and macrophages. METHODS: Murine knockout (KO) mouse models (IRAP-KO and kit-Wsh/sh) were used to study inflammatory disease models and to measure and mechanistically investigate cytokine secretion and degranulation in bone marrow-derived mast cells in vitro. RESULTS: IRAP-KO mice are protected from TNF-α-dependent kidney injury and inflammatory arthritis. In the absence of IRAP, TNF-α and IL-6 but not IL-10 fail to be efficiently secreted. Moreover, chemical targeting of IRAP endosomes reduced proinflammatory cytokine secretion. Mechanistically, impaired TNF-α export from the Golgi and reduced colocalization of vesicle-associated membrane protein (VAMP) 3-positive TNF-α transport vesicles with syntaxin 4 (aka Stx4) was observed in IRAP-KO mast cells, while VAMP8-dependent exocytosis of secretory granules was facilitated. CONCLUSION: IRAP plays a novel role in mast cell-mediated inflammation through the regulation of exocytic trafficking of cytokines.

Neuropilin-1 cooperates with PD-1 in CD8+ T cells predicting outcomes in melanoma patients treated with anti-PD1.

Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by restoring antitumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Neuropilin-1 (NRP1) is a transmembrane glycoprotein required for nervous system and angiogenesis embryonic development, also expressed in immune cells. We hypothesized that NRP1 could be an immune checkpoint co-receptor modulating CD8+ T cells activity in the context of the antitumor immune response. Here, we show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T cells, cooperates and enhances PD-1 activity. In mice, CD8+ T cells specific deletion of Nrp1 improves anti-PD1 antibody antitumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T cells predicts poor outcome of patients treated with anti-PD1. NRP1 is a promising target to overcome resistance to anti-PD1 therapies.

Skeletal Stem/Progenitor Cells in Periosteum and Skeletal Muscle Share a Common Molecular Response to Bone Injury.

Bone regeneration involves skeletal stem/progenitor cells (SSPCs) recruited from bone marrow, periosteum, and adjacent skeletal muscle. To achieve bone reconstitution after injury, a coordinated cellular and molecular response is required from these cell populations. Here, we show that SSPCs from periosteum and skeletal muscle are enriched in osteochondral progenitors, and more efficiently contribute to endochondral ossification during fracture repair as compared to bone-marrow stromal cells. Single-cell RNA sequencing (RNAseq) analyses of periosteal cells reveal the cellular heterogeneity of periosteum at steady state and in response to bone fracture. Upon fracture, both periosteal and skeletal muscle SSPCs transition from a stem/progenitor to a fibrogenic state prior to chondrogenesis. This common activation pattern in periosteum and skeletal muscle SSPCs is mediated by bone morphogenetic protein (BMP) signaling. Functionally, Bmpr1a gene inactivation in platelet-derived growth factor receptor alpha (Pdgfra)-derived SSPCs impairs bone healing and decreases SSPC proliferation, migration, and osteochondral differentiation. These results uncover a coordinated molecular program driving SSPC activation in periosteum and skeletal muscle toward endochondral ossification during bone regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Oral Manifestations of Erythema Multiforme due to Methotrexate Intoxication

ABSTRACT: To report a rare case of erythema multiforme (EM) associated with methotrexate (MTX) with cutaneous and oral manifestations and to compare it to existing cases in which MTX was not used for cancer treatment. A 56-years- old female, in physical examination skin lesions and multiple oral ulcers associated with pain during manipulation were observed, and underwent treatment for rheumatoid arthritis with Methotrexate 2.5mg. During examination patient-reported that 15 days ago she had undergone a rheumatoid factor examination, doubling the MTX dosage (10mg / day) without doctor's consent. The diagnostic hypothesis of EM. The medical conduct consisted of the suspension of MTX and prescription of a vitamin complex with folinic acid. Local dental therapy for to control oral lesions, pain control and lip hydration was performed using low-level laser therapy (Twin Laser, P: 40mW, T: 50s, DE: 50J / cm), benzydamine hydrochloride spray, purified lanolin for lip dryness, and toothpaste without sodium lauryl sulfate to prevent burning. After 12 days, there was significant remission of oral and skin signs and symptoms, which confirmed the diagnosis was EM due to MTX intoxication. Thorough clinical evaluation and anamnesis favored diagnosis and early multi-professional management provided remission of oral and skin lesions, prevented systemic complications.

RESUMEN: El objetivo de este trabajo fue informar un caso raro de eritema multiforme (EM) asociado a metotrexato (MTX) con manifestaciones cutáneas y orales y compararlo con casos existentes en los que no se utilizó MTX para el tratamiento del cáncer. Caso clínico: Mujer de 56 años, en el examen físico se observaron lesiones cutáneas y múltiples úlceras de la cavidad oral asociadas a dolor durante la manipulación.Se sometió a tratamiento para la artritis reumatoide con metotrexato 2,5 mg. Durante el examen, la paciente informó que hacía 15 días se había sometido a un examen de factor reumatoide, duplicando la dosis de MTX (10 mg / día) sin el consentimiento del médico. La hipótesis diagnóstica de EM. La conducta médica consistió en la suspensión de MTX y prescripción de un complejo vitamínico con ácido folínico. La terapia dental local para el control de las lesiones orales, el control del dolor y la hidratación de los labios se realizó mediante terapia con láser de bajo nivel (Twin Laser, P: 40mW, T: 50s, DE: 50J / cm), aerosol de clorhidrato de bencidamina, lanolina purificada para la sequedad de labios y pasta de dientes sin lauril sulfato de sodio para evitar quemaduras. Después de 12 días, hubo una remisión significativa de los signos y síntomas orales y cutáneos, lo que confirmó el diagnóstico de ME por intoxicación por MTX. La evaluación clínica exhaustiva y la anamnesis favorecieron el diagnóstico y el manejo multiprofesional precoz proporcionó la remisión de las lesiones orales y cutáneas, evitando además complicaciones sistémicas.

Endophytic Trichoderma strains isolated from forest species of the Cerrado-Caatinga ecotone are potential biocontrol agents against crop pathogenic fungi.

The indiscriminate use of chemical pesticides increasingly harms the health of living beings and the environment. Thus, biological control carried out by microorganisms has gained prominence, since it consists of an environmentally friendly alternative to the use of pesticides for controlling plant diseases. Herein, we evaluated the potential role of endophytic Trichoderma strains isolated from forest species of the Cerrado-Caatinga ecotone as biological control agents of crop pathogenic fungi. Nineteen Trichoderma strains were used to assess the antagonistic activity by in vitro bioassays against the plant pathogens Colletotrichum truncatum, Lasiodiplodia theobromae, Macrophomina phaseolina, and Sclerotium delphinii isolated from soybean, cacao, fava bean, and black pepper crops, respectively. All Trichoderma strains demonstrated inhibitory activity on pathogen mycelial growth, with maximum percent inhibition of 70% against C. truncatum, 78% against L. theobromae, 78% against M. phaseolina, and 69% against S. delphinii. Crude methanol extracts (0.5 to 2.0 mg mL-1) of Trichoderma strains were able to inhibit the growth of C. truncatum, except Trichoderma sp. T3 (UFPIT06) and T. orientale (UFPIT09 and UFPIT17) at 0.5 mg mL-1, indicating that the endophytes employ a biocontrol mechanism related to antibiosis, together with multiple mechanisms. Discriminant metabolites of Trichoderma extracts were unveiled by liquid chromatography-tandem mass spectrometry-based metabolomics combined with principal component analysis (PCA), which included antifungal metabolites and molecules with other bioactivities. These results highlight the biocontrol potential of Trichoderma strains isolated from the Cerrado-Caatinga ecotone against crop pathogenic fungi, providing support for ongoing research on disease control in agriculture.

Fatores associados à violência física grave contra crianças e adolescentes com transtornos mentais / Factors associated with severe physical violence against children and adolescents with mental disorders / Factores asociados a la violencia física grave contra niños y adolescentes con trastornos mentales

Objetivo: analisar os fatores associados à ocorrência de violência física grave em crianças e adolescentes com transtornos mentais. Método: estudo transversal com 274 pacientes atendidos em uma unidade de atenção psicossocial de Nova Iguaçu, entre outubro e dezembro de 2016. Além de dados sociodemográficos e clínicos dos cuidadores e crianças, a violência familiar foi apreendida pelo "Parent-Child Conflict Tactics Scales". Resultados: o tempo de atendimento na unidade de saúde combinada com a jornada semanal de cuidado pelo cuidador resultaram em altas chances de ocorrência de violência física grave (OR 5,0; p-valor 0,002). Por outro lado, a participação em programas de transferência de renda (OR 0,5; p-valor 0,015) demonstrou proteção das crianças e adolescentes às violências. Conclusão: as características sociodemográficas e clínicas parecem estar relacionadas à ocorrência de maus-tratos físicos. Para prevenir episódios, principalmente devido à sobrecarga dos cuidadores, parece imprescindível que as famílias sejam inseridas no cotidiano do cuidado mental.

Objective: to analyze factors associated with the occurrence of severe physical violence in children and adolescents with mental disorders. Method: cross-sectional study with 274 patients attending a psychosocial care unit in Nova Iguaçu between October and December 2016. In addition to sociodemographic and clinical data on caregivers and children, family violence was measured by the "Parent-Child Conflict Tactics Scales". Results: The time spent in the health unit combined with the week's schedule of care by the caregiver resulted in high chances of serious physical abuse (OR 5.0; p-value 0.002). On the other hand, participation in cash transfer programs (OR 0.5, p-value 0.015) was found to protect children and adolescents from violence. Conclusion: sociodemographic and clinical characteristics seem to be related to the occurrence of physical abuse. To prevent such episodes, it seems essential to include families in daily mental care, mainly because caregivers are overloaded.

Objetivo: analizar los factores asociados a la ocurrencia de violencia física grave en niños y adolescentes con trastornos mentales. Método: estudio transversal junto a 274 pacientes atendidos en una unidad de atención psicosocial en Nova Iguaçu, entre octubre y diciembre de 2016. Además de los datos sociodemográficos y clínicos sobre los cuidadores y los niños, la violencia familiar fue medida por las "Parent-Child Conflict Tactics Scales". Resultados: El tiempo de permanencia en la unidad de salud combinado con la jornada semanal de cuidado por parte del cuidador resultaron en altas probabilidades de violencia física grave (OR 5,0; p-valor 0,002). Por otro lado, la participación en programas de transferencia de ingresos (OR 0,5; p-valor 0,015) demostró protección de los niños y adolescentes contra la violencia. Conclusión: las características sociodemográficas y clínicas parecen estar relacionadas con la ocurrencia de maltratos físicos. Para prevenir episodios, principalmente derivados de la sobrecarga de los cuidadores, parece ser fundamental que se incluyan las familias en el cotidiano de cuidado mental.

Acute-Phase Levels of CXCL8 as Risk Factor for Chronic Arthralgia Following Chikungunya Virus Infection.

The immunopathogenesis of chikungunya virus (CHIKV) infection and the role of acute-phase immune response on joint pain persistence is not fully understood. We investigated the profile of serum chemokine and cytokine in CHIKV-infected patients with acute disease, compared the levels of these biomarkers to those of patients with other acute febrile diseases (OAFD) and healthy controls (HC), and evaluated their role as predictors of chronic arthralgia development. Chemokines and cytokines were measured by flow Cytometric Bead Array. Patients with CHIKV infection were further categorized according to duration of arthralgia (≤ 3 months vs >3 months), presence of anti-CHIKV IgM at acute-phase sample, and number of days of symptoms at sample collection (1 vs 2-3 vs ≥4). Patients with acute CHIKV infection had significantly higher levels of CXCL8, CCL2, CXCL9, CCL5, CXCL10, IL-1ß, IL-6, IL-12, and IL-10 as compared to HC. CCL2, CCL5, and CXCL10 levels were also significantly higher in patients with CHIKV infection compared to patients with OAFD. Patients whose arthralgia lasted > 3 months had increased CXCL8 levels compared to patients whose arthralgia did not (p<0.05). Multivariable analyses further indicated that high levels of CXCL8 and female sex were associated with arthralgia lasting >3 months. Patients with chikungunya and OAFD had similar cytokine kinetics for IL-1ß, IL-12, TNF, IFN-γ, IL-2, and IL-4, although the levels were lower for CHIKV patients. This study suggests that chemokines may have an important role in the immunopathogenesis of chronic chikungunya-related arthralgia.

Cone-beam computed tomography artifacts in the presence of dental implants and associated factors: an integrative review.

PURPOSE: This study was conducted to review the literature regarding the types of cone-beam computed tomography (CBCT) artifacts around dental implants and the factors that influence their formation. MATERIALS AND METHODS: A search strategy was carried out in the PubMed, Embase, and Scopus databases to identify published between 2010 and 2020, and 9 studies were selected. The implants included 306 titanium, titanium-zirconium, and zirconia implants, as well as 5 titanium cylinders. RESULTS: The artifacts around the implants were the beam-hardening artifact, the streaking artifact, and band-like radiolucent areas. Some factors that influenced the formation of artifacts were the implant material, bone type, evaluated regions, distance, type of CBCT, field of view (FOV) size, milliamperage, peak kilovoltage (kVp), and voxel size. The beam-hardening artifact was the most widely reported, and it was minimized in protocols with a smaller FOV, larger voxels, and higher kVp. CONCLUSION: The risk and benefit of these protocols in individuals with dental implants must be considered, and clinical examinations and complementary radiographs play an essential role in implantology.

Activation of an Effective Immune Response after Yellow Fever Vaccination Is Associated with the Genetic Background and Early Response of IFN-γ and CLEC5A.

The yellow fever vaccine (YF17DD) is highly effective with a single injection conferring protection for at least 10 years. The YF17DD induces polyvalent responses, with a TH1/TH2 CD4+ profile, robust T CD8+ responses, and synthesis of interferon-gamma (IFN-γ), culminating in high titers of neutralizing antibodies. Furthermore, C-type lectin domain containing 5A (CLEC5A) has been implicated in innate outcomes in other flaviviral infections. Here, we conducted a follow-up study in volunteers immunized with YF17DD, investigating the humoral response, cellular phenotypes, gene expression, and single nucleotide polymorphisms (SNPs) of IFNG and CLEC5A, to clarify the role of these factors in early response after vaccination. Activation of CLEC5A+ monocytes occurred five days after vaccination (DAV). Following, seven DAV data showed activation of CD4+ and CD8+T cells together with early positive correlations between type II IFN and genes of innate antiviral response (STAT1, STAT2, IRF7, IRF9, OAS1, and RNASEL) as well as antibody levels. Furthermore, individuals with genotypes rs2430561 AT/AA, rs2069718 AG/AA (IFNG), and rs13237944 AC/AA (CLEC5A), exhibited higher expression of IFNG and CLEC5A, respectively. Together, we demonstrated that early IFN-γ and CLEC5A responses, associated with rs2430561, rs2069718, and rs13237944 genotypes, may be key mechanisms in the long-lasting immunity elicited by YF17DD.

FGFR3 in Periosteal Cells Drives Cartilage-to-Bone Transformation in Bone Repair.

Most organs and tissues in the body, including bone, can repair after an injury due to the activation of endogenous adult stem/progenitor cells to replace the damaged tissue. Inherent dysfunctions of the endogenous stem/progenitor cells in skeletal repair disorders are still poorly understood. Here, we report that Fgfr3Y637C/+ over-activating mutation in Prx1-derived skeletal stem/progenitor cells leads to failure of fracture consolidation. We show that periosteal cells (PCs) carrying the Fgfr3Y637C/+ mutation can engage in osteogenic and chondrogenic lineages, but following transplantation do not undergo terminal chondrocyte hypertrophy and transformation into bone causing pseudarthrosis. Instead, Prx1Cre;Fgfr3Y637C/+ PCs give rise to fibrocartilage and fibrosis. Conversely, wild-type PCs transplanted at the fracture site of Prx1Cre;Fgfr3Y637C/+ mice allow hypertrophic cartilage transition to bone and permit fracture consolidation. The results thus highlight cartilage-to-bone transformation as a necessary step for bone repair and FGFR3 signaling within PCs as a key regulator of this transformation.

The impact of medication-related osteonecrosis of the jaws on the quality of life in cancer patients.

BACKGROUND: To evaluate the impact of oral health on the quality of life (QOL) of individuals undergoing cancer treatment at the time of diagnosis of medication-related osteonecrosis of the jaw (MRONJ). MATERIAL AND METHODS: The present cross-sectional study analyzed patients with MRONJ from 2013 to 2019. The collected data included demographic data, base disease, medications associated with MRONJ, route of administration and time of use, signs, symptoms, and tomographic features of acute MRONJ, staging according to American Association of Oral and maxillofacial Surgeons position paper 2014 (AAOMS), type of dental treatment performed, outcome, and the responses to the Oral Health Impact Profile questionnaire (OHIP-14). Statistical analysis was performed using the Tukey test to study the association between oral condition and the QOL. A p-value of less than 0.05 was considered statistically significant. RESULTS: The sample consisted of 16 medical records of patients with MRONJ. Psychological discomfort showed alarmingly significant results (p< 0.001) with strong negative impact on the QOL of the patients. Functional limitation was the least affected dimension (p = 0.747). The other dimensions did not show statistically significant results. CONCLUSIONS: MRONJ compromises oral health and negatively impacts the QOL, especially with respect to the psychological discomfort (worry and stress). The OHIP-14 questionnaire proved to be an effective tool in the assessment of this impact. Key words:Medication-related osteonecrosis of the jaw, quality of life, oral health, OHIP-14.

Transmission of Chikungunya Virus in an Urban Slum, Brazil.

After a chikungunya outbreak in Salvador, Brazil, we performed a cross-sectional, community-based study of 1,776 inhabitants to determine chikungunya virus (CHIKV) seroprevalence, identify factors associated with exposure, and estimate the symptomatic infection rate. From November 2016 through February 2017, we collected sociodemographic and clinical data by interview and tested serum samples for CHIKV IgG. CHIKV seroprevalence was 11.8% (95% CI 9.8%-13.7%), and 15.3% of seropositive persons reported an episode of fever and arthralgia. Infections were independently and positively associated with residences served by unpaved streets, a presumptive clinical diagnosis of chikungunya, and recall of an episode of fever with arthralgia in 2015-2016. Our findings indicate that the chikungunya outbreak in Salvador may not have conferred sufficient herd immunity to preclude epidemics in the near future. The unusually low frequency of symptomatic disease points to a need for further longitudinal studies to better investigate these findings.

Vitamin D Receptor Controls Cell Stemness in Acute Myeloid Leukemia and in Normal Bone Marrow.

Vitamin D (VD) is a known differentiating agent, but the role of VD receptor (VDR) is still incompletely described in acute myeloid leukemia (AML), whose treatment is based mostly on antimitotic chemotherapy. Here, we present an unexpected role of VDR in normal hematopoiesis and in leukemogenesis. Limited VDR expression is associated with impaired myeloid progenitor differentiation and is a new prognostic factor in AML. In mice, the lack of Vdr results in increased numbers of hematopoietic and leukemia stem cells and quiescent hematopoietic stem cells. In addition, malignant transformation of Vdr-/- cells results in myeloid differentiation block and increases self-renewal. Vdr promoter is methylated in AML as in CD34+ cells, and demethylating agents induce VDR expression. Association of VDR agonists with hypomethylating agents promotes leukemia stem cell exhaustion and decreases tumor burden in AML mouse models. Thus, Vdr functions as a regulator of stem cell homeostasis and leukemic propagation.