H2 antihistamines: May be useful for combination therapies in cancer?

Cancer morbimortality is still a great concern despite advances in research and therapies. Histamine and its receptors' ligands can modulate different biological responses according to the cell type and the receptor subtype involved. Besides the wide variety of histamine functions in normal tissues, diverse roles in the acquisition of hallmarks of cancer such as sustained proliferative signaling, resistance to cell death, angiogenesis, metastasis, altered immunity and modified microenvironment have been described. This review summarizes the present knowledge of the various roles of histamine H2 receptor (H2R) ligands in neoplasias. A bioinformatic analysis of human tumors showed dissimilar results in the expression of the H2R gene according to tumor type when comparing malignant versus normal tissues. As well, the relationship between patients' survival parameters and H2R gene expression levels also varied, signaling important divergences in the role of H2R in neoplastic progression in different cancer types. Revised experimental evidence showed multiple effects of H2R antihistamines on several of the cited hallmarks of cancer. Interventional and retrospective clinical studies evaluated different H2R antihistamines in cancer patients with two main adjuvant uses: improving antitumor efficacy (which includes regulation of immune response) and preventing toxic adverse effects produced by chemo or radiotherapy. While there is a long path to go, research on H2R antihistamines may provide new opportunities for developing more refined combination therapeutic strategies for certain cancer types to improve patients' survival and health-related quality of life.

Co-design of a Community-based Rehabilitation Program to Decrease Musculoskeletal Disabilities in a Mayan-Yucateco Municipality.

BACKGROUND: Chronic musculoskeletal (MSK) diseases are an important cause of disability in the Mayan community of Chankom in Yucatán, Mexico. OBJECTIVE: To understand a community-based participatory research (CBPR) strategy implemented in Chankom to design a community-based rehabilitation (CBR) program for people living with MSK diseases. METHODS: Qualitative descriptive thematic analysis from an ethnographic work conducted in Chankom, during the implementation of a CBPR strategy from 2014 to 2017. RESULTS: Four main themes describe the main processes that formed our CBPR strategy: 1) forming and maintaining an alliance between academic and community members, 2) prioritizing community needs, 3) integrating local and global knowledge and 4) shared-decision-making. This CBPR strategy allowed the design of a CBR program formed by six main interventions: 1) health services coordination, 2) personal support, 3) community venous blood sampling services, 4) community specialized services, 5) health promotion, and 6) health transportation services. CONCLUSIONS: Co-designing a CBR program for people living with chronic MSK diseases in Chankom was possible through an extensive community engagement work structured around four main processes, including the essential principles of CBPR. The designed CBR program includes culturally sensitive interventions aimed at improving the quality, availability, accessibility, and acceptability of health care services. Moreover, the program mainly addressed the "health" component of the World Health Organization-CBR matrix, suggesting a need for a new CBPR cycle after it is implemented and evaluated in the future.

Radiotherapy for Brain Metastases Near the End of Life: Characterizing Patients and Tumor Features.

PURPOSE: Patients with brain metastases are often referred for brain radiotherapy (BrRT) when exclusive palliative management would be more appropriate. To assess the indication of BrRT during end-of-life (EOL) care and evaluate the characteristics of the patients who underwent the treatment. METHODS: This retrospective study comprised patients from four independent oncology centers who had undergone BrRT for metastases. The variables included were Karnofsky performance status (KPS), primary tumor site, metastatic status, neurologic symptomatic status, the number and size of metastases, posterior fossa or meningeal involvement, type of BrRT, having undergone brain metastasectomy, and the availability of systemic therapies after BrRT. Patients were allocated into three subgroups with ≤30, 31-60, and 61-90 days of survival, and a control group of patients who survived >90 days. RESULTS: A total of 546 patients were included in the study. A KPS of <70 (P = .021), the number of brain metastases (P = .001), the lack of brain metastasectomy (P = .006), and the lack of systemic therapies after BrRT (P = .047) were significantly associated with the EOL subgroups. Multivariate analysis showed that a KPS of <70 (P < .001), the lack of brain metastasectomy (P = .015), and the lack of systemic therapies after BrRT (P = .027) were significantly associated with worse survival. In all, 241 (44.1%) patients died within 90 days-120 (22.0%) within 30 days, 75 (13.7%) within 31-60 days, and 46 (8.4%) within 61-90 days of BrRT. Patients with colorectal cancer were significantly more likely to die within 90 days of BrRT than >90 days. CONCLUSION: Considering patients' performance status and whether they are candidates for brain metastasectomy or systemic therapies after BrRT is critical to improving BrRT benefits in scenarios of EOL.

"Effect of Heat Generated by Endodontic Obturation Techniques on Bond Strength of Bioceramic Sealers to Dentine".

INTRODUCTION: Gutta-percha combined with an endodontic sealer remains the most widely used obturation technique. Bioceramic sealers (BS) were developed for root canal obturation in combination with gutta-percha cones using the cold single-cone technique. Few studies have assessed the effect of thermal treatment on the performance of BS. The present study evaluated the effect of heat on BS adhesion to root dentine in the apical third of the root canal of extracted human lower premolars. MATERIALS AND METHODS: Three BS combined with a hydraulic condensation technique, a warm vertical compaction technique, and a carrier-based technique were evaluated. Sixty three lower premolars were prepared following the same surgical protocol to standardize root canal shape at the level of the apex, randomly assigned to one of nine groups, and obturated accordingly. One millimeter-thick sections were subjected to a push-out test using a universal testing machine and classified according to mode of failure. Two-way ANOVA was applied using SPSS software (IBM Corp). RESULTS: No significant differences in maximum load or failure mode were observed among BS, techniques, or when considering the interaction between sealers and techniques. CONCLUSIONS: The heat generated by the obturation techniques used here did not affect BS adhesion to the dentinal wall.

Effect of Dentin Conditioning with EDTA and Diode Lasers on Expression of Odontoblast-like Cell Markers of Dental Pulp Stem Cells.

Regenerative endodontic procedures rely on the delivery of mesenchymal stem cells into the root canal and on the effect of local growth factors from the dentin and blood clot. The aim of this study was to assess the effect of dentin conditioning with ethylenediamine tetraacetic acid (EDTA) and diode lasers with different wavelengths (808 nm and 980 nm) on the expression of odontoblast-like cell markers. Forty dentin cylinders were divided into four groups according to the irrigation protocol: EDTA, EDTA + 808 nm diode laser, EDTA + 980 nm diode laser, and phosphate-buffered saline as the control group. Dental pulp stem cells were seeded into the previously conditioned cylinders and incubated for 14 days. The quantitative real-time polymerase chain reaction was used to evaluate the expression of dentin sialophosphoprotein (DSPP), dentin morphoprotein-1 (DMP-1), and transforming growth factor-beta 1 (TGF-ß1). Data analysis was performed using the Kruskal-Wallis test. The activation of EDTA with 980 nm and 808 nm diode lasers resulted in lower DSPP and DMP-1 expression than that for EDTA alone (p < 0.05 and p < 0.01, respectively). The expression of TGF was similar among all groups. The highest level of expression of odontoblast-like differentiation markers was observed with EDTA alone. However, the use of an 808 nm diode laser during EDTA irrigation reduced the expression of odontoblastic differentiation markers.

Genomic history of coastal societies from eastern South America.

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr BP) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr BP from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr BP, corroborating evidence of cultural change.

Lesiones perirradiculares asociadas a primeros molares superiores tratados endodónticamente: estudio a través de tomografías computadas / Periradicular lesions associated with endodontically treated maxillary first molars: study through computed tomography

Objetivos: Estudiar con tomografías computadas de haz cónico (CBCT) las lesiones perirradiculares de primeros molares superiores tratados endodónticamente; evaluar la lo- calización y, en los que tenían lesión en la raíz mesiovestibu- lar (MV), evaluar la frecuencia del conducto MV2. Materiales y métodos: A partir de una muestra de 179 tomografías, que incluían primeros molares superiores, se seleccionaron y analizaron aquellas en las cuales estos ha- bían recibido un tratamiento endodóntico previo, presentaban lesiones perirradiculares y conservaban una restauración co- ronaria. Las variables analizadas fueron: la localización de áreas radiolúcidas compatibles con lesiones perirradiculares de origen endodóntico y la correlación entre diferentes loca- lizaciones y la calidad del tratamiento realizado (adecuado, defectuoso o sin tratamiento). Los datos fueron analizados mediante la prueba de chi-cuadrado y la prueba de Spearman. Resultados: De las 179 CBCT que incluían primeros molares superiores, 90 reunían las condiciones requeridas. La frecuencia de las lesiones perirradiculares fue significativa- mente mayor en la raíz MV al compararla con las raíces disto- vestibular y palatina (p<0,05). El conducto MV1 presentó un tratamiento adecuado en todos los casos. El conducto MV2 recibió un tratamiento adecuado en 4 casos (4,44%), defec- tuoso en 4 casos (4,44%) y no tratado en 82 casos (91,1%); con una diferencia estadísticamente significativa (p<0,05). Conclusiones: En la muestra analizada, la localización de lesiones perirradiculares postratamiento endodóntico en primeros molares superiores se encontró con mayor frecuencia asociada a la raíz mesiovestibular, donde en la mayoría de los casos el con- ducto MB2 no fue tratado o presentó un tratamiento defectuoso (AU)

Aim: To study with cone-beam computed tomography (CBCT) the periradicular lesions of maxillary first molars with endodontical treatment; to evaluate its localization and, in those with a mesiobuccal root (MB) injury, assess the fre- quency of the MB2 root canal. Materials and methods: From a sample of 179 tomog- raphies (CBCT) that included maxillary first molars, those in which they had received previous endodontic treatment, pre- sented periradicular lesions and had a coronary restoration were selected and analyzed. The analyzed variables were: localization of radiolucent areas compatible with periradic- ular lesions of endodontic origin and the correlation between different localizations and quality of the performed treatment (adequate, defective, or untreated). Data were analyzed by the chi-square test and the Spearman test. Results: Of the 179 CBCT that included maxillary first molars, 90 met the required conditions. The frequency of periradicular lesions was significantly higher in the MB root when compared with distobuccal and palatal roots (P<0,05). The MB1 canal presented an adequate treatment in all cas- es. The MB2 canal received adequate treatment in 4 cases (4.44%), a defective one in 4 cases (4.44%) and was untreated in 82 cases (91.1%). The differences among these frequencies were statistically significant (P<0.05). Conclusions: In the analyzed sample, the localization of periradicular lesions after endodontic treatment in maxillary first molars was associated more frequently with the mesio- buccal root in which in the majority of cases the MB2 canal was untreated or presented a defective treatment

Non-tumorigenic epithelial breast cells and ionizing radiation cooperate in the enhancement of mesenchymal traits in tumorigenic breast cancer cells.

AIMS: Radioresistance and recurrences are crucial hindrances in cancer radiotherapy. Fractionated irradiation can elicit a mesenchymal phenotype in irradiated surviving cells and a deep connection exists between epithelial mesenchymal transition, radioresistance, and metastasis. The aim of this study was to analyze the effect of the secretoma of irradiated non-tumorigenic mammary epithelial cells on surviving irradiated breast tumor cells regarding the gain of mesenchymal traits and migratory ability. MAIN METHODS: MDA-MB-231 and MCF-7 breast cancer cells, irradiated or not, were incubated with conditioned media from MCF-10A non-tumorigenic epithelial breast cells, irradiated or not. After five days, we evaluated the expression and localization of epithelial and mesenchymal markers (by western blot and indirect immunofluorescence), cell migration (using transwells) and metalloproteinases activity (by zymography). We also assessed TGF-ß1 content in conditioned media by immunoblot, and the effect of A83-01 (a selective inhibitor of TGF-ß receptor I) and PP2 (a Src-family tyrosine kinase inhibitor) on nuclear Slug and cell migration. KEY FINDINGS: Conditioned media from MCF-10A cells caused phenotypic changes in breast tumor cells with attainment or enhancement of mesenchymal traits mediated at least in part by the activation of the TGF-ß type I receptor and a signaling pathway involving Src activation/phosphorylation. The effects were more pronounced mostly in irradiated tumor cells treated with conditioned media from irradiated MCF-10A. SIGNIFICANCE: Our results suggest that non-tumorigenic epithelial mammary cells included in the irradiation field could affect the response to irradiation of post-surgery residual cancer cells enhancing EMT progression and thus modifying radiotherapy efficacy.

Morphometric affinities and direct radiocarbon dating of the Toca dos Coqueiros' skull (Serra da Capivara, Brazil).

The biological variation of the earliest skeletons of South America has been intensely debated for the last two centuries. One of the major research constraints has been the limited number of available samples dating to the early Holocene. We here present the first direct radiocarbon-date for the early Holocene human skeleton from Toca dos Coqueiros (Serra da Capivara, Brazil), also known as "Zuzu" (8640 ± 30 BP; 9526-9681 cal years BP). We performed craniometric analyses using exclusively samples from Brazil, to revisit the sex of the skeleton, and to discuss the evolutionary processes involved in the occupation of the continent. The sex of the individual was estimated as a female when compared to late and early Holocene individuals, but as a male when compared only to the early Holocene series. We also found that Zuzu presents the strongest differences with the late Holocene Guajajara individuals, located nearby, and the strongest similarities with the early Holocene series from Lagoa Santa, attesting for solid biological affinities among early Holocene individuals from Brazil, as well as a moderate level of morphological variation among them. This suggests that the early individuals were part of the same heterogeneous lineage, possibly a different one from which late Holocene populations diverged.

Adaptación al español chileno de la Evaluación Cognitiva Dinámica de Terapia Ocupacional de Loewenstein (DLOTCA) / Adaptação Transcultural para o espanhol chileno da Avaliação Cognitiva Dinâmica de Terapia Ocupacional de Loewenstein (DLOTCA) / Adaptation to Chilean Spanish of Dynamic Loewenstein Occupational Therapy Cognitive Assessment (DLOTCA)

Resumen Objetivo Adaptar la décima versión en inglés de la Dynamic Loewestein Occupational Therapy Cognitive Assessment al español chileno. Método Se realizó adaptación al español del manual de aplicación de DLOTCA. El proceso siguió las pautas generales para la traducción y adaptación de instrumentos de la Organización Mundial de la Salud (OMS), con traducción directa, panel de discusión de expertos, retrotraducción, pruebas previas y entrevistas cognitivas con usuarios. Resultados Se obtuvo una traducción directa al español por dos terapeutas ocupacionales bilingües que fue sometida a ajustes por un panel de expertos compuesto por 6 terapeutas ocupacionales, del total de 28 sub test el comité de expertos no tuvo discrepancia en 20 de ellos, de los 8 restantes se realizaron modificaciones. Se realiza una retrotraducción de la versión obtenida, donde solo hubo discrepancias con un término lo que fue resuelto por el equipo investigador. Finalmente se aplicó una prueba previa/pre test a 13 personas adultas con daño cerebral, los ajustes en esta etapa fueron ortográficos y de sustitución de algunos términos por palabras más comúnmente utilizados en la lengua chilena, verificando la consistencia en la comprensión de los ítems independientemente de los resultados obtenidos. Se produjeron tres versiones antes de la versión final, todas las etapas se desarrollaron de manera sistemática, logrando una traducción comprensible y consistente con la población chilena. Conclusiones Finalmente se ha puesto a disposición de la comunidad científica una versión en español chileno del instrumento DLOTCA.

Resumo ObjetivoAdaptar a décima versão em inglês do Dynamic Loewestein Occupational Therapy Cognitive Assessment para o espanhol chileno. MétodoO manual de aplicação DLOTCA foi adaptado para o espanhol. O processo seguiu as diretrizes gerais para tradução e adaptação de instrumentos da Organização Mundial da Saúde (OMS), com tradução direta, painel de discussão de especialistas, retrotradução, pré-testes e entrevistas cognitivas com os usuários. ResultadosA tradução direta para o espanhol foi obtida por dois terapeutas ocupacionais bilíngues que foi submetida a ajustes por um painel de especialistas composto por 6 terapeutas ocupacionais, do total de 28 subtestes, o comitê de especialistas não apresentou discrepância em 20 deles, das quais 8 modificações restantes foram feitas. Foi realizada a retrotradução da versão obtida, com apenas discrepâncias com um termo, o que foi resolvido pela equipe de pesquisa. Por fim, uma prova prévia / pré-teste foi aplicado a 13 adultos com lesão cerebral, os ajustes nesta etapa foram de grafia e substituição de alguns termos por palavras mais utilizadas na língua chilena, verificando a consistência na compreensão dos itens, independentemente dos resultados obtidos. Três versões foram produzidas antes da versão final, toda as etapas foram desenvolvidas de forma sistemática, alcançando uma tradução compreensível e consistente para a população chilena. Conclusões: Uma versão em espanhol chileno do instrumento DLOTCA foi finalmente disponibilizada para a comunidade científica.

Abstract Objective To adapt the tenth version in English of the Dynamic Loewenstein Occupational Therapy Cognitive Assessment to Chilean Spanish. Method The DLOTCA application manual was adapted into Spanish. The process followed the general guidelines for the translation and adaptation of instruments of the World Health Organization (WHO), with direct translation, a panel discussion of experts, back translation, pre-tests, and cognitive interviews with users. Results A direct translation into Spanish was obtained by two bilingual occupational therapists that were subjected to adjustments by a panel of experts composed of 6 occupational therapists, of the total of 28 sub-tests, the expert committee had no discrepancy in 20 of them, of which 8 remaining modifications were made. A back translation of the version obtained is carried out, where there were only discrepancies with one term, which was resolved by the research team. Finally, a pre-test was applied to 13 adults with brain damage, the adjustments in this stage were spelling and substitution of some terms for words more commonly used in the Chilean language, verifying the consistency in the understanding of the items independently of the results obtained. Three versions were produced before the final version, all stages were developed in a systematic way, achieving an understandable and consistent translation with the Chilean population. Conclusions A version in Chilean Spanish of the DLOTCA instrument has finally been made available to the scientific community.

Effects of Endodontic Infections on the Maxillary Sinus: A Case Series of Treatment Outcome.

This article shows the follow-up of several cases of maxillary sinusitis of dental (usually endodontic) origin, with different manifestations, diagnostic challenges, and outcomes.Cases from 14 patients from 3 countries and treated by 7 different endodontists are presented, all of them with inflammatory sinus changes represented by mucositis, osteoperiostitis, and/or partial/full obstruction. All cases showed dental and/or sinus signs/symptoms that resolved after dental management. In 13 cases, the sinus condition had an endodontic origin, 4 of them concurrently with periodontal involvement. In 1 case, sinusitis was caused by trauma to the face. All cases but 1 had a satisfactory response of the periradicular tissues and maxillary sinus to treatment that consisted of root canal therapy, root amputation, extraction, or trauma management.The successful management of most cases reported in this article emphasizes the importance of endodontics as a specialty engaged in saving teeth and promoting health not only in the oral cavity but also in other areas that may be affected by infections of endodontic origin, including the maxillary sinus.

Root dentine thickness in C-shaped lower second molars after instrumentation: A CBCT and micro-CT study.

Stripping perforation is a possible complication in instrumentation of C-shaped canals. This study evaluated the minimum thickness of the root canal wall in C-shaped teeth after instrumentation. Twelve extracted C-shaped mandibular second molars (four teeth of type I, II and III each) were examined by CBCT (voxel size 90 µm) before and after instrumentation with WOG primary file. Micro-CT scans (voxel size 30 µm) were obtained after instrumentation. Percentage of canal wall area touched by the file and minimum thickness of dentine were measured and compared between CBCT and micro-CT. In type I C-shape canals, less than 10% of the canal wall area was touched by the instrument. In ten teeth, the shortest distance to root surface was from the instrumented area; no perforations occurred. CBCT and micro-CT measurements were in good agreement in ten cases; in two teeth, micro-CT revealed considerably shorter distance to root surface. The two shortest distances were 0.27 and 0.41 mm.

Efecto de selladores endodónticos sobre el pH del medio al cual son inmersos / Effect of endodontic sealers on pH of the medium in which they are immersed

INTRODUCTION: The endodontic sealers are essential for three-dimensional root canal obturation. The sealers are based on epoxy resin, AH Plus and bioceramic sealers, Bio-C Sealer and BioRoot RCS, which are bioactive materials due to the ability to cause a specific biologic reaction in integration with the receptor tissue, with a pH of 12,5. OBJECTIVE: To evaluate in vitro, the capacity of different endodontic sealers to modify the pH of the solution in which they are immersed, at different time. MATERIALS AND METHODS: Fifteen samples of sealers were prepared and placed into holes of blister packs, which set for 24 hours in store at 37 degrees Celsius. Then, each sample was immersed in sterile plastic bottles with 30 millimeters of physiological solution. Samples were divided into three groups(n=5) according to the sealer: 1) BioRoot RCS, 2) Bio-C Sealer and 3) AHPlus. The pH measurements were performed in different periods of time with a digital pH meter: immediate, 40 min, 24 and 48 hs, 7, 14, 21 and 30 days. Data were made by means of the Variance Analysis Test with repeated measurements. RESULTS: The pH of AH Plus did not change during the experience. At 24 hs, both bioceramic sealers increased medium pH up to alkaline value, which was maintained with BioRoot sealer (mean 11,54) until 30 days. At 7 days, the pH of the medium with Bio-C Sealer started decreasing. Evolution of sealers pH along the time revealed statistical significant difference (p<0,001). CONCLUSION: AH Plus sealer did not modifie the pH of the medium Both bioceramic sealers increased the pH, reaching to the maximum alkaline value at 7 days, which was maintained with BioRoot RCS and lightly decreased with Bio-C Sealer at 30 days.

INTRODUCCIÓN: El uso de selladores en la obturación endodóntica es fundamental para lograr un sellado tridimensional del conducto radicular. Según su composición, se presentan selladores a base de resina epóxica, como el AH Plus y de biocerámico, como Bio-C Sealer y BioRoot RCS, siendo considerados los últimos como materialesbioactivos, por su capacidad de promover una reacción biológica específica sobre el tejido receptor, por la liberación de calcio y pH alcalino OBJETIVO: Evaluar, in vitro la capacidad de diferentes selladores endodónticos para modificar el pH de la solución en la cual son inmersos, en distintos períodos de tiempo. MATERIALES Y METODOS: Se prepararon 15 probetas de sellador en un molde de plástico. Se dejaron fraguar 24 hs en estufa a 37° C y posteriormente, cada una fue inmersa en un frasco consolución fisiológica. La muestra se dividió en tres grupos (n=5) según el sellador: 1) BioRoot RCS, 2) Bio-C Sealer y 3) AHPlus. Se determinó el pH de la solución de cada grupo en diferentes períodos de tiempo: inmediato, 40 min, 24 y 48 hs, 7, 14, 21 y 30 días. Los resultados fueron analizados estadísticamente mediante Análisis de Varianza con Medidas Repetidas (ANOVA). RESULTADOS: El sellador AH Plus mantuvo constante el pH del medio durante toda la experiencia. Ambos selladores biocerámicos elevaron el pH del medio hasta llegar a ser alcalino (11,2 y 11,5) a las 24 hs, el cual se mantuvo para el grupo BioRoot RCS hasta los 30 días, con un pH promedio de 11.5. Mientras que, a partir de los 7 días, en el grupoBio-C Sealer comenzó a descender el pH del medio. La evolución del pH a lo largo del tiempo arrojó diferencias significativas entre los distintos selladores evaluados (p<0,001). CONCLUSIONES: Bajo las condiciones del presente estudio, AH Plus no modificó el pH del medio y ambos selladores biocerámicos elevaron el pH, alcanzado su máximo valor de alcalinidad a los 7 días; a partir de los cuales, BioRoot RCS mantuvo el pH elevado del medio y con Bio-C Sealer se observó un ligero descenso del pH hasta los 30 días.

The secretome of non-tumorigenic mammary cells MCF-10A elicits DNA damage in MCF-7 and MDA-MB-231 breast cancer cells.

Radiotherapy is used in breast cancer to destroy tumor cells lingering after surgery. It is accepted that lethal effects of ionizing radiation occur as a result of damage to DNA in irradiated (IR) cells. However, response mechanisms may promote cell survival with efficient DNA repair or genomic alterations. Chromosomal aberrations are frequent in surviving cells and may enhance chromosomal instability (CIN) which is associated with increased risk of recurrence and metastasis. Intercellular communication can affect the response in IR cells and cause damage in non-irradiated (N-IR) cells. We evaluated the effect of the secretome of non-tumorigenic mammary cells (MCF-10A) on proliferation and DNA damage in breast cancer cells (MCF-7 and MDA-MB-231). Results showed that conditioned media from IR and N-IR MCF-10A cells produced cycles of DNA double-strand breaks in N-IR and IR tumor cells leaving them with residual damage. CIN markers (micronuclei, nucleoplasmic bridges, nuclear buds) were also increased in IR and N-IR tumor cells, being the effect of conditioned media from IR MCF-10A greater in many cases. The inhibition of phosphorylation/activation of Src kinase in cancer cells hindered CIN markers' increment. Besides, clonogenic survival of tumor cells was differentially modulated by conditioned media from MCF-10A: decreased in MCF-7 and enhanced in MDA-MB-231 cells. These results signal the relevance of tumor-host interaction in tumor behavior and the response to radiotherapy.

Selladores biocerámicos y técnicas de obturación en endodoncia / Bioceramic sealants and obturation techniques in Endodontics

El objetivo principal de la obturación endodóntica es rellenar de manera hermética y tridimensional el sistema de conductos radiculares con materiales inertes, antisépticos y/o bioactivos que estimulen el proceso de reparación o no lo interfieran. La utilización de agentes selladores para la obturación endodóntica es esencial para rellenar las irregularidades del conducto y las pequeñas discrepancias entre la pared dentinaria y el material sólido de obturación. En los últimos años, han surgido en el mercado una gran variedad de selladores endodónticos biocerámicos Se han difundido en su uso clínico de manera muy vertiginosa, por sus ventajas y propiedades que favorecen sobre todo a los procesos de reparación ósea, dado que son materiales bioactivos. Se buscó literatura relacionada al tema planteado en la plataforma Pubmed y Medline para desarrollar esta revisión narrativa, con el fin de estudiar la relación entre los nuevos selladores biocerámicos y las diferentes técnicas de obturación termoplásticas aplicadas en Endodoncia. Es importante destacar la poca evidencia científica respecto del comportamiento clínico de los selladores biocerámicos durante la obturación endodóntica, más aún cuando se aplica calor como parte de la técnica.

Estudio tridimensional de reabsorciones internas obturadas con gutapercha inyectable o cono único de gutapercha más sellador biocerámico / Three-dimensional study of internal resorptions obturated with injected gutta-percha or single guttapercha cone and bioceramic sealer

Objetivo: Evaluar ex vivo, mediante reconstrucción tridimensional con tomografía computarizada de haz cónico, la presencia de vacíos, el volumen y la adaptación de la obturación a las paredes de conductos con reabsorciones dentinarias internas simuladas empleando gutapercha inyectable o cono único de gutapercha más sellador biocerámico. Materiales y métodos: Se utilizaron 10 incisivos centrales superiores humanos extraídos, en cada uno de los cuales se talló una reabsorción artificial para su obturación. La muestra fue sometida, de manera sucesiva, a dos condiciones experimentales diferentes: grupo 1, gutapercha inyectable con sistema EQ-V Master; grupo 2, cono de gutapercha más sellador biocerámico BioRoot RCS. Luego, se realizaron tomografías computarizadas de haz cónico y se hizo el estudio tridimensional. A continuación, se utilizó un programa para identificar los vacíos en la obturación y analizar cuantitativamente el volumen y la superficie cubierta por la obturación en los tercios coronario, medio (ampolla) y apical. Los datos fueron evaluados con la prueba de Wilcoxon (P<0,05). Resultados: El volumen de obturación y la superficie dentinaria en contacto con la obturación fueron similares para las dos técnicas empleadas. Las diferencias entre ambos grupos no fueron estadísticamente significativas (P>0,05). Conclusión: Aunque se observaron vacíos con ambas técnicas (en contacto con la superficie dentinaria cuando se empleó gutapercha inyectable, y en el interior de la obturación cuando se usó cono único de gutapercha más sellador BioRoot RCS), las dos rellenaron adecuadamente las reabsorciones simuladas (AU)

Aim: Ex vivo, tridimensional evaluation with cone beam computed tomography (CBCT), of the presence of voids, the obturation volume and adaption to the root canal walls with simulated internal root resorption, using injected gutta-percha or bioceramic sealer with single gutta-percha cone. Materials and methods: Ten maxillary extracted central human incisors were used and artificial internal root resorption was created in each one. For the root canal obturation, each tooth was subjected to two different experimental conditions successively, conforming two matched groups: Group I: EQ-V Master injected thermo plasticized gutta-percha system. Group II: gutta- percha point plus BioRoot RCS bioceramic sealer. First, the root canals were filled with injected gutta-percha and then, with the bioceramic sealer. Then the teeth were scanned with CBCT and subsequently a digital three-dimensional reconstruction was performed. The presence of voids, obturation volumne and the dentin wall surface covered by the filling material was quantitative analyzed through a software; at the coronal, middle (blister) and apical thirds. The data was analyzed by using Wilcoxon test (P<0.05). Results: The filling material volume and the dentin wall surface covered by it, was similar in both root canal obturation techniques. There was no significant difference between both groups (P>0.05). Conclusion: Although voids were observed in both groups (when the injected thermo plasticized gutta-percha system was used the voids were at the external surface and when BioRoot RCS + gutta-percha cone was used the voids were into the filling material), the obturation of simulated root canal resorption cavities was similar with both obturation techniques (AU)

Obturación endodóntica de las raíces mesiales de molares inferiores con sellador Bio-C Sealer y AHPlus / Endodontic obturation of mesial roots of mandibular molars with Bio-C Sealer and AHPlus

La obturación del conducto radicular se realiza con conos de gutapercha y un sellador endodóntico, el cual rellena los espacios entre la pared dentinaria y el material obturador; y las irregularidades del conducto radicular. El sellador Bio-C Sealer es un cemento biocerámico con propiedades bioactivas, mientras que el sellador AH Plus es un cemento a base de resina. La hipótesis del presente estudio fue que el sellador BioC Sealer ocupa mayor volumen y superficie, respecto del sellador AH Plus. OBJETIVO: Comparar el uso del sellador Bio-C Sealer con el sellador AH Plus en la obturación de conductos mesiales de molares inferiores. MATERIALES Y MÉTODOS: Se seleccionaron 40 conductos (20 mesio-vestibulares y 20 mesiolinguales) de 20 raíces mesiales de molares inferiores permanentes. Los conductos fueron instrumentados con limas Wave One Gold Small (Dentsply, Maillefer) y WaneOne Gold Primary e irrigados con hipoclorito de sodio. Para la obturación, la muestra se dividió en dos grupos de 20 conductos cada uno, de acuerdo al sellador endodóntico utilizado. Grupo A: sellador AH Plus (Dentsply, Maillefer) y Grupo B: sellador Bio-C Sealer (Angelus). Finalizada la obturación, se utilizó la microtomografía computada (microCT) de alta resolución con un detector tipo flat-panel certificado de la compañía Varian R (USA) modelo PaxScan 2020+ para obtener 180 proyecciones tomográficas de cada muestra. Luego se reconstruyó la imagen 3D de la muestra utilizando algoritmos específicos dedicados en el software MatLab (MathWorks, USA), y con desarrollos propios del equipo de investigación en lenguaje Python en las instalaciones del LIIFAMIRx de la Universidad Nacional de Córdoba. Los datos obtenidos fueron analizados estadísticamente mediante el test de Mann Whitney. RESULTADOS: No se encontraron diferencias significativas en el volumen de obturación entre las muestras tratadas con sellador AH Plus y sellador Bio C- Sealer (p>0,05). Respecto al volumen de espacios vacíos, la frecuencia de casos en los cuales pudieron detectarse volúmenes de vacíos mensurables (≥ 0,01 mm3) fue del 15%; registrándose 2 en el grupo BIO-C sealer (5%) y 4 en AH Plus (10%). CONCLUSIÓN: Bajo las condiciones de este estudio, puede concluirse que ambos selladores AH Plus y Bio-C Sealer resultaron adecuados para la obturación de los conductos mesio-vestibulares y mesiolinguales de molares inferiores. Sin embargo, el volumen de espacios vacíos fue menor cuando se usó el sellador biocerámico Bio-C Sealer

Histamine H4 receptor agonists induce epithelial-mesenchymal transition events and enhance mammosphere formation via Src and TGF-ß signaling in breast cancer cells.

Epithelial-mesenchymal transition (EMT) contributes to cell invasion and metastasis during the progression of epithelial cancers. Though preclinical evidence suggests a role for histamine H4 receptor (H4R) in breast cancer growth, its function in the EMT is less known. In this study we proposed to investigate the effects of H4R ligands on EMT and mammosphere formation as a surrogate assay for cancer stem cells in breast cancer cells with different invasive phenotype. We also investigated the participation of Src and TGF-ß signaling in these events. Breast cancer cells were treated with the H4R agonists Clobenpropit, VUF8430 and JNJ28610244 and the H4R antagonist JNJ7777120. Immunodetection studies showed cytoplasmic E-cadherin, cytoplasmic and nuclear beta-catenin, nuclear Slug and an increase in vimentin and α-smooth muscle actin expression. There was also an enhancement in cell migration and invasion assessed by transwell units. All these effects were prevented by JNJ7777120. Moreover, H4R agonists induced an increase in phospho-Src levels detected by Western blot. Results revealed the involvement of phospho-Src in EMT events. Upon treatment with H4R agonists there was an increase in phospho-ERK1/2 and TGF-ß1 levels by Western blot, in Smad2/3 positive nuclei by indirect immunofluorescence, and in tumor spheres formation by the mammosphere assay. Notably, the selective TGF-ß1 kinase/activin receptor-like kinase inhibitor A83-01 blocked these effects. Moreover, cells derived from mammospheres exhibited higher Slug expression and enhanced migratory behavior. Collectively, findings support the interaction between H4R and TGF-ß receptor signaling in the enhancement of EMT features and mammosphere formation and point out intracellular TGF-ß1 as a potential mediator of these events.

Efecto de los irrigantes sobre la resistencia a la fractura de premolares / Effect of irrigant solutions on fracture resistance of premolars

INTRODUCCIÓN: La endodoncia regenerativa ha sido definida como procedimientos basados biológicamente y diseñados para reemplazar estructuras pérdidas, incluyendo dentina y estructuras radiculares, y células del complejo dentino-pulpar con tejidos vivos. Ha sido considerada una alternativa para el tratamiento de dientes permanentes jóvenes con ápices inmaduros y necrosis pulpar. El procedimiento clínico se basa en la desinfección y posterior formación de un coágulo de sangre en el conducto radicular. Las soluciones irrigantes como el hipoclorito de sodio (NaOCl) y EDTA se usan no sólo para la desinfección sino también para el acondicionamiento de la dentina, con el fin de liberar factores de crecimiento de la matriz dentinaria, que guían la diferenciación celular. OBJETIVO: Evaluar el efecto de la irrigación sobre la resistencia a la fractura de premolares tratados con el protocolo para endodoncia regenerativa, con hipoclorito de sodio y con irrigación final con EDTA. MATERIALES Y METODOS: Se seleccionaron 10 pares de premolares humanos extraídos homólogos, a los cuales se tomaron fotografías y radiografías periapicales. Se realizaron las aperturas camerales correspondientes, se prepararon los conductos con ensanchador de Peeso para simular un diente inmaduro con ápice abierto y se envolvieron las raíces con teflón para simular el ligamento periodontal. Los 20 dientes se dividieron en 2 grupos de 10 premolares cada uno (n=10), asegurando que en cada grupo hubiera un premolar homólogo de cada par. Grupo A (control) se irrigó con NaOCl al 2,5% y el grupo B (experimental) se irrigó con NaOCl al 2,5% seguido de EDTA al 17%. Posteriormente, se selló el tercio coronario del conducto y la cavidad de acceso con Biodentine. Las muestras fueron seccionadas transversalmente a 3 mm coronarios al límite amelo cementario y fueron montadas en una resina de composite para mantener los premolares verticales en una máquina universal para ensayos mecánicos (Instron Corp,Canton, MA, USA). Se aplicó una carga compresiva con una velocidad de desplazamiento de cabezal de 1 mm/minuto sobre la raíz apoyada sobre un cono de acero que ejerció un efecto cuña y se determinó la fuerza necesaria para fracturar la raíz. Los resultados fueron analizados estadísticamente con prueba T. RESULTADOS: La media de la fuerza (N) necesaria para generar la fractura de las raíces en el grupo donde se usó sólo NaOCl fue de 337,84, mientras que para el grupo donde se usó EDTA e NaOCl fue de 345,54. Al comparar ambos grupos con la prueba de t, las diferencias no resultaron estadísticamente significativas (p>0.05). CONCLUSIONES: La irrigación final con EDTA no disminuyó la resistencia a la fractura de premolares con ápices inmaduros previamente irrigados con hipoclorito de sodio al 2,5%. (AU)

INTRODUCTION: Regenerative endodontic procedures have been defined as biological procedures designed to replace damaged structures including dentin and radicular structures, as well as cells of the dentin complex, with vital tissue. They are considered as an alternative for treatment immature permanent teeth with necrotic pulp. The clinical procedure is based in disinfection and subsequent a blood clot formation in the root canal. Sodium hypochlorite (NaOCL) and EDTA are irrigation solutions frequently used not only for disinfection but also for dentin conditioning, in order to release growth factors from dentin matrix to guide stem cells differentiation. The hypothesis of the present study is that final irrigation of root canal with EDTA decreases fracture resistance in immature human teeth. OBJECTIVE: Evaluate the effect of irrigation with EDTA on the fracture resistance of premolars with open foramen, previously irrigated with sodium hypochlorite. MATERIALS AND METHODS: Ten pairs of healthy human premolars were selected, extracted for orthodontic reasons. They were photographed and preoperative radiograph were taken. The access cavity was performed, root canals were instrumented and Peeso drills were used to simulate immature teeth. The external surfaces of the root were covered with teflon band to simulate a periodontal ligament. The twenty teeth were randomly assigned into two groups of ten premolars each (n=10). Group A (control) was irrigated with NaOCL 2.5% and group B (experimental) was irrigated with NaOCL 2.5% followed by 17% EDTA. The access cavity was sealed with Biodentine and the crown was sectioned 3 mm coronal to the CEJ. Samples were mounted in a composite resin, in order to keep them up perpendicularly to support base, placed in an Instron testing machine (InstronCorp, Canton, MA, USA). By displacement of the machine's head, a metal cone produced a wedge effect on the root. The compressive force necessary to result in root fracture was determined with a head speed displacement of 1mm per min. The force required to root fracture was registered as Newton values. Data was statistically analyzed by using T test (P<0,05). RESULTS: The force required to fracture the roots of premolars irrigated with NaOCl was of 337,84 Newton (mean value); while in the group irrigated with NaOCl followed by EDTA was of 345,54 Newton. The difference was not statistically significant when comparing both groups by the t test (p> 0.05). CONCLUSION: The final irrigation with EDTA did not reduce fracture resistance of premolars with immature apex, previously irrigated with 2.5% sodium hypochlorite. (AU)