Bacteriemia asociada a catéteres venosos centrales no tunelizados en niños en hemodiálisis crónica / Bacteremia associated with non-tunneled central venous catheters in children undergoing chronic hemodialysis

Introducción. La infección asociada a catéter venoso central (CVC) es la principal complicación que presentan los pacientes en hemodiálisis en los que se usa este tipo de acceso. Objetivo. Estimar la incidencia de bacteriemia asociada a CVC no tunelizado, analizar la frecuencia de agentes causales y explorar factores de riesgo asociados en niños en hemodiálisis. Población y métodos. Estudio retrospectivo realizado en niños en hemodiálisis por CVC no tunelizado entre el 1 junio de 2015 y el 30 de junio de 2019. Para evaluar factores de riesgo predictores de bacteriemia asociada a CVC, se realizó regresión logística. Los factores de riesgo independiente se expresaron con odds ratio con sus respectivos intervalos de confianza del 95 %. Se consideró estadísticamente significativo un valor de p <0,05. Resultados. En este estudio se incluyeron 121 CVC no tunelizados. La incidencia de bacteriemia fue de 3,15 por 1000 días de catéter. El microorganismo aislado con mayor frecuencia fue Staphylococcus epidermidis (16 casos, 51,5 %). La infección previa del catéter fue el único factor de riesgo independiente encontrado para el desarrollo de bacteriemia asociada a CVC no tunelizado (OR: 2,84; IC95%: 1,017,96; p = 0,04). Conclusiones. El uso prolongado de los CVC no tunelizados para hemodiálisis crónica se asoció con una incidencia baja de bacteriemia. Los gérmenes grampositivos predominaron como agentes causales. La presencia de infección previa del CVC aumentó en casi 3 veces el riesgo de bacteriemia asociada a CVC en nuestra población pediátrica en hemodiálisis.

Introduction. Central venous catheter (CVC)-related infection is the main complication observed in patients undergoing hemodialysis with this type of venous access. Objective. To estimate the incidence of non-tunneled CVC-related bacteremia, analyze the frequency ofcausative agents, and explore associated risk factors in children undergoing hemodialysis. Population and methods. Retrospective study in children receiving hemodialysis via a non-tunneled CVC between June 1 st, 2015 and June 30 th, 2019. A logistic regression was carried out to assess risk factors that were predictors of CVC-related bacteremia. Independent risk factors were described as odds ratios with their corresponding 95% confidence interval (CI). A value of p < 0.05 was considered statistically significant. Results. A total of 121 non-tunneled CVCs were included in this study. The incidence of bacteremia was 3.15 per 1000 catheter-days. The most commonly isolated microorganism was Staphylococcus epidermidis(16 cases, 51.5%). Prior catheter infection was the only independent risk factor for the development of bacteremia associated with non-tunneled CVC (OR: 2.84, 95% CI: 1.01­7.96, p = 0.04). Conclusions. Prolonged use of non-tunneled CVCs for chronic hemodialysis was associated with a low incidence of bacteremia. Gram-positive microorganisms prevailed among causative agents. A prior CVC infection almost trebled the risk for CVC-related bacteremia in our pediatric population receiving hemodialysis.

Interleukin (IL)-1/IL-6-Inhibitor-Associated Drug Reaction With Eosinophilia and Systemic Symptoms (DReSS) in Systemic Inflammatory Illnesses.

BACKGROUND: After introducing IL-1/IL-6 inhibitors, some patients with Still and Still-like disease developed unusual, often fatal, pulmonary disease. This complication was associated with scoring as DReSS (drug reaction with eosinophilia and systemic symptoms) implicating these inhibitors, although DReSS can be difficult to recognize in the setting of systemic inflammatory disease. OBJECTIVE: To facilitate recognition of IL-1/IL-6 inhibitor-DReSS in systemic inflammatory illnesses (Still/Still-like) by looking at timing and reaction-associated features. We evaluated outcomes of stopping or not stopping IL-1/IL-6 inhibitors after DReSS reaction began. METHODS: In an international study collaborating primarily with pediatric specialists, we characterized features of 89 drug-reaction cases versus 773 drug-exposed controls and compared outcomes of 52 cases stopping IL-1/IL-6 inhibitors with 37 cases not stopping these drugs. RESULTS: Before the reaction began, drug-reaction cases and controls were clinically comparable, except for younger disease-onset age for reaction cases with preexisting cardiothoracic comorbidities. After the reaction began, increased rates of pulmonary complications and macrophage activation syndrome differentiated drug-reaction cases from drug-tolerant controls (P = 4.7 × 10-35 and P = 1.1 × 10-24, respectively). The initial DReSS feature was typically reported 2 to 8 weeks after initiating IL-1/IL-6 inhibition. In drug-reaction cases stopping versus not stopping IL-1/IL-6-inhibitor treatment, reaction-related features were indistinguishable, including pulmonary complication rates (75% [39 of 52] vs 76% [28 of 37]). Those stopping subsequently required fewer medications for treatment of systemic inflammation, had decreased rates of macrophage activation syndrome, and improved survival (P = .005, multivariate regression). Resolution of pulmonary complications occurred in 67% (26 of 39) of drug-reaction cases who stopped and in none who continued inhibitors. CONCLUSIONS: In systemic inflammatory illnesses, recognition of IL-1/IL-6-inhibitor-associated reactions followed by avoidance of IL-1/IL-6 inhibitors significantly improved outcomes.

Bacteremia associated with non-tunneled central venous catheters in children undergoing chronic hemodialysis. / Bacteriemia asociada a catéteres venosos centrales no tunelizados en niños en hemodiálisis crónica.

Introduction. Central venous catheter (CVC)-related infection is the main complication observed in patients undergoing hemodialysis with this type of venous access. Objective. To estimate the incidence of non-tunneled CVC-related bacteremia, analyze the frequency of causative agents, and explore associated risk factors in children undergoing hemodialysis. Population and methods. Retrospective study in children receiving hemodialysis via a non-tunneled CVC between June 1st, 2015 and June 30th, 2019. A logistic regression was carried out to assess risk factors that were predictors of CVC-related bacteremia. Independent risk factors were described as odds ratios with their corresponding 95% confidence interval (CI). A value of p < 0.05 was considered statistically significant. Results. A total of 121 non-tunneled CVCs were included in this study. The incidence of bacteremia was 3.15 per 1000 catheter-days. The most commonly isolated microorganism was Staphylococcus epidermidis (16 cases, 51.5%). Prior catheter infection was the only independent risk factor for the development of bacteremia associated with non-tunneled CVC (OR: 2.84, 95% CI: 1.01-7.96, p = 0.04). Conclusions. Prolonged use of non-tunneled CVCs for chronic hemodialysis was associated with a low incidence of bacteremia. Gram-positive microorganisms prevailed among causative agents. A prior CVC infection almost trebled the risk for CVC-related bacteremia in our pediatric population receiving hemodialysis.

Introducción. La infección asociada a catéter venoso central (CVC) es la principal complicación que presentan los pacientes en hemodiálisis en los que se usa este tipo de acceso. Objetivo. Estimar la incidencia de bacteriemia asociada a CVC no tunelizado, analizar la frecuencia de agentes causales y explorar factores de riesgo asociados en niños en hemodiálisis. Población y métodos. Estudio retrospectivo realizado en niños en hemodiálisis por CVC no tunelizado entre el 1 junio de 2015 y el 30 de junio de 2019. Para evaluar factores de riesgo predictores de bacteriemia asociada a CVC, se realizó regresión logística. Los factores de riesgo independiente se expresaron con odds ratio con sus respectivos intervalos de confianza del 95 %. Se consideró estadísticamente significativo un valor de p <0,05. Resultados. En este estudio se incluyeron 121 CVC no tunelizados. La incidencia de bacteriemia fue de 3,15 por 1000 días de catéter. El microorganismo aislado con mayor frecuencia fue Staphylococcus epidermidis (16 casos, 51,5 %). La infección previa del catéter fue el único factor de riesgo independiente encontrado para el desarrollo de bacteriemia asociada a CVC no tunelizado (OR: 2,84; IC95%: 1,017,96; p =0,04). Conclusiones. El uso prolongado de los CVC no tunelizados para hemodiálisis crónica se asoció con una incidencia baja de bacteriemia. Los gérmenes grampositivos predominaron como agentes causales. La presencia de infección previa del CVC aumentó en casi 3 veces el riesgo de bacteriemia asociada a CVC en nuestra población pediátrica en hemodiálisis.

Política pública en cuidados paliativos y sus implicaciones sobre servicios, opioides y educación en Colombia / Public policy on palliative care and its implications for services, opioids, and education in Colombia

Introducción: El desarrollo de cuidados paliativos exige la intervención de múltiples dimensiones de salud pública, incluyendo la disponibilidad de servicios de salud, medicamentos esenciales y programas educativos. En Colombia se han realizado diversos cambios en las políticas públicas para promover la atención de personas con necesidades paliativas. Objetivo: Evaluar empíricamente las políticas públicas, existentes en cuidados paliativos y sus implicaciones sobre disponibilidad de servicios, opioides y programas educativos en los años 2010 ­ 2019 en Colombia. Materiales y métodos: Se diseñó un estudio mixto exploratorio secuencial en tres fases: identificación de indicadores empíricos de políticas nacionales, diagnostico situacional de cuidados paliativos y evaluación cualitativa de los resultados de la implementación de políticas en siete nodos territoriales de Colombia. Resultados: Se revisaron siete normas obteniendo 12 indicadores empíricos para la evaluación, seis de ellos no contaban con fuentes de información. El diagnostico nacional evidencia un aumento gradual de servicios y consumo de opioides en los años hito del desarrollo de políticas. 44 profesionales de cuidados paliativos perciben un efecto positivo de las políticas públicas en el consumo de opioides y bajos resultados para el dominio de servicios y educación Conclusiones: Existe una relación positiva entre políticas públicas y consumo de opioides, una relación cuantitativa positiva para servicios de cuidados paliativos y una relación cuanticualitativa negativa para programas educativos, lo que denota un bajo estatus operativo de las políticas construidas para mejorar el dolor y sufrimiento asociado a la enfermedad crónica avanzada.

Introduction: Palliative care development requires the intervention of multiple dimensions of public health, including the availability of health services, essential medicines, and educational programs. In Colombia, several changes have been made in public policy to promote the care of people with palliative needs. Objective: To empirically evaluate existing public policies on palliative care and their implications for the availability of services, opioids, and educational programs during the years 2010 to 2019 in Colombia. Materials and methods: A mixed sequential exploratory study was designed in three phases: identification of empirical indicators of national policies, palliative care situational diagnosis, and qualitative assessment of the results of policy implementation in seven regional nodes in Colombia. Results: Seven standards were reviewed, yielding 12 empirical indicators for assessment, six of which had no sources of information. The national diagnosis shows a gradual increase in services and opioid use during the landmark years of policy development. Forty-four palliative care professionals perceive a positive effect of public policy on opioid use and low outcomes for service and education domains. Conclusions: There is a positive relationship between public policy and opioid use, a positive quantitative relationship with palliative care services, and a negative quantitative-qualitative relationship with educational programs. This indicates a low operational status of policies designed to alleviate the pain and suffering associated with advanced chronic diseases.

Introdução: O desenvolvimento dos cuidados paliativos requer a intervenção de múltiplas dimensões da saúde pública, incluindo a disponibilidade de serviços de saúde, medicamentos essenciais e programas educativos. Na Colômbia, várias mudanças foram feitas nas políticas públicas para promover o cuidado de pessoas com necessidades paliativas. Objetivo: Avaliar empiricamente as políticas públicas existentes em cuidados paliativos e suas implicações na disponibilidade de serviços, opioides e programas educacionais nos anos 2010 - 2019 na Colômbia. Materiais e métodos: Desenhou-se um estudo misto exploratório sequencial em três fases: identificação de indicadores empíricos de políticas nacionais, diagnóstico situacional de cuidados paliativos e avaliação qualitativa dos resultados da implementação de políticas em sete nodos territoriais da Colômbia. Resultados: Sete normas foram revisadas, obtendo-se 12 indicadores empíricos para avaliação, seis delas não possuíam fontes de informação. O diagnóstico nacional mostra um aumento gradual nos serviços e consumo de opioides nos anos marcantes do desenvolvimento de políticas. 44 profissionais de cuidados paliativos percebem efeito positivo das políticas públicas sobre o consumo de opioides e resultados baixos para o domínio serviços e educação Conclusões: Existe relação positiva entre políticas públicas e consumo de opioides, relação quantitativa positiva para serviços de cuidados paliativos e negativa relação quantitativo-qualitativa para programas educativos, o que denota um baixo status operacional das políticas destinadas a melhorar a dor e o sofrimento associados à doença crônica avançada.

Restoratively guided orthodontic treatment: The pre-orthodontic bonding concept.

OBJECTIVE: Communication between the orthodontist and the restorative dentist has always been difficult due to the inability of the orthodontist to achieve the desired orthodontic goals with just words in a referral note. CLINICAL CONSIDERATIONS: A better method of communication is for the restorative dentist to create the ideal tooth anatomy either before or during orthodontic treatment to direct the orthodontic tooth movement. CONCLUSION: It is the purpose of this article to present a technique, which makes the pre-restorative orthodontic treatment both more accurate and more efficient. CLINICAL SIGNIFICANCE: It is very difficult for the orthodontist to move teeth into their correct positions when the teeth are anatomically incorrect due to attrition/erosion or due to developmental malformation. When the restorative dentist makes the teeth anatomically correct with either pre-orthodontic or intermediate orthodontic bonding, the orthodontist has the benefit of ideal tooth anatomy to finalize the tooth positions. This then allows the restorative dentist to create final restorations, which are ideal, both functionally and esthetically.

Cross-cultural adaptation of four instruments to measure stigma towards people with mental illness and substance use problems among primary care professionals in Chile.

Stigma toward people with mental illness and substance use problems is a significant global concern, and prevents people with these conditions from accessing treatment, particularly in primary health care (PHC) settings. Stigma is a cultural phenomenon that is influenced by particular contexts and can differ by country and region. The majority of stigma research focuses on Europe or North America leading to a lack of culturally relevant stigma research instruments for the Latin American context. The present study describes and discusses the methodology for cross-culturally adapting four stigma measurement scales to the Chilean context. The cross-cultural adaptation process included nine phases: (1) preparation; (2) independent translations; (3) synthesis 1 with expert committee; (4) focus groups and interviews with researchers, PHC professionals, and PHC users; (5) synthesis 2 with expert committee; (6) independent back translations; (7) synthesis 3 with expert committee; (8) pilot with PHC professionals; and (9) final revisions. The adaptation process included an array of diverse voices from the PHC context, and met three adaptation objectives defined prior to beginning the process (Understandability, Relevance, and Acceptability and Answer Options). The resulting, culturally adapted questionnaire is being validated and implemented within PHC settings across Chile to provide in-depth insight into stigma among PHC professionals in the country. The authors hope it will be useful for future research on mental illness and substance use stigma in similar settings across Latin America.

Control of Ca2+ and metabolic homeostasis by the Na+/Ca2+ exchangers (NCXs) in health and disease.

Spatial and temporal control of calcium (Ca2+) levels is essential for the background rhythms and responses of living cells to environmental stimuli. Whatever other regulators a given cellular activity may have, localized and wider scale Ca2+ events (sparks, transients, and waves) are hierarchical determinants of fundamental processes such as cell contraction, excitability, growth, metabolism and survival. Different cell types express specific channels, pumps and exchangers to efficiently generate and adapt Ca2+ patterns to cell requirements. The Na+/Ca2+ exchangers (NCXs) in particular contribute to Ca2+ homeostasis by buffering intracellular Ca2+ loads according to the electrochemical gradients of substrate ions - i.e., Ca2+ and sodium (Na+) - and under a dynamic control of redundant regulatory processes. An interesting feature of NCX emerges from the strict relationship that connects transporter activity with cell metabolism: on the one hand NCX operates under constant control of ATP-dependent regulatory processes, on the other hand the ion fluxes generated through NCX provide mechanistic support for the Na+-driven uptake of glutamate and Ca2+ influx to fuel mitochondrial respiration. Proof of concept evidence highlights therapeutic potential of preserving a timed and balanced NCX activity in a growing rate of diseases (including excitability, neurodegenerative, and proliferative disorders) because of an improved ability of stressed cells to safely maintain ion gradients and mitochondrial bioenergetics. Here, we will summarize and review recent works that have focused on the pathophysiological roles of NCXs in balancing the two-way relationship between Ca2+ signals and metabolism.

El vínculo en la intervención social: un componente paradójico del acompañamiento domiciliario / O vínculo na intervenção social: um componente paradoxico do acompanhamento domiciliar / Relationship bonds in social intervention: a paradoxical component of home accompaniment

RESUMEN. Este estudio4 cualitativo describe las percepciones de profesionales de la salud acerca del componente relacional de un Modelo de Visita Domiciliaria Avanzada (ViDA). La implementación del modelo contempló una fase de capacitación de los profesionales y al mismo tiempo su participación en la puesta en práctica. Los datos cualitativos se obtuvieron de la aplicación de una entrevista telefónica a 12 profesionales, una entrevista en profundidad a 6 profesionales, 3 de ellos directores de centros de salud familiar, y del análisis de 85 reportes individuales de 34 profesionales capacitados en el modelo ViDA, pertenecientes a dos comunas de la Región Metropolitana de Chile. Los datos fueron organizados por temas y analizados usando el análisis de contenido. Los resultados señalan que el componente vincular del modelo es percibido como un aspecto clave en la realización de las visitas, siendo valorado positivamente por las y los profesionales. Desde su percepción este componente favorece la vinculación con las personas visitadas, motiva una actitud más favorable al cambio, genera transformaciones más profundas, facilita el logro de los objetivos de la intervención y promueve el empoderamiento de las mujeres. Asimismo, perciben desafíos que la capacitación no resuelve: la mejora en los registros, la planificación de la intervención y la formulación de objetivos de la visita.

RESUMO. Este estudo qualitativo descreve as percepções dos profissionais da saúde sobre o componente relacional de um Modelo de Visita Domiciliar Avançada (ViDA). A implementação do modelo considerou uma fase de capacitação dos profissionais e ao mesmo tempo a participação deles na práctica. O dados qualitativos foram obtidos através de uma entrevista telefônica à 12 profissionais, uma entrevista em profundidade à 6 profissionais, 3 deles eram diretores de centros de saúde familiar, e da análise de 85 informes individuais de 34 profissionais capacitados no modelo ViDA, que pertencem a duas comunas da Região Metropolitana do Chile. Os dados foram organizados por temas e trabalhados usando a análise de conteúdo. Os resultados mostram que o componente relacional do modelo é percebido como um aspecto central na realização das visitas, sendo valorizado positivamente pelo/as profissionais. A partir da percepção dele/as, este componente favorece a vinculação com as pessoas visitadas, motiva uma atitude mais favorável à mudanças, gera transformações mais profundas, facilita alcançar os objetivos da intervenção e promove o empoderamento das mulheres. Além disso, o/as profissionais também percebem desafios que a capacitação não resolve: a melhora nos registros, a planificaçao da intervenção e a formulação dos objetivos da visita.

ABSTRACT. This qualitative study describes the insights of health professionals on the relationship component of an Advanced Home Visit Model (ViDA). The implementation of this model involved a training stage for professionals together with their participation in the execution stage. Qualitative data were obtained through phone interviews to 12 professionals, in-depth interviews to 6 professionals, being 3 of them directors of family healthcare centers, and the analysis of 85 individual reports from 34 professionals trained in the ViDA model in two districts of the Metropolitan Region of Chile. Data were organized by subject and analyzed through content analysis. Results highlight the relationship component of the model is perceived as a key aspect in the home visit schedule and is also valued by the professionals as a positive aspect. From such point of view, this component favors the bonding of visited people, increases a favorable attitude towards change, generates deeper transformations, facilitated the achievement of goals, and promotes women empowerment. Also, professionals remarked some challenges the training stage is not solving such as improvement in records, planning of interventions and development of visit purposes.

Treatment Options for the Replacement of the Missing Maxillary Lateral Incisor.

The replacement of the missing maxillary lateral incisor continues to be a challenge for the interdisciplinary dental treatment team. Over the past two decades the dental implant has become a primary method of replacement for this tooth. However, while implants offer numerous benefits, some significant potential problems are associated with implant treatment, including the possible need for tissue grafting, the long-term stability of bone and soft tissue overlying the facial surface of the implant, as well as the continued growth of alveolar bone and eruption of teeth adjacent to the implant. This article discusses various treatment options for the replacement of the missing maxillary lateral incisor with an emphasis on the bonded zirconia bridge.

In vivo detection of vertical root fractures in endodontically treated teeth: Accuracy of cone-beam computed tomography and assessment of potential predictor variables.

BACKGROUND: This study aimed: (a) to determine the diagnostic performance of cone-beam computed tomography (CBCT) for detection of vertical root fractures (VRFs); (b) to evaluate the predictive value of diagnostic criteria regarding the definition of VRFs; and (c) to examine the robustness of the association of patient-, tooth-, and treatment-related variables with VRFs. MATERIAL AND METHODS: 130 root-filled teeth with signs/symptoms of VRFs underwent clinical and CBCT assessments. Definite diagnosis of VRF was confirmed by endodontic microsurgical (EMS) exploration. Determination of diagnostic performance of CBCT was based on standard algorithms derived from two-way contingency table analysis. Predictive value of diagnostic criteria and the association between predictor variables with VRFs were analyzed using logistic regression models. RESULTS: VRFs were detected during EMS in 50% of the teeth. Based on the finding of fracture lines on CBCT scans, sensitivity, specificity, and accuracy were 86.2%, 13.8%, and 50%, respectively. Teeth having more than three diagnostic criteria present had significant higher odds for VRF diagnosis. After logistic regression analysis, parafunctional habits, one-canal roots, excessive root canal enlargement, and absence of intra-radicular posts remained as robust predictor variables of VRFs. CONCLUSIONS: Although the sensitivity of CBCT for VRFs detection is high, the risk of false-positive results related to its low specificity makes that all suspected cases must be confirmed by surgical exploration. VRFs cannot be reliably diagnosed by isolated clinical signs/symptoms; instead those teeth possessing more than three diagnostic criteria might be considered practically pathognomonic. The parafunctional habits, one-canal roots, excessive root canal enlargement, and the absence of intra-radicular posts may act strongly/independently for the occurrence of VRFs in endodontically treated teeth. Key words:Cone-beam computed tomography, diagnostic accuracy, diagnostic surgery, predictor variables, root canal treatment, vertical root fracture.

Laser Photobiomodulation 808 nm: Effects on Gene Expression in Inflammatory and Osteogenic Biomarkers in Human Dental Pulp Stem Cells.

The tissue engineering of dental oral tissue is tackling significant advances and the use of stem cells promises to boost the therapeutical approaches of regenerative dentistry. Despite advances in this field, the literature is still scarce regarding the modulatory effect of laser photobiomodulation (PBM) on genes related to inflammation and osteogenesis in Postnatal Human Dental Pulp Stem cells (DPSCs). This study pointedly investigated the effect of PBM treatment in proliferation, growth and differentiation factors, mineralization, and extracellular matrix remodeling genes in DPSCs. Freshly extracted human third molars were used as a source for DPSCs isolation. The isolated DPSCs were stimulated to an inflammatory state, using a lipopolysaccharide (LPS) model, and then subjected or not to laser PBM. Each experiment was statistically evaluated according to the sample distribution. A total of 85 genes related to inflammation and osteogenesis were evaluated regarding their expression by RT-PCR. Laser PBM therapy has shown to modulate several genes expression in DPSCs. PBM suppressed the expression of inflammatory gene TNF and RANKL and downregulated the gene expression for VDR and proteolytic enzymes cathepsin K, MMP-8 and MMP-9. Modulation of gene expression for proteinase-activated receptors (PARs) following PBM varied among different PARs. As expected, PBM blocked the odontoblastic differentiation of DPSCs when subjected to LPS model. Conversely, PBM has preserved the odontogenic potential of DPSCs by increasing the expression of TWIST-1/RUNEX-2/ALP signaling axis. PBM therapy notably played a role in the DPSCs genes expression that mediate inflammation process and tissue mineralization. The present data opens a new perspective for PBM therapy in mineralized dental tissue physiology.

BRAF and NRAS mutated melanoma: Different Ca2+ responses, Na+/Ca2+ exchanger expression, and sensitivity to inhibitors.

Calcium is a ubiquitous intracellular second messenger, playing central roles in the regulation of several biological processes. Alterations in Ca2+ homeostasis and signaling are an important feature of tumor cells to acquire proliferative and survival advantages, which include structural and functional changes in storage capacity, channels, and pumps. Here, we investigated the differences in Ca2+ homeostasis in vemurafenib-responsive and non-responsive melanoma cells. Also, the expression of the Na+/Ca2+ exchanger (NCX) and the impact of its inhibition were studied. For this, it was used B-RAFV600E and NRASQ61R-mutated human melanoma cells. The intracellular Ca2+ chelator BAPTA-AM decreased the viability of SK-MEL-147 but not of SK-MEL-19 and EGTA sensitized NRASQ61R-mutated cells to vemurafenib. These cells also presented a smaller response to thapsargin and ionomycin regarding the cytosolic Ca2+ levels in relation to SK-MEL-19, which was associated to an increased expression of NCX1, NO basal levels, and sensitivity to NCX inhibitors. These data highlight the differences between B-RAFV600E and NRASQ61R-mutated melanoma cells in response to Ca2+ stimuli and point to the potential combination of clinically used chemotherapeutic drugs, including vemurafenib, with NCX inhibitors as a new therapeutic strategy to the treatment of melanoma.

The interaction of sodium trimetaphosphate with collagen I induces conformational change and mineralization that prevents collagenase proteolytic attack.

OBJECTIVES: This study evaluated the cell viability and expression of different major genes involved in mineralization in odontoblast-like cells exposed to sodium trimetaphosphate (STMP). It was also investigated the influence of STMP on the rate of calcium phosphate crystal growth, its anti-proteolytic action against the enzymatic degradation of type I collagen, the binding mechanism of STMP to collagen fibrils, and the potential mechanism to induce collagen stabilization. METHODS: Immortalized rat odontoblast MDPC-23 cells were cultured. Cell viability was assessed by trypan blue staining, and the changes in gene expression balance induced by STMP were assessed by quantitative reverse transcription (qRT) PCR assays. Crystalline particle formation was monitored by light-scattering detectors to estimate pH variation and the radial size of the crystalline particles as a function of reaction time (pH 7.4, 25°C) in the presence of STMP in supersaturated calcium phosphate solution (Ca/P=1.67). Images were obtained under atomic force microscopy (AFM) to measure the particle size in the presence of STMP. A three-point bending test was used to obtain the elastic modulus of fully demineralized dentin beams after immersion in STMP solution. The binding mechanism of STMP to collagen fibrils and potential stabilization mechanism was assessed with circular dichroism spectrometry (CD). The data were analyzed statistically (α=0.05). RESULTS: STMP had no significant influence on the cell viability and gene expression of the MDPC-23 cells. STMP greatly increased the rate of crystal growth, significantly increasing the average radial crystal size. AFM corroborated the significant increase of STPM-treated crystal size. Mineralized collagen I fibrils exhibited less collagenase degradation with lower STMP concentration. CD analysis demonstrated changes in the conformational stability after STMP binding to type I collagen. SIGNIFICANCE: The increased resistance of collagen against the proteolytic activity of collagenases appears to be related to the conformational change induced by STMP binding in collagen I and the STMP capacity for promoting biomimetic mineralization in type I collagen fibrils.

Cathepsin B-associated Activation of Amyloidogenic Pathway in Murine Mucopolysaccharidosis Type I Brain Cortex.

Mucopolysaccharidosis type I (MPS I) is caused by genetic deficiency of α-l-iduronidase and impairment of lysosomal catabolism of heparan sulfate and dermatan sulfate. In the brain, these substrates accumulate in the lysosomes of neurons and glial cells, leading to neuroinflammation and neurodegeneration. Their storage also affects lysosomal homeostasis-inducing activity of several lysosomal proteases including cathepsin B (CATB). In the central nervous system, increased CATB activity has been associated with the deposition of amyloid plaques due to an alternative pro-amyloidogenic processing of the amyloid precursor protein (APP), suggesting a potential role of this enzyme in the neuropathology of MPS I. In this study, we report elevated levels of protein expression and activity of CATB in cortex tissues of 6-month-old MPS I (Idua -/- mice. Besides, increased CATB leakage from lysosomes to the cytoplasm of Idua -/- cortical pyramidal neurons was indicative of damaged lysosomal membranes. The increased CATB activity coincided with an elevated level of the 16-kDa C-terminal APP fragment, which together with unchanged levels of ß-secretase 1 was suggestive for the role of this enzyme in the amyloidogenic APP processing. Neuronal accumulation of Thioflavin-S-positive misfolded protein aggregates and drastically increased levels of neuroinflammatory glial fibrillary acidic protein (GFAP)-positive astrocytes and CD11b-positive activated microglia were observed in Idua -/- cortex by confocal fluorescent microscopy. Together, our results point to the existence of a novel CATB-associated alternative amyloidogenic pathway in MPS I brain induced by lysosomal storage and potentially leading to neurodegeneration.

Calidad de la relación entre matrones y cuidadores en la visita domiciliaria del Chile crece contigo en localidades rurales del valle de Aconcagua / Quality of the relationship between midwives and caregivers in Chile crece contigo home visit in rural locations from the Aconcagua valley

INTRODUCCIÓN Y OBJETIVOS: La visita domiciliaria (VD) es una actividad clave del Programa de Apoyo al Desarrollo Biopsicosocial (PADB) del Chile Crece Contigo (ChCC). Para mejorar su implementación, esta investigación tiene como objetivo analizar la relación entre matrones y la familia que accede a la VD, considerando las competencias y habilidades relacionales de los visitadores. MÉTODOS: Se utilizó un diseño observacional con enfoque cualitativo, de alcance exploratorio. Tres matrones que realizan VD en centros de salud familiar rurales de la provincia de Aconcagua aceptaron participar y ocho visitas del programa ChCC fueron grabadas, de 30 minutos promedio. El análisis cualitativo se realizó en base al Home Visit Rating Scale A+. RESULTADOS: Las cuatro categorías que orientaron la evaluación de las visitas fueron responsividad de la familia, relación con la familia, facilitación de la interacción padres - hijo/a y no intrusividad y colaboración. Estas categorías, en su mayoría,puntuaron con un nivel adecuado. No obstante, se requiere entrenamiento en habilidades relacionales para cumplir con una visita catalogada como buena o excelente, sobre todo en las áreas en las que hay que facilitar el vínculo y la interacción entre padre e hijo/a, con el fin de evitar una atención de carácter paternalista. CONCLUSIONES: Esta investigación pionera en el área rural, entregó información relevante para mejorar la VD en este contexto. Aunque los matrones cuentan con formación técnica en el área biomédica, es importante reforzar y/o capacitar en las características esenciales de una VD, para fortalecer la alianza entre el profesional y la familia.

INTRODUCTION AND OBJECTIVES: The home visit (HV) is a key activity in the Support Program for Biopsychosocial Development of Chile Crece Contigo (ChCC). To improve its implementation, this research aims to analyze the relationship between a midwife and the family that accesses the HV based on the competence and relational skills of the visitor. METHODS: An observational design with a qualitative approach of exploratory scope was used. Three midwives performing HV in rural family health centers in the Aconcagua province accepted to participate, and eight visits of the ChCC program were recorded, with an average of 30 minutes. The Home Visit Rating Scale A + was applied to these visits, for further qualitative analysis. RESULTS: The four categories that guided the evaluation of the visits were family responsiveness, relationship with the family, facilitation of parent-child interaction and non-intrusion and collaboration. These scored mostly with an adequate level but requires training in relational skills is required to meet a visit rated as good or excellent, especially in areas where it is necessary to facilitate the link and interaction between father and son, evidencing a paternalistic character of the attention model. CONCLUSIONS: This pioneering research in the rural area, provided relevant information to improve the HV in this context. Although midwives have technical training in the biomedical area, it is important to reinforce and / or train in the essential characteristics of a HV, to strengthen the alliance between the professional and the family.

Harmful phytoplankton in the Beagle Channel (South America) as a potential threat to aquaculture activities.

The Beagle Channel is a remote subantarctic environment where mussel aquaculture initiatives have existed since the early 1990s. Here we analyze phytoplankton biomass and composition, and the occurrence of harmful microalgae species and their toxins at three sites during the period 2015-2016. The occurrence of potentially harmful algae was observed throughout the study period, including toxigenic dinoflagellates such as Alexandrium catenella (Group I of the A. tamarense complex), A. ostenfeldii, Dinophysis acuminata, Gonyaulax spinifera, Azadinium sp., and the diatoms Pseudo-nitzschia australis and P. fraudulenta. Toxic dinoflagellates were detected in low densities whereas a Pseudo-nitzschia bloom was observed in late February. Isolates of A. catenella and P. delicatissima sensu stricto were phylogenetically characterized. The toxin profile of A. catenella was dominated by GTX4, while P. delicatissima sensu stricto showed no production of the neurotoxin domoic acid in culture conditions. The results provide base-line information for the management of harmful algal blooms in this little explored subantarctic area.

Paraganglioma of the tongue with SDHB gene mutation in a patient with Graves' disease.

We report a case of an apparently sporadic paraganglioma of the tongue with a germ-line mutation in a female patient with asymptomatic Graves' disease. The tongue is an unusual primary location. Genetic testing is mandatory in all cases. Thyroid gland dysfunction and autoimmune phenomena could be associated with some paragangliomas.

Caracterización de la Aplicación del Test MINI para Evaluar Salud Mental. Cuenca - Ecuador, 2017 / Characterization of the MINI Test Application to Evaluate Mental Health. Cuenca-Ecuador, 2017

INTRODUCCIÓN: La evaluación de la salud mental en los servicios de salud no se realiza de forma regular, generando un subregistro diagnóstico que afecta la planificación y distribución de recursos. El Test Mini Entrevista Neuropsiquiátrica Internacional es una entrevista breve y estructurada que permite diagnosticar los principales trastornos psiquiátricos; su confiabilidad es alta al compararla pruebas similares. El presente estudio tuvo como objetivo caracterizar la aplicación de éste instrumento entre la población que acude a las unidades de primer nivel de atención. MÉTODOS: Estudio descriptivo-transversal con una muestra de 155 personas que acudieron a los centros de primer nivel de las parroquias urbanas y rurales del cantón Cuenca en el mes de abril de 2017. Se aplicó el test Mini Entrevista Neuropsiquiátrica Internacional y una encuesta para recolectar información relacionada con las variables estudiadas. Los resultados fueron analizados en SPSS versión 25.0 RESULTADOS: El tiempo promedio de aplicación del Test fue 21.6 minutos sin diferencia importante entre sexo, edad e instrucción; y 20.93 minutos en quienes presentaron trastornos psiquiátricos. La depresión mayor fue la patología más frecuente, presente mayormente en personas viudas, sin instrucción y con discapacidad. CONCLUSIÓN: No existe diferencia importante entre el tiempo de aplicación del Test considerando las distintas variables demográficas respecto al modelo estándar; se lo considera como una herramienta útil para ser utilizado en el primer nivel de atención.(au)

BACKGROUND: The evaluation of mental health in health services is not carried out on a regular basis. This led to an underreport diagnosis that affected the planning and distribution of resources. The Mini-International Neuropsychiatric Interview is a brief and structured interview that allows diagnosing the main psychiatric disorders with high reliability when compared similar evaluations. The aim of this study was to characterize the application of this instrument in the population that went to the first level care units. METHODS: Cross-sectional descriptive study with a sample of 155 people who attended the first level centers of the urban and rural communities in Cuenca. The Mini-International Neuropsychiatric Interview and a survey were applied to collect additional information related to the studied variables. The results were analyzed in SPSS 25.0. RESULTS: The average time of application of the test was 21.6 minutes without significant difference between sex, age and instruction; and 20.93 minutes in those with psychiatric disorders. Depressive disorder was the most frequent and it was present in widowed, uneducated and disabled people. CONCLUSION: No significant difference was found between the test application times considering the different demographic variables with respect to the standard model, so it is considered as a useful tool to be used in the first level of care.(au)

Oxidative stress induced by self-adhesive resin cements affects gene expression, cellular proliferation and mineralization potential of the MDPC-23 odontoblast-like cells.

OBJECTIVE: Clinical issues have been raised about problems related to cytotoxic effects caused when applying self-adhesive cement. It was hypothesized that byproducts eluted from self-adhesive cements modulate oxidative stress response, the gene expression of signaling pathways of inflammatory process/transcriptional activators, and the expression and activity of interstitial collagenases, and modify the phenotypic characteristics of cellular proliferation and mineral deposition in odontoblastic-like cells. METHODS: Cements (MaxCem Elite [MAX] and RelyX U200 [U200)]) were mixed, dispensed into moulds, and photoactivated according to the manufacturers' instructions. Immortalized rat odontoblast-like cells (MDPC-23) were cultured and exposed to polymerized specimens of cements for 4 h. Reactive oxidative specimen production and quantification of gene expression were evaluated. Cell proliferation assay and alizarin red staining were also performed to evaluate the disturbance induced by the cements on cellular proliferation and mineralization. RESULTS: Despite their cytotoxic effects, both self-adhesive cements influenced the metabolism in the odontoblast cells on different scales. MAX induced significantly higher oxidative stress in odontoblast cells than U200. Gene expression varied as a function of exposure to self-adhesive cements; MAX induced the expression of pro-inflammatory cytokines such as TNF-α, whereas U200 downregulated, virtually depleted TNF-α expression, also inducing overexpression of the transcriptional factor Runx2. Overexpression of heme oxygenase-1 (HO-1) and thioredoxin reductase 1 (TRXR1) occurred after exposure to both cements, antioxidant genes that are downstream of Keap1-Nrf2-ARE system. MAX significantly induced the overexpression of collagenase MMP-1, and U200 induced the expression of gelatinase MMP-2. MAX significantly inhibited cell proliferation whereas U200 significantly activated cell proliferation. Alizarin red staining revealed significantly decreased mineral deposition especially when exposed to MAX. SIGNIFICANCE: These results support the hypothesis that byproducts of different self-adhesive cements play important roles in the highly orchestrated process which ultimately affect the cellular proliferation and the mineral deposition in odontoblastic-like cells, possibly delaying the reparative dentin formation after cementation of indirect restorations, especially on recently exposed dentin preparations.