Epidemiological Study of Frontal Sinus Fractures: Evaluation of 16 Years of Care at the Faculty of Dentistry of Ribeirão Preto/Brazil.

Purpose: Aiming to evaluate and study the epidemiological profile of frontal sinus fractures treated in the region of Ribeirão Preto-Brazil. Methods: Sixteen years of activity in the Oral and Maxillofacial service of the Faculty of Dentistry of Ribeirão Preto/SP (FORP/USP), totaling 9,736 consultations, 4,524 with facial fractures, those diagnosed with frontal sinus fracture (113) were evaluated and selected for the study. Results: Frontal sinus fractures accounted for 2.5% of facial fractures, the majority occurring in men (89.4%), concentrated in the age group 21-30 years old, with 52.2% of cases being caused by road traffic accidents (RTA). Associations with other facial fractures are common and appeared in 75.2% of cases. Treatment was followed either surgically, by open reduction internal fixation (52.2%) or conservatively (35.4%). Analyzing only the 28 isolated frontal sinus fractures, the most common treatment was conservative (46.4%). surgical treatment dropped to 25%. The most common postoperative complications were temporal branch paralysis and supraorbital nerve paresthesia, both occurring in 30.5% of surgical cases. Conclusion: The frequency of frontal sinus fractures may be decreasing, but the pattern of occurrence in young men due to road traffic accidents does not seem to change, fortunately the appearance of serious complications is not common and it is usually associated with more severe trauma.

Changes in the Perioperative Management and Outcomes of Patients With Upper Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy at Memorial Sloan Kettering Cancer Center: Over 20 Years of Experience.

INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.

Assessing Endoscopic Suture Performance of Gynecology and Obstetrics Residents Following Methodic Training.

OBJECTIVE: To evaluate the performance of residents in gynecology and obstetrics before and after practicing laparoscopic sutures, to establish when the training shows the best results, in addition to comparing whether being in different years of residency influences this progression. METHODS: A prospective cohort study involving 32 medical residents evaluated with a pretest to establish their previous knowledge in laparoscopic suture. This test consisted of knotting two wires, one made of polypropylene and the other of polyglactin, with a blocking sequence of five semi-knots. We set a 30-minute limit to complete the task. Then, the residents held four training meetings, focusing on suture, Gladiator rule, knot, and symmetries, in addition to executing blocking sequences. A second test to establish progress was performed. RESULTS: Regarding the time spent to make the stiches using polyglactin wire, a statistically significant time improvement (p < 0.01) was observed, with a 10.67-minute pretraining median (mean 12.24 minutes) and a 2.53-minute posttraining median (mean 3.25 minutes). Regarding the stitches with polypropylene wire, a statistically significant time improvement (p < 0.05) was also observed, with a 9.38-minute pretraining median (mean 15.43 minutes) and a 3.65-minute posttraining median (mean 4.54 minutes). A total of 64.2% of the residents had been able to make the knot with polypropylene previously. One hundred percent were able to complete the task in the posttest. CONCLUSION: Model training using the Gladiator rule for laparoscopic suture improves the knotting time with statistically similar performance, regardless of the year of residency, after systematic training.

OBJETIVO: Avaliar a performance de residentes em ginecologia e obstetrícia antes e depois de praticarem suturas laparoscópicas, com o intuito de estabelecer quando o treinamento mostra os melhores resultados, comparando se estar em diferentes da residência influencia essa progressão. MéTODOS: Um estudo coorte prospectivo envolvendo 32 médicos residentes avaliados com um teste pré-treinamento para avaliar seus conhecimentos prévios em sutura laparoscópica. Esse teste consistia em atar nós em dois fios, um de polipropileno e o outro de poliglactina, com uma sequencia de bloqueio de cinco seminós. Definiu-se um limite de 30 minutos para se completar a tarefa. Depois, os residentes tiveram quatro reuniões de treinamento, focadas em sutura, técnica da Regra do Gladiador, nós e simetria, executando, ainda, uma sequência de pontos. Um segundo teste foi feito para avaliar o progresso. RESULTADOS: Com relação ao tempo para realizarem os pontos com fio de poliglactina, uma melhora de tempo estatisticamente significativa (p < 0.01) foi observada, com uma mediana de 10.67 minutos no pré-treinamento (média de 12.24 minutos) e uma mediana de 2.53 minutos no pós-treinamento (média de 3.25 minutos). Com relação ao fio de polipropileno, uma melhora de tempo estatisticamente significativa (p < 0.05) também foi observada, com uma mediana de pré-treinamento de 9.38 minutos (média de 15.43 minutos) e uma mediana de pós-treinamento de 3.65 minutos (média de 4.54 minutos). Um total de 64.2% dos residentes foram capazes de realizar os nós com polipropileno inicialmente. Cem por cento do residentes foram capazes de completar a tarefa no pós-teste. CONCLUSãO: O modelo de treino usando a técnica da Regra do Gladiador para sutura laparoscópica melhora o tempo de atar nós com uma performance estatisticamente similar, não havendo diferenças quanto ao ano da residência, após treinamento sistematizado.

HBA1C point-of-care testing for diabetes control in a low-income population: A before and after study and cost-parity analysis HbA1c point-of-care testing for diabetes control.

OBJECTIVE: To evaluate the results of a program that offered access to HbA1c POC tests for the glycemic control of patients with diabetes in small and poor municipalities of Minas Gerais, Brazil. METHODS: Using a before and after study, we compared four groups: patients submitted to (i) POC tests; (ii) conventional tests; (iii) both tests; and (iv) neither test. The analysis considered three periods: before the program; before the pandemic; and during the pandemic. A cost comparison was conducted under the societal perspective and a cost-parity model was designed. RESULTS: 1349 patients previously diagnosed with diabetes were included in the analysis. The rate of consultations and the rate of HbA1c testing were significantly different between all periods and groups. Group iii had a much higher consultation and testing rate. The costs were around 89.45 PPP-USD for POC tests and between 32.44 and 54.66 PPP-USD for conventional tests. Cost-parity analysis suggests that the technology would be acceptable if the annual number of tests was between 247 and 771. CONCLUSION: Using POC devices improved access to HbA1c testing but not glycemic control. Even in small towns, the number of tests necessary to achieve cost-parity is low enough to enable their incorporation into the public health system.

Association of human papillomavirus (HPV), p16, p53 and p63 expression with non-bilharzia-associated squamous cell carcinoma of the bladder and algorithm construction for histopathological grading prediction.

OBJECTIVE: To investigate the expression of human papillomavirus (HPV), p16, p53, and p63 in non-schistosomiasis-related squamous cell carcinoma of the bladder and to develop an accurate and automated tool to predict histological classification based on clinicopathological features. METHODS: Twenty-eight patients with primary bladder pure squamous cell carcinoma who underwent cystectomy or transurethral resection of bladder tumor (TURBT) for bladder cancer between January 2011 and July 2017 were evaluated. Clinical data and follow-up information were obtained from medical records. Formalin-fixed, paraffin-embedded surgical specimens were used for immunohistochemical staining for p16, p53, and p63. Human papillomavirus detection was evaluated by PCR. Statistical analysis was performed, and statistical significance was set at p<0.05. Finally, decision trees were built to classify patients' prognostic features. Leave-one-out cross-validation was used to test the generalizability of the model. RESULTS: Neither direct HPV detection nor its indirect marker (p16 protein) was identified in most cases. The absence of p16 was correlated with less aggressive histological grading (p=0.040). The positive p16 staining detection found only in pT1 and pT2 cases in our sample suggests a possible role for this tumor suppressor protein in the initial stages of bladder squamous cell carcinoma. The decision trees constructed described the relationship between clinical features, such as hematuria/dysuria, the level of tumor invasion, HPV status, lymphovascular invasion, gender, age, compromised lymph nodes, and tumor degree differentiation, with high classification accuracy. CONCLUSION: The algorithm classifier approach established decision pathways for semi-automatic tumor histological classification, laying the foundation for tailored semi-automated decision support systems for pathologists.

Scale up of implementation of a multidimensional intervention to enhance hypertension and diabetes care at the primary care setting: A protocol for a cluster-randomized study in Brazil.

BACKGROUND: Hypertension and diabetes mellitus (DM) are highly prevalent in low and middle-income countries (LMICs), and the proportion of patients with uncontrolled diseases is higher than in high-income countries. Innovative strategies are required to surpass barriers of low sources, distance and quality of health care. Our aim is to assess the uptake and effectiveness of the implementation of an integrated multidimensional strategy in the primary care setting, for the management of people with hypertension and diabetes mellitus in Brazil. METHODS: This scale up implementation study called Control of Hypertension and diAbetes in MINas Gerais (CHArMING) Project has mixed-methods, and comprehends 4 steps: (1) needs assessment, including a standardized structured questionnaire and focus groups with health care practitioners; (2) baseline period, 3 months before the implementation of the intervention; (3) cluster randomized controlled trial (RCT) with a 12-months follow-up period; and (4) a qualitative study after the end of follow-up. The cluster RCT will randomize 35 centers to intervention (n = 18) or usual care (n = 17). Patients ≥18 years old, with diagnosis of hypertension and/or DM, of 5 Brazilian cities in a resource-constrained area will be enrolled. The intervention consists of a multifaceted strategy, with a multidisciplinary approach, including telehealth tools (decision support systems, short message service, telediagnosis), continued education with an approach to issues related to the care of people with hypertension and diabetes in primary care, including pharmacological and non-pharmacological treatment and behavioral change. The project has actions focused on professionals and patients. CONCLUSIONS: This study consists of a multidimensional strategy with multidisciplinary approach using digital health to improve the control of hypertension and/or DM in the primary health care setting. We expect to provide the basis for implementing an innovative management program for hypertension and DM in Brazil, aiming to reduce the present and future burden of these diseases in Brazil and other LMICs. CLINICAL TRIAL IDENTIFIER: This study was registered in ClinicalTrials.gov. (NCT05660928).

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Collagen/κ-Carrageenan-Based Scaffolds as Biomimetic Constructs for In Vitro Bone Mineralization Studies.

Tissue engineering offers attractive strategies to develop three-dimensional scaffolds mimicking the complex hierarchical structure of the native bone. The bone is formed by cells incorporated in a molecularly organized extracellular matrix made of an inorganic phase, called biological apatite, and an organic phase mainly made of collagen and noncollagenous macromolecules. Although many strategies have been developed to replicate the complexity of bone at the nanoscale in vitro, a critical challenge has been to control the orchestrated process of mineralization promoted by bone cells in vivo and replicate the anatomical and biological properties of native bone. In this study, we used type I collagen to fabricate mineralized scaffolds mimicking the microenvironment of the native bone. The sulfated polysaccharide κ-carrageenan was added to the scaffolds to fulfill the role of noncollagenous macromolecules in the organization and mineralization of the bone matrix and cell adhesion. Scanning electron microscopy images of the surface of the collagen/κ-carrageenan scaffolds showed the presence of a dense and uniform network of intertwined fibrils, while images of the scaffolds' lateral sides showed the presence of collagen fibrils with a parallel alignment, which is characteristic of dense connective tissues. MC3T3-E1 osteoblasts were cultured in the collagen scaffolds and were viable after up to 7 days of culture, both in the absence and in the presence of κ-carrageenan. The presence of κ-carrageenan in the collagen scaffolds stimulated the maturation of the cells to a mineralizing phenotype, as suggested by the increased expression of key genes related to bone mineralization, including alkaline phosphatase (Alp), bone sialoprotein (Bsp), osteocalcin (Oc), and osteopontin (Opn), as well as the ability to mineralize the extracellular matrix after 14 and 21 days of culture. Taken together, the results described in this study shed light on the potential use of collagen/κ-carrageenan scaffolds to study the role of the structural organization of bone-mimetic synthetic matrices in cell function.

"Non-metastatic, Castration-resistant Prostate Cancer: Diagnostic and Treatment Recommendations by an Expert Panel from Brazil".

INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.

Association of human papillomavirus (HPV), p16, p53 and p63 expression with non-bilharzia-associated squamous cell carcinoma of the bladder and algorithm construction for histopathological grading prediction

ABSTRACT Objective To investigate the expression of human papillomavirus (HPV), p16, p53, and p63 in non-schistosomiasis-related squamous cell carcinoma of the bladder and to develop an accurate and automated tool to predict histological classification based on clinicopathological features. Methods Twenty-eight patients with primary bladder pure squamous cell carcinoma who underwent cystectomy or transurethral resection of bladder tumor (TURBT) for bladder cancer between January 2011 and July 2017 were evaluated. Clinical data and follow-up information were obtained from medical records. Formalin-fixed, paraffin-embedded surgical specimens were used for immunohistochemical staining for p16, p53, and p63. Human papillomavirus detection was evaluated by PCR. Statistical analysis was performed, and statistical significance was set at p<0.05. Finally, decision trees were built to classify patients' prognostic features. Leave-one-out cross-validation was used to test the generalizability of the model. Results Neither direct HPV detection nor its indirect marker (p16 protein) was identified in most cases. The absence of p16 was correlated with less aggressive histological grading (p=0.040). The positive p16 staining detection found only in pT1 and pT2 cases in our sample suggests a possible role for this tumor suppressor protein in the initial stages of bladder squamous cell carcinoma. The decision trees constructed described the relationship between clinical features, such as hematuria/dysuria, the level of tumor invasion, HPV status, lymphovascular invasion, gender, age, compromised lymph nodes, and tumor degree differentiation, with high classification accuracy. Conclusion The algorithm classifier approach established decision pathways for semi-automatic tumor histological classification, laying the foundation for tailored semi-automated decision support systems for pathologists.

Assessing Endoscopic Suture Performance of Gynecology and Obstetrics Residents Following Methodic Training / Avaliando a performance em sutura endoscópica de residentes de ginecologia e obstetrícia após treinamento metódico

Abstract Objective To evaluate the performance of residents in gynecology and obstetrics before and after practicing laparoscopic sutures, to establish when the training shows the best results, in addition to comparing whether being in different years of residency influences this progression. Methods A prospective cohort study involving 32 medical residents evaluated with a pretest to establish their previous knowledge in laparoscopic suture. This test consisted of knotting two wires, one made of polypropylene and the other of polyglactin, with a blocking sequence of five semi-knots. We set a 30-minute limit to complete the task. Then, the residents held four training meetings, focusing on suture, Gladiator rule, knot, and symmetries, in addition to executing blocking sequences. A second test to establish progress was performed. Results Regarding the time spent to make the stiches using polyglactin wire, a statistically significant time improvement (p< 0.01) was observed, with a 10.67-minute pretraining median (mean 12.24 minutes) and a 2.53-minute posttraining median (mean 3.25 minutes). Regarding the stitches with polypropylene wire, a statistically significant time improvement (p< 0.05) was also observed, with a 9.38-minute pretraining median (mean 15.43 minutes) and a 3.65-minute posttraining median (mean 4.54 minutes). A total of 64.2% of the residents had been able to make the knot with polypropylene previously. One hundred percent were able to complete the task in the posttest. Conclusion Model training using the Gladiator rule for laparoscopic suture improves the knotting time with statistically similar performance, regardless of the year of residency, after systematic training.

Resumo Objetivo Avaliar a performance de residentes em ginecologia e obstetrícia antes e depois de praticarem suturas laparoscópicas, com o intuito de estabelecer quando o treinamento mostra os melhores resultados, comparando se estar em diferentes da residência influencia essa progressão. Métodos Um estudo coorte prospectivo envolvendo 32 médicos residentes avaliados com um teste pré-treinamento para avaliar seus conhecimentos prévios em sutura laparoscópica. Esse teste consistia em atar nós em dois fios, um de polipropileno e o outro de poliglactina, com uma sequencia de bloqueio de cinco seminós. Definiu-se um limite de 30 minutos para se completar a tarefa. Depois, os residentes tiveram quatro reuniões de treinamento, focadas em sutura, técnica da Regra do Gladiador, nós e simetria, executando, ainda, uma sequência de pontos. Um segundo teste foi feito para avaliar o progresso. Resultados Com relação ao tempo para realizarem os pontos com fio de poliglactina, uma melhora de tempo estatisticamente significativa (p< 0.01) foi observada, com uma mediana de 10.67 minutos no pré-treinamento (média de 12.24 minutos) e uma mediana de 2.53 minutos no pós-treinamento (média de 3.25 minutos). Com relação ao fio de polipropileno, uma melhora de tempo estatisticamente significativa (p< 0.05) também foi observada, com uma mediana de pré-treinamento de 9.38 minutos (média de 15.43 minutos) e uma mediana de pós-treinamento de 3.65 minutos (média de 4.54 minutos). Um total de 64.2% dos residentes foram capazes de realizar os nós com polipropileno inicialmente. Cem por cento do residentes foram capazes de completar a tarefa no pós-teste. Conclusão O modelo de treino usando a técnica da Regra do Gladiador para sutura laparoscópica melhora o tempo de atar nós com uma performance estatisticamente similar, não havendo diferenças quanto ao ano da residência, após treinamento sistematizado.

Targeted Therapies in Advanced and Metastatic Urothelial Carcinoma.

This review describes the current landscape of targeted therapies in urothelial carcinoma. The standard of care for advanced urothelial carcinoma patients remains platinum-based combination chemotherapy followed by immunotherapy. However, median overall survival for these patients is still <1 year and there is an urgent need for alternative therapies. The advent of next-generation sequencing has allowed widespread comprehensive molecular characterization of urothelial tumors and, subsequently, the development of therapies targeting specific molecular pathways implicated in carcinogenesis such as FGFR inhibition, Nectin-4, Trop-2, and HER2 targeting. As these therapies are demonstrated to be effective in the second-line setting, they will be advanced in the treatment paradigm to localized and even non-muscle invasive disease.

Contrast phase recognition in liver computer tomography using deep learning.

Hepatocellular carcinoma (HCC) has become the 4th leading cause of cancer-related deaths, with high social, economical and health implications. Imaging techniques such as multiphase computed tomography (CT) have been successfully used for diagnosis of liver tumors such as HCC in a feasible and accurate way and its interpretation relies mainly on comparing the appearance of the lesions in the different contrast phases of the exam. Recently, some researchers have been dedicated to the development of tools based on machine learning (ML) algorithms, especially by deep learning techniques, to improve the diagnosis of liver lesions in imaging exams. However, the lack of standardization in the naming of the CT contrast phases in the DICOM metadata is a problem for real-life deployment of machine learning tools. Therefore, it is important to correctly identify the exam phase based only on the image and not on the exam metadata, which is unreliable. Motivated by this problem, we successfully created an annotation platform and implemented a convolutional neural network (CNN) to automatically identify the CT scan phases in the HCFMUSP database in the city of São Paulo, Brazil. We improved this algorithm with hyperparameter tuning and evaluated it with cross validation methods. Comparing its predictions with the radiologists annotation, it achieved an accuracy of 94.6%, 98% and 100% in the testing dataset for the slice, volume and exam evaluation, respectively.

Strontium Carbonate and Strontium-Substituted Calcium Carbonate Nanoparticles Form Protective Deposits on Dentin Surface and Enhance Human Dental Pulp Stem Cells Mineralization.

Strontium acetate is applied for dental hypersensitivity treatment; however, the use of strontium carbonates for this purpose has not been described. The use of Sr-carbonate nanoparticles takes advantage of both the benefits of strontium on dentin mineralization and the abrasive properties of carbonates. Here in, we aimed to synthesize strontium carbonate and strontium-substituted calcium carbonate nanoparticles and test them as potential compounds in active dentifrices for treating dental hypersensitivity. For this, SrCO3, Sr0.5Ca0.5CO3, and CaCO3 nanoparticles were precipitated using Na2CO3, SrCl2, and/or CaCl2 as precursors. Their morphology and crystallinity were evaluated by electron microscopy (SEM) and X-ray diffraction, respectively. The nanoparticles were added to a poly (vinyl alcohol) gel and used to brush dentin surfaces isolated from human third molars. Dentin chemical composition before and after brushing was investigated by infrared spectroscopy (FTIR) and X-ray dispersive energy spectroscopy. Dentin tubule morphology, obliteration, and resistance of the coatings to acid attack were investigated by SEM and EDS. The cytotoxicity and ability of the particles to trigger the mineralization of hDPSCs in vitro were studied. Dentin brushed with the nanoparticles was coated by a mineral layer that was also able to penetrate the tubules, while CaCO3 remained as individual particles on the surface. FTIR bands related to carbonate groups were intensified after brushing with either SrCO3 or Sr0.5Ca0.5CO3. The shift of the phosphate-related FTIR band to a lower wavenumber indicated that strontium replaced calcium on the dentin structure after treatment. The coating promoted by SrCO3 or Sr0.5Ca0.5CO3 resisted the acid attack, while calcium and phosphorus were removed from the top of the dentin surface. The nanoparticles were not toxic to hDPSCs and elicited mineralization of the cells, as revealed by increased mineral nodule formation and enhanced expression of COL1, ALP, and RUNX2. Adding Sr0.5Ca0.5CO3 as an active ingredient in dentifrices formulations may be commercially advantageous since this compound combines the well-known abrasive properties of calcium carbonate with the mineralization ability of strontium, while the final cost remains between the cost of CaCO3 and SrCO3. The novel Sr0.5Ca0.5CO3 nanoparticles might emerge as an alternative for the treatment of dental hypersensitivity.

The Effect of Octenidine on Proliferation, Migration, and Osteogenic Differentiation of Human Dental Pulp and Apical Papilla Stem Cells.

INTRODUCTION: The research for alternative irrigating solutions is ongoing, since no "ideal" solution has yet been found. Octenidine dihydrochloride (OCT) has been indicated as an endodontic irrigant because it has adequate antimicrobial and biological properties. The present study aimed to assess the effects of OCT on proliferation, migration, and induction of the osteogenic phenotype of stem cells from human dental pulp and apical papilla. METHODS: Cells were collected from human third molars and exposed to different doses of OCT, chlorhexidine (CHX), sodium hypochlorite (NaOCl), and ethylenediaminetetraacetic acid (EDTA) to determine cell viability by alamarBlue assay; proliferation by bromodeoxyuridine incorporation; migration by the Transwell assay; alkaline phosphatase activity by thymolphthalein release; and production of mineralized nodules by alizarin red staining. The results were analyzed by 1- or 2-way analysis of variance and Tukey (α = .05). RESULTS: CHX promoted lower cell viability, followed by OCT, NaOCl, and EDTA, especially at intermediate doses (P < .05). Cells exposed to CHX had less proliferation than the other groups (P < .05). The Transwell assay revealed no differences among OCT, EDTA, and culture medium (control group) (P > .05). OCT and EDTA induced greater migration than CHX and NaOCl (P < .05). OCT and EDTA induced higher alkaline phosphatase activity than NaOCl and CHX (P < .05). No difference was detected among the groups using alizarin red staining (P > .05). CONCLUSIONS: OCT induced high migration, proliferation, and alkaline phosphatase activity of stem cells from human dental pulp and apical papilla, which could be advantageous for regenerative endodontic procedures.

Synthesis of Antibacterial Hybrid Hydroxyapatite/Collagen/Polysaccharide Bioactive Membranes and Their Effect on Osteoblast Culture.

Inspired by the composition and confined environment provided by collagen fibrils during bone formation, this study aimed to compare two different strategies to synthesize bioactive hybrid membranes and to assess the role the organic matrix plays as physical confinement during mineral phase deposition. The hybrid membranes were prepared by (1) incorporating calcium phosphate in a biopolymeric membrane for in situ hydroxyapatite (HAp) precipitation in the interstices of the biopolymeric membrane as a confined environment (Methodology 1) or (2) adding synthetic HAp nanoparticles (SHAp) to the freshly prepared biopolymeric membrane (Methodology 2). The biopolymeric membranes were based on hydrolyzed collagen (HC) and chitosan (Cht) or κ-carrageenan (κ-carr). The hybrid membranes presented homogeneous and continuous dispersion of the mineral particles embedded in the biopolymeric membrane interstices and enhanced mechanical properties. The importance of the confined spaces in biomineralization was confirmed by controlled biomimetic HAp precipitation via Methodology 1. HAp precipitation after immersion in simulated body fluid attested that the hybrid membranes were bioactive. Hybrid membranes containing Cht were not toxic to the osteoblasts. Hybrid membranes added with silver nanoparticles (AgNPs) displayed antibacterial action against different clinically important pathogenic microorganisms. Overall, these results open simple and promising pathways to develop a new generation of bioactive hybrid membranes with controllable degradation rates and antimicrobial properties.

Survival Impact of Variant Histology Diagnosis in Upper Tract Urothelial Carcinoma.

PURPOSE: Little is known regarding the prognostic implications of variant histology in upper tract urothelial carcinoma (UTUC). We sought to evaluate the impact of variant histology UTUC on patient survival outcomes at our institution. MATERIALS AND METHODS: We identified 705 patients who underwent nephroureterectomy for UTUC at our institution between January 1995 and December 2018. We tested the association between variant histology and cancer-specific survival (CSS) and overall survival (OS) using separate multivariable Cox models after adjusting for pathological stage. RESULTS: Forty-seven patients (6.7%) had variant histology, with prevalence increasing over time (p=0.003). Other demographic and surgical characteristics were similar between variant histology and pure urothelial carcinoma groups. While patients with variant histology were more likely to receive neoadjuvant chemotherapy (38% vs 15%, p <0.001), they were also more likely to have a higher pathological T stage (p <0.001). Variant histology was associated with significantly worse CSS (HR: 2.14; 95% CI 1.33, 3.44; p=0.002) and OS (HR: 1.74; 95% CI 1.15, 2.63; p=0.008). After adjusting for pathological T stage, variant histology was not significantly associated with CSS (HR: 1.17; 95% CI 0.72, 1.89; p=0.5) or OS (HR: 1.20; 95% CI 0.79, 1.84; p=0.4). CONCLUSIONS: Variant histology UTUC is associated with advanced stage and poor survival, and could serve as a useful biomarker for high-risk disease when pathological stage is unknown. However, the inferior CSS and OS with variant histology can be explained by the higher tumor stage on nephroureterectomy. Thus, finding variant histology on surgical pathology does not provide additional prognostic information beyond stage.

Curcumin-loaded carrageenan nanoparticles: Fabrication, characterization, and assessment of the effects on osteoblasts mineralization.

The use of Curcumin (CR) as a bioactive molecule to prevent and treat inflammation- related diseases is widespread. However, the high hydrophobicity hinders the in vivo bioavailability of CR, reducing its therapeutic index. In the present study, we described the use of nanoparticles (NPs) made of kappa-carrageenan (κ-Carr), a sulphated polysaccharide, as cost-effective, biodegradable and biocompatible CR carriers. CR-loaded κ-Carr nanoparticles (CR@Carr NPs) were prepared by mixing a κ-Carr aqueous solution with a CR ethanolic solution. The final suspension was centrifuged and re-suspended in phosphate buffer solution. The NPs' size was tuned by changing the concentration of the polysaccharide. CR@CarrNPs displayed high CR incorporation efficiency (~80 wt%) and a double-exponential curve of CR release at physiological conditions (37 °C and pH 7.4) with a cumulative drug release of 32 wt% after 24 h for the smaller NP. Our results also showed that CR@CarrNPs were not cytotoxic to osteoblasts at concentrations up to 1 µM. Confocal microscopy images revealed the internalization of CR by the cells guided by the NPs. Cells treated with CR@CarrNPs exhibited higher activity of alkaline phosphatase and higher expression of the main osteogenic genes (Sp7, Col1 and Runx2), and mineralized the extracellular matrix in a higher extent compared to the cells cultivated in absence of the NPs. We posited that these effects were related to the NP-driven internalization of CR by osteoblasts. Our study sheds light on the possible use of CR@CarrNPs as efficient and safe therapeutic tools for the treatment of bone-related diseases.