Therapeutic potential of LINS01 histamine H3 receptor antagonists as antineoplastic agents for triple negative breast cancer.

The aims of this work were to evaluate the expression of histamine H3 receptor (H3R) in triple negative breast cancer (TNBC) samples and to investigate the antitumoral efficacy and safety of the LINS01 series of H3R antagonists, through in silico, in vitro, and in vivo approaches. Antitumor activity of LINS01009, LINS01010, LINS01022, LINS01023 was assayed in vitro in 4T1 and MDA-MB-231 TNBC cells (0.01-100 µM), and in vivo in 4T1 tumors orthotopically established in BALB/c mice (1 or 20 mg/kg). Additionally, H3R expression was assessed in 50 human TNBC samples. We have described a higher H3R mRNA expression in basal-like/TNBC tumors vs. matched normal tissue using TCGA Pan-Cancer Atlas data, and a higher H3R expression in human tumor samples vs. peritumoral tissue evidenced by immunohistochemistry associated with poorer survival. Furthermore, while all the essayed compounds showed antitumoral properties, LINS01022 and LINS01023 exhibited the most potent antiproliferative effects by: i) inducing cell apoptosis and suppressing cell migration in 4T1 and MDA-MB-231 TNBC cells, and ii) inhibiting cell growth in paclitaxel-resistant 4T1 cells (potentiating the paclitaxel antiproliferative effect). Moreover, 20 mg/kg LINS01022 reduced tumor size in 4T1 tumor-bearing mice, exhibiting a safe toxicological profile and potential for druggability estimated by ADME calculations. We conclude that the H3R is involved in the regulation of TNBC progression, offering promising therapeutic potential for the novel LINS01 series of H3R antagonists.

The histamine H4 receptor antagonist 1-[(5-chloro-2,3-dihydro-1-benzofuran-2-yl)methyl]-4-methyl-piperazine(LINS01007) prevents the development of DSS-induced colitis in mice.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with growing incidence worldwide. Our group reported the compound 5-choro-1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazine (LINS01007) as H4R antagonist (pKi 6.2) and therefore the effects and pharmacological efficacy on a DSS-induced mice model of UC were assessed in this work. Experimental acute colitis was induced in male BALB/c mice (n = 5-10) by administering 3 % DSS in the drinking water for six days. The test compound LINS01007 was administered daily i.p. (5 mg/kg) and compared to control group without treatment. Body weight, water and food consumption, and the presence of fecal blood were monitored during 7-day treatment period. The levels of inflammatory markers (PGE2, COX-2, IL-6, NF-κB and STAT3) were also analyzed. Animals subjected to the acute colitis protocol showed a reduction in water and food intake from the fourth day (p < 0.05) and these events were prevented by LINS01007. Histological signs of edema, hyperplasia and disorganized intestinal crypts, as well as neutrophilic infiltrations, were found in control mice while these findings were significantly reduced in animals treated with LINS01007. Significant reductions in the levels of PGE2, COX-2, IL-6, NF-κB and STAT3 were observed in the serum and tissue of treated animals. The results demonstrated the significant effects of LINS01007 against DSS-induced colitis, highlighting the potential of H4R antagonism as promising treatment for this condition.

The Impact of Technology Teaching in the Dental Predoctoral Curriculum on Students' Perception of Digital Dentistry.

The goal was to assess dental students' perception of digital technologies after participating in a CAD/CAM exercise for scanning, designing, and manufacturing computer-aided provisional fixed dental restorations. A survey was conducted among second- (pre-D2 and post-D2), first- (D1, negative control), third-, and fourth-year dental students (D3 and D4, positive controls). Only OSU College of Dentistry students who completed the activity and completed the surveys were included. Seven questions were rated, which evaluated changes in knowledge, skill, interest, the importance of technology availability in an office, patients' perception of technology, the importance of having the technology, and the expected frequency of clinics utilizing the technology. Statistical analysis was performed with a significance level of 0.05. A total of 74 pre-D2 and 77 post-D2 questionnaires were completed. Additionally, 63 D1, 43 D3, and 39 D4 participants responded to the survey. Significant differences were found for "knowledge" and "skill" between the pre-D2 and post-D2 and pre-D2 and control groups (p < 0.001). There was a significant difference between the post-D2 participants and all the controls in terms of "interest" (p = 0.0127) and preference for in-practice technology availability (p < 0.05). There were significant results between the post-D2 participants and all the controls regarding the importance of technology availability in an office (p < 0.001) and the expected frequency of clinics utilizing the technology (p = 0.01). No significance was found for "value of technology to patients" and "the importance of having the technology". The presence of technology in practice and in educational academic environments significantly improved students' interest and perception of their knowledge and skill.

Implant Stability and Histomorphometric Analysis Comparing Two Different Implant Macrogeometries Placed in Fresh Sockets: An Experimental Study in Sheep.

PURPOSE: The aim of the present animal study was to examine the impact of two implant designs that promote different insertion torque values on implant stability and evaluate, histomorphometrically, the bone healing for immediate implant placement in fresh sockets. MATERIALS AND METHODS: Twelve female sheep (35.0±5.0kg) and 48 conical Morse-taper dental implants divided into two groups (n = 24 per group): G1 group, where the implants present a design that can provide high insertion torque values; and G2 group, where the implants present a design that can provide low insertion torque values. Both had the same surface treatment, and dimensions (4.0 mm in diameter and 10 mm in length). The first two posterior teeth (both sides) were extracted carefully. Sequentially, there were osteotomies in the mesial socket of each molar tooth. The final implant position was 2 mm below the buccal bone crest level. On the right side, implants of the G1 were placed anteriorly, followed by implants of the G2; and, on the left side, it was the reverse. A digital torquemeter was used to measure the maximum final insertion torque value (f-IT). The initial implant stability quotient (ISQ) was measured immediately after the implant insertion (T0) and immediately after the euthanasia and removing the mandibles with the implants. The animals were euthanized (n=6 animals/ time) at 21 days (T1) and 35 days (T2). The t-test was used to compare statistical differences for each intragroup parameter analyzed. Pearson's correlation was used to analyze possible correlations: f-IT and BIC%, f-IT and ISQ, and ISQ and %BIC. RESULTS: Regarding the insertion torque, the G1 presented higher values than the G2, with a statistically significant difference (p<0.0001). The ISQ mean values were higher in the B-L direction than those obtained for M-D for both groups. %BIC measurements showed higher values in samples from G2 than G1 at both times and in both directions. New bone, medullary spaces, and collagen matrix had statistical differences between the groups at each evaluation time. CONCLUSION: Using implants with a modified macrogeometry plays a significant role in implant stability and the healing process of bone tissue around the implant. It is important for clinicians to carefully consider implant macrogeometry when planning dental implant surgery to achieve optimal implant stability and successful osseointegration, mainly in cases of immediate implant placement.

Desafios e possibilidades da jurimetria na judicialização em saúde: uma investigação em Minas Gerais do período 2014 a 2020 / Challenges and possibilities of jurimetry in health judicialization: an investigation in Minas Gerais state from 2014 2020 / Desafíos y posibilidades de la jurimetría en la judicialización de la salud: una investigación en Minas Gerais de 2014 a 2020

Objetivo: analisar os processos de saúde, de medicamentos e de medicamentos antineoplásicos em Minas Gerais, em 2014 a 2020, a partir da comparação de diferentes bases de dados. Metodologia: foram utilizadas técnicas de pareamento de bases de dados entre os processos existentes no Tribunal de Justiça do Estado de Minas Gerais e os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais, descreveram-se as dificuldades encontradas na identificação e quantificação desses processos, e os resultados encontrados foram comparados com informações provenientes de outras fontes. Resultados: nas bases do Tribunal de Justiça de Minas Gerais foram identificados 564.763 processos de saúde. Houve um aumento significativo do número de processos até 2017 e uma estabilização, em patamares altos, a partir de 2017. Ao comparar com os resultados obtidos pelo Instituto Superior de Ensino e Pesquisa e pelo Laboratório de Inovação, Inteligência e Objetivos de Desenvolvimento Sustentável, houve uma importante divergência nos números de processos. Tomando como exemplo a judicialização de saúde contra o estado de Minas Gerais, não foi possível encontrar de forma direta todos os processos recebidos pela Secretaria Estadual de Saúde de Minas Gerais nas diversas bases fornecidas pelo Tribunal de Justiça de Minas Gerais, tendo sido necessária uma integração entre as diferentes bases de dados e uma busca adicional para identificar todos os processos. Conclusão: recomendam-se a padronização e organização dos dados dos processos judiciais em saúde, já na entrada de dados, para facilitar a realização de estudos quantitativos sobre a judicialização da saúde.

Objective: to analyze the health, drug, and antineoplastic drug lawsuits in Minas Gerais, in 2014 to 2020, from the comparison of different databases. Methodology: database pairing techniques were used to link lawsuits from the Minas Gerais State Court of Justice with the processes received by the Minas Gerais Health State Department, the difficulties encountered in identifying and quantifying these processes were described, and the results found were compared with information from other sources. Results: in the Minas Gerais State Court of Justice databases, 564,763 health lawsuits were identified in the studied period. There was a significant increase in the number of processes until 2017 and a stabilization, at high levels, from 2017 onwards. In comparison with the results obtained by the Institute of Higher Education and Research and the Laboratory of Innovation, Intelligence and Sustainable Development Goals there was a great divergence in the number of processes found. Conclusion: taking the health judicialization against Minas Gerais state as an example, it was not possible to directly find all the processes received by Minas Gerais Health State Department in the various databases provided by the Minas Gerais State Court of Justice, requiring integration between the different databases and an additional search to identify all processes.

Objetivo: analizar los juicios de salud, drogas y medicamentos antineoplásicos en Minas Gerais, en 2014 a 2020, a partir de la comparación de diferentes bases de datos. Metodología: técnicas de emparejamiento de bases de datos fueron utilizadas para vincular los juicios existentes en el Tribunal de Justicia del Estado de Minas Gerais con los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais, las dificultades encontradas en la identificación y cuantificación de esos procesos fueron descritas, y los resultados encontrados fueron comparados con informaciones de otras fuentes. Resultados: en las bases del Tribunal de Justicia del Estado de Minas Gerais se identificaron 564.763 procesos de salud. Hubo un aumento significativo en el número de procesos hasta 2017 y una estabilización, en niveles altos, a partir de 2017. Sin embargo, al comparar con los resultados obtenidos por el Instituto Superior de Educación e Investigación y por el Laboratorio de Innovación, Inteligencia y Objetivos de Desarrollo Sostenible hubo una divergencia importante en el número de procesos. Conclusión: tomando como ejemplo la judicialización de la salud contra el estado de Minas Gerais, no era posible encontrar directamente todos los procesos recibidos por la Secretaría de Estado de Salud de Minas Gerais en las diversas bases de datos proporcionadas por el Tribunal de Justicia del Estado de Minas Gerais, lo que requería una integración entre las diferentes bases de datos y una búsqueda adicional a identificar todos los procesos.

Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined using real-time quantitative polymerase chain reaction, while EV species were identified by 5'UTR region sequencing. Median viral load was 5.72 log10 copies/mL and did not differ by subjects' age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.

Fibroblasts and osteoblasts behavior after contact with different titanium surfaces used as implant abutment: An in vitro experimental study.

Background: The goal of this in vitro study was to compare three different surfaces: two types of implant surfaces commercially available ([a] smooth/machined and [b] acid-treated surface) versus (c) anodized surface. Discs were manufactured with commercially pure titanium (CP) grade IV, which were subsequently analyzed by scanning microscopy and fibroblastic and osteoblastic cell cultures. Methods: Ninety-nine discs (5 × 2 mm) were manufactured in titanium grade IV and received different surface treatments: (i) Mach group: machined; (ii) AA group: double acid etch; and (iii) AN group: anodizing treatment. Three discs from each group were analyzed by Scanning Electron Microscopy (SEM) to obtain surface topography images and qualitatively analyzed by EDS. Balb/c 3T3 fibroblasts and pre-osteoblastic cells (MC3T3-E1 lineage) were used to investigate each group's biological response (n = 10/cellular type). The data were compared statistically using the ANOVA one-way test, considered as a statistically significant difference p < 0.05. Results: The AA group had numerous micropores with diameters between 5 and 10 µm, while nanopores between 1 and 5 nm were measured in the AN group. The EDX spectrum showed a high titanium concentration in all the analyzed samples. The contact angle and wetting tension were higher in the AA, whereas similar results were observed for the other groups. A lower result was observed for base width in the AA, which was higher in the other two groups. The AN showed the best values in the fibroblast cells, followed by Mach and AA; whereas, in the culture of the MC3T3 cells, the result was precisely the opposite (AA > Mach > AN). There was similar behavior for cell adhesion for the test groups (Mach and AN), with greater adhesion of Balb/c 3T3 fibroblasts compared to MC3T3 cells; in the AA group, there was greater adherence for MC3T3 cells compared to Balb/c 3T3 fibroblasts. Conclusions: The findings suggest that different surface characteristics can produce different biological responses, possibly cell-line dependent. These findings have important implications for the design of implantable medical devices, where the surface characteristics can significantly impact its biocompatibility.

Flap of the sternocephalicus muscle in the repair of a partial defect in the trachea of a rabbit (Oryctolagus cuniculus).

PURPOSE: The current study aimed at evaluating the repair of a partial defect of the trachea with a muscle flap, an advanced technique that employs combined suture patterns. METHODS: Sixteen healthy male New Zealand white rabbits were used as an experimental model. A partial defect in the trachea within the ventral region of the fourth to eighth tracheal ring was created. Subsequently, repair was initiated with a flap of the sternocephalicus muscle. The animals were divided into four groups for postoperative evaluation using clinical, tracheoscopic, and histopathological analyses. Each group was separated according to the time of euthanasia, programmed at interval of seven (G7), 15 (G15), 30 (G30), and 60 days (G60). RESULTS: One animal from the G60 group died, whereas the other animals had good surgical recovery without serious changes in the breathing pattern. The major clinical signs observed were stridor and coughing. Tracheoscopy revealed secretions in the tracheal lumen, exuberant granulation, and stenosis. Histopathological analysis showed growth of the ciliary respiratory epithelium at the flap site 30 days after implantation. CONCLUSIONS: Partial repair showed satisfactory results owing to the anatomical location of the muscle, adequate vascular support, and structural and physiological maintenance without serious changes in the respiratory system.

The Use of Tissue Grafts Associated with Immediate Implant Placement to Achieve Better Peri-Implant Stability and Efficacy: A Systematic Review and Meta-Analysis.

Background: The goal of this systematic study and meta-analysis was to evaluate the efficacy of hard and/or soft tissue grafts associated with type-1 implants on healing and treatment outcomes. The primary outcomes studied were implant survival rate, pocket depth, marginal peri-implant recession, bone loss, bone thickness (volumetric change), interproximal bone level, mesial and distal papilla migration, and radiographic evaluation; and the secondary parameters were Pink Esthetic Score (PES), vertical distance from implant shoulder and bone, Visual Analogue Score (VAS), Implant Stability Quotient (ISQ), and biological complications (fistulas, pain, mucositis, and peri-implantitis). Methods: The PICO strategy was used to formulate the hypothesis under study: "For patients who underwent extraction and immediate implant placement, what is the efficacy of using any type of graft (bone or soft tissue) compared to non-grafting regarding the peri-implant parameters?" The electronic search process was performed on the MedLine/PubMed and Cochrane databases. It included randomized controlled trials (RCTs) from the last 11 years (from 2012 to November 2023), which were identified and analyzed. Results: Nine RCTs (κ = 0.98) were selected (403 patients and 425 implants); they were divided into three groups: bone graft (75 patients and 75 implants inserted), bone graft and membrane (213 patients and 235 implants inserted), and without bone graft (115 patients and 115 implants inserted). Three studies calculated the mid-facial mucosa level and two reported better results when a connective tissue graft was combined with the xenograft, whereas another study found better results in the combination of a dual-zone technique with a xenograft. Three studies evaluated the total Pink Esthetic Score (PES) at 12 months, where the authors found no significant difference in using a xenogeneic graft with or without a membrane. In the same period, the facial bone thickness was assessed in two articles; the authors reported better results in graft-treated and flapless groups. The risk-of-bias assessment found four studies with low risk, four with moderate risk, and one with a high risk of bias. The meta-analysis showed a medium level of heterogeneity for the mid-facial mucosa level analysis (I2 = 46%) and an overall effect size of 0.79 (95% CI [0.18; 1.40]), a statistically significant results (p = 0.01), with a tendency to favor the experimental group. Also, there was a medium level of heterogeneity among studies regarding total PES (I2 = 45%), with no significant differences between studies (p = 0.91). Homogeneous results (I2 = 0%) were found among studies analyzing facial bone thickness, favoring the experimental group; the forest plot showed an effect of 0.37 (95% CI [0.25; 0.50]), which was statistically significant (p < 0.00001) for this parameter. Conclusions: Then, it was possible to conclude that using bone and soft tissue grafting techniques associated with immediate implant placement (IIP), even though they are not fundamental, was a valuable resource to prevent significant tissue reduction, reaching greater bone stability and higher levels in the Pink Esthetic Score (PES) and Visual Analogue Score (VAS).

Evaluation of pathogen from the FilmArray meningitis/encephalitis panel and recommendations on atypical findings.

BACKGROUND: Infectious meningoencephalitis is a potentially fatal clinical condition that causes inflammation of the central nervous system secondary to the installation of different microorganisms. The FilmArray meningitis/encephalitis panel allows the simultaneous detection of 14 pathogens with results in about one hour. OBJECTIVE: This study is based on retrospectively evaluating the implementation of the FilmArray meningitis/encephalitis panel in a hospital environment, highlighting the general results and, especially, analyzing the consistency of the test results against the clinical and laboratory conditions of the patients. METHODS: Data were collected through the results reported by the BioFire FilmArray system software from the meningitis/encephalitis panel. The correlated laboratory tests used in our analysis, when available, included biochemical, cytological, direct and indirect microbiological tests. RESULTS: In the analyzed period, there were 496 samples with released results. Of the total of 496 samples analyzed, 88 (17.75%) were considered positive, and 90 pathogens were detected, and in 2 of these (2.27%) there was co-detection of pathogens. Viruses were the agents most frequently found within the total number of pathogens detected. Of the 496 proven samples, 20 (4.03%) were repeated, 5 of which were repeated due to invalid results, 6 due to the detection of multiple pathogens and 9 due to disagreement between the panel results and the other laboratory tests and/or divergence of the clinical-epidemiological picture. Of these 20 repeated samples, only 4 of them (20%) maintained the original result after repeating the test, with 16 (80%) being non-reproducible. The main factor related to the disagreement of these 16 samples during retesting was the detection of bacterial agents without any relationship with other laboratory tests or with the patients' clinical condition. CONCLUSION: In our study, simply reproducing tests with atypical results from the FilmArray meningitis/encephalitis panel proved, in most cases, effective and sufficient for interpreting these results.

ANTECEDENTES: A meningoencefalite infecciosa é uma condição clínica potencialmente fatal que causa inflamação do sistema nervoso central secundária à instalação de diversos microrganismos. O painel de meningite/encefalite FilmArray permite a detecção simultânea de 14 patógenos, com resultados em cerca de uma hora. OBJETIVO: Este estudo baseia-se em avaliar retrospectivamente a implementação do painel de meningite/encefalite FilmArray em ambiente hospitalar, destacando os resultados gerais e, principalmente, analisando a consistência dos resultados do teste frente às condições clínicas e laboratoriais dos pacientes. MéTODOS: Os dados foram coletados por meio dos resultados relatados pelo software do sistema BioFire FilmArray do painel de meningite/encefalite. Os exames laboratoriais correlacionados utilizados em nossa análise, quando disponíveis, incluíram exames bioquímicos, citológicos, microbiológicos diretos e indiretos. RESULTADOS: No período analisado, foram 496 amostras com resultados divulgados. Do total de 496 amostras analisadas, 88 (17,75%) foram consideradas positivas e 90 patógenos foram detectados, sendo que em duas destas (2,27%) houve codetecção de patógenos. Os vírus foram os agentes mais frequentemente encontrados dentro do total de patógenos detectados. Das 496 amostras analisadas, 20 (4,03%) foram repetidas, sendo 5 repetidas por resultado inválido, 6 pela detecção de múltiplos patógenos e 9 por discordância dos resultados do painel com os demais exames laboratoriais e/ou divergência do quadro clínico-epidemiológico. Destas 20 amostras repetidas, apenas 4 delas (20%) mantiveram o resultado original após a repetição do teste, sendo 16 (80%) não reprodutíveis. O principal fator relacionado à discordância destas 16 amostras na retestagem foi a detecção de agentes bacterianos sem qualquer relação com os demais exames laboratoriais ou com o quadro clínico dos pacientes. CONCLUSãO: Em nosso estudo, a simples repetição dos testes com resultados atípicos do painel de meningite/encefalite FilmArray mostrou-se, na maior dos casos, efetiva e suficiente para a interpretação destes achados.

Evaluating Glass Ionomer Cement Longevity in the Primary and Permanent Teeth-An Umbrella Review.

The aim of this umbrella review was to evaluate the longevity of glass ionomer cement (GIC) as a restorative material for primary and permanent teeth. Research in the literature was conducted in three databases (MedLine/PubMed, Web of Science, and Scopus). The inclusion criteria were: (1) to be a systematic review of clinical trials that (2) evaluated the clinical longevity of GICs as a restorative material in primary and/or permanent teeth; the exclusion criteria were: (1) not being a systematic review of clinical trials; (2) not evaluating longevity/clinical performance of GICs as a restorative material; and (3) studies of dental restorative materials in teeth with enamel alterations, root caries, and non-carious cervical lesions. Twenty-four eligible articles were identified, and 13 were included. The follow-up periods ranged from 6 months to 6 years. Different types of GICs were evaluated in the included studies: resin-modified glass ionomer cement (RMGIC), compomers, and low- and high-viscosity glass ionomer cement. Some studies compared amalgam and composite resins to GICs regarding longevity/clinical performance. Analyzing the AMSTAR-2 results, none of the articles had positive criteria in all the evaluated requisites, and none of the articles had an a priori design. The criteria considered for the analysis of the risk of bias of the included studies were evaluated through the ROBIS tool, and the results of this analysis showed that seven studies had a low risk of bias; three studies had positive results in all criteria except for one criterion of unclear risk; and two studies showed a high risk of bias. GRADE tool was used to determine the quality of evidence; for the degree of recommendations, all studies were classified as Class II, meaning there was still conflicting evidence on the clinical performance/longevity of GICs and their recommendations compared to other materials. The level of evidence was classified as Level B, meaning that the data were obtained from less robust meta-analyses and single randomized clinical trials. To the best of our knowledge, this is the first umbrella review approaching GIC in permanent teeth. GICs are a good choice in both dentitions, but primary dentition presents more evidence, especially regarding the atraumatic restorative treatment (ART) technique. Within the limitation of this study, it is still questionable if GIC is a good restorative material in the medium/long term for permanent and primary dentition. Many of the included studies presented a high risk of bias and low quality. The techniques, type of GIC, type of cavity, and operator experience highly influence clinical performance. Thus, clinical decision-making should be based on the dental practitioner's ability, each case analysis, and the patient's wishes. More evidence is needed to determine which is the best material for definitive restorations in permanent and primary dentition.

Minimally invasive periodontal regeneration with the buccal approach: a systematic review and meta-analysis of clinical studies.

OBJECTIVE: The aim of this study was to investigate clinical periodontal parameters after treatment using the Minimally Invasive Surgical Technique (MIST), Modified Minimally Invasive Surgical Technique (M-MIST), and/or any technique for papilla preservation, such as Entire Papilla Preservation (EPP), modified-papilla preservation technique (M-PPT), or simplified-papilla preservation technique (SPPT). METHODS: The focus question was "For patients with periodontal intrabony defects (P), what is the best minimally invasive regenerative approach (I), comparing MIST, M-MIST, and papilla preservation techniques' outcomes (C) to improve PD, CAL, GR, and periodontal stability (O)?" An online search was conducted on PubMed, Cochrane Library, and Embase. Only randomized clinical trials and case series with a minimum of 10 enrolled patients were included. The risk of bias was evaluated using the Critical Appraisal tools in JBI Systematic Reviews. The meta-analysis compared the data obtained for the periodontal parameters analyzed, and the heterogeneity was verified. RESULTS: After the screening, nine articles were included. Seven studies applied MIST and its modifications; two used M-PPT, one SPPT, and one approached EPP. A general statistically significant PD reduction and CAL gain were noted between the groups, comparing baseline and follow-up for all articles, independently of the technique or materials used. Also, all studies showed a non-significant increase in the gingival recession. Four studies had a low risk of bias, four had a moderate risk, and only 1 had a high risk. Moderate heterogeneity was found in one analysis for CAL (65.73%); moderate and substantial heterogeneity was found in the PD results (71.91% and 89.19%); and no heterogeneity was found within all analyses for gingival recession (0%). CONCLUSION: MIST, M-MIST, and papilla preservation techniques demonstrated their potential and efficacy to improve periodontal conditions of sites with intrabony defects with minimal morbidity.

Acute disseminated encephalomyelitis following Saint Louis encephalitis virus infection.

Saint Louis encephalitis virus (SLEV) infection is an arbovirosis associated with a broad spectrum of neurological complications. We present a case of a 55-year-old man hailing from Manaus, a city situated in the heart of the Amazon Rainforest, who exhibited symptoms of vertigo, tremors, urinary and fecal retention, compromised gait, and encephalopathy 3 weeks following SLEV infection. Neuroaxis MRI revealed diffuse, asymmetric, and poorly defined margins hyperintense lesions with peripheral and ring enhancement in subcortical white matter, as well as severe spinal cord involvement. Serology for SLEV was positive both on serum and cerebrospinal fluid. To the best of our knowledge, the present report is the first to show brain lesions along with myelitis as a post-infectious complication of SLEV infection.

Is the facial bone wall critical to achieving esthetic outcomes in immediate implant placement with immediate restoration? A systematic review.

BACKGROUND: Rehabilitation in the anterior region requires specific conditions for success, such as the presence of papilla, emergence profile, and balance between pink and white esthetic. OBJECTIVES: This systematic review aimed to evaluate the esthetic risk associated with immediate implant placement with immediate restoration in the anterior superior area, where the facial bone plate may be absent or deficient. MATERIAL AND METHODS: The search was done in PubMed, Embase, Cochrane, Lilacs, Scopus, Scielo, and Google Scholar databases. The investigation involved clinical studies and observational studies published between January 2012 and July 2023. Studies were excluded if there was less than 12-month follow-up, no immediate restoration or facial defect, heavy smokers, or systemic disease. The risk of bias was assessed using the ROBINS-I and Modified-Cochrane RoB tools. RESULTS: Twelve studies were included in this systematic review. The thinner the facial plate, the higher the alveolus's risk of gingival recession or shrinkage. There was an increased interproximal recession when the thin phenotype was associated with flap surgery. An increase in pink esthetic score (PES) was reached when immediate implant placement (IIP) and immediate restoration were done. Soft tissue augmentation achieved more gingival-level stability. Regardless of the initial phenotype, an esthetic outcome was delivered. The risk of bias was high in 1 study and moderate in 3 studies. CONCLUSION: It is possible to conclude that esthetic results and increased final PES or patient satisfaction index in IIP treatments associated with immediate restoration could be obtained even in buccal bone wall defects or gingival recession, regardless of their extension.

Critical-size defects reconstruction with four different bone grafts associated with e-PTFE membrane: A histomorphometric experimental in vivo study.

OBJECTIVES: The goal of this study was to assess the newly formed bone and the remnant biomaterial by comparing four different bone grafts used to treat critical-size defects, associated or not with the non-resorbable membrane. MATERIALS AND METHODS: Two calvaria critical-size bone defects were created in 50 male Wistar rats. They were divided into blood (G1), autogenous (G2), bioglass (G3), hydroxyapatite (G4), and xenograft (G5) groups, associated or not with e-PTFE. The experimental periods were 15 and 45 days. Sections were prepared for histomorphometric assessment. All data were analyzed by the mixed-effects model with multiple comparisons (significance level, p < .05). RESULTS: A similar level of new bone was observed for all groups, associated with a high level of vascularization. G1 and G2 ensured sovereignty over the greater quantity of new bone. A non-significant result was reported comparing groups with and without membranes. No significant result was found between the experimental synthetic biomaterials (G3 and G4). G5L achieved 22.0% of new bone after 45 days (p > .05). All groups had a stable volume of biomaterial kept in the short term (p > .05). G2 was the best material for new bone formation and final volume of biomaterial, followed by G4 < G5 < G3. Thus, it is possible that G4 had a better degradation profile among the experimental groups. CONCLUSIONS: The best results were found in the autogenous group, with higher resorption and integration; non-significative new bone was found among the experimental groups; and the regeneration of critical bone defects using an e-PTFE barrier did not present significant results on new bone formation.

Flap of the sternocephalicus muscle in the repair of a partial defect in the trachea of a rabbit (Oryctolagus cuniculus)

Purpose: The current study aimed at evaluating the repair of a partial defect of the trachea with a muscle flap, an advanced technique that employs combined suture patterns. Methods: Sixteen healthy male New Zealand white rabbits were used as an experimental model. A partial defect in the trachea within the ventral region of the fourth to eighth tracheal ring was created. Subsequently, repair was initiated with a flap of the sternocephalicus muscle. The animals were divided into four groups for postoperative evaluation using clinical, tracheoscopic, and histopathological analyses. Each group was separated according to the time of euthanasia, programmed at interval of seven (G7), 15 (G15), 30 (G30), and 60 days (G60). Results: One animal from the G60 group died, whereas the other animals had good surgical recovery without serious changes in the breathing pattern. The major clinical signs observed were stridor and coughing. Tracheoscopy revealed secretions in the tracheal lumen, exuberant granulation, and stenosis. Histopathological analysis showed growth of the ciliary respiratory epithelium at the flap site 30 days after implantation. Conclusions: Partial repair showed satisfactory results owing to the anatomical location of the muscle, adequate vascular support, and structural and physiological maintenance without serious changes in the respiratory system.

Evaluation of pathogen from the FilmArray meningitis/encephalitis panel and recommendations on atypical findings / Avaliação do patógeno do painel de meningite/encefalite FilmArray e recomendações sobre achados atípicos

Abstract Background Infectious meningoencephalitis is a potentially fatal clinical condition that causes inflammation of the central nervous system secondary to the installation of different microorganisms. The FilmArray meningitis/encephalitis panel allows the simultaneous detection of 14 pathogens with results in about one hour. Objective This study is based on retrospectively evaluating the implementation of the FilmArray meningitis/encephalitis panel in a hospital environment, highlighting the general results and, especially, analyzing the consistency of the test results against the clinical and laboratory conditions of the patients. Methods Data were collected through the results reported by the BioFire FilmArray system software from the meningitis/encephalitis panel. The correlated laboratory tests used in our analysis, when available, included biochemical, cytological, direct and indirect microbiological tests. Results In the analyzed period, there were 496 samples with released results. Of the total of 496 samples analyzed, 88 (17.75%) were considered positive, and 90 pathogens were detected, and in 2 of these (2.27%) there was co-detection of pathogens. Viruses were the agents most frequently found within the total number of pathogens detected. Of the 496 proven samples, 20 (4.03%) were repeated, 5 of which were repeated due to invalid results, 6 due to the detection of multiple pathogens and 9 due to disagreement between the panel results and the other laboratory tests and/or divergence of the clinical-epidemiological picture. Of these 20 repeated samples, only 4 of them (20%) maintained the original result after repeating the test, with 16 (80%) being non-reproducible. The main factor related to the disagreement of these 16 samples during retesting was the detection of bacterial agents without any relationship with other laboratory tests or with the patients' clinical condition. Conclusion In our study, simply reproducing tests with atypical results from the FilmArray meningitis/encephalitis panel proved, in most cases, effective and sufficient for interpreting these results.

Resumo Antecedentes A meningoencefalite infecciosa é uma condição clínica potencialmente fatal que causa inflamação do sistema nervoso central secundária à instalação de diversos microrganismos. O painel de meningite/encefalite FilmArray permite a detecção simultânea de 14 patógenos, com resultados em cerca de uma hora. Objetivo Este estudo baseia-se em avaliar retrospectivamente a implementação do painel de meningite/encefalite FilmArray em ambiente hospitalar, destacando os resultados gerais e, principalmente, analisando a consistência dos resultados do teste frente às condições clínicas e laboratoriais dos pacientes. Métodos Os dados foram coletados por meio dos resultados relatados pelo software do sistema BioFire FilmArray do painel de meningite/encefalite. Os exames laboratoriais correlacionados utilizados em nossa análise, quando disponíveis, incluíram exames bioquímicos, citológicos, microbiológicos diretos e indiretos. Resultados No período analisado, foram 496 amostras com resultados divulgados. Do total de 496 amostras analisadas, 88 (17,75%) foram consideradas positivas e 90 patógenos foram detectados, sendo que em duas destas (2,27%) houve codetecção de patógenos. Os vírus foram os agentes mais frequentemente encontrados dentro do total de patógenos detectados. Das 496 amostras analisadas, 20 (4,03%) foram repetidas, sendo 5 repetidas por resultado inválido, 6 pela detecção de múltiplos patógenos e 9 por discordância dos resultados do painel com os demais exames laboratoriais e/ou divergência do quadro clínico-epidemiológico. Destas 20 amostras repetidas, apenas 4 delas (20%) mantiveram o resultado original após a repetição do teste, sendo 16 (80%) não reprodutíveis. O principal fator relacionado à discordância destas 16 amostras na retestagem foi a detecção de agentes bacterianos sem qualquer relação com os demais exames laboratoriais ou com o quadro clínico dos pacientes. Conclusão Em nosso estudo, a simples repetição dos testes com resultados atípicos do painel de meningite/encefalite FilmArray mostrou-se, na maior dos casos, efetiva e suficiente para a interpretação destes achados.

Bone tissue regeneration in peri-implantitis: A systematic review of randomized clinical trials.

Objectives: The goal of this systematic review was to analyze, in randomized controlled clinical trials (RCTs), regenerative techniques used to treat peri-implantitis (PI). Methods: Three databases (PubMed/Medline, EMBASE, and On-Line Knowledge Library) were accessed, applying the PICO strategy (Population [P], Intervention [I], Comparison [C], and Outcomes [O]), with the following focused questions: (i) "In patients who received regenerative treatments for peri-implantitis (P), is the regenerative surgical treatment (I) clinically effective and predictable compared to non-regenerative (C) to treat PI (O)?"; and (ii) "In patients who received regenerative treatments for peri-implantitis (P), the regenerative approach (I), compared to non-regenerative (C), significantly increase the prognosis and implant survival rate in the mid- and long-term (O)?" The inclusion criteria were RCTs published in English between 2012 and 2022, with at least a one-year follow-up, which applied regenerative techniques to treat peri-implantitis. Cochrane's collaboration tool for assessing the risk of bias was used. Main results: Nine articles were included with 404 patients (225 females and 179 males; mean age of 60.44 years). One study evaluated patients after 48 months and another after 88 months. The techniques and devices used were: (i) implantoplasty with Er:YAG laser, (ii) blood concentrate (growth factors), and (iii) EMD, with no statistically significant outcome. Two studies considered the use of titanium granules with a significant increase in radiographic bone identification, whereas regenerative techniques with bone graft (autogenous, alloplastic, and xenograft) were the majority chosen, associated or not, with a collagen membrane. Xenograft had better results radiographically when compared to the autogenous bone graft and presented better results for bone level. There was an overall decrease in bleeding on probing, independent of the control or test group, and a reduction in pocket depth in the groups analyzed. Titanium granules, EMD, Er:YAG laser, and CGF had non-significant results; better results were observed when using bone grafts. The RoB showed a low risk in four studies (44.44%), three with moderate (33.33%), and two with high risk (22.23%). Conclusion: Surgical regenerative treatment was a predictable option in the management of PI and in improving the clinical parameters of peri-implant tissues in the short term, mainly when using porous titanium granules, alloplastic bone grafts, and xenografts.

Mixed-Thickness Tunnel Access (MiTT) through a Linear Vertical Mucosal Incision for a Minimally Invasive Approach for Root Coverage Procedures in Anterior and Posterior Sites: Technical Description and Case Series with 1-Year Follow-Up.

PURPOSE: The goal of this article was to introduce a new root coverage (RC) technique, the mixed-thickness tunnel access (MiTT) technique, which approaches a full-split design and intends to augment soft tissues coronal to the gingival margin. It was shown step-by-step, and the results were presented in a case series. METHODS: Healthy individuals (non-diabetics) and non-smokers with gingival recession (GR) type 1 or 2 (RT1 or RT2) were included. After evaluation, prophylaxis was performed 14 days before the surgical procedure. During the surgical appointment, one or two vertical incision(s) on the mucosa (around 1-2 mm apical to the MGJ), lateral to the papilla base, was/were performed after anesthesia. Initially, there was a partial incision to detach the mucosa of the muscles (split design). It was permitted (but not mandatory) to perform intrasulcular incisions. Through the vertical incision, internally, subperiosteal access from the MGJ toward the gingival margin (coronally) was performed to create a full-thickness tunnel. Then, communication from the vertical incision with the gingival sulcus and the papilla base occurred, keeping the papilla tip intact. A connective tissue graft was harvested and inserted through the linear incision or intrasulcularly. There were interrupted sutures. An adjunctive material may be applied (e.g., Endogain). The root coverage was measured using a periodontal probe and considered fully covered when the gingival margin was 1 mm coronal to the cementum-enamel junction (CEJ). RESULTS: Nine healthy individuals (seven females and two males) aged 19 and 43 were enrolled. They were treated following the MiTT steps. Four cases had a single GR; two patients had two teeth involved; and three others had three or four GR. There were seven cases of RT1 and two RT2. All RT1 cases achieved 100% RC, while the mean RC obtained for RT2 was around 80%. CONCLUSION: The MiTT technique can be considered a more straightforward approach for minimally invasive surgical techniques, which is a feasible option to treat RC with a high success rate, predictability, and esthetic preservation. Therefore, there is a technical sensitivity to performing the full-split design procedure.

Discussion on cervical cytology in postmenopausal women.

BACKGROUND: Considering the cervix at the climacteric period, important changes take place in the morphology of the epithelium and stroma due to hypoestrogenism. Therefore, the aim of the present study was to compare the presence of transformation zone cells in the cervix of premenopausal and postmenopausal women. METHODS: In a private laboratory in São Paulo (Brazil) a retrospective analysis of cervical cytology results was performed. A total of 1,026,671 satisfactory cytology tests were evaluated between January 2010 and December 2015. RESULTS: A marked decline in transformation zone cells with age was evident, with a greater decrease in the ≥50 years age groups. Only 35% of women ≥50 years of age had transformation zone cells in cytology, while in those <50 years, the figure was 67.5% (P<0.001). The prevalence of negative cytological results in these two age groups was respectively 89.9% and 95.3%; however, it was observed that the most serious cytological results occurred in the group after menopause. CONCLUSIONS: Although cytology is the recommended screening method for cervical cancer in Brazil, the low number of transformation zone cells in cytology in menopausal patients could be less sensitive for screening of dysplasia and cancer. So, we suggest routine high-risk HPV DNA testing, when possible, given that this test is considered more sensitive for detecting cervical lesions in this group of patients. When HPV DNA testing is not possible, cytology should be collected, and for cytology sampling we suggest regular topical estrogenization and use of appropriate technique.