Oral Administration of Lactobacillus acidophilus LA5 Prevents Alveolar Bone Loss and Alters Oral and Gut Microbiomes in a Murine Periodontitis Experimental Model.

Periodontitis is a destructive inflammatory response triggered by dysbiosis. Lactobacillus acidophilus LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the effect of LA5 on alveolar bone loss in a periodontitis murine model and investigated its effect on the oral and gut microbiomes. Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus gordonii were inoculated in C57BL/6 mice (P+), with LA5 (L+). SHAM infected controls (P- and/or L- groups) were also evaluated. After 45 days, alveolar bone loss in the maxilla and oral and gut microbiomes were determined. The administration of LA5 controlled the microbial consortium-induced alveolar bone loss. Periodontopathogens infection resulted in shifts in the oral and gut microbiomes consistent with dysbiosis, and LA5 reshaped these changes. The oral microbiome of P+L- group showed the increased abundance of Enterococaccea, Streptoccocaceae, Staphylococcaceae, Moraxellaceae, and Pseudomonadaceae, which were attenuated by the administration of LA5 to the infected group (P+L+). The administration of LA5 to otherwise non-infected mice resulted in the increased abundance of the superphylum Patescibacteria and the family Saccharamonadaceae in the gut. These data indicate L. acidophilus LA5 as a candidate probiotic for the control of periodontitis.

The use of lateral arthroscopy portals for the management of a fragmented lateral coronoid process in an English Bulldog.

OBJECTIVE: To report a case of unilateral lateral coronoid process fragmentation in a dog treated via lateral elbow arthroscopy portals. ANIMAL: A 9-month old male intact English Bulldog. STUDY DESIGN: Case report. METHODS: The dog presented with a history of intermittent right thoracic limb lameness. Orthopedic examination on presentation was unremarkable. Computed tomography of the right thoracic limb was pursued and revealed a mineralized focus along the lateral margin of the lateral coronoid process as well as sclerosis of the medial coronoid process and subtrochlear region of the ulna. Elbow arthroscopy was performed via a lateral approach and revealed chondromalacia of the entire lateral coronoid process. Abrasion arthroplasty of the lateral coronoid process was performed. RESULTS: Complete resolution of the lameness was achieved within two weeks of surgery. At 6 weeks postoperatively, the dog remained sound and a gradual return to normal activity was recommended. At the final follow up assessment, 5 months after surgery, no abnormalities were found on orthopedic examination and the owners reported excellent limb function with no observable lameness. CONCLUSION: Lateral coronoid disease can occur as a rare component of elbow dysplasia in dogs. Abrasion arthroplasty via lateral arthroscopic portals may have resulted in a successful outcome in this case and may form an effective treatment option for lateral coronoid disease in dogs.

Comparison of the distraction index and Norberg angle with radiographic grading of canine hip dysplasia.

The Orthopedic Foundation for Animals (OFA) radiographic grading system stands as a well-established benchmark for categorizing hip dysplasia in canines. Although more objective techniques to quantify early hip laxity in young dogs, such as the Norberg angle (NA) and distraction index (DI), have been documented, there is a scarcity of published studies that directly compare these radiographic measures. The primary objectives of this prospective, analytical study were to assess and compare the NA and DI measures with OFA grades within a cohort of dogs. Thirty dogs (57 hip joints) were evaluated, with a mean age of 5.4 ± 2.9 years and a mean body weight of 34.3 ± 7.1 kg. The discriminative power of hip dysplasia for DI and NA used OFA as a reference were compared by multivariate discriminant analysis test. Using the DI (≤0.3) 12 joints were classified as normal, using NA (≥105°) 24 joints and using OFA (≤3) 29. When comparing the discriminant power of NA with OFA resulting similar (P = .8324) with correct classifications of 81% using cross validation, however, the discriminant power of dysplasia of the DI resulted significantly greater (P = .0034) than OFA with correct classifications of only 59% using cross-validation, consequently it was possible determined that of 29 patients with OFA ≤ 3, 20 had DI > 0.3. These findings demonstrated that phenotypic healthy dogs according to OFA grading can present passive hip joint laxity, as demonstrated by radiographic evaluation with distraction. Furthermore, DI can contribute to the screening of CHD when evaluated in conjunction with OFA grading.

Identifying New Contributors to Brain Metastasis in Lung Adenocarcinoma: A Transcriptomic Meta-Analysis.

Lung tumors frequently metastasize to the brain. Brain metastasis (BM) is common in advanced cases, and a major cause of patient morbidity and mortality. The precise molecular mechanisms governing BM are still unclear, in part attributed to the rarity of BM specimens. In this work, we compile a unique transcriptomic dataset encompassing RNA-seq, microarray, and single-cell analyses from BM samples obtained from patients with lung adenocarcinoma (LUAD). By integrating this comprehensive dataset, we aimed to enhance understanding of the molecular landscape of BM, thereby facilitating the identification of novel and efficient treatment strategies. We identified 102 genes with significantly deregulated expression levels in BM tissues, and discovered transcriptional alterations affecting the key driver 'hub' genes CD69 (a type II C-lectin receptor) and GZMA (Granzyme A), indicating an important role of the immune system in the development of BM from primary LUAD. Our study demonstrated a BM-specific gene expression pattern and revealed the presence of dendritic cells and neutrophils in BM, suggesting an immunosuppressive tumor microenvironment. These findings highlight key drivers of LUAD-BM that may yield therapeutic targets to improve patient outcomes.

Short-term Clinical and Microbiological Performance of Resin-modified Glass Ionomer Cement Containing Chlorhexidine for Atraumatic Restorative Treatment.

Aim: This study evaluated the short-term clinical and microbiological performance of resin-modified glass ionomer cement (RM-GIC) cement containing chlorhexidine (CHX) for atraumatic restorative treatment (ART) in primary teeth. Materials and methods: The clinical trial was conducted in 36 children that received ART in primary molars either with GIC (group I, n = 18) or GIC containing 1.25% CHX (group II, n = 18). The survival rate of restorations was checked 7 days, 3, and 6 months after their application when saliva and biofilm were collected for microbiological assessment of mutans streptococci (MS) counts. Data were analyzed using the Kruskal-Wallis/Mann-Whitney U tests for clinical analysis and microbiological evaluations (p < 0.05). Results: The survival rate of restorations was similar comparing groups I with II. Microbiological analysis showed a significant reduction in MS levels 7 days after the treatment in both saliva and biofilm of children treated with RM-GIC containing CHX (group II); however, MS counts at 3 and 6 months did not differ from the initial counts. Conclusion: A total of 1.25% CHX improved the microbiological properties of GIC in the short term without impairing the clinical performance of ART restorations. Clinical significance: Glass ionomer cement (GIC) containing CHX could be an alternative in ART procedures with the objective of promoting an additional antimicrobial effect, which is interesting for children with high counts of MS during the initial phase of adaptation to dental treatment. How to cite this article: da Silva ME, de Sena MD, Colombo NH, et al. Short-term Clinical and Microbiological Performance of Resin-modified Glass Ionomer Cement Containing Chlorhexidine for Atraumatic Restorative Treatment. Int J Clin Pediatr Dent 2023;16(S-1):S27-S32.

Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach.

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid ß peptide, ß catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.

The use of lateral arthroscopy portals for the management of bilateral osteochondritis dissecans of the radial head in an English bulldog.

OBJECTIVE: To report a case of bilateral radial head osteochondritis dissecans (OCD) in a dog treated via lateral elbow arthroscopy portals. STUDY DESIGN: Case report. ANIMALS: Six month old female spayed English bulldog. METHODS: The dog was presented for a left thoracic limb lameness localized to the elbow. Computed tomography revealed bilaterally symmetrical mineralized fragments in the lateral compartment of the elbow joint and blunting of the medial coronoid processes. The fragments were associated with a thin donation bed along the caudolateral articular surface of the radial head with moderate surrounding subchondral bone sclerosis. Bilateral elbow arthroscopy was pursued. Arthroscopy was initiated via a standard medial approach, which allowed for abrasion arthroplasty of the radial incisure and medial coronoid process but provided insufficient access to the radial head lesions. A lateral arthroscopic approach was subsequently performed and provided excellent access to the radial head for fragment retrieval and abrasion arthroplasty. RESULTS: Histopathology of the radial head fragments revealed mild cartilage degeneration and retention of cartilaginous cores within subchondral bone, consistent with OCD. Complete resolution of lameness and elbow pain were observed on clinical examination 5 months postoperatively. CONCLUSION: Radial head OCD can occur as a rare component of elbow dysplasia in growing dogs, and fragment retrieval with abrasion arthroplasty via lateral arthroscopic portals may be an effective treatment option.

Synthesis and Morphology of High-Molecular-Weight Polyisobutylene-Polystyrene Block Copolymers Containing Dynamic Covalent Bonds.

Incorporating dynamic covalent bonds into block copolymers provides useful molecular level information during mechanical testing, but it is currently unknown how the incorporation of these units affects the resultant polymer morphology. High-molecular-weight polyisobutylene-b-polystyrene block copolymers containing an anthracene/maleimide dynamic covalent bond are synthesized through a combination of postpolymerization modification, reversible addition-fragmentation chain-transfer polymerization, and Diels-Alder coupling. The bulk morphologies with and without dynamic covalent bond are characterized by atomic force microscopy  and small-angle X-ray scattering, which reveal a strong dependence on annealing time and casting solvent. Morphology is largely unaffected by the inclusion of the mechanophore. The high-molecular-weight polymers synthesized allow interrogation of a large range of polymer domain sizes.

Diketoenamine-Based Vitrimers via Thiol-ene Photopolymerization.

Likened to both thermosets and thermoplastics, vitrimers are a unique class of materials that combine remarkable stability, healability, and reprocessability. Herein, this work describes a photopolymerized thiol-ene-based vitrimer that undergoes dynamic covalent exchanges through uncatalyzed transamination of enamines derived from cyclic ß-triketones, whereby the low energy barrier for exchange facilitates reprocessing and enables rapid depolymerization. Accordingly, an alkene-functionalized ß-triketone, 5,5-dimethyl-2-(pent-4-enoyl)cyclohexane-1,3-dione, is devised which is then reacted with 1,6-diaminohexane in a stoichiometrically imbalanced fashion (≈1:0.85 primary amine:triketone). The resulting networks exhibit subambient glass transition temperature (Tg = 5.66 °C) by differential scanning calorimetry. Using a Maxwell stress-relaxation fit, the topology-freezing temperature (Tv ) is calculated to be -32 °C. Small-amplitude oscillatory shear rheological analysis enables to identify a practical critical temperature above which the vitrimer can be successfully reprocessed (Tv,eff ). Via the introduction of excess primary amines, this work can readily degrade the networks into monomeric precursors, which are in turn reacted with diamines to regenerate reprocessable networks. Photopolymerization provides unique spatiotemporal control over the network topology, thereby opening the path for further investigation of vitrimer properties. As such, this work expands the toolbox of chemical upcycling of networks and enables their wider implementation.

Tucuxi-BLAST: Enabling fast and accurate record linkage of large-scale health-related administrative databases through a DNA-encoded approach.

Background: Public health research frequently requires the integration of information from different data sources. However, errors in the records and the high computational costs involved make linking large administrative databases using record linkage (RL) methodologies a major challenge. Methods: We present Tucuxi-BLAST, a versatile tool for probabilistic RL that utilizes a DNA-encoded approach to encrypt, analyze and link massive administrative databases. Tucuxi-BLAST encodes the identification records into DNA. BLASTn algorithm is then used to align the sequences between databases. We tested and benchmarked on a simulated database containing records for 300 million individuals and also on four large administrative databases containing real data on Brazilian patients. Results: Our method was able to overcome misspellings and typographical errors in administrative databases. In processing the RL of the largest simulated dataset (200k records), the state-of-the-art method took 5 days and 7 h to perform the RL, while Tucuxi-BLAST only took 23 h. When compared with five existing RL tools applied to a gold-standard dataset from real health-related databases, Tucuxi-BLAST had the highest accuracy and speed. By repurposing genomic tools, Tucuxi-BLAST can improve data-driven medical research and provide a fast and accurate way to link individual information across several administrative databases.

AUSTWICKIA CHELONAE IN A WILD GOPHER TORTOISE (GOPHERUS POLYPHEMUS) AND EVIDENCE OF POSITIVE SELECTION ON THE DIPHTHERIA-LIKE TOXIN GENE.

Austwickia (Dermatophilus) chelonae is a filamentous, Gram-positive Actinobacteria in the Dermatophilaceae family. It has caused fatal granulomatous disease in diverse captive reptile species on three continents, but its presence in wild or free-ranging populations was unknown. An adult female gopher tortoise (Gopherus polyphemus) was presented euhydrated, but cachectic and infested with ticks, with two firm, encapsulated masses over the cranioventral neck and right stifle. The tortoise had moderate nonregenerative anemia and evidence of inflammation; plasma biochemistry data was within normal limits. Fine needle aspirate of the neck lesion revealed abundant necrosis and aggregates of cocci. Computed tomography delineated the masses and revealed an additional mass adjacent to the left zygomatic bone. After surgical excision, histology identified chronic granulomas with intralesional filamentous bacteria. Pan-bacterial 16S rRNA PCR and sequencing of the masses identified A. chelonae. Despite treatment with oxytetracycline and ceftazidime, the tortoise deteriorated and was euthanatized. An esophageal lesion consistent with A. chelonae was seen on postmortem examination, although it was determined that the tortoise ultimately succumbed to fungal pneumonia caused by Metarhizium robertsii, an entomopathogenic biotoxin sprayed as insect control. This case reveals A. chelonae is present in free-ranging chelonians in North America. This organism produces a toxin gene similar to diphtheria toxin, one of the most potent known biotoxins, which has not been previously identified outside the genus Corynebacterium. Novel PCR primers were designed for the toxin and rpoB genes, which were amplified and sequenced from two cases and compared with two available genomes. Selection analysis revealed that the toxin gene is under positive selection, which implies it interacts significantly with the immune system, making it a good candidate for immunodiagnostic test development.

Decreased miR-497-5p Suppresses IL-6 Induced Atrophy in Muscle Cells.

Interleukin-6 (IL-6) is a pro-inflammatory cytokine associated with skeletal muscle wasting in cancer cachexia. The control of gene expression by microRNAs (miRNAs) in muscle wasting involves the regulation of thousands of target transcripts. However, the miRNA-target networks associated with IL6-induced muscle atrophy remain to be characterized. Here, we show that IL-6 promotes the atrophy of C2C12 myotubes and changes the expression of 20 miRNAs (5 up-regulated and 15 down-regulated). Gene Ontology analysis of predicted miRNAs targets revealed post-transcriptional regulation of genes involved in cell differentiation, apoptosis, migration, and catabolic processes. Next, we performed a meta-analysis of miRNA-published data that identified miR-497-5p, a down-regulated miRNAs induced by IL-6, also down-regulated in other muscle-wasting conditions. We used miR-497-5p mimics and inhibitors to explore the function of miR-497-5p in C2C12 myoblasts and myotubes. We found that miR-497-5p can regulate the expression of the cell cycle genes CcnD2 and CcnE1 without affecting the rate of myoblast cellular proliferation. Notably, miR-497-5p mimics induced myotube atrophy and reduced Insr expression. Treatment with miR-497-5p inhibitors did not change the diameter of the myotubes but increased the expression of its target genes Insr and Igf1r. These genes are known to regulate skeletal muscle regeneration and hypertrophy via insulin-like growth factor pathway and were up-regulated in cachectic muscle samples. Our miRNA-regulated network analysis revealed a potential role for miR-497-5p during IL6-induced muscle cell atrophy and suggests that miR-497-5p is likely involved in a compensatory mechanism of muscle atrophy in response to IL-6.

Moderate-intensity exercise with blood flow restriction on cardiopulmonary kinetics and efficiency during a subsequent high-intensity exercise in young women: A cross-sectional study.

ABSTRACT: Blood flow restriction (BFR) training applied prior to a subsequent exercise has been used as a method to induce changes in oxygen uptake pulmonary kinetics (O2P) and exercise performance. However, the effects of a moderate-intensity training associated with BFR on a subsequent high-intensity exercise on O2P and cardiac output (QT) kinetics, exercise tolerance, and efficiency remain unknown.This prospective physiologic study was performed at the Exercise Physiology Lab, University of Brasilia. Ten healthy females (mean ±â€ŠSD values: age = 21.3 ±â€Š2.2 years; height = 1.6 ±â€Š0.07 m, and weight = 55.6 ±â€Š8.8 kg) underwent moderate-intensity training associated with or without BFR for 6 minutes prior to a maximal high-intensity exercise bout. O2P, heart rate, and QT kinetics and gross efficiency were obtained during the high-intensity constant workload exercise test.No differences were observed in O2P, heart rate, and QT kinetics in the subsequent high-intensity exercise following BFR training. However, exercise tolerance and gross efficiency were significantly greater after BFR (220 ±â€Š45 vs 136 ±â€Š30 seconds; P < .05, and 32.8 ±â€Š6.3 vs 27.1 ±â€Š5.4%; P < .05, respectively), which also resulted in lower oxygen cost (1382 ±â€Š227 vs 1695 ±â€Š305 mL min-1).We concluded that moderate-intensity BFR training implemented prior to a high-intensity protocol did not accelerate subsequent O2P and QT kinetics, but it has the potential to improve both exercise tolerance and work efficiency at high workloads.

The relationship between cytokine and neutrophil gene network distinguishes SARS-CoV-2-infected patients by sex and age.

The fact that the COVID-19 fatality rate varies by sex and age is poorly understood. Notably, the outcome of SARS-CoV-2 infections mostly depends on the control of cytokine storm and the increasingly recognized pathological role of uncontrolled neutrophil activation. Here, we used an integrative approach with publicly available RNA-Seq data sets of nasopharyngeal swabs and peripheral blood leukocytes from patients with SARS-CoV-2, according to sex and age. Female and young patients infected by SARS-CoV-2 exhibited a larger number of differentially expressed genes (DEGs) compared with male and elderly patients, indicating a stronger immune modulation. Among them, we found an association between upregulated cytokine/chemokine- and downregulated neutrophil-related DEGs. This was correlated with a closer relationship between female and young subjects, while the relationship between male and elderly patients was closer still. The association between these cytokine/chemokines and neutrophil DEGs is marked by a strongly correlated interferome network. Here, female patients exhibited reduced transcriptional levels of key proinflammatory/neutrophil-related genes, such as CXCL8 receptors (CXCR1 and CXCR2), IL-1ß, S100A9, ITGAM, and DBNL, compared with male patients. These genes are well known to be protective against inflammatory damage. Therefore, our work suggests specific immune-regulatory pathways associated with sex and age of patients infected with SARS-CoV-2 and provides a possible association between inverse modulation of cytokine/chemokine and neutrophil transcriptional signatures.

Preparation and Thermogravimetric and Antimicrobial Investigation of Cd (II) and Sn (II) Adducts of Mercaptopyridine, Amino Triazole Derivatives, and Mercaptothiazoline Organic Ligand Moieties.

The solid adducts of SnCl2.(3amt).H2O, SnCl2.2(3amt).H2O, CdCl2.(3amt), CdCl2.2(3amt), SnCl2.(2mct).0.5H2O, SnCl2.2(2mct), CdCl2.(2mct), CdCl2.2(2mct).H2O, SnCl2.(2mcp).1.5H2O, >2.2(2mcp).4H2O, CdCl2.(2mcp), CdCl2.2(2mcp), SnCl2.(4amt).4H2O, SnCl2.2(4amt).1.5H2O, CdCl2.(4amt).H2O, and CdCl2.2(4amt) (where the 3amt, 4amt, 2mct, and 2mcp represent 3-amino-1,2,4-triazole, 4-amino-1,2,4-triazole, 2-mercaptothiazoline, and 2-mercaptopyridine simple organic chelates, respectively) were prepared using a solid-state route and investigated by CHN elemental analysis and infrared spectroscopy. Additionally, we investigated the thermogravimetric characterization and antimicrobial proprieties. It is verified that for 3amt and 4amt adducts, the coordination occurs through nitrogen atom. For 2mct compounds, the coordination occurs through nitrogen (Sn) or sulfur (Cd). For 2mcp adducts, both coordination sites nitrogen and sulfur are involved. By examination of TG curves, it is confirmed that for each hydrated compounds, the first mass loss step is linked with the release of water molecules followed by the release of ligand molecules and sublimation of the metal chloride. Furthermore, it is verified that, considering only the release of ligand molecules (3amp, 4amp, 2mct, or 2mcp), the cadmium adducts are always more stable than the correspondent tin adducts probably due to the formation of cross-linking bonds in these compounds. Finally, of these 16 adducts, 14 showed antimicrobial activities against different bacterial and fungal strains.

Integrative microRNAome analysis of skeletal muscle of Colossoma macropomum (tambaqui), Piaractus mesopotamicus (pacu), and the hybrid tambacu, based on next-generation sequencing data.

BACKGROUND: Colossoma macropomum (tambaqui) and Piaractus mesopotamicus (pacu) are good fish species for aquaculture. The tambacu, individuals originating from the induced hybridization of the female tambaqui with the male pacu, present rapid growth and robustness, characteristics which have made the tambacu a good choice for Brazilian fish farms. Here, we used small RNA sequencing to examine global miRNA expression in the genotypes pacu (PC), tambaqui (TQ), and hybrid tambacu (TC), (Juveniles, n = 5 per genotype), to better understand the relationship between tambacu and its parental species, and also to clarify the mechanisms involved in tambacu muscle growth and maintenance based on miRNAs expression. RESULTS: Regarding differentially expressed (DE) miRNAs between the three genotypes, we observed 8 upregulated and 7 downregulated miRNAs considering TC vs. PC; 14 miRNAs were upregulated and 10 were downregulated considering TC vs. TQ, and 15 miRNAs upregulated and 9 were downregulated considering PC vs. TQ. The majority of the miRNAs showed specific regulation for each genotype pair, and no miRNA were shared between the 3 genotype pairs, in both up- and down-regulated miRNAs. Considering only the miRNAs with validated target genes, we observed the miRNAs miR-144-3p, miR-138-5p, miR-206-3p, and miR-499-5p. GO enrichment analysis showed that the main target genes for these miRNAs were grouped in pathways related to oxygen homeostasis, blood vessel modulation, and oxidative metabolism. CONCLUSIONS: Our global miRNA analysis provided interesting DE miRNAs in the skeletal muscle of pacu, tambaqui, and the hybrid tambacu. In addition, in the hybrid tambacu, we identified some miRNAs controlling important molecular muscle markers that could be relevant for the farming maximization.

Clinical and radiographic analysis of traumatized primary teeth and permanent successors: Longitudinal study.

BACKGROUND: Dental trauma can determine the occurrence of sequelae in the deciduous tooth and due to the anatomical proximity to the germ of the successor permanent tooth, it frequently causes changes to the developing teeth. AIMS: The objective of this study was to analyze clinically and radiographically traumatized primary teeth and permanent successors in children aged 0-8 years. MATERIALS AND METHODS: Initially, a sample selection of medical records was made, designating the patients who fit the requirements; 247 patients were analyzed, totaling 379 traumatized primary teeth and 162 successive permanent teeth. STATISTICAL ANALYSIS: The results were developed using the Proportion Test and the Chi-square test at the 5% significance level. RESULTS: Injuries to hard tissue prevailed (57%), with emphasis on coronary enamel fracture (49.1%). After clinical and radiographic examinations, 78% of traumatized primary teeth maintained pulpal vitality. At the clinical evaluation, the frequency of the developmental disorders observed in permanent successors was 10.5%, with enamel hypocalcification being the most common sequela. 17.3% of the clinical changes in the successor permanent teeth were caused by trauma to the supporting tissue, with the intrusive dislocation being responsible for the largest number of damages (37.5%). CONCLUSION: Based on the results found, it was concluded that the trauma occurring in the primary dentition were recorded and monitored more precisely and about the evaluated successive permanent teeth, except for the prevalence of sequelae found, the other factors are in agreement with the findings in the literature.

The Influence of Environmental Features on the Morphometric Variation in Mauritia flexuosa L.f. Fruits and Seeds.

The environmental heterogeneity may reflect the different morphological and phenotypic traits of individuals belonging to a single species. We used 14 morphological traits of Mauritia flexuosa L.f. to understanding the relation between environment and phenotypic traits. Twenty-five fruits were collected from each of the 10 individuals sampled in each study site: Chapada dos Guimarães (CG), Vila Bela da Santíssima Trindade (VB), and Alta Floresta (AF). We analyzed the genetic divergence, using the standardized Euclidean distance, the sequential method of Tocher, unweighted pair group method with arithmetic mean (UPGMA), and the projection of the distances onto 2D plane, and calculated the relative importance of the traits evaluated. The analysis showed the partition of individuals into three main groups: Two groups comprising the majority of individuals. Fresh fruit weight, pulp rate, fresh pulp weight, and moisture rate were the traits that most helped explaining the difference between materials. The results shown in the current study evidenced the influence of these three different environments on the biometric traits of M. flexuosa. Such influence has led to the formation of Alta Floresta and Vila Bela da Santíssima Trindade individuals in different groups, whereas the Chapada dos Guimarães individuals were able to permeate the two other groups, although they showed stronger tendency to group with individuals from Vila Bela da Santíssima Trindade.

Deregulated microRNAs Are Associated with Patient Survival and Predicted to Target Genes That Modulate Lung Cancer Signaling Pathways.

(1) Background: Although the advances in diagnostic and treatment strategies, lung cancer remains the leading cause of cancer-related deaths, worldwide, with survival rates as low as 16% in developed countries. Low survival rates are mainly due to late diagnosis and the lack of effective treatment. Therefore, the identification of novel, clinically useful biomarkers is still needed for patients with advanced disease stage and poor survival. Micro(mi)RNAs are non-coding RNAs and potent regulators of gene expression with a possible role as diagnostic, prognostic and predictive biomarkers in cancer. (2) Methods: We applied global miRNA expression profiling analysis using TaqMan® arrays in paired tumor and normal lung tissues (n = 38) from treatment-naïve patients with lung adenocarcinoma (AD; n = 23) and lung squamous cell carcinoma (SCC; n = 15). miRNA target genes were validated using The Cancer Genome Atlas (TCGA) lung AD (n = 561) and lung SCC (n = 523) RNA-Seq datasets. (3) Results: We identified 33 significantly deregulated miRNAs (fold change, FC ≥ 2.0 and p < 0.05) in tumors relative to normal lung tissues, regardless of tumor histology. Enrichment analysis confirmed that genes targeted by the 33 miRNAs are aberrantly expressed in lung AD and SCC, and modulate known pathways in lung cancer. Additionally, high expression of miR-25-3p was significantly associated (p < 0.05) with poor patient survival, when considering both tumor histologies. (4) Conclusions: miR-25-3p may be a potential prognostic biomarker in non-small cell lung cancer. Genes targeted by miRNAs regulate EGFR and TGFß signaling, among other known pathways relevant to lung tumorigenesis.

Circulating miR-16-5p, miR-92a-3p, and miR-451a in Plasma from Lung Cancer Patients: Potential Application in Early Detection and a Regulatory Role in Tumorigenesis Pathways.

BACKGROUND: Micro(mi)RNAs, potent gene expression regulators associated with tumorigenesis, are stable, abundant circulating molecules, and detectable in plasma. Thus, miRNAs could potentially be useful in early lung cancer detection. We aimed to identify circulating miRNA signatures in plasma from patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), and to verify whether miRNAs regulate lung oncogenesis pathways. METHODS: RNA isolated from 139 plasma samples (40 LUAD, 38 LUSC; 61 healthy/non-diseased individuals) were divided into discovery (38 patients; 21 controls for expression quantification using an 800-miRNA panel; Nanostring nCounter®) and validation (40 patients; 40 controls; TaqMan® RT-qPCR) cohorts. Elastic net, Maximizing-R-Square Analysis (MARSA), and C-Statistics were applied for miRNA signature identification. RESULTS: When compared to healthy individuals, 580 of 606 deregulated miRNAs in LUAD and 221 of 226 deregulated miRNAs in LUSC had significantly increased levels. Among the 10 most significantly overexpressed miRNAs, 6 were common to patients with LUAD and LUSC. Further analysis identified three signatures composed of 12 miRNAs. Signatures included miRNAs commonly overexpressed in patient plasma. Enriched pathways included target genes modulated by three miRNAs in the C-Statistics signature: miR-16-5p, miR-92a-3p, and miR-451a. CONCLUSIONS: The 3-miRNA signature (miR-16-5p, miR-92a-3p, miR-451a) had high specificity (100%) and sensitivity (84%) to predict cancer (LUAD and LUSC). These miRNAs are predicted to modulate genes and pathways with known roles in lung tumorigenesis, including EGFR, K-RAS, and PI3K/AKT signaling, suggesting that the 3-miRNA signature is biologically relevant in adenocarcinoma and squamous cell carcinoma of the lung.