Microsurgical management of radicular cyst using guided tissue regeneration technique: A case report.

BACKGROUND: Radicular cyst is a lesion of odontogenic origin that arises from epithelial remains due to periapical periodontitis caused by inflammatory reactions generated at the apex of affected teeth with infected or necrotic pulps. The therapeutic management of radicular cysts is controversial. There is only one case report of enucleation of a radicular cyst managed with microsurgery and apicoectomy, but without the use of the guided tissue regeneration (GTR) technique in the same surgical procedure. The present clinical case describes the management of a radicular cyst with microsurgical approach, performance of an apicoectomy of the tooth associated with the entity, application of GTR technique, use of a resorbable membrane of type I bovine collagen, and bovine xenograft. CASE SUMMARY: A 68-year-old patient presented with a radicular cyst from an upper lateral incisor. The microsurgical management used was aimed at enucleating the chemical membrane, performing apicoectomy of the tooth along with careful and precise retrograde filling, and implementing GTR technique using a resorbable collagen membrane and bovine xenograft. The diagnosis of radicular cyst was confirmed using histopathological analysis. The patient underwent follow-up evaluations at 10 and 30 d postoperatively. At 4 months postoperative evaluation, she remained asymptomatic, and radiographs showed significant periapical healing with adequate bone formation. CONCLUSION: These results suggest that microsurgical management using the GTR technique with collagen membrane and xenograft, contributes to bone regeneration.

Oral Pyogenic Granuloma: A Narrative Review.

Pyogenic granuloma (PG) is a benign vascular lesion found predominantly in the oral cavity. Characterized by rapid growth and propensity to bleed, PG presents diagnostic challenges due to its similarity and alarming proliferation. This narrative review synthesizes current knowledge on the epidemiology, etiopathogenesis, clinical manifestations, and management of oral PG, with emphasis on recent advances in diagnostic and therapeutic approaches. The epidemiology of the injury is meticulously analyzed, revealing a higher incidence in women and a wide range of ages of onset. It delves into the etiopathogenesis, highlighting the uncertainty surrounding the exact causal factors, although historical attributions suggest an infectious origin. It exhaustively analyzes the clinical and histopathological aspects of oral PG, offering information on its various presentations and the importance of an accurate diagnosis to guide effective treatment. It details treatment strategies, emphasizing the personalized approach based on individual patient characteristics. This comprehensive review consolidates current knowledge on oral PG, highlighting the need for further research to clarify its pathogenesis and optimize treatment protocols.

Unusual clinical presentation of oral pyogenic granuloma with severe alveolar bone loss: A case report and review of literature.

BACKGROUND: Pyogenic granuloma (PG) is a localized, reddish and vascularized hyperplastic lesion of the connective tissue which occurs in the oral cavity. In most cases, the presence of this lesion does not show alveolar bone resorption. The pathology is diagnosed clinically with some caution. However, the diagnosis and treatment are usually corroborated with histopathological evidence. CASE SUMMARY: Three clinical cases of PG associated with bone loss were described in this study. The three patients presented tumor-like growth which bled on touch, and were associated with local irritant factors. Radiographs showed bone loss. All cases were treated with conservative surgical excision. The scarring was satisfactory, and there was no case of recurrence. The diagnoses were based on clinical findings, and were confirmed histopathologically. CONCLUSION: The occurrence of oral PG with bone loss is unusual. Therefore, clinical and radiographic evaluations are important for the diagnosis.

Gingival enlargement induced by cyclosporine in Medullary aplasia: A case report.

BACKGROUND: Cyclosporine is an immunosuppressive agent used effectively for treatment of a rare haematological disorder known as medullary aplasia. This drug prevents several side effects, including gingival enlargement (GE) which compromises aesthetics, phonetics and chewing, and also predisposes patients to periodontitis. CASE SUMMARY: This clinical case reports a 41-year-old woman who presented with cyclosporine-induced GE with underlying periodontitis and medullary aplasia. The management of the disease was approached through multidisciplinary strategy which allowed for accurate diagnosis and a strategic treatment based on the systemic condition and severity of oral pathology. The diagnosis was confirmed through histopathological analysis. The treatment was carried out in phases: Initial (oral hygiene motivation, mechanical supragingival plaque control, and non-surgical therapy); systemic treatment, corrective treatment, and maintenance. CONCLUSION: Multidisciplinary management of cyclosporine-induced GE and medullary aplasia allows for correct diagnosis and effective treatment of this pathological expression through a phased therapeutic approach.

Isothiocyanate-Rich Extracts from Cauliflower (Brassica oleracea Var. Botrytis) and Radish (Raphanus sativus) Inhibited Metabolic Activity and Induced ROS in Selected Human HCT116 and HT-29 Colorectal Cancer Cells.

Cruciferous vegetables such as cauliflower and radish contain isothiocyanates exhibiting chemoprotective effects in vitro and in vivo. This research aimed to assess the impact of cauliflower (CIE) and radish (RIE) isothiocyanate extracts on the metabolic activity, intracellular reactive oxygen species (ROS), and LDH production of selected human colorectal adenocarcinoma cells (HCT116 and HT-29 for early and late colon cancer development, respectively). Non-cancerous colon cells (CCD-33Co) were used as a cytotoxicity control. The CIE samples displayed the highest allyl isothiocyanate (AITC: 12.55 µg/g) contents, whereas RIE was the most abundant in benzyl isothiocyanate (BITC: 15.35 µg/g). Both extracts effectively inhibited HCT116 and HT-29 metabolic activity, but the CIE impact was higher than that of RIE on HCT116 (IC50: 0.56 mg/mL). Assays using the half-inhibitory concentrations (IC50) of all treatments, including AITC and BITC, displayed increased (p < 0.05) LDH (absorbance: 0.25-0.40 nm) and ROS release (1190-1697 relative fluorescence units) in both cell lines. BITC showed the highest in silico binding affinity with all the tested colorectal cancer molecular markers (NF-kB, ß-catenin, and NRF2-NFE2). The theoretical evaluation of AITC and BITC bioavailability showed high values for both compounds. The results indicate that CIE and RIE extracts display chemopreventive effects in vitro, but additional experiments are needed to validate their effects.

Impacts of Pesticides on Oral Cavity Health and Ecosystems: A Review.

Pesticides are chemical substances used to control, prevent, or destroy agricultural, domestic, and livestock pests. These compounds produce adverse changes in health, and they have been associated with the development of multiple chronic diseases. This study aimed to present a detailed review of the effect of pesticides on the oral cavity and the oral microbiome. In the oral cavity, pesticides alter and/or modify tissues and the microbiome, thereby triggering imbalance in the ecosystem, generating an inflammatory response, and activating hydrolytic enzymes. In particular, the imbalance in the oral microbiome creates a dysbiosis that modifies the number, composition, and/or functions of the constituent microorganisms and the local response of the host. Pesticide exposure alters epithelial cells, and oral microbiota, and disrupts the homeostasis of the oral environment. The presence of pesticides in the oral cavity predisposes the appearance of pathologies such as caries, periodontal diseases, oral cancer, and odontogenic infections. In this study, we analyzed the effect of organochlorines, organophosphates, pyrethroids, carbamates, bipyridyls, and triazineson oral cavity health and ecosystems.

STUB1 is an intracellular checkpoint for interferon gamma sensing.

Immune checkpoint blockade (ICB) leads to durable and complete tumour regression in some patients but in others gives temporary, partial or no response. Accordingly, significant efforts are underway to identify tumour-intrinsic mechanisms underlying ICB resistance. Results from a published CRISPR screen in a mouse model suggested that targeting STUB1, an E3 ligase involved in protein homeostasis, may overcome ICB resistance but the molecular basis of this effect remains unclear. Herein, we report an under-appreciated role of STUB1 to dampen the interferon gamma (IFNγ) response. Genetic deletion of STUB1 increased IFNGR1 abundance on the cell surface and thus enhanced the downstream IFNγ response as showed by multiple approaches including Western blotting, flow cytometry, qPCR, phospho-STAT1 assay, immunopeptidomics, proteomics, and gene expression profiling. Human prostate and breast cancer cells with STUB1 deletion were also susceptible to cytokine-induced growth inhibition. Furthermore, blockade of STUB1 protein function recapitulated the STUB1-null phenotypes. Despite these encouraging in vitro data and positive implications from clinical datasets, we did not observe in vivo benefits of inactivating Stub1 in mouse syngeneic tumour models-with or without combination with anti-PD-1 therapy. However, our findings elucidate STUB1 as a barrier to IFNγ sensing, prompting further investigations to assess if broader inactivation of human STUB1 in both tumors and immune cells could overcome ICB resistance.

Allyship in Residency: An Introductory Module on Medical Allyship for Graduate Medical Trainees.

INTRODUCTION: Lack of diversity impacts research, medical curricula, and medical trainees' ability to provide equitable patient care. The concept of allyship, defined as a supportive association between identities with power and privilege and marginalized identities, provides an optimal framework for enhancing education about health equity. Currently, there are no established curricula focused on allyship and limited mention within current medical training literature. We propose use of allyship to increase graduate medical trainee understanding of diversity and focus on health equity. METHODS: We developed a 1-hour workshop aimed at helping residents understand the definition of allyship, effective allyship to patients and colleagues, and allyship differences across communities. The workshop consisted of pre- and postassessment surveys, a didactic presentation module, and facilitated case study discussions. It was conducted locally on four occasions across pediatrics, family medicine, surgery, and emergency medicine residency programs. RESULTS: An analysis of the 101 preassessment and 58 postassessment survey responses revealed an increased level of knowledge regarding allyship (p < .001) and increased comprehension of allyship competencies (p < .001). All workshop learning objectives demonstrated positive change postmodule. DISCUSSION: With an increasing need for curricula to address health equity in medical trainees, this workshop serves as a unique and effective approach to expanding cultural responsiveness skills under the lens of allyship. Specifically, the workshop functions as a constructive introduction to allyship principles and practices and can serve as a foundation on which residents can build more robust skills as a part of their allyship journey.

Geographic partitioning or environmental selection: What governs the global distribution of bacterial communities inhabiting floral nectar?

Floral nectar harbors microbial communities which have significant impacts on its chemistry, volatiles, nutritional contents, and attractiveness for pollinators. Yet, fundamental knowledge regarding the structure and composition of nectar-associated microbiomes remains largely unknown. Especially elusive are the environmental factors and spatial effects that shape nectar-inhabiting microbial communities. The aim of this study was to explore and analyze the role of geographical and environmental factors affecting the composition and global distribution of floral nectar microbiota. We explored and compared the structure of bacterial communities inhabiting the floral nectar of the widely spread and invasive tobacco tree (Nicotiana glauca) in six continents: South and North America, Australia, Europe, Africa, and Asia, using 16S rRNA gene sequencing. Environmental abiotic data for each sampled plant was obtained from the Worldclim database and applied for inferring the effects of environmental conditions on bacterial community structure and diversity. Most abundant in the nectar were the Proteobacteria, Firmicutes, and Actinobacteria phyla, with Acinetobacter and Rosenbergiella (Proteobacteria) being the dominant bacterial genera that contributed most to the dissimilarities between sites. Acinetobacter and Rosenbergiella abundances were negatively correlated and significantly higher in the Mediterranean regions (Greece, Israel, and the Canary Islands) compared to Argentina and Australia. Temperature, site-elevation, rainfall, and density of vegetation were found to have significant effects on the structure and diversity of these bacterial communities in the nectar. Vegetation density was positively correlated with microbial diversity, while increased temperatures and elevation reduced the diversity and evenness of bacterial communities. Mantel's test showed that the similarity between the bacterial communities' composition significantly decreased as distances between them increased. We conclude that both geographical distance and local environmental abiotic conditions affect and shape the composition and diversity of nectar inhabiting bacterial communities.

A Multidisciplinary Evaluation of Barriers to Enrolling Cancer Patients into Early Phase Clinical Trials: Challenges and Patient-centric Recommendations.

Introduction: Early phase clinical trials are the first clinical research step to bringing new cancer therapeutics to patients. At this stage, a new drug's safety, dosing, and scheduling profiles are established as the main endpoints. However, excellent responses due to biomarker-guided and immune checkpoint trials in early phase have resulted in direct approvals of new anti-cancer drugs. Despite doubling of the success rate of new drug approvals, many barriers exist to expeditiously bring active new drugs to the clinic. Areas covered: This review covers roles of members of the early phase program and the challenges they face in enrolling advanced cancer patients to trials. Practical solutions are provided from the perspective of the investigators, regulatory, investigational pharmacy, research nurses, clinical research coordinators, budgets, contracts, and data management. Expert opinion: We are witnessing a burgeoning era in drug development with rapid approval of efficacious drugs. This is achieved by a strong collaboration between investigators, academic institutions, pharmaceutical sponsors, scientists, Food and Drug Administration (FDA), and community practices. Herein, we discuss some of the challenges faced by early phase clinical trials programs and discuss methods of improvement.

Virulence Traits of Environmental and Clinical Legionella pneumophila Multilocus Variable-Number Tandem-Repeat Analysis (MLVA) Genotypes.

Legionella pneumophila causes water-based infections resulting in severe pneumonia. Recently, we showed that different MLVA-8 (multilocus variable-number tandem-repeat analysis using 8 loci) genotypes dominated different sites of a drinking-water distribution system. Each genotype displayed a unique temperature-dependent growth behavior. Here we compared the pathogenicity potentials of different MLVA-8 genotypes of environmental and clinical strains. The virulence traits studied were hemolytic activity and cytotoxicity toward amoebae and macrophages. Clinical strains were significantly more hemolytic than environmental strains, while their cytotoxicity toward amoebae was significantly lower at 30°C. No significant differences were detected between clinical and environmental strains in cytotoxicity toward macrophages. Significant differences in virulence were observed between the environmental genotypes (Gt). Gt15 strains showed a significantly higher hemolytic activity. In contrast, Gt4 and Gt6 strains were more infective toward Acanthamoeba castellanii Moreover, Gt4 strains exhibited increased cytotoxicity toward macrophages and demonstrated a broader temperature range of amoebal lysis than Gt6 and Gt15 strains. Understanding the virulence traits of Legionella genotypes may improve the assessment of public health risks of Legionella in drinking water.IMPORTANCELegionella pneumophila is the causative agent of a severe form of pneumonia. Here we demonstrated that clinical strains were significantly more cytotoxic toward red blood cells than environmental strains, while their cytotoxicity toward macrophages was similar. Genotype 4 (Gt4) strains were highly cytotoxic toward amoebae and macrophages and lysed amoebae in a broader temperature range than to the other studied genotypes. The results can explain the relatively high success of Gt4 in the environment and in clinical samples; thus, Gt4 strains should be considered a main factor for the assessment of public health risks of Legionella in drinking water. Our findings shed light on the ecology, virulence, and pathogenicity potential of different L. pneumophila genotypes, which can be a valuable parameter for future modeling and quantitative microbial risk assessment of Legionella in drinking-water systems.

Effect of Common Drinking Water Disinfectants, Chlorine and Heat, on Free Legionella and Amoebae-Associated Legionella.

Chlorine and thermal treatments are the most commonly used procedures to control and prevent Legionella proliferation in drinking water systems of large buildings. However, cases of legionellosis still occur in facilities with treated water. The purpose of this work was to model the effect of temperature and free chlorine applied in similar exposure conditions as in drinking water systems on five Legionella spp. strains and two amoebal strains of the genera Acanthamoeba. Inactivation models obtained were used to determine the effectiveness of the treatments applied which resulted more effective against Legionella than Acanthamoeba, especially those in cystic stages. Furthermore, to determine the influence of the relationship between L. pneumophila and Acanthamoeba spp. on the treatment effectiveness, inactivation models of the bacteria-associated amoeba were also constructed and compared to the models obtained for the free living bacteria state. The Legionella-amoeba association did not change the inactivation models, but it reduced the effectiveness of the treatments applied. Remarkably, at the lowest free chlorine concentration, 0.5 mg L-1, as well as at the lowest temperatures, 50°C and 55°C, the influence of the Legionella-amoeba associate state was the strongest in reducing the effectiveness of the treatments compared to the free Legionella state. Therefore, the association established between L. pneumophila and amoebae in the water systems indicate an increased health risk in proximal areas of the system (close to the tap) where lower free chlorine concentrations and lower temperatures are commonly observed.

Optimized cell transplantation using adult rag2 mutant zebrafish.

Cell transplantation into adult zebrafish has lagged behind mouse models owing to the lack of immunocompromised strains. Here we have created rag2(E450fs) mutant zebrafish that have reduced numbers of functional T and B cells but are viable and fecund. Mutant fish engraft muscle, blood stem cells and various cancers. rag2(E450fs) mutant zebrafish are the first immunocompromised zebrafish model that permits robust, long-term engraftment of multiple tissues and cancer.

Clonal evolution enhances leukemia-propagating cell frequency in T cell acute lymphoblastic leukemia through Akt/mTORC1 pathway activation.

Clonal evolution and intratumoral heterogeneity drive cancer progression through unknown molecular mechanisms. To address this issue, functional differences between single T cell acute lymphoblastic leukemia (T-ALL) clones were assessed using a zebrafish transgenic model. Functional variation was observed within individual clones, with a minority of clones enhancing growth rate and leukemia-propagating potential with time. Akt pathway activation was acquired in a subset of these evolved clones, which increased the number of leukemia-propagating cells through activating mTORC1, elevated growth rate likely by stabilizing the Myc protein, and rendered cells resistant to dexamethasone, which was reversed by combined treatment with an Akt inhibitor. Thus, T-ALL clones spontaneously and continuously evolve to drive leukemia progression even in the absence of therapy-induced selection.

[Renal metastasis of classic seminoma]. / Metástasis renal de seminoma clásico.

INTRODUCTION: Seminoma comprises approximately 50% of testicular germ cell tumors. Renal metastases are infrequent, and are usually recognized at necropsy. CLINICAL CASE: A 24 years-old man with history of left radical orchiectomy due to classical seminoma (stage I), and adjuvant radiotherapy, showed elevated levels of beta-human chorionic gonadotropin and lactate dehydrogenase in the eleven month follow-up. Computed tomography showed a 9 × 8 cm lobulated, heterogeneous tumor in the left kidney. The histopathological and immunohistochemical assay demonstrated a classical metastatic seminoma. CONCLUSION: The majority of renal tumors represent primary neoplasm; in patients with extra-renal tumors we must consider the possibility of a metastatic disease.

A tubulin polymerization microassay used to compare ligand efficacy.

We developed tubulin purification strategies that allowed sufficient material to be produced for compound-screening projects. Tubulins were polymerized in the presence of compounds using either turbidometric or fluorescence polymerization assays. IC50 and EC50 values were calculated and used to determine ratios between host and target tubulin (TT) (e.g., IC50-neuronal tubulin/IC50-TT). This ratio can be compared between compounds to identify the ones which are most selective for a particular TT. We found ratios for different compounds ranged from 0.16 to 4.0 between neuronal and cancer cell tubulin indicating that the sequence and posttranslational heterogeneity between these tubulins are sufficient to identify selective ligands for the TT. Likewise, compounds compared between neuronal and fungal tubulin had ratios ranging from 0.03 to 0.60, and compounds compared between neuronal to plant tubulin had ratios ranging from 0.03 to 52. Considering these data, we believe cancer cell tubulin-targeted drugs could be obtained with ratios in excess of 20, herbicides with ratios in excess of 200, and fungicides in excess of 200.