Engineering a nanoantibiotic system displaying dual mechanism of action.

In recent decades, peptide amphiphiles (PAs) have established themselves as promising self-assembling bioinspired materials in a wide range of medical fields. Herein, we report a dual-therapeutic system constituted by an antimicrobial PA and a cylindrical protease inhibitor (LJC) to achieve broad antimicrobial spectrum and to enhance therapeutic efficacy. We studied two strategies: PA-LJC nanostructures (Encapsulation) and PA nanostructures + free LJC (Combination). Computational modeling using a molecular theory for amphiphile self-assembly captures and explains the morphology of PA-LJC nanostructures and the location of encapsulated LJC in agreement with transmission electron microscopy and two-dimensional (2D) NMR observations. The morphology and release profile of PA-LJC assemblies are strongly correlated to the PA:LJC ratio: high LJC loading induces an initial burst release. We then evaluated the antimicrobial activity of our nanosystems toward gram-positive and gram-negative bacteria. We found that the Combination broadens the spectrum of LJC, reduces the therapeutic concentrations of both agents, and is not impacted by the inoculum effect. Further, the Encapsulation provides additional benefits including bypassing water solubility limitations of LJC and modulating the release of this molecule. The different properties of PA-LJC nanostructures results in different killing profiles, and reduced cytotoxicity and hemolytic activity. Meanwhile, details in membrane alterations caused by each strategy were revealed by various microscopy and fluorescent techniques. Last, in vivo studies in larvae treated by the Encapsulation strategy showed better antimicrobial efficacy than polymyxin B. Collectively, this study established a multifunctional platform using a versatile PA to act as an antibiotic, membrane-penetrating assistant, and slow-release delivery vehicle.

Evaluating the antimicrobial and anti-biofilm activity of three synthetic antimicrobial Citropin analogs and their ability to fight against Staphylococcus aureus and Staphylococcus pseudintermedius.

AIMS: We developed three new analogs of the antimicrobial peptide (AMP) Citropin 1.1: DAN-1-13, AJP-1-1, and HHX-2-28, and tested their potential antimicrobial and antibiofilm activities against Staphylococcus aureus and S. pseudintermedius. Potential cytotoxic or hemolytic effects were determined using cultured human keratinocytes and erythrocytes to determine their safety. METHODS AND RESULTS: To assess the antimicrobial activity of each compound, minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined against methicillin-resistant and methicillin-susceptible strains of S. aureus and S. pseudintermedius. Activity against newly formed and mature biofilms was determined in two clinical isolates using spectrophotometry and scanning electron microscopy (SEM). All three compounds exhibited antimicrobial and bactericidal activity against all studied S. aureus and S. pseudintermedius strains, with MICs ranging from 4-32 µg ml-1 and MBCs ranging from 8-128 µg ml-1. Subinhibitory concentrations of all compounds also showed ant-biofilm activity in the two tested isolates. All compounds exhibited limited cytotoxic and hemolytic activity. CONCLUSIONS: Novel analogs of Citropin 1.1 exhibit antimicrobial and bactericidal activities against S. aureus and S. pseudintermedius isolates and inhibit the biofilm formation of these bacteria.

Oral and cutaneous immune-related adverse events in cancer patients: Prevalence and overall survival.

OBJECTIVES: To assess the prevalence of cutaneous and oral immune-related adverse events (irAEs) in cancer patients, risk factors for its development, and overall survival (OS). MATERIALS AND METHODS: This retrospective observational study which included 748 medical records of cancer patients who received immune checkpoint inhibitors (ICIs). Demographic and clinicopathological characteristics were collected and analyzed. RESULTS: Most patients were male (59.4%), with stage IV cancer (65%) and received pembrolizumab (46.7%). Four hundred fourteen (55.34%) patients developed cutaneous lesions, 84 (11.2%) developed oral mucosal lesions, and 70 (9.3%) developed xerostomia. The median time for irAEs development was 11 weeks for cutaneous and oral mucosal lesions, and 21.5 weeks for xerostomia. Patients who received PD-1 + CTLA-4 had a higher risk for developing cutaneous irAEs (p = 0.001), while those who underwent ICI and concurrent chemotherapy had a higher risk (p = 0.008) for developing oral mucosal lesions. Patients who presented oral and cutaneous irAEs had better OS than those who did not present (p = 0.0001). CONCLUSION: Cutaneous effects affected more than half of the patients, while oral effects and xerostomia were found in around 11% and 9% of patients, respectively. Concurrent chemotherapy and PD-1 + CTLA-4 were more associated with oral and cutaneous irAEs, respectively. Patients who developed such irAEs had better overall survival.

Surgical protocols for oral leukoplakia and precancerous lesions across three different anatomic sites.

OBJECTIVE: This systematic review and meta-analysis aimed to compare the risk of recurrence and cancer progression after surgical treatment for oral potentially malignant disorders (OPMD) and precancerous lesions in different anatomical sites. MATERIALS AND METHODS: A comprehensive search was conducted in nine databases and grey literature. We included randomized controlled trials assessing surgical treatment efficacy for OPMD and precancerous lesions of cervical, vaginal, anal, and penile sites. Excision or ablation surgical treatments were considered. RESULTS: Overall, 12 studies met the eligibility criteria for oral leukoplakia (OL), proliferative verrucous leukoplakia, cervical intraepithelial neoplasia (CIN), vaginal intraepithelial neoplasia, and anal intraepithelial neoplasia (AIN). In qualitative analysis of surgical protocols, the lack of margin description impacts the clinical outcomes of OL and AIN, and the ablative protocols were heterogeneous in both OPMD and precancerous lesions. No significant difference in OL (risk ratio 0.82 [95% CI: 0.59-1.15]) and CIN (risk ratio 0.31 [95% CI: 0.09-1.09]) for recurrence was observed when cold-knife was compared with ablative protocols. OL exhibited higher recurrence and cancer progression rates compared to CIN and AIN. CONCLUSION: There is no difference in recurrence risk post-surgical treatment for OL and CIN. Surgical protocols for oral leukoplakia and CIN/AIN lack standardized approaches.

Directional Multi-Resonant Micro-Electromechanical System Acoustic Sensor for Low Frequency Detection.

This paper reports on the design, modeling, and characterization of a multi-resonant, directional, MEMS acoustic sensor. The design builds on previous resonant MEMS sensor designs to broaden the sensor's usable bandwidth while maintaining a high signal-to-noise ratio (SNR). These improvements make the sensor more attractive for detecting and tracking sound sources with acoustic signatures that are broader than discrete tones. In-air sensor characterization was conducted in an anechoic chamber. The sensor was characterized underwater in a semi-anechoic pool and in a standing wave tube. The sensor demonstrated a cosine-like directionality, a maximum acoustic sensitivity of 47.6 V/Pa, and a maximum SNR of 88.6 dB, for 1 Pa sound pressure, over the bandwidth of the sensor circuitry (100 Hz-3 kHz). The presented design represents a significant improvement in sensor performance compared to similar resonant MEMS sensor designs. Increasing the sensitivity of a single-resonator design is typically associated with a decrease in bandwidth. This multi-resonant design overcomes that limitation.

Glandular odontogenic cyst misdiagnosed and treated as a periapical inflammatory lesion for 6 years in an older adult.

OBJECTIVES: To document the case of a patient who underwent several endodontic treatments due to a glandular odontogenic cyst misdiagnosed as an inflammatory periapical lesion. BACKGROUND: Glandular odontogenic cysts behave more aggressively, while others have an indolent course. There is limited information on this cyst in the gerodontologic literature. MATERIALS AND METHODS: A 76-year-old male patient presented with an asymptomatic expansive lesion in the anterior mandible resistant to several endodontic treatments. Cone-beam computed tomography revealed a multilocular osteolytic lesion measuring 6.0 × 4.0 cm, with cortical bone perforation. RESULTS: Histopathological analysis of a biopsy specimen was consistent with glandular odontogenic cyst. The patient underwent marginal mandibulectomy with preservation of the base of the mandible. CONCLUSION: A strict diagnostic process is important to avoid unwanted consequences, particularly in the geriatric population.

Window therapeutic of extraoral photobiomodulation for prevention of oral mucositis in HSCT patients: additional arm.

PURPOSE: This study aimed to evaluate the efficacy of 1W extraoral photobiomodulation (EOPBM) and to compare with our previous results of 2W EOPBM and intraoral photobiomodulation (IOPBM) protocols in the management of oral mucositis (OM) related to hematopoietic stem cell transplantation (HSCT). METHODS: A total of 30 patients underwent autologous or allogenic HSCT. Experimental protocol of 1W EOPBM was performed daily beginning in the first day of the conditioning regimen until 5 days after transplantation. The application areas included six points on the face and three points on the cervical area. Additional application of IOPBM was performed if patients had ulcered mucositis. Its severity was assessed daily according to WHO (World Health Organization) and NCI (National Cancer Institute) scales. Oral and oropharynx pains were scored daily by visual analogue scale (VAS). RESULTS: The 1W EOPBM protocol was well tolerated without any complaints. Of total, 13 patients were male and 17 were female and the mean age was 49.3 years old. Most patients (21 patients - 70%) received autologous HSCT, and 24 patients (80%) underwent myeloablative conditioning (MAC) regime and 6 patients (20%) reduced intensive conditioning regime. Nineteen patients (63.3%) developed OM according to WHO criteria, 3 patients grade I, 10 grade II and 6 grade III. NCI mucositis grades were similar to WHO grades. OM outcomes of 1W EOPBM were similar when compared to our previous groups and no significant differences were observed. No differences were found between pain and the protocols (1W EOPBM, IOPBM and 2W EOPBM). CONCLUSION: This 1W EOPBM protocol seemed to be as effective as IOPBM and 2W EOPBM in the prevention of OM in HSCT patients. In addition, we might assume that there is a window of application on EOPBM.

Impact of photobiomodulation for prevention of oral mucositis on the quality of life of patients with head and neck cancer: a systematic review.

The aim of this study was to perform a systematic review to evaluate the impact of photobiomodulation therapy (PBMT) for the prevention of oral mucositis (OM) on the quality of life (QoL) of patients with head and neck cancer (HNC) undergoing radiation therapy. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search strategy was performed in five electronic databases (Cochrane, Embase, PubMed, Scopus, and Web of Science). The included studies assessed the QoL of patients undergoing radiation therapy (RT) for HNC and undergoing PBMT for the management of OM. Seven articles met the eligibility criteria. Data extraction was performed in the selected studies including the PBMT parameters (active medium, application procedure, wavelength, fluence, power, irradiance, irradiation time, spot size, energy per point, schedule of irradiation, and total energy). The included studies were qualitatively analyzed, and descriptive analyses were performed. Also, summary results were evaluated for group comparison analysis. All included studies confirmed a decrease in the QoL of the patients that developed OM throughout the RT progress when compared to baseline. Of the informed cases, most of the patients who received PBMT showed grades 1 and 2 OM, while the control group showed more individuals with severe forms of OM (grades 3 and 4). In this sense, patients submitted to PBMT reported better QoL at the end of the treatment compared with the control group. PBMT used for the management of OM preserves the QoL of patients with head and neck cancer.

Directional Resonant MEMS Acoustic Sensor and Associated Acoustic Vector Sensor.

This paper reports on the design, modeling, analysis, and evaluation of a micro-electromechanical systems acoustic sensor and the novel design of an acoustic vector sensor array (AVS) which utilized this acoustic sensor. This research builds upon previous work conducted to develop a small, lightweight, portable system for the detection and location of quiet or distant acoustic sources of interest. This study also reports on the underwater operation of this sensor and AVS. Studies were conducted in the lab and in the field utilizing multiple acoustic sources (e.g., generated tones, gun shots, drones). The sensor operates at resonance, providing for high acoustic sensitivity and a high signal-to-noise ratio (SNR). The sensor demonstrated a maximum SNR of 88 dB with an associated sensitivity of -84.6 dB re 1 V/µPa (59 V/Pa). The sensor design can be adjusted to set a specified resonant frequency to align with a known acoustic signature of interest. The AVS demonstrated an unambiguous, 360-degree, in-plane, azimuthal coverage and was able to provide an acoustic direction of arrival to an average error of within 3.5° during field experiments. The results of this research demonstrate the potential usefulness of this sensor and AVS design for specific applications.

Antivirulence Bispecific Monoclonal Antibody-Mediated Protection against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model.

Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa. We characterized the correlates of protection with MEDI3902, a bispecific human IgG1 monoclonal antibody that targets the P. aeruginosa type 3 secretion system PcrV protein and the Psl exopolysaccharide, in a rabbit model of ventilator-associated pneumonia using lung-protective, low-tidal-volume mechanical ventilation. Rabbits infused with MEDI3902 prophylactically were protected, whereas those pretreated with irrelevant isotype-matched control IgG (c-IgG) succumbed between 12 and 44 h postinfection (100% survival [8/8 rabbits] versus 0% survival [8/8 rabbits]; P < 0.01 by log rank test). Lungs from rabbits pretreated with c-IgG, but not those pretreated with MEDI3902, had bilateral, multifocal areas of marked necrosis, hemorrhage, neutrophilic inflammatory infiltrate, and diffuse fibrinous edema in alveolar spaces. All rabbits pretreated with c-IgG developed worsening bacteremia that peaked at the time of death, whereas only 38% of rabbits pretreated with MEDI3902 (3/8 rabbits) developed such high-grade bacteremia (two-sided Fisher's exact test, P = 0.026). Biomarkers associated with acute respiratory distress syndrome were evaluated longitudinally in blood samples collected every 2 to 4 h to assess systemic pathophysiological changes in rabbits pretreated with MEDI3902 or c-IgG. Biomarkers were sharply increased or decreased in rabbits pretreated with c-IgG but not those pretreated with MEDI3902, including the ratio of arterial oxygen partial pressure to the fraction of inspired oxygen of <300, hypercapnia or hypocapnia, severe lactic acidosis, leukopenia, and neutropenia. Cytokines and chemokines associated with acute respiratory distress syndrome were significantly downregulated in lungs from rabbits pretreated with MEDI3902, compared with c-IgG. These results suggest that MEDI3902 prophylaxis could have potential clinical utility for decreasing the severity of P. aeruginosa ventilator-associated pneumonia.

Characterization of initial/early histologic features of proliferative leukoplakia and correlation with malignant transformation: a multicenter study.

The aim of this multicenter retrospective study is to characterize the histopathologic features of initial/early biopsies of proliferative leukoplakia (PL; also known as proliferative verrucous leukoplakia), and to analyze the correlation between histopathologic features and malignant transformation (MT). Patients with a clinical diagnosis of PL who have at least one biopsy and one follow-up visit were included in this study. Initial/early biopsy specimens were reviewed. The biopsies were evaluated for the presence of squamous cell carcinoma (SCCa), oral epithelial dysplasia (OED), and atypical verrucous hyperplasia (AVH). Cases that lacked unequivocal features of dysplasia were termed "hyperkeratosis/parakeratosis not reactive (HkNR)". Pearson chi-square test and Wilcoxon test were used for statistical analysis. There were 86 early/initial biopsies from 59 patients; 74.6% were females. Most of the cases had a smooth/homogenous (34.8%) or fissured appearance (32.6%), and only 13.0% had a verrucous appearance. The most common biopsy site was the gingiva/alveolar mucosa (40.8%) and buccal mucosa (25.0%). The most common histologic diagnosis was OED (53.5%) followed by HkNR (31.4%). Of note, two-thirds of HkNR cases showed only hyperkeratosis and epithelial atrophy. A lymphocytic band was seen in 34.8% of OED cases and 29.6% of HkNR cases, mostly associated with epithelial atrophy. Twenty-eight patients (47.5%) developed carcinoma and 28.9% of early/initial biopsy sites underwent MT. The mortality rate was 11.9%. Our findings show that one-third of cases of PL do not show OED with most exhibiting hyperkeratosis and epithelial atrophy, but MT nevertheless occurred at such sites in 3.7% of cases.

Oral manifestations of graft-versus-host disease in patients submitted to allogeneic hematopoietic stem cell transplantation: the experience of a Brazilian Cancer Center.

PURPOSE: Graft-versus-host disease (GVHD) is an important complication of allogeneic hematopoietic stem cell transplantation (AHCT) that affects several organs, including the mouth. OBJECTIVES: The aim of the present study was to describe the prevalence and clinical manifestations of oral GVHD, to determine the time interval from AHCT to the onset of oral GVHD manifestations, to identify predictive factors of oral GVHD, and to evaluate the survival rates of patients diagnosed with oral GVHD. METHODS: Medical records of 147 patients who underwent AHCT between January 2010 and January 2015 were reviewed for clinical features and the statistical establishment of risk factors. RESULTS: Of the 147 patients in the study, 99 (67.3%) developed GVHD. The skin was the most affected site (45.6%), followed by the gastrointestinal tract (27.9%) and oral cavity (17.7%). The mean post-AHCT oral GVHD development time was 229 days. Among patients with oral GVHD, pain was the main complaint (96.2%) followed by xerostomia (65.4%). The most common oral manifestations were ulcers (53.8%) followed by striae-associated ulcers (19.2%), mostly affecting the buccal mucosa and tongue. Seventy-three patients (48.6%) died within 20 months of receiving AHCT. Cox regression analysis indicated that patients who received myeloablative conditioning regimen had higher survival rate than those who underwent a reduced-intensity conditioning regimen (RR = 0.541; 95% CI, 0.334-0.878; p = 0.03). CONCLUSION: The mouth was the third most common GVHD-affected site. Pain, xerostomia, and ulcers with or without striae were the main clinical manifestations of GVHD observed in our study cohort. Reduced-intensity conditioning regimen showed significant relationship with mortality risk.

Oral manifestations of immune-related adverse events in cancer patients treated with immune checkpoint inhibitors.

Immunotherapy with immune checkpoint inhibitors (ICIs) has transformed cancer treatment over the past decade, improving survival rates in numerous advanced cancers. Immune-related adverse events (irAEs) are common and can affect any organ system, with many of these toxicities being well-characterized with clear grading criteria and management approaches. There has been less emphasis on oral manifestations of irAEs. This review provides an overview of oral manifestations of irAEs, including mucosal and salivary gland toxicities, and proposes a grading system and management guidelines. irAEs are common treatment-related toxicities in patients treated with ICIs. Oral irAEs can range from asymptomatic white reticulations to life-threatening mucocutaneous reactions requiring aggressive management with corticosteroids and/or permanent discontinuation of ICIs. Oral healthcare providers should be prepared to identify and manage oral irAEs in collaboration with oncologists and other specialists.

Is serum C-terminal telopeptide cross-link of type 1 collagen a reliable parameter for predicting the risk of medication-related osteonecrosis of the jaws? A systematic review and meta-analysis of diagnostic test accuracy.

OBJECTIVE: To determine the usefulness of Serum C-terminal telopeptide cross-link of type 1 collagen (sCTX) as a preoperative marker for predicting the risk of developing medication-related osteonecrosis of the jaws (MRONJ) after invasive oral surgery in patients on antiresorptive medication. MATERIALS AND METHODS: Two authors independently searched four electronic databases up to March 25, 2021, for case-control studies and prospective and retrospective cohort studies that assessed preoperative sCTX levels in patients taking antiresorptive medication who underwent oral surgery procedures. The main outcome was the number of MRONJ cases in patients with an sCTX value lower and higher than 150 pg/mL. Qualitative and quantitative data was extracted in tables and the risk of bias was assessed using the QUADAS-2 tool. Estimates of diagnostic accuracy were expressed as sensitivity, specificity, negative and positive likelihood ratio (LR - and LR +), and diagnostic odds ratio (DOR), with a 95% confidence interval (95%CI). The data were combined using random-effects models based on the inverse variance method. RESULTS: Seven studies were included in the meta-analysis. The results were as follows: sensitivity 57% (95%CI: 41-71%), specificity 72% (95%CI: 64-79%), LR + 2 (95%CI: 1.3-3.1), LR - 0.6 (95%CI: 0.4-0.9), and DOR 3.4 (95%CI: 1.5-7.7). CONCLUSIONS: The low overall performance of sCTX indicates that this parameter is not suitable for predicting MRONJ risk in patients on antiresorptive medication who need an oral surgery procedure. CLINICAL RELEVANCE: sCTX should not be considered a reliable preoperative marker to predict MRONJ development.

Dual Band MEMS Directional Acoustic Sensor for Near Resonance Operation.

In this paper, we report on the design and characterization of a microelectromechanical systems (MEMS) directional sensor inspired by the tympana configuration of the parasitic fly Ormia ochracea. The sensor is meant to be operated at resonance and act as a natural filter for the undesirable frequency bands. By means of breaking the symmetry of a pair of coupled bridged membranes, two independent bending vibrational modes can be excited. The electronic output, obtained by the transduction of the vibration to differential capacitance and then voltage through charge amplifiers, can be manipulated to tailor the frequency response of the sensor. Four different frequency characteristics were demonstrated. The sensor exhibits, at resonance, mechanical sensitivity around 6 µm/Pa and electrical sensitivity around 13 V/Pa. The noise was thoroughly characterized, and it was found that the sensor die, rather than the fundamental vibration, induces the predominant part of the noise. The computed average signal-to-noise (SNR) ratio in the pass band is about 91 dB. This result, in combination with an accurate dipole-like directional response, indicates that this type of directional sensor can be designed to exhibit high SNR and selectable frequency responses demanded by different applications.

MEMS Underwater Directional Acoustic Sensor in Near Neutral Buoyancy Configuration.

A MEMS directional acoustic sensor housed in an air cavity and operated underwater in a near-neutral buoyancy configuration is demonstrated. The sensor consists of two wings connected by a bridge and attached to a substrate by two centrally mounted torsional legs. The frequency response showed two resonant peaks corresponding to a rocking mode (wings moving in opposite directions) and a bending mode (wings moving in the same direction). Initial tests of the sensor using a shaker table showed that the response is highly dependent on the vibration direction. In air, the sensor showed a maximum sensitivity of about 95 mV/Pa with a cosine directional response. Underwater, the maximum sensitivity was about 37 mV/Pa with a similar cosine directional response. The measured maximum SNR was about 38 dB for a signal generated by a sound stimulus of 1 Pa when the sensor is operated near the bending resonance. The results indicate that this type of MEMS sensor can be operated in a near-neutral buoyant configuration and achieve a good directional response.

Intraoral versus extraoral photobiomodulation therapy in the prevention of oral mucositis in HSCT patients: a randomized, single-blind, controlled clinical trial.

To compare the efficacy of intraoral and extraoral photobiomodulation (PBM) protocols for the prevention of oral mucositis (OM) in hematopoietic stem cell transplantation (HSCT) patients. A total of 60 patients was randomized into intraoral PBM (IOPBM) and extraoral PBM (EOPBM) groups. Both PBM protocols were well tolerated and no side effects were observed. EOPBM session times were one fourth of IOPBM durations. Of 60 patients, 35 (58.3%) developed ulcerated OM between day +3 and day +12. No intergroup difference was observed in OM healing times (p = 0.424). The lateral border of the tongue was the most common site affected in both groups. However, the incidence of mucositis on buccal mucosa was significantly reduced in the EOPBM group (p = 0.021). Young patients (OR.5.35, 95%CI 0.94-30.4, p = 0.058) and those who had received myeloablative conditioning (OR.55.1, 95%CI 2.69-1129.3, p = 0.009) were more likely to develop ulcerated OM, whereas autologous HSCT recipients (OR 0.079, 95% CI 0.009-0.67, p = 0.021) had a lower probability of developing ulcerated OM independent of PBM protocol. EOPBM protocol was as effective as IOPBM in the management of OM in HSCT patients, with the advantage of shorter treatment sessions. Trial registration number: RBR-7nww56. Date of trial registration submission: 30th September 2019.

Epidemiological profile and clinical implications of oral squamous cell carcinoma adjacent to dental implants.

OBJECTIVES: Describe the epidemiological profile of patients with oral squamous cell carcinoma (OSCC) around dental implants (DI), investigate the spectrum of clinical and pathological characteristics, and discuss the implications of diagnosis delay of these lesions. METHODS: Retrospective analysis of patients treated of OSCC adjacent to DI at A.C. Camargo Cancer Center between 2009 and 2020. RESULTS: Thirty one patients were identified, being women the majority (58.1%). The mean age of the patients was 68.8 years. Never smoker corresponds to 46.9% and never alcohol consumer to 54.9% of the sample. OPMD was reported in 45.2% of patients, affecting mainly women (78.5%). Leukoplakia (63.7%) followed by oral lichen planus (36.3%) was the most common OPMD found in women. OSCC adjacent to DI occurred in the inferior gingiva/alveolar mucosa in 48.3% of cases, and ulceration was the most common clinical appearance (87%). Peri-implantitis (PI) was initial clinical diagnosis in 16.1% of cases. CONCLUSIONS: Oral squamous cell carcinoma adjacent to DI was more common in women over 70 years old, non-smokers and non-drinker, and the majority had oral leukoplakia before the diagnosis of OSCC. OSCC may present clinical and radiographic features that resemble PI which can delay the diagnosis and impair the prognosis.

Population Genetics of Polyploid Complex Psidium cattleyanum Sabine (Myrtaceae): Preliminary Analyses Based on New Species-Specific Microsatellite Loci and Extension to Other Species of the Genus.

Polyploidy is a phenomenon that alters the genetic diversity of populations and has been reported as one of the most important evolutionary forces for plant diversification. The Psidium cattleyanum complex comprises a group of wild populations with several ploidy levels reported in the literature. The multiple cytotypes, associated with its wide distribution area, make this species a potential key model for understanding evolutionary processes related to polyploidization. In this study, we isolated and characterized nuclear microsatellite markers of P. cattleyanum and tested their transferability to other nine species of the genus. We performed a preliminary analysis of genetic diversity and population structure in three populations of P. cattleyanum. The three populations analyzed had different chromosome numbers, being polyploid cytotypes (2n = 6x = 66, 2n = 7x = 77 and 2n = 8x = 88). We designed 46 primer pairs and successfully amplified 37 markers, from which the 10 best were selected for analysis. Considering both the PIC and DP values, most of markers were highly informative. The new SSR markers were used to assess the levels of genetic diversity of the populations and detected one population with predominance of sexual reproduction. DAPC analysis pointed the formation of three groups, which corresponded to the populations analyzed. The markers were successfully amplified in related species, with some species presenting 80% transferability. By producing this panel of polymorphic microsatellites, we contribute to the understanding evolution in groups of natural polyploids for future studies.

The Brazilian octocoral Phyllogorgia dilatata as a source of cytotoxic compounds.

The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 µg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC50 values of 3.18 and 17.80 µg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.