Tumor-intrinsic perinuclear LOXL2: Prognostic relevance and relationship with YAP1 activation status in oral squamous cell carcinoma.

INTRODUCTION: Lysyl Oxidase-Like 2 (LOXL2) expression and function is frequently altered in different cancers, but scarcely explored in oral squamous cell carcinoma (OSCC). This prompted us to investigate the clinical relevance of LOXL2 expression pattern in OSCC and also a possible crosstalk with Hippo/YAP1 pathway signaling. METHODS: Immunohistochemical analysis of LOXL2 protein expression was performed in 158 OSCC patient samples, together with Yes-associated protein 1 (YAP1) activation status. Correlations with clinicopathological parameters and patient survival were assessed. RESULTS: Tumor cell-intrinsic LOXL2 expression showed two distinct expression patterns: diffuse cytoplasmic staining (64.6%), and heterogeneous perinuclear staining (35.4%). Remarkably, perinuclear LOXL2 staining was significantly associated with lymph node metastasis, advanced clinical stage and perineural invasion. Moreover, patients harboring tumors with perinuclear LOXL2 expression exhibited significantly poorer disease-specific survival (DSS) rates. Strikingly, we also found that perinuclear LOXL2 positivity gradually increased in relation to YAP1 activation, and patients harboring tumors with concomitant perinuclear LOXL2 and fully active YAP1 exhibited the worst DSS. Multivariate Cox analysis further revealed combined perinuclear LOXL2 and fully active YAP1 as a significant independent predictor of poor DSS. CONCLUSION: Tumor-intrinsic perinuclear LOXL2 emerges as a clinically and biologically relevant feature associated with advanced disease, tumor aggressiveness, and poor prognosis in OSCC. Moreover, this study unprecedentedly uncovers a functional relationship between perinuclear LOXL2 and YAP1 activation with major prognostic implications. Notably, combined perinuclear LOXL2 and fully active YAP1 was revealed as independent predictor of poor prognosis. These findings encourage targeting oncogenic LOXL2 functions for personalized treatment regimens.

Outcomes associated with ventilator-associated events (VAE), respiratory infections (VARI), pneumonia (VAP) and tracheobronchitis (VAT) in ventilated pediatric ICU patients: A multicentre prospective cohort study.

OBJECTIVES: An objective categorization of respiratory infections based on outcomes is an unmet clinical need. Ventilator-associated pneumonia and tracheobronchitis remain used in clinical practice, whereas ventilator-associated events (VAE) are limited to surveillance purposes. RESEARCH METHODOLOGY/DESIGN: This was a secondary analysis from a multicentre observational prospective cohort study. VAE were defined as a sustained increase in minimum Oxygen inspired fraction (FiO2) and/or Positive end-expiratory pressures (PEEP) of ≥ 0.2/2 cm H2O respectively, or an increase of 0.15 FiO2 + 1 cm H20 positive end-expiratory pressures for ≥ 1 calendar-day. SETTING: 15 Paediatric Intensive Care Units. MAIN OUTCOME MEASURES: Mechanical ventilation duration, intensive care and hospital length of stay; (LOS) and mortality. RESULTS: A cohort of 391 ventilated children with an age (median, [Interquartile Ranges]) of 1 year[0.2-5.3] and 7 days[5-10] of mechanical ventilation were included. Intensive care and hospital stays were 11 [7-19] and 21 [14-39] days, respectively. Mortality was 5.9 %. Fifty-eight ventilator-associated respiratory infections were documented among 57 patients: Seventeen (29.3 %) qualified as ventilator-associated pneumonia (VAP) and 41 (70.7 %) as ventilator-associated tracheobronchitis (VAT). Eight pneumonias and 16 tracheobronchitis (47 % vs 39 %,P = 0.571) required positive end-expiratory pressure or oxygen increases consistent with ventilator-associated criteria. Pneumonias did not significantly impact on outcomes when compared to tracheobronchitis. In contrast, infections (pneumonia or tracheobronchitis) following VAEs criteria were associated with > 6, 8 and 15 extra-days of ventilation (16 vs 9.5, P = 0.001), intensive care stay (23.5 vs 15; P = 0.004) and hospital stay (39 vs 24; P = 0.015), respectively. CONCLUSION: When assessing ventilated children with respiratory infections, VAE apparently is associated with higher ventilator-dependency and LOS compared with pneumonia or tracheobronchitis. IMPLICATIONS FOR PRACTICE: Incorporating the modification of ventilatory settings for further categorization of the respiratory infections may facilitate therapeutic management among ventilated patients.

Increase in Incidence Rates and Risk Factors for Multidrug Resistant Bacteria in Septic Children: A Nationwide Spanish Cohort Study (2013-2019).

The emergence of multidrug-resistant (MDR) bacteria in children is a growing concern, particularly among septic patients, given the need for first-right dosing. Our aim was to determine the incidence rates and factors associated with MDR-sepsis in the pediatric intensive care unit (PICU), using data from the Spanish ENVIN-HELICS PICU registry between 2013 and 2019. The rate of MDR bacteria among septic children ranged between 5.8 and 16.2% throughout this study period, with a significant increase since 2015 (p = 0.013). MDR-gram-negative bacteria (92%), particularly EBL-Enterobacterales (63.7%), were the most frequent causative microorganisms of MDR-sepsis. During this study period, sixteen MDR-sepsis (32.6%) corresponded to intrahospital infections, and 33 (67.4%) had community-onset sepsis, accounting for 10.5% of the overall community-onset sepsis. Independent risk factors associated with MDR-sepsis were antibiotics 48 h prior to PICU admission (OR 2.38) and PICU onset of sepsis (OR 2.58) in >1 year-old children, and previous malnourishment (OR 4.99) in <1 year-old children. Conclusions: There was an alarming increase in MDR among septic children in Spain, mainly by gram-negative (ESBL-Enterobacterales), mostly coming from the community setting. Malnourished infants and children on antibiotics 48 h prior to PICU are at increased risk and therefore require closer surveillance.

Prognostic Significance of ß-Catenin in Relation to the Tumor Immune Microenvironment in Oral Cancer.

The aim of this study was to investigate the prognostic relevance of ß-catenin expression in oral squamous cell carcinoma (OSCC) and to explore relationships with the tumor immune microenvironment. Expression of ß-catenin and PD-L1, as well as lymphocyte and macrophage densities, were evaluated by immunohistochemistry in 125 OSCC patient specimens. Membranous ß-catenin expression was detected in 102 (81.6%) and nuclear ß-catenin in 2 (1.6%) tumors. There was an association between ß-catenin expression, tumoral, and stromal CD8+ T-cell infiltration (TIL) and also the type of tumor immune microenvironment (TIME). Tumors harboring nuclear ß-catenin were associated with a type II TIME (i.e., immune ignorance defined by a negative PD-L1 expression and low CD8+ TIL density), whereas tumors with membranous ß-catenin expression were predominantly type IV (i.e., immune tolerance defined by negative PD-L1 and high CD8+ TIL density). Combined, but not individual, high stromal CD8+ TILs and membranous ß-catenin expression was independently associated with better disease-specific survival (HR = 0.48, p = 0.019). Taken together, a combination of high stromal CD8+ T-cell infiltration and membranous ß-catenin in the tumor emerges as an independent predictor of better survival in OSCC patients.

Emerging Role of Decoy Receptor-2 as a Cancer Risk Predictor in Oral Potentially Malignant Disorders.

The aim of this study was to evaluate the expression of the senescence markers, Decoy Receptor 2 (DcR2) and Differentiated Embryo-Chondrocyte expressed gen 1 (DEC1), in oral potentially malignant disorders (OPMDs) to ascertain their possible association with oral cancer risk. The immunohistochemical analysis of DcR2 and DEC1 expression (along with p16 and Ki67 expression) was carried out in 60 patients with clinically diagnosed oral leukoplakia. Fifteen cases (25%) subsequently developed an invasive carcinoma. Correlations between protein marker expression, histological grade and oral cancer risk were assessed. DcR2, DEC1 and Ki67 protein expressions were found to correlate significantly with increased oral cancer risk, and also with an increased grade of dysplasia. Multivariate analysis demonstrated that DcR2 and Ki67 expression are independent predictors of oral cancer development. Our results evidence for the first time the potential of DcR2 as an early biomarker to assess oral cancer risk in patients with oral leukoplakia (HR = 59.7, p = 0.015), showing a superior predictive value to histology (HR = 4.225, p = 0.08). These findings reveal that the increased expression of DcR2 and DEC1 occurred frequently in OPMDs. In addition, DcR2 expression emerges as a powerful biomarker for oral cancer risk assessment in patients with oral leukoplakia.

Characteristics and management of patients with SARS-CoV2 infection admitted to pediatric intensive care units: Data analysis of the Spanish national multicenter registry.

INTRODUCTION: The purpose of this study is to describe the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) disease characteristics and management in children admitted to the pediatric intensive care units (PICU). METHODS: The present study was based on a national multicentric prospective registry including PICU patients with SARS-CoV2 infection or symptoms of multisystem inflammatory syndrome in children (MIS-C). RESULTS: A total of 298 patients were admitted to 41 different Spanish PICUs. A total of 76% of them were previously healthy. The most frequent manifestation was MIS-C (69.8%). On admission, 59.4% of patients did not have respiratory distress, and only 17.4% needed conventional mechanical ventilation (MV). The need for MV was associated with age (incidence rate ratios [IRR] 1.21, p < .012), pediatric sequential organ failure assessment score (p-SOFA) Score (IRR 1.12, p = .001), and need for transfusion (IRR 4.5, p < .004) in MIS-C patients, and with vasoactive drug use (IRR 2.73, p = .022) and the diagnosis of acute respiratory distress syndrome (IRR 2.83, p = .018) in patients admitted for other reasons. During the first day of admission, 56% of patients met shock criteria and 50.7% needed vasoactive drugs. In MIS-C patients, their use was associated with higher p-SOFA score (IRR 1.06, p < .001) and with the diagnosis of shock (IRR 5.78, p < .001). In patients without MIS-C, it was associated with higher p-SOFA score (IRR 1.05, p = .022). The mortality rate was 3%, being lower in MIS-C patients compared to patients admitted for other reasons (0.5% vs. 9.4%, p < .001). It was also lower in previously healthy patients compared to patients with previous comorbidities (0.9% vs. 9.7%, p < .001). CONCLUSIONS: Severe SARS-CoV2 infection is uncommon in the pediatric population. In our series, respiratory distress was rare, being MIS-C the most frequent cause of PICU admission related to SARS-CoV2. In most cases, the course of the disease was mild except in children with previous diseases.

The epidemiology and management of odontomas: a European multicenter study.

INTRODUCTION: Odontoma is the most commonly diagnosed odontogenic tumor of the oral cavity. The objective of the present study was to assess the demographic variables, patterns, diagnostic features, and management issues of odontomas treated at several European departments of maxillofacial and oral surgery. MATERIALS AND METHODS: This study was conducted at 8 European departments of oral surgery between January 1, 2004, and December 31, 2018. Only patients with odontomas were included. The following data were recorded for each patient: gender, age, comorbidities, site, size of odontomas, radiographic features, type of odontoma, treatment of odontomas, treatment of associated teeth, complications, and recurrence. RESULTS: A total of 127 patients (70 male and 57 female patients) with odontomas were included. The mean age was 22 years; 71 odontomas were found in the mandible, whereas 56 in the maxilla. In the mandible, the most frequently involved subsite was the parasymphysis, while in the maxilla, the most common subsite was the upper incisor region. The mean size of included odontomas was 15.3 mm. On the whole, 62 complex odontomas, 50 compound odontomas, and 15 mixed-type odontomas were observed. Complete excision of the odontomas was performed in 121 patients. In 24 patients, the extraction of deciduous teeth was performed, and in 43 patients, one or more permanent teeth were removed. Finally, in 9 patients, a partial excision of the odontoma was performed. Recurrence was observed in 4 cases out of 127 patients. CONCLUSIONS: Dental practitioners should be aware of the distinct clinical and radiographic features of odontoma in order to perform an appropriate and early diagnosis. Conventional radiography, such as panoramic radiograph, is often sufficient technique for a diagnosis after clinical suspicion or for an incidental diagnosis to prevent later complications, such as impaction or failure of eruption of teeth.

Device Exposure and Patient Risk Factors' Impact on the Healthcare-Associated Infection Rates in PICUs.

Healthcare-associated infections related to device use (DA-HAIs) are a serious public health problem since they increase mortality, length of hospital stay and healthcare costs. We performed a multicenter, prospective study analyzing critically ill pediatric patients admitted to 26 Spanish pediatric intensive care units (PICUs) over a 3-month period each year from 2014 to 2019. To make comparisons and evaluate the influence of HAI Zero Bundles (care bundles that intend to reduce the DA-HAI rates to zero) on PICU HAI rates, the analysis was divided into two periods: 2014-2016 and 2017-2019 (once most of the units had incorporated all the Zero Bundles). A total of 11,260 pediatric patients were included. There were 390 episodes of HAIs in 317 patients and the overall rate of HAIs was 6.3 per 1000 patient days. The DA-HAI distribution was: 2.46/1000 CVC days for central-line-associated bloodstream infections (CLABSIs), 5.75/1000 MV days for ventilator-associated pneumonia (VAP) and 3.6/1000 UC days for catheter-associated urinary tract infections (CAUTIs). Comparing the two periods, the HAI rate decreased (p = 0.061) as well as HAI episodes (p = 0.011). The results demonstrate that exposure to devices constitutes an extrinsic risk factor for acquiring HAIs. The multivariate analysis highlights previous bacterial colonization by multidrug-resistant (MDR) bacteria as the most important extrinsic risk factor for HAIs (OR 20.4; 95%CI 14.3-29.1). In conclusion, HAI Zero Bundles have been shown to decrease HAI rates, and the focus should be on the prompt removal of devices, especially in children with important intrinsic risk factors.

Drowning Accidents in a Spanish Pediatric Intensive Care Unit: An Observational Study for 29 Years.

INTRODUCTION: Drowning is one of the most frequent accidents in children. We aimed to describe demographic and epidemiological characteristics of drowned children who required admission to a pediatric intensive care unit (PICU) to identify risk factors to guide possible preventive measures to avoid severe drowning. METHODS: We conducted an observational study for 29 years (retrospective between 1991 and 2004; prospective between 2005 and 2019) that included all children (0-15 years old) requiring PICU admission after drowning. Data regarding patient characteristics, accident circumstances, and neurological outcomes at PICU discharge were analyzed. RESULTS: A total of 160 patients were included, with no significant decrease over the study period. There was a predominance of males (75%), young age (60%; 1-5 years), summer months (91.1%; May-September), tourists (14.12 [95% confidence interval, 9.2-21.7] times higher risk of drowning than residents), swimming pool accidents (88.8%), and inadequate supervision (77.9%). The mortality was 18.7%, and 7.5% of admitted children had severe neurological sequelae. The initial resuscitation maneuvers by accident witnesses were incorrect in nearly half of the patients in whom these could be analyzed. CONCLUSIONS: Emphasis should be placed on implementing preventive measures, focused on the described risk groups, and insisting on adequate supervision, swimming training programs, and training of the general population in safe rescue and cardiopulmonary resuscitation.

Antimicrobial Stewardship Improvement in Pediatric Intensive Care Units in Spain-What Have We Learned?

Antibiotic misuse in pediatric intensive care units (PICUs) can lead to increased antimicrobial resistance, antibiotic-triggered side effects, hospital costs, and mortality. We performed a multicenter, prospective study, analyzing critically ill pediatric patients (≥1 month to ≤18 years) admitted to 26 Spanish PICUs over a 3-month period each year (1 April−30 June) from 2014−2019. To make comparisons and evaluate the influence of AMS programs on antibiotic use in PICUs, the analysis was divided into two periods: 2014−2016 and 2017−2019 (once 84% of the units had incorporated an AMS program). A total of 11,260 pediatric patients were included. Total antibiotic prescriptions numbered 15,448 and, overall, 8354 patients (74.2%) received at least one antibiotic. Comparing the two periods, an increase was detected in the number of days without antibiotics in patients who received them divided by the number of days in PICUs, for community-acquired infections (p < 0.001) and healthcare-associated infections (HAIs) acquired in PICUs (p < 0.001). Antibiotics were empirical in 7720 infections (85.6%), with an increase in appropriate antibiotic indications during the second period (p < 0.001). The main indication for antibiotic adjustment was de-escalation, increasing in the second period (p = 0.045). Despite the high rate of antibiotic use in PICUs, our results showed a significant increase in appropriate antibiotic use and adjustment following the implementation of AMS programs.

Hybridization fuelled diversification in Spialia butterflies.

The importance of hybridization and introgression is well documented in the evolution of plants but, in insects, their role is not fully understood. Given the fact that insects are the most diverse group of organisms, assessing the impact of reticulation events on their evolution may be key to comprehend the emergence of such remarkable diversity. Here, we used an insect model, the Spialia butterflies, to gather genomic evidence of hybridization as a promoter of novel diversity. By using double-digest RADseq (ddRADseq), we explored the phylogenetic relationships between Spialia orbifer, S. rosae and S. sertorius, and documented two independent events of interspecific gene flow. Our data support that the Iberian endemism S. rosae probably received genetic material from S. orbifer in both mitochondrial and nuclear DNA, which could have contributed to a shift in the ecological preferences of S. rosae. We also show that admixture between S. sertorius and S. orbifer probably occurred in Italy. As a result, the admixed Sicilian populations of S. orbifer are differentiated from the rest of populations both genetically and morphologically, and display signatures of reproductive character displacement in the male genitalia. Additionally, our analyses indicated that genetic material from S. orbifer is present in S. sertorius along the Italian Peninsula. Our findings add to the view that hybridization is a pervasive phenomenon in nature and in butterflies in particular, with important consequences for evolution due to the emergence of novel phenotypes.

The epidemiology and management of odontogenic keratocysts (OKCs): A European multicenter study.

The objective of the present study was to assess the epidemiology including demographic variables, diagnostic features, and the management of odontogenic keratocyst (OKCs) at several European departments of maxillofacial and oral surgery. This study is based on a systematic computer-assisted database that allowed the recording of data from treated OKCs. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, site, size, radiographic features, treatment of OKCs, length of hospital stay, complications, recurrence, management and complications of eventual recurrence. A total of 405 patients, 249 male and 156 female, with 415 OKCs (407 sporadic and 8 syndromic lesions) were included in the study: 320 lesions were found in the mandible, whereas 95 were found in the maxilla. In the mandible, the most frequently involved subsite was the angle, whereas in the maxilla it was the molar region. The most frequently performed treatment option was enucleation plus curettage/peripheral ostectomy in 204 OKCs (recurrence rate, 9%). Decompression without residual cystectomy (recurrence rate, 66%), marsupialization with residual enucleation with the use of Carnoy's solution (recurrence rate, 50%), decompression with residual cystectomy (recurrence rate, 43%), and simple enucleation (recurrence rate, 24%) were the treatment options with the highest recurrence rates. An appropriate management of odontogenic keratocysts should be individualized, taking into consideration clinical and radiological findings, as well as patients' age and comorbidities.

Quality of life following maxillofacial trauma in the elderly: a multicenter, prospective study.

BACKGROUND/AIMS: When facial trauma involves elderly patients, the possible presence of frailty and comorbidities in victims of trauma may worsen the posttraumatic symptoms and decrease quality of life. The aim of this multicenter study was to assess the quality of life following surgical or non-operative management of maxillofacial trauma in elderly patients. MATERIALS AND METHODS: This cohort study was based on the administration of validated self-administered questionnaires to all the geriatric patients (70 years or more) with facial fractures from the involved maxillofacial surgical units across Europe, since 1st January 2019 to 31st June 2019. The following questionnaires were administered: SF36 questionnaire; the VFQ-25 questionnaire; the Oral Health Impact Profile - 14 (OHIP14). Outcome variables were VFQ-25 and OHIP-14 results. RESULTS: A total of 37 patients (14 male and 23 female patients) met the inclusion criteria and were included in the study. Elderly patients had an improvement in almost all the categories examined by the SF-36 questionnaire 6 months after trauma, with the only exception of a worsening as for role limitations due to physical health. An improvement was observed in almost all the categories at SF-36 test. A worsening of scores of OHIP-14 for all the considered dimensions in the whole study population was observed too. CONCLUSIONS: Elderly patients following facial trauma experience significant emotional, social, and functional disturbances. We observed that emotional problems, energy/fatigue, social functioning, and generally social limitations played a great role in the decrease of QoL in elderly patients following maxillofacial trauma.

The epidemiology and management of ameloblastomas: A European multicenter study.

The present study aimed at assessing the epidemiology including demographic variables, diagnostic features, and management of ameloblastomas at several European departments of maxillofacial and oral surgery. The following data were recorded for each patient: gender, age, voluptuary habits, comorbidities, site, size, radiographic features, type, histopathological features, kind of treatment, length of hospital stay, complications, recurrence, management and complications of the recurrence. A total of 244 patients, 134 males and 110 females with ameloblastomas were included in the study. Mean age was 47.4 years. In all, 81% of lesions were found in the mandible, whereas 19% were found in the maxilla. Mean size of included ameloblastomas was 38.9 mm. The most frequently performed treatment option was enucleation plus curettage/peripheral ostectomy in 94 ameloblastomas, followed by segmental resection (60 patients), simple enucleation (46 patients), and marginal resection (40 patients). A recurrence (with a mean follow up of 5 years) was observed in 47 cases out of 244 ameloblastomas (19.3%). Segmental resection was associated with a low risk of recurrence (p = 0003), whereas enucleation plus curettage/peripheral ostectomy was associated with a high risk of recurrence (p = 0002). A multilocular radiographic appearance was associated with a high risk of recurrence (p < .05), as well as the benign solid/multicystic histologic type (p < .05). Within the limitations of the study it seems that the management of ameloblastomas will probably remain controversial even in the future. Balancing low surgical morbidity with a low recurrence rate is a difficult aim to reach.

Prognostic Relevance of CD4+, CD8+ and FOXP3+ TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers.

This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4+, CD8+ and FOXP3+ TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and cancer stem cell (CSC) markers (NANOG, SOX2, OCT4, Nestin and Podoplanin (PDPN)) are assessed. CD4+ and CD8+ TILs are significantly associated with smoking and alcohol habits. CD4+ and CD8+ TILs show an inverse relationship with NANOG and SOX2 expression, and FOXP3+ TILs is significantly correlated with Nestin and PDPN expression. High infiltration of CD4+ and CD8+ TILs and a high tumoral CD8+/FOXP3+ ratio are significantly associated with tumors harboring positive PD-L1 expression. Infiltration of stromal/tumoral FOXP3+ TILs and a low stromal CD8+/FOXP3+ ratio are significantly associated with better disease-specific survival. Multivariate analysis reveals that the stromal CD8+/FOXP3+ TILs ratio is a significant independent prognostic factor. Regarding OSCC patient survival, the CD8+/FOXP3+ TILs ratio is an independent prognostic factor. TILs may act as biomarkers and potential therapeutic targets for OSCC.

Functional results of swallowing and aspiration after oral cancer treatment and microvascular free flap reconstruction: A retrospective observational assessment.

This study aimed to assess the functional swallowing outcomes in cohort of oral cancer patients treated with tumor resection and reconstruction by means of microvascular free flaps. Duration from onset to the last examination was classified into three periods: less than 12 months, from 13 to 24 months, and more than 24 months. Type of feeding, dysphagia, and laryngeal aspiration were the dependent variables, and the study was mainly focused on the data from the multivariate analysis. Fifty-one patients were included in the study. Twenty-one patients had dysphagia, 11 showed stasis in vallecula and pyriform sinuses, 9 experienced laryngeal penetration, and 8 aspirations. Surgery combined with radiochemotherapy was associated with a higher prevalence of dysphagia (p = 0.03). Frequency of dysphagia was higher in the first year after treatment and less frequent after 24 months (p = 0.003). Dysphagia was associated with laryngeal penetration (p = 0.001), and this with aspiration (p < 0.0005). In conclusion, as it seems that the method of reconstruction has a major influence on swallowing, when there are relevant alternatives in the way the reconstruction is done, always the approach should be chosen that reduces dysphagia to a minimum.

Genes involved in the epithelial-mesenchymal transition in oral cancer: A systematic review.

OBJECTIVE: Epithelial-mesenchymal transition (EMT) is considered the initial step in the invasion-metastasis cascade. The aim of this systematic review was to study the signature of genes involved in the EMT process in oral cancer (OC) confirmed by protein expression and its possible relationship with oral squamous cell carcinoma (OSCC) prognostic variables. MATERIALS AND METHODS: A search of the scientific literature was carried out with no start date restriction until 17 September 2020 in the electronic databases Pubmed/MEDLINE, Web of Science, Cochrane Library and Scopus, following specific eligibility criteria. The methodological quality of the included studies was assessed using the Newcastle-Ottawa tool. RESULTS: A total of 8 retrospective cohort studies were included, all of them performed in China and with low risk of bias. Overexpression of the genes HNRNPC, ITGA5, HMGA2 and SRSF3, and low expression of ALDH3A1 and ARID2 promote EMT in OC. The more advanced clinical stages of the TNM classification were significantly associated with overexpression of HNRNPC, ITGA5, HMGA2 and SRSF3, and low expression of ARID2. CONCLUSIONS: HNRNPC, ITGA5, HMGA2, SRSF3, ALDH3A1 and ARID2 genes were associated with EMT process. Over- or under-expression of these genes is associated with worse stages of OSCC and/or worse prognosis of the tumor. Further studies on this topic are needed in different countries to be able to confirm these results, since the detection of these genes can help to know which tumors have a worse prognosis.

Effect of region-dependent viscoelastic properties on the TMJ articular disc relaxation under prolonged clenching.

The disc of the temporomandibular joint (TMJ) is located between the mandibular condyle and temporal bone, and has an important load-bearing and stress absorbing function. The TMJ disc presents viscoelastic characteristics that are largely dependent on its collagen fibre and proteoglycan composition and organization. The purpose of this study is to investigate the possible effects of region-specific dynamic viscoelastic properties on stress relaxation during prolonged clenching. Two finite element models were used to compare the stress distribution within the TMJ disc, namely, one with uniform disc material property and another one with region-specific disc material properties. Similar results were observed in both models with slight differences in the location of maximum stress. Larger stresses were observed in all cases for the model with uniform disc material property. Moreover, the higher values for the model with uniform disc material property appeared in the lateral region, while in the model with region-specific disc properties, these values moved to the lateral and central region. This investigation confirms that both models are sufficiently accurate to investigate stress distribution in the TMJ disc, and, particularly, the model with the region-specific disc material properties ensure better simulations of the TMJ disc behaviour.