Chemotherapy increases the prevalence of radiotherapy-related trismus in head and neck cancer patients: A systematic review and meta-analysis.

Background: To evaluate the influence of chemotherapy on the prevalence of trismus in irradiated head and neck cancer patients. Material and Methods: This systematic review guided by PRISMA-2020 and registered in PROSPERO (CRD42021255377) screened 963 articles in 7 scientific-databases (PubMed, Lilacs, Livivo, Scopus, Embase, Web of Science, EBSCO) and 3 grey-literature databases (Open Grey, Google Scholar, ProQuest) and eight articles were included for qualitative synthesis, meta-analysis (combined odds ratio, inverse variance method plus random effects), heterogeneity analysis (I² and Tau²), one-of-out evaluation and publication bias analysis (Eggs' and Begg's tests) (RevMan®, p<0.05). The Newcastle-Ottawa Quality Assessment Scale Cohort Studies was used to assess the risk of bias (RoB). The classification assessment, development, and recommendations (GRADE) approach was used to assess the certainty of evidence. Results: The eight articles evaluated 1474 patients treated with chemoradiotherapy and 858 patients treated with radiotherapy. Five articles had low RoB, and three had high RoB. Chemoradiotherapy significantly (p=0.0003) increased the prevalence of trismus (OR=2.55, 95% CI = 1.53-4.23) compared to radiotherapy, with significant (p=0.010) but low heterogeneity (I²=59%;Tau²=0.29). There was no significant risk of publication bias, one-out analysis showed no significant difference between studies, and GRADE showed a moderate level of evidence. Trismus was directly associated to worse quality of life. Conclusions: The incidence of trismus increases when chemotherapy is combined with radiotherapy for head and neck cancer, which negatively impacts the quality of life. Key words:Radiotherapy, Chemoradiotherapy, Head and Neck Neoplasms, Trismus, Quality of Life.

Salivary immunoglobulin levels and periodontal indices in Brazilian children with and without type 1 diabetes.

This cross-sectional study evaluated the association between salivary immunoglobulins, plaque index, and gingival index in Brazilian children with and without type 1 diabetes mellitus (DM1). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for the reporting of observational studies was followed. The DM1 group had 38 children, and an equal number of volunteers matched by sex and age were recruited as controls. Clinical examination was performed for plaque index and gingival index determination. Non-stimulated whole saliva was collected. Concentrations of IgA, IgG, and IgM were determined by ELISA test. Data were tested by the Kolmogorov-Smirnov, Mann-Whitney, and Spearman tests and a multiple linear regression model (p<0.05) was performed. Gingival index was higher in the Control (DM1: 0.16±0.17; Control: 0.24±0.23, p=0.040). In DM1, there was a correlation between IgA and age (rho=0.371, p=0.024), IgM and IgG (rho=0.459, p=0.007), and IgM and gingival index (rho=0.394, p=0.014). In DM1, multiple linear regression showed that age (p=0.041; ß=0.363), gingival index (p=0.041; ß=0.398), and plaque index (p=0.008; ß=-0.506) were good predictors of IgA levels in saliva. Thus, IgA was the only researched immunoglobulin that was directly associated with plaque and gingival indices in Brazilian children with DM1, but not in control subjects.

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

WITHANICANDRIN ISOLATED FROM Datura Ferox PROMOTES ANTINOCICEPTION BY MODULATING THE ASICS AND TRPS CHANNELS AND ANTI-INFLAMMATION IN ADULT ZEBRAFISH.

This is the first study to analyze the anti-inflammatory and antinociceptive effect of withanicandrin, isolated from Datura Ferox leaves, and the possible mechanism of action involved in adult zebrafish (ZFa). To this end, the animals were treated intraperitoneally (i.p.) with withanicandrin (4; 20 and 40 mg/kg; 20 µL) and subjected to locomotor activity and acute toxicity. Nociception tests were also carried out with chemical agents, in addition to tests to evaluate inflammatory processes induced by κ-Carrageenan 1.5% and a Molecular Docking study. As a result, withanicandrin reduced nociceptive behavior by capsaicin at a dose of 40 mg/kg and by acid saline at doses of 4 and 40 mg/kg, through neuromodulation of TRPV1 channels and ASICs, identified through blocking the antinociceptive effect of withanicandrin by the antagonists capsazepine and naloxone. Furthermore, withanicandrin caused an anti-inflammatory effect through the reduction of abdominal edema, absence of leukocyte infiltrate in the liver tissue and reduction of ROS in thel liver tissue and presented better affinity energy compared to control morphine (TRPV1) and ibuprofen (COX-1 and COX-2).

Does the use of universal adhesive systems improve the durability of the bond strength of orthodontic brackets to enamel?

Background: Universal adhesive systems used for restorative clinical procedures are like orthodontics and may be a viable option. This study evaluated the effectiveness of universal adhesive systems in enhancing the durability of the shear bond strength (SBS) and adhesive remnant index (ARI) of orthodontic brackets to enamel. Material and Methods: 100 bovine incisors were divided into five groups (n=20), according to the applied adhesive systems: Primer Transbond XT; Ambar; Ambar Universal; Single Bond Universal; Adper Single Bond 2. Bracket from each tooth were submitted to SBS test after 24 hours, and 12 months later. The amount of remaining adhesive was evaluated through ARI. Results: After 24 hours, there was no difference in BS between the control and the other groups (p>0.05). However, there were difference between TOTALETCHING1 group and the Ambar Universal (p=0.015) and Single Bond Universal groups (p=0.011). After 12 months, Primer Transbond XT, Ambar, Ambar Universal and Adper Single Bond 2 showed no differences in the SBS (p>0.05). Nonetheless, Single Bond Universal presented superior result when compared to Primer Transbond XT (p=0.046) and Ambar (p=0.011) groups. The SBS of all groups reduced significantly after 12 months (p<0.05). There was no difference between ARI scores in each individually assessed group (p>0.05), for both periods. Following 24 hours, a difference was observed between the groups (p=0.043), fact that didn't occur after 12 months (p=0.109). Conclusions: Adhesive systems, such as Ambar Universal and Single Bond Universal are efficient in bonding orthodontic brackets to enamel when associated with Transbond XT adhesive paste. Key words:Bond strength; Primer Transbond XT, orthodontic brackets, adhesive systems.

Role of induced nitric oxide synthases in orofacial nociception/discomfort after dental tooth bleaching with hydrogen peroxide.

OBJECTIVE: To evaluate the role of induced nitric oxide synthase (iNOS) in nociception/orofacial discomfort in rats submitted to tooth whitening with hydrogen peroxide (H2O2). DESIGN: Wistar rats were divided into three groups (n = 24/group): a sham group not submitted to whitening treatment, a saline group submitted to whitening treatment, and a test group submitted to whitening treatment and blockade of iNOS with aminoguanidine 50 mg/kg/day. After 24 and 48 h, and 7 days, the animals were euthanized to collect trigeminal ganglia and maxillae to histomorphometric analysis (size of neuronal bodies and percentage of pulp area filled by vessels) and behavior/nociception (Grimace scales, scratching and biting counting, weight loss and nociception assay). ANOVA-1- or - 2-way tests were used (p < 0.05, GraphPadPrism 5.0). RESULTS: The aminoguanidine-treated group showed a reduction in nociceptive threshold in the masseteric region (p < 0.001), Grimace scale scores (p < 0.001), number of scratching (p = 0.011) and body mass loss (p = 0.007). After 24 and 48 h of tooth bleaching, the saline group showed a significant increase in the mean area of the blood vessels (p = 0.020) and iNOS immunostaining in odontoblasts (p = 0.002) and non-odontoblasts cells (p = 0.025). Aminoguanidine reversed both increases. Tooth bleaching reduced the mean area of neuronal bodies, and aminoguanidine significantly reversed it (p = 0.019), but an increase in GFAP immunostaining in neuronal bodies did not reduce after seven-days or after aminoguanidine treatment (p = 0.003). CONCLUSION: iNOS blockage by aminoguanidine plays an important role in nociception and orofacial discomfort by control of inflammation in dental pulp after tooth bleaching with hydrogen peroxide (H2O2) 35%.

Risk factors for oral mucositis in patients with solid tumorsunder treatment with cetuximab: a retrospective cross-sectional study

Background: This study retrospectively analyzed the risk factors for oral mucositis (OM) during cetuximab treatment. Material and Methods: We screened patients using cetuximab and retrospectively evaluated the presence of OM based on medical records. We collected information from 2 years of evaluations. Patient medical records were reviewed to obtain data on chemotherapy cycle and dose, sex, age, primary tumor, TNM stage, and head and neck radiotherapy (HNR) history. The X2 test and multinomial logistic regression were used for statistical analysis (SPSS 20.0, p < 0.05). Results: Among 1831 patients, OM was showed in 750 in any grade (41%), during cetuximab treatment. Most patients were female (n=944, 51.6%), <70years-old (n=1149, 62.8%), had larynx cancer (n=789, 43.1%) in T4 (n=579, 47.7%), N0 (n=509, 52.6%) stages. Primary tumor surgery was performed in 1476 (80.6%) patients, radiotherapy in 606 (33.1%) patients and cetuximab protocols most used involved up to four cycles (n=1072, 58.5%) of <400mg (n=996, 54.4%) cetuximab doses. Female (OR [odds ratio] = 2.17, CI95% = 1.26-3.75), >70 years-old patients (OR = 16.02, CI95% = 11.99-21.41), with HHNR (OR = 1.84, 1.41-2.40), treated with >4 cycles (OR = 1.52, CI95% = 1.16-2.01) and high doses of cetuximab (OR = 3.80, CI95% = 2.52-5.71) are the greatest risk factors for OM. Conclusions: Since the clinical benefit of cetuximab in the treatment of older patients is limited and there is a high OM, especially in women with head and neck treated with radiotherapy, high doses and a high number of cetuximab cycles must be administered with caution. (AU)

Role of collagen and immunostaining for TGF-β in the clinical andmicroscopic findings of pyogenic granuloma and peripheral ossifying fibroma

Background: Collagen is a component of Pyogenic Granuloma (PG) and Peripheral Ossifying Fibroma (POF) and performs different functions in these lesions. The objective of this study is to evaluate the role of collagen and immunostaining for Transforming Growth Factor beta (TGF-β) in the clinical and microscopic findings of PG and POF. Material and Methods: PG (n=20) and POF (n=20) were selected for clinical evaluation (sex, age, localization, size and evolution time) and microscopic analysis (picrosirius red staining for collagen analysis and immunohistochemistry for TGF-β) performed in the superficial and deep areas of the two lesions. ANOVA/Bonferroni and t-test, Pearson correlation and χ2 were used to compare the sites and parameters analyzed (p<0.05, GraphPad Prism 5.0). Results: The depth of PG presented the highest amount of collagen (p<0.001), and its surface showed the lowest amount of type 1 collagen (yellow-red strong birefringence). Type 1 collagen gradually increased in depth of PG, surface and depth of POF (p<0.001). The number of TGF-β+ cells was lower on the surface of PG compared with the depth of PG and the two areas of POF (p<0.001). Sex and localization did not affect these parameters, but the profile of collagen and immunostaining for TGF-β suffered from modifications by the time of evolution and the size of the lesion. Conclusions: Although PG and POF are reactive gingival lesions, the expression of TGF-β and its role in collagen showed different biological behaviors in these lesions, suggesting different biological origins for its components. (AU)

Deficiency in infiltration of CD8/CD3 positive lymphocytes and macrophages plays a role in lip carcinogenesis: an immunohistochemical study.

OBJECTIVE: To evaluate the immunoexpression profile for CD8, CD3, CD20 and CD68 in the process and carcinogenesis of Carcinoma of the vermilion lip. METHODS: Average cell count with positive expression for CD3, CD8, CD20 and CD68. The CD8/CD3 ratio calculated in the region was based on the percentage of positive cells in a total of malignant cells. Kruska-Wallis/Dunn, Mann-Whitney and Spearman correlation tests (SPSS, p < 0.05) were used. RESULTS: In the Aquitic Cheilitis samples, there was an increase in intraepithelial CD8+ and CD68+. In LSCCs, there was an increase in peritumoral and intratumoral CD3+, CD8+, CD20+ and CD68+ cells. In peritumoral LSCC, CD3+ and CD8+ showed a direct correlation (p = 0.004), and CD68+ and CD8+ (p = 0.017). In the intraepithelial region, CD8+ correlated with CD20+ (p = 0.014) and CD68+ (p = 0.013). In the CAs, CD3 (p < 0.001) and CD8 (p = 0.025) correlated intraepithelial and subepithelial. In LSCC CD3+ (p = 0.002), CD8+ (p = 0.001) and CD68+ (p = 0.030) had intra and peritumoral correlation. CONCLUSION: CD68+ is the first interacting cell with the greatest capacity to migrate to the tumor and interact with CD3, CD8 and CD20. Apparently, CD20 affects perineural invasion. LEVEL OF EVIDENCE: Level 2.

Photoanthropometric craniofacial parameters in individuals with osteogenesis imperfecta / Parámetros craneofaciales fotoantropométricos en personas con osteogénesis imperfecta

Background: This study aimed to evaluate facial photoanthropometric parameters in patients with OI.Material and Methods: We selected 20 Brazilian patients diagnosed with OI treated at the Extension Service forMinors in Need of Specialized Treatment of the Dentistry Course at the Federal University of Ceará (Fortaleza,Brazil), of both sexes, without age restriction, and able to understand and sign the informed consent form (ICF).As a control group, 38 non-syndromic Brazilian individuals, categorized as ASA I, able to understand and sign theICF, matched by sex, age, and Legan and Burstone facial profile were selected. The exclusion criteria were: previ-ous orthodontic treatment, craniofacial trauma and/or surgery, and the presence of any other systemic diseases.Photoanthropometric analysis of the 18 facial parameters proposed by Stengel-Rutkowski et al. (1984), previouslyestablished in the literature for craniofacial syndromes, were conducted. A single examiner digitally performedall effective and angular measurements with the CorelDRAWX7® software.Results: Horizontally shortened ears (p<0.001) but larger in height in relation to the face (p=0.012) were shownto be alterations belonging to individuals with OI.Conclusions: OI patients present distinct photoanthropometric parameters inherent in this condition.(AU)

Computed tomography assessment of maxillary sinus hypoplasia and associated anatomical variations: a systematic review and meta-analysis of global evidence.

OBJECTIVE: To summarize the scientific evidence on the prevalence of maxillary sinus hypoplasia (MSH) and associated anatomical variations as assessed by computed tomography scans. STUDY DESIGN: This PROSPERO-registered systematic review followed the recommendations of the PRISMA guidelines. Search algorithms were constructed for each of the six databases and gray literature. After screening the references (Rayyan®), the extracted data were meta-analyzed according to a random-effects model. The joanna briggs critical appraisal tool assessed the methodological quality of the included studies. The GRADE approach was used to estimate the certainty of the evidence. RESULTS: From a total of 2781 studies screened, 22 were considered for four meta-analysis. The prevalence of MSH in 7358 patients was 5.65% (CI95% = 4.07-7.47%) with significant heterogeneity between studies (p < 0.001, I2 = 89.30%). MSH was identified in 295 patients, of whom 82.38% (CI95% = 75.82-88.09%) had unilateral hypoplasia and 17.62% (CI95% = 11.91-24.18%) bilateral hypoplasia with moderate heterogeneity between studies (p < 0.0503, I2 = 42.87%). The prevalence of MSH in 9998 maxillary sinuses was 3.77% (95% CI = 2.44-5.38%), with significant heterogeneity between studies (p < 0.001, I2 = 92.84%). Hypoplastic/aplastic uncinate process, concha bullosa and paradoxical concha were the most reported anatomical variations. The studies presented a low-moderate methodological quality. The certainty of the evidence was very low to moderate. CONCLUSION: The prevalence of maxillary sinus hypoplasia observed was 5.65%, with most cases being unilateral.

Through the fingers: Use of plastinated anatomical specimens for visually impaired students.

The plastination technique produces non-toxic human tissues, ensuring their safe handling in educational settings. This investigation aimed to understand if visually impaired students profit from the use of plastinated anatomical specimens in learning the anatomy of the nervous system. For this purpose, their learning performance was compared to sighted and blindfolded students recruited from three primary schools in Fortaleza city, in the state of Ceará. Initially, a questionnaire was applied before carrying out the pedagogical practice, followed by an anatomy lecture with practical components with the use of plastinated anatomical specimens and synthetic anatomical models of the nervous system. After these steps, the students answered the questionnaire previously applied. Our results showed that the tactile perception of the visually impaired participants was significantly more developed compared to sighted (p < 0.001) and the blindfolded (p < 0.0001) students. The average of correct answers in the reapplied questionnaire was higher in the groups that used plastinated specimens (p < 0.05). In conclusion, the use of plastinated specimens has proven to be an effective tool in promoting a better understanding of anatomical structures, mainly for students with or without visual impairments, making it a valuable asset in anatomy teaching.

Anthropometric measures and obstructive sleep apnea in children and adolescents: a systematic review of the literature and meta-analysis.

BACKGROUND: Anthropometric measurements can be used to identify children at risk of developing obstructive sleep apnea (OSA). The study aimed to assess which anthropometric measurements (AMs) are most associated with an increased predisposition to develop OSA in healthy children and adolescents. METHODS: We performed a systematic review (PROSPERO #CRD42022310572) that searched eight databases and gray literature. RESULTS: In eight studies with low-to-high risk of bias, investigators reported the following AMs: body mass index (BMI), neck circumference, hip circumference, waist-to-hip ratio, neck-to-waist ratio, waist circumference, waist-to-height ratio, and facial AMs. The meta-analysis showed that the OSA group had an average of 1.00 cm greater for the neck circumference (p < 0.001; Cohen's d = 2.26 [0.72, 5.23]), 3.07 cm greater for the waist circumference (p = 0.030; Cohen's d = 0.28 [0.02, 0.53]), 3.96 cm greater for the hip circumference (p = 0.040; Cohen's d = 0.28 [0.02, 0.55]), 5.21° greater for the cervicomental angle (p = 0.020; Cohen's d = 0.31 [0.03, 0.59]), and 1.23° greater for maxillary-mandibular relationship angle (p < 0.001; Cohen's d = 0.47 [0.22, 0.72]) than the control group. The mandibular depth angle had a reduction of 1.86° (p = 0.001; Cohen's d = -0.36° [-0.65, -0.08]) in control than in patients with OSA. The BMI (p = 0.180), waist-to-hip ratio (p = 0.280), neck-to-waist ratio (p = 0.070), maxillary depth angle (p = 0.250), and upper/lower face height ratio (p = 0.070) showed no significant differences between groups. CONCLUSIONS: Compared to the control group, the OSA group exhibited a greater mean difference in neck circumference, the only anthropometric measurement with high certainty of evidence.

Desenvolvimento de uma plataforma móvel de apoio ao ensino de infectologia para alunos de graduação em medicina de um centro universitário em fortaleza/ce / Development of a mobile platform to support the teaching of infectiology for undergraduate medicine students at a university center in fortaleza/ce / Desarrollo de una plataforma móvil de apoyo a la enseñanza de infectiología para estudiantes de grado de medicina en un centro universitario de fortaleza/ce

O rápido avanço tecnológico na área da saúde tem impacto relevante e positivo na educação médica. O amplo uso de recursos digitais teve crescimento com a pandemia de Covid-19 e impulsionou a disponibilidade de novas formas de desenvolver o ensino por meio de plataformas digitais, para o ensino híbrido e EaD. Nesse sentido, o objetivo deste estudo foi elaborar uma plataforma móvel de suporte educacional em Infectologia para graduação em Medicina. Foi avaliada a aplicabilidade e usabilidade do sistema, o seu impacto na facilitação do ensino e o grau de satisfação do usuário com a nova ferramenta. Trata-se de um estudo quantitativo, experimental, descritivo, em que a plataforma desenvolvida foi avaliada por 42 estudantes de Medicina do quarto semestre do Centro Universitário Christus (Unichristus), por meio de questionários, visando estimar a repercussão nos diferentes cenários educacionais e o grau de satisfação com esse instrumento. Quanto à sua eficácia, foi aplicada a Escala de Usabilidade de Sistema (System Usabillity Scale - SUS). Como resultado, foi analisado que a plataforma apresentou o escore SUS de 84,64, com desvio-padrão de 13,8, sendo evidenciada uma correlação de Spearman estatisticamente significativa (p<0,05). Conclui-se que a plataforma móvel em infectologia é uma ferramenta com boa aceitabilidade e facilidade na utilização, permitindo uma alternativa de abordagem eficaz de ensino na graduação de medicina.

The rapid technological advancement in the field of healthcare has a significant and positive impact on medical education. The widespread use of digital resources has seen growth with the Covid-19 pandemic and has driven the availability of new ways to deliver education through digital platforms for hybrid and distance learning. In this regard, the objective of this study was to develop a mobile educational support platform in Infectious Diseases for undergraduate medical education. The applicability and usability of the system, its impact on facilitating education, and the user satisfaction with the new tool were evaluated. This was a quantitative, experimental, descriptive study in which the developed platform was assessed by 42 fourth-semester medical students at Christus University Center (Unichristus) through questionnaires to estimate its impact on various educational scenarios and the level of satisfaction with this tool. In terms of its effectiveness, the System Usability Scale (SUS) was applied. As a result, it was found that the platform scored an SUS score of 84.64 with a standard deviation of 13.8, and a statistically significant Spearman correlation (p<0.05) was evident. It is concluded that the mobile platform in Infectious Diseases is a tool with good acceptability and ease of use, allowing for an effective alternative approach to medical education at the undergraduate level.

El rápido avance tecnológico en el campo de la salud tiene un impacto significativo y positivo en la educación médica. El uso generalizado de recursos digitales ha experimentado un crecimiento con la pandemia de Covid-19 y ha impulsado la disponibilidad de nuevas formas de brindar educación a través de plataformas digitales para la enseñanza híbrida y a distancia. En este sentido, el objetivo de este estudio fue desarrollar una plataforma de apoyo educativo móvil en Enfermedades Infecciosas para la educación médica de pregrado. Se evaluó la aplicabilidad y la usabilidad del sistema, su impacto en facilitar la educación y el nivel de satisfacción del usuario con la nueva herramienta. Este fue un estudio cuantitativo, experimental y descriptivo en el que la plataforma desarrollada fue evaluada por 42 estudiantes de medicina en su cuarto semestre en el Centro Universitario Christus (Unichristus) a través de cuestionarios para estimar su impacto en diversos escenarios educativos y el nivel de satisfacción con esta herramienta. En términos de su eficacia, se aplicó la Escala de Usabilidad del Sistema (SUS). Como resultado, se encontró que la plataforma obtuvo una puntuación de SUS de 84.64 con una desviación estándar de 13.8, y se evidenció una correlación de Spearman estadísticamente significativa (p<0.05). Se concluye que la plataforma móvil en Enfermedades Infecciosas es una herramienta con buena aceptabilidad y facilidad de uso, que permite un enfoque alternativo efectivo para la educación médica a nivel de pregrado.

Expression of tumoral GSK3-ß, PD-L1, and CD8 cell density in urothelial carcinomas, association with tumor grade and overall survival.

Bladder cancer is the most common malignancy in the urinary tract, and is biologically and clinically quite heterogeneous. Around 90% of diagnoses are made in the 6th decade, being more prevalent in males. The programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) axis play a putative role in immune checkpoint and as a means through which cancer evades the immune system. Inhibition of the glicogênio synthase kinase (GSK) 3 leads to the downregulation of PD-1 via upregulation of the transcription factor Tbet. The use of biomarkers PD-L1 and GSK-3ß and evaluation of the immune infiltrate have very promising correlations with urothelial carcinoma prognosis and treatment prediction. OBJECTIVE: To investigate the protein expression of PD-L1 and GSK-3ß and the CD8-positive immune infiltrates in bladder carcinomas. MATERIALS AND METHODS: This was a cross-sectional study of 140 samples of urothelial carcinomas from 2015 to 2018. Automated digitally assisted scoring and conventional analyses of the markers of GSK-3ß (27C10), CD8 (7103ß) and PDL-1 (22c3), were reviewed by two pathologists independently and a histologic score was calculated. The density of CD8 was also measured. RESULTS: The immunoexpression of GSK-3ß (91%) was presented in most samples, PD-L1 in 62.9% and CD8 cells present in 46.3% of cases. When analyzed in conjunction, the levels of GSK-3ß and PD-L1 (P = 0.033), and CD8 and PD-L1 (P<0.002) showed significant correlations. No significant associations were observed between GSK-3ß and CD8. The positivity of GSK-3ß and PD-L1 was predominant in high-grade tumors. CONCLUSION: Despite the tumor microenvironment heterogeneity, the expression of CD8, GSK-3ß and PDL1 could be valuable and GSK-3ß could be a potential target in advanced bladder cancer, especially in the context of immunotherapy.

Influence of p16 Protein Immunostaining on Histopathological Features of Pleomorphic Adenoma and Carcinoma ex- Pleomorphic Adenoma.

The objective of this study was to evaluate the role of p16 in histologic characteristics and transition of Pleomorphic Adenoma (PA) to Carcinoma ex-PA (CxPA). So, 60 PA and 4 CxPA were histologic reviewed based on microscopic characteristics proposed by Hellquist, Triantafyllou and Dulguerov (PA) and Morais, Antony and Toluie (CxPA). Immunostaining for p16 was associated in different parenchyma and stroma of both tumors and Fisher's/chi-square tests and Mann-Whitney test were performed (SPSS v20.0, p<0.05). In PA the periductal cells were predominantly p16- and that ductal and myoepithelial cells showed a significant increase in p16+ cells (p<0.001). In CxPA, none of the cases showed p16+ in periductal cells, most parotid cases showed p16+ in ductal cells, and one case of parotid and the submandibular case showed mild immunostaining for myoepithelial cells. There was a small reduction in p16+ in CxPA compared to PA (p=0.537), but in both tumors there was less p16+ cells in solid stroma than other (p<0.001). The p16+ cases of PA had a higher capsular thickness (p=0.047). So, the loss of p16 immunostaining does not seem to be associated with the transition from PA to CxPA, but in both tumors the loss of p16+ cells are related to microscopic aggressiveness.

Usability and Efficacy of Artificial Intelligence Chatbots (ChatGPT) for Health Sciences Students: Protocol for a Crossover Randomized Controlled Trial.

BACKGROUND: The integration of artificial intelligence (AI) into health sciences students' education holds significant importance. The rapid advancement of AI has opened new horizons in scientific writing and has the potential to reshape human-technology interactions. AI in education may impact critical thinking, leading to unintended consequences that need to be addressed. Understanding the implications of AI adoption in education is essential for ensuring its responsible and effective use, empowering health sciences students to navigate AI-driven technologies' evolving field with essential knowledge and skills. OBJECTIVE: This study aims to provide details on the study protocol and the methods used to investigate the usability and efficacy of ChatGPT, a large language model. The primary focus is on assessing its role as a supplementary learning tool for improving learning processes and outcomes among undergraduate health sciences students, with a specific emphasis on chronic diseases. METHODS: This single-blinded, crossover, randomized, controlled trial is part of a broader mixed methods study, and the primary emphasis of this paper is on the quantitative component of the overall research. A total of 50 students will be recruited for this study. The alternative hypothesis posits that there will be a significant difference in learning outcomes and technology usability between students using ChatGPT (group A) and those using standard web-based tools (group B) to access resources and complete assignments. Participants will be allocated to sequence AB or BA in a 1:1 ratio using computer-generated randomization. Both arms include students' participation in a writing assignment intervention, with a washout period of 21 days between interventions. The primary outcome is the measure of the technology usability and effectiveness of ChatGPT, whereas the secondary outcome is the measure of students' perceptions and experiences with ChatGPT as a learning tool. Outcome data will be collected up to 24 hours after the interventions. RESULTS: This study aims to understand the potential benefits and challenges of incorporating AI as an educational tool, particularly in the context of student learning. The findings are expected to identify critical areas that need attention and help educators develop a deeper understanding of AI's impact on the educational field. By exploring the differences in the usability and efficacy between ChatGPT and conventional web-based tools, this study seeks to inform educators and students on the responsible integration of AI into academic settings, with a specific focus on health sciences education. CONCLUSIONS: By exploring the usability and efficacy of ChatGPT compared with conventional web-based tools, this study seeks to inform educators and students about the responsible integration of AI into academic settings. TRIAL REGISTRATION: ClinicalTrails.gov NCT05963802; https://clinicaltrials.gov/study/NCT05963802. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51873.

Photobiomodulation therapy in the treatment of radiotherapy-related trismus of the head and neck.

This study evaluated photobiomodulation therapy (PBMT) for treatment of trismus in patients undergoing radiotherapy for head and neck cancer (HNC). Sixteen patients, 10 men and 6 women, who had a mouth opening < 35 mm and underwent RT were included. The patients were evaluated daily before and after the PBMT application, measuring mouth opening and performing pain scores for the masticatory muscles using the visual analog scale (VAS). We used the infrared laser (~ 808 nm) extraorally, 0.1 W power, 3 J energy, 30 s (107 J/cm2) per point, applied to temporalis anterior, masseter muscles, and temporomandibular joints (TMJ). An intraoral point was made in the trigonoretromolar region towards the medial pterygoid muscle. The mean mouth opening of the patients increased by more than 7 mm throughout the treatment. The pain scores on the initial days showed an immediate reduction after PBMT on the ipsilateral side in the muscles and TMJ. Throughout PBMT applications, there was a significant reduction in pain scores in all muscles and the TMJ. The radiation dose of all patients was above 40 Gy, which is the threshold dose for the risk of developing trismus. SPSS software was used and adopted a confidence of 95%. The Kolmogorov-Smirnov normality test, Wilcoxon test, and Spearman correlation were performed. PBMT controls muscular pain and reduced mouth opening limitation in HNC during radiotherapy. Further studies are needed to evaluate the preventive capacity of PBMT protocols for RT trismus-related HNC.

Management of Cancer Therapy-Induced Oral Mucositis Using Photobiomodulation Therapy: An Overview of Systematic Reviews.

Objective: To systematically summarize the evidence for photobiomodulation therapy (PBMT) in the prevention and treatment of oral mucositis (OM) in patients undergoing cancer treatment. An electronic search was conducted in 8 databases and grey literature. Background: PBMT is recommended for the management of OM resulting from cancer treatment, with several systematic reviews (SRs) being published in recent years on this topic. Methods: Only SRs with outcomes from clinical trials were included, with no language or year restriction. The AMSTAR 2 tool was used to assess the methodological quality of the SRs. Results: Five thousand eight hundred fifty-six references were found, and 16 were selected for this review. OM prevention and treatment were favorable for PBMT in most studies, with a significant reduction in OM severity. Most studies obtained moderate confidence. Conclusions: PBMT represents an effective strategy in the management of OM, and this evidence is supported by studies with acceptable methodological quality.