Oral lesions of systemic lupus erythematosus: A collaborative Latin American study.

BACKGROUND: Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease that may affect the oral mucosa. The variable spectrum of oral lesions observed in SLE can pose challenges in diagnosis, particularly when the lesions occur in isolation. The aim of this study was to describe the oral lesions occurring in patients with SLE from Latin America. METHODS: This collaborative record-based study involving 11 oral and maxillofacial pathology and medicine services across Venezuela, Argentina, Chile, Brazil, and Mexico describes the clinicopathological profile of SLE-related oral lesions. RESULTS: Seventy patients with SLE and oral lesions were included in the study. The majority were females (75.7%; female/male ratio: 3.1:1) and white (62.1%), with a mean age of 38.4 years (range: 11-77 years). The most common site of oral lesions was the hard/soft palate (32.0%). Clinically, oral lesions predominantly presented as ulcers (26.6%), erosions (26.6%), and white lesions (23.4%). Isolated oral lesions occurred in 65.2% of individuals, while cutaneous manifestations occurred in 80.3%. The main clinical diagnostic hypothesis in 71.4% of cases was an immune-mediated disease. Oral biopsies followed by histopathological analysis were performed in 50 cases. CONCLUSION: Oral lesions of SLE exhibit a variety of clinical and histopathological features. A key point in diagnosis is that unusual oral changes without an obvious local cause may indicate a possible systemic condition presenting with oral lesions. A multidisciplinary approach, which includes regular oral examination, is warranted to identify oral lesions and provide treatment.

Is imiquimod a promising drug to treat oral mucosa diseases? A scoping review and new perspectives.

Imiquimod (IMQ) is a chemotherapeutic and immunostimulant drug that is applied topically, demonstrating antitumor and antiviral activities. The objective of this review was to compile data on the off-label use of IMQ in oral mucosal diseases. IMQ has exhibited effectiveness in the treatment of various oral mucosal conditions, including oral carcinogenic lesions, neoplasms, HPV-related lesions and autoimmune disorders. Although IMQ holds promise as a potential strategy for addressing oral mucosal lesions, it is important to note that significant side effects have been frequently reported. Nonetheless, it is crucial to develop and test new technological systems, such as the combination of nanotechnology with innovative drug delivery platforms. These advancements aim to minimize side effects and prolong the drug's contact time with the mucosa, preventing its removal by salivary flow.

Is vitamin D receptor (VDR) polymorphism associated with head and neck cancer risk? A systematic review and meta-analysis.

BACKGROUND: Head and neck cancer encompasses neoplasms affecting the oral cavity, pharynx, larynx, and thyroid. Identifying factors that modulate the carcinogenesis process can aid in identifying subgroups at higher risk of developing the disease, enabling implementation of prevention programs. Vitamin D receptor polymorphisms can affect the carcinogenesis of various tumors by altering vitamin D metabolism and cellular response. METHODS: To elucidate the role of vitamin D receptor polymorphisms in head and neck cancer, a systematic review was performed, searching the Embase, PubMed, Scopus, and Lilacs databases. A total of 19 articles met the inclusion criteria. The frequency of vitamin D receptors polymorphism alleles (FokI, ApaI, BsmI, TaqI, Cdx2, rs2107301, rs2238135) was recorded and pooled to calculate the odds ratio in a meta-analysis using the Review Manager software. RESULTS: Subgroup analysis demonstrated significant associations in the anatomical site of cancer (oral cancer in ApaI and BsmI, and unspecified subsites of head and neck cancer in TaqI), genotyping method (FokI and BsmI), and continent of the study (ApaI, FokI, and BsmI). CONCLUSION: Our findings were heterogeneous, as with other evidence available in the literature. Therefore, more clinical studies with larger sample sizes are needed to obtain more accurate results on the relationship between vitamin D receptor polymorphism and head and neck cancer.

Efficacy and safety of a 0.05 % nanoencapsulated imiquimod hydrogel for the treatment of actinic cheilitis: Drug release analysis and clinical study.

Actinic cheilitis (AC) is a lip disorder, with no standard treatment. Imiquimod (IMIQ) is an immunomodulator that treat precancerous lesions; however, its commercial form causes severe adverse effects. This study aimed to assess IMQ release from a chitosan hydrogel containing 0.05 % nanoencapsulated (NANO) imiquimod (IMIQ-0.05 %-NANO) and its efficacy in AC treatment. The hydrogels were prepared by incorporating chitosan into polymeric nanocapsules (NCimiq) loaded with IMQ, produced using the interfacial deposition of preformed polymer method. IMQ release was evaluated using automated Franz Cells. A triple-blind randomized controlled trial (49 subjects) compared the efficacy of: IMIQ-0.05 %-NANO, 5 % free imiquimod (IMIQ-5 %), 0.05 % free imiquimod (IMIQ-0.05 %), and placebo hydrogel. The IMIQ-NANO-0.05 % and IMIQ-5 % groups exhibited significantly higher rates of clinical improvement (p < 0.05); however, the IMIQ-5 % group experienced more adverse effects (92.3 % of subjects) compared to other groups (p < 0.05). In conclusion, in the studied sample, IMIQ-NANO-0.05 % was a safe and effective option to treat AC.

Oral cancer screening using cytopathology: An advanced proposal with the Bethesda classification.

BACKGROUND: Oral cancer screening requires analysis capable of detecting changes preceding the clinical manifestation. Oral cytopathology studies as an oral cancer screening have shown promising results. This study aims to evaluate the use of cytopathology in a quali-quantitative analysis using Papanicoloau staining. METHODS: Four experimental groups were evaluated: control (CG), exposed to carcinogens (EG), potentially malignant disorder with and without epithelial dysplasia (D-OPMDG and ND-OPMDG) and oral squamous cell carcinoma (OSCCG). Oral smears were collected using a Cytobrush® and conventional exfoliative cytology. RESULTS: Oral Papanicolaou smears from 143 individuals were analysed in 8100 images. Qualitatively, non-lesional groups exhibited minimal suspected cases (20% in CG and 5% in EG), in the OPMD groups the ability to identify altered cells was low (40% in D-OPMDG and 0% in ND-OPMDG). Conversely, a notable 100% accuracy was achieved in the OSCCG. Quantitatively, a higher percentage of anucleated and a lower percentage of intermediate cells were observed in the OPMDG; a higher proportion of parabasal/suspicious cells was observed in OSCCG. The optimal threshold for improved accuracy in detecting suspected malignancies occurs when the count of parabasal/suspicious cells exceeds 8/100 cells examined. Cytomorphometric analysis revealed a higher nucleus/cytoplasm ratio (N/C) in OSCCG, with a best cutoff point indicating enhanced accuracy in discerning suspected malignancies when exceeding 17% of cells exhibiting this elevated ratio. CONCLUSION: It is possible to suggest updates in cytomorphometric and quantitative analysis in the modified Bethesda system for the oral cavity including objective criteria in the risk classification, therefore improving oral cancer screening.

Efficacy of ozone therapy for oral mucosa wound healing: a systematic review and meta-analysis.

OBJECTIVES: To conduct a systematic review and meta-analysis to assess the effectiveness of ozone therapy in oral ulcers healing when compared to placebo or active treatments. MATERIALS AND METHODS: The search was carried out using PubMed, EMBASE, Scopus, and Lilacs databases. Clinical trials involving human participants were included. The Risk Ratio (RR) and the standardized mean difference (SMD) with 95%CI (confidence interval) were calculated. The ROBINS-I (risk of bias in non-randomized studies of interventions) and RoB2 (risk of bias tool for randomized trials) assessment tool was used to detect bias. RESULTS: After the selection process, 12 studies were included. The meta-analysis showed that ozone therapy helps to reduce the size of the traumatic and autoimmune ulcers (RR=-0.44; 95% CI -0.71,-0.17; I2=0%) in comparison to placebo. Regarding pain reduction, ozone was superior to placebo (RR = 1.29, 95% CI -1.6 to -0.95); I2=0%), and equivalent to topical corticosteroid and laser photobiomodulation (RR = 0.26, 95% CI -0.27,0.78, p = 0.34). CONCLUSION: Ozone therapy is an alternative for accelerating healing and reducing pain for both traumatic and autoimmune ulcers. However, the quality of evidence is limited. CLINICAL RELEVANCE: Oral ulcerations are usually painful and impact quality of life requiring different approaches to boost wound healing and reduce symptoms. For this purpose, ozone therapy is a promising strategy.

Topical tacrolimus orabase versus topical clobetasol propionate orabase in the treatment of symptomatic oral lichen planus: a pilot randomized study.

OBJECTIVES: This pilot study aimed to compare the efficacy of 0.1% tacrolimus and 0.05% clobetasol propionate in orabase for treating symptomatic oral lichen planus (OLP). MATERIALS AND METHODS: Pilot, randomized, and controlled study conducted on 21 patients with symptomatic OLP, selected according to the clinical and histopathological criteria of Cheng et al. 2016. Twelve patients received 0.1% tacrolimus, and nine received 0.05% clobetasol, both in orabase for 30 days with a two-month follow-up. The patients were examined for scores of signs (ODSS), symptoms (VAS), quality of life (OHIP-14), anxiety (Beck Anxiety Scale), and treatment satisfaction (Hedonic Scale). RESULTS: Both treatments were effective in reducing ODSS, VAS, and Beck Anxiety Scale scores and performed well on the hedonic scale, yet without statistical difference between them. However, at the 1-month follow-up, patients in group Clobetasol showed a greater percentage reduction in ODSS score compared to baseline by 50% (p = 0.02) and significantly lower average values (p = 0.03) than those in group Tacrolimus. Longitudinal intragroup analysis revealed significant improvements over time in both groups for ODSS, and only in the tacrolimus group for OHIP-14 and Beck scores. CONCLUSIONS: Both tested protocols were effective over a three-month follow-up. However, due to the lower cost of clobetasol propionate it can be considered the first-choice option. Tacrolimus in orabase formulation may be a promising alternative for refractory lesions that do not respond to topical steroids. CLINICAL RELEVANCE: Managing symptomatic OLP is challenging. Comparisons between tacrolimus and clobetasol propionate in orabase formulations have not yet been thoroughly explored.

Knowledge, Attitudes, Practices, and Perceptions of Brazilian Dentists About Oral Cancer.

Dentists play a pivotal role in the early detection of oral cancer. Consequently, they are expected to possess the knowledge and the capability to recognize the features of this disease. The objective of the study is to evaluate dentists from different regions of Brazil regarding their level of knowledge and self-confidence regarding oral cancer. An online self-administered questionnaire was completed by dentists across Brazil registered on the TelessaúdeRS-UFRGS platform. This questionnaire encompassed inquiries related to knowledge, attitudes, and practices regarding oral cancer. A total of 1291 dentists from all regions of the country responded to the questionnaire. The majority of participants were females (75.5%), with an average age of 36.3 years, predominantly from the public sector (46.8%). A reasonable level of knowledge regarding oral cancer was observed among dentists, although 48.6% of these professionals felt uncertain about diagnosis procedures. Dentists less than 8 years since graduation perceived themselves as more prepared to perform oral cancer diagnoses than those with more experience. Around 55% of participants had never performed a biopsy. Based on the obtained results, it is concluded that continuous education activities focused on oral cancer and implementing practical training during undergraduate studies are imperative. These strategies can improve professionals' self-confidence and diagnostic accuracy, thereby facilitating early disease diagnosis and, consequently, a more favorable prognosis.

Amitriptyline effectiveness in burning mouth syndrome: An in-depth case series analysis.

OBJECTIVES: To assess the effectiveness of amitriptyline (AMT), and to identify the determinants of the treatment's effectiveness in patients diagnosed with burning mouth syndrome (BMS). BACKGROUND: Treatment of BMS is challenging and no established treatment protocol is available. AMT may be an important treatment option, cout not all patients benefit from this drug. Studies assessing factors related to treatment response are valuable in improving decision-making. MATERIALS AND METHODS: This case series study examined the medical records of all patients diagnosed with BMS at an oral medicine unit in a university hospital from 2008 to 2022. The patients were divided into responders to AMT and non-responders to AMT. Data on demographic information, comorbidities, medications, types of symptoms and oral subsites affected were collected. Descriptive and bivariate analyses were conducted to assess the association between the independent variables and the outcome, using the Chi-squared test (P < .05). RESULTS: Three hundred and fourty-nine patients reported a burning mouth sensation, 50 of them (14.3%) being diagnosed with primary BMS. Of these, 35 were treated with AMT, and 26 (74.2%) responded significantly to AMT. All males responded to AMT, whereas only 67.9% of females responded. The mean dose of AMT among responders was 29.8 ± 12.3 mg, with most patients achieving a response with 25 mg (61.5% of patients), followed by 50 mg (23%). The concomitant use of an anticonvulsant resulted in non-response. CONCLUSIONS: AMT may be effective in BMS management for most patients.

Does liraglutide alleviate inflammation in brain-dead donors? A randomized clinical trial.

Brain death triggers an inflammatory cascade that damages organs before procurement, adversely affecting the quality of grafts. This randomized clinical trial aimed to compare the efficacy of liraglutide compared to placebo in attenuating brain death-induced inflammation, endoplasmic reticulum stress, and oxidative stress. We conducted a double-blinded, placebo-controlled, randomized clinical trial with brain-dead donors. Fifty brain-dead donors were randomized to receive subcutaneous liraglutide or placebo. The primary outcome was the reduction in IL-6 plasma levels. Secondary outcomes were changes in other plasma pro-inflammatory (IL-1ß, interferon-γ, TNF) and anti-inflammatory cytokines (IL-10), expression of antiapoptotic ( BCL2 ), endoplasmic reticulum stress markers ( DDIT3/CHOP , HSPA5/BIP ), and antioxidant ( superoxide dismutase 2 , uncoupling protein 2 ) genes, and expression TNF, DDIT3, and superoxide dismutase 2 proteins in liver biopsies. The liraglutide group showed lower cytokine levels compared to the placebo group during follow-up: Δ IL-6 (-28 [-182, 135] vs. 32 [-10.6, 70.7] pg/mL; p = 0.041) and Δ IL-10 (-0.01 [-2.2, 1.5] vs. 1.9 [-0.2, 6.1] pg/mL; p = 0.042), respectively. The administration of liraglutide did not significantly alter the expression of inflammatory, antiapoptotic, endoplasmic reticulum stress, or antioxidant genes in the liver tissue. Similar to gene expression, expressions of proteins in the liver were not affected by the administration of liraglutide. Treatment with liraglutide did not increase the organ recovery rate [OR = 1.2 (95% CI: 0.2-8.6), p = 0.82]. Liraglutide administration reduced IL-6 and prevented the increase of IL-10 plasma levels in brain-dead donors without affecting the expression of genes and proteins related to inflammation, apoptosis, endoplasmic reticulum stress, or oxidative stress.

Metastatic Melanoma: A Preclinical Model Standardization and Development of a Chitosan-Coated Nanoemulsion Containing Temozolomide to Treat Brain Metastasis.

Melanoma is the most aggressive type of skin cancer. Brain metastasis is the worst scenario in metastatic melanoma and the treatment options for these patients are limited. Temozolomide (TMZ) is a chemotherapy agent used to treat primary central nervous system tumors. Our objective was to develop chitosan-coated nanoemulsion containing temozolomide (CNE-TMZ) for nasal route administration to melanoma brain metastasis treatment. A preclinical model of metastatic brain melanoma was standardized, and the efficiency of the developed formulation was further determined in vitro and in vivo. The nanoemulsion was done by spontaneous emulsification method and the formulation was characterized by size, pH, polydispersity index, and zeta potential. Culture assessments to determine cell viability were done in the A375 human melanoma cell line. To determine the safety of formulation, healthy C57/BL6 mice were treated with a nanoemulsion without TMZ. The model in vivo used B16-F10 cells implanted by stereotaxic surgery in C57/BL6 mice brains. The results demonstrate that the preclinical model used showed to be useful to analyze the efficiency of new candidate drugs to treat melanoma brain metastasis. The chitosan-coated nanoemulsions with TMZ showed the expected physicochemical characteristics and demonstrated safety and efficacy, reducing around 70% the tumor size compared to control mice, and presenting a tendency in mitotic index reduction, becoming an interesting approach to treat melanoma brain metastasis.

Systemic non-steroidal immunomodulators for oral lichen planus treatment-a scoping review.

OBJECTIVE: The aim of this scoping review was to evaluate the efficacy and safety of the use of systemic nonsteroidal immunomodulators (SNSI) for oral lichen planus (OLP) treatment. MATERIALS AND METHODS: This review was conducted according to PRISMA-ScR guidelines and registered at PROSPERO (CRD42021243524). Consulted databases were Pubmed, Embase, Scopus, and Web of Science. The inclusion criteria was as follows: clinical trials, case series, prospective, and retrospective studies conducted with participants presenting OLP of any sex and age. RESULTS: Thirty-two studies were selected, assessing 9 different SNSI: methotrexate, dapsone, levamisole, hydroxychloroquine, thalidomide, metronidazole, azathioprine, mycophenolate mofetil, and colchicine. Methotrexate and dapsone were the drugs with the best evidence among the options included, regarding number and quality of studies. Methotrexate resulted in significant improvement in the clinical condition and remission of symptoms, ranging between 63 and 93% of cases. Dapsone presented a similar effect to the use of topical corticosteroids and tacrolimus CONCLUSION: Among SNSI therapeutic options, methotrexate, and dapsone showed promising efficacy and safety. However, large-scale randomized clinical trials are still needed. CLINICAL RELEVANCE: SNSI have been used in the treatment of recalcitrant OLP; however, so far, it is not clear which are the best options. This scoping review highlights the potential use of methotrexate and dapsone.

Clinical and immunological features of chronic ulcerative stomatitis: A systematic review.

Chronic ulcerative stomatitis (CUS) is a rare disease of the mucous membranes with characteristics similar to other autoimmune diseases. The aim of this study was to conduct a systematic review of the literature to recover all reported cases of CUS in order to summarize what are the clinical, demographic, microscopic, immunological features of CUS and its therapeutic response to different drugs. A systematic review of the literature was carried out following the statements of preferred reporting items for systematic reviews and meta-analyses (PRISMA). The searches were performed in the electronic databases PubMed, Scopus, EMBASE, LILACS, Opengrey, and Google scholar. Inclusion criteria were articles or abstracts reporting at least one case with a final diagnosis of CUS. A total of 696 records were identified through databases, and 25 studies were selected reporting 81 cases. CUS affects more females (92%), and a greater number of cases are reported in Caucasian patients (53%). The age of patients ranged from 20 to 86 years with a mean age of 60 years (±13.86), and 15% of cases reported concomitantly skin lesions. The clinical and histopathological characteristics of CUS are very similar to those of oral lichen planus. The direct immunofluorescence (DIF) remains the gold-standard diagnostic resource and was performed in 69 cases, revealing a dotted pattern of deposition of stratified epithelium-specific antibodies (SES-ANA). The serum of 38 patients was collected for the performance of the indirect immunofluorescence (IIF), and the use of epithelial substrates such as monkey and guinea pig esophagus often resulted in positive SES-ANA IgG. Most patients were treated with antimalarials, and the treatment of choice that proved to be effective is hydroxychloroquine (HCQ). This entity must be considered in the differential diagnosis of other autoimmune diseases, as it may be underreported.

Minimizing patient morbidity after free gingival graft harvesting:A triple-blind randomized-controlled clinical trial.

OBJECTIVES: This study aimed to evaluate the effect of photobiomodulation therapy (PBMT) on patient morbidity and donor site healing after free gingival graft (FGG) harvesting. METHODS: Forty-four patients requiring FGG were selected for this trial. Individuals were randomly assigned to test group (PBMT, n = 22) or control group (placebo, n = 22) applied immediately after surgery, 24 and 48 h after. Demographic, surgical-related and psychosocial variables possibly associated with treatment response were collected. The primary outcome was postoperative pain at the donor site evaluated using Visual Analog Scale (VAS) immediately after surgery and 6, 24, 48 and 72 h after. Secondary outcomes include medication consumption, patient-reported outcome measures (PROMs) and percentage of wound closure. RESULTS: Intragroup analysis showed no differences in VASLOG means for placebo group throughout the study (p > .05), whereas a significant difference in PBMT group at 6 h, 24 h, 48 h and 72 h (p < .05) were observed. Postoperative rescue analgesic requirement was significantly higher in the placebo group (p = .004). The number needed to treat(NNT) was 2.43. PBMT group reported significant better function related to sleeping, going to work/school and daily routine activities, less restriction to mouth opening, chewing and food consumption, less swelling and bleeding (p < .05), mainly in the first 48 h. PBMT group presented a significantly higher palatal wound closure at 7 days compared to placebo group (33.41 vs. 21.20 respectively, p = .024) after adjustment for confounding. No adverse effects were reported. CONCLUSIONS: Photobiomodulation therapy accelerated the pain resolution time and palatal closure, decreased rescue medication consumption and significantly improved patient satisfaction in the postoperative period.

Physicochemical and biological properties of experimental dental adhesives doped with a guanidine-based polymer: an in vitro study.

OBJECTIVES: The objective of this study is to formulate experimental dental adhesives with different polyhexamethylene guanidine hydrochloride concentrations (PHMGH) and evaluate their physical, chemical, and biological properties. MATERIALS AND METHODS: The experimental adhesives were formulated with 0 (control, GCTRL), 0.5 (G0.5%), 1 (G1%), or 2 (G2%) wt.% into the adhesive. The adhesives were analyzed for degree of conversion (DC%), softening in solvent (ΔKHN%), ultimate tensile strength (UTS), microtensile bond strength (µTBS) immediately and after 1 year of aging, antibacterial activity, and cytotoxicity. RESULTS: There were no differences among groups for DC%, ΔKHN%, and UTS (p > 0.05%). There were no differences between each PHMGH-doped adhesive compared to GCTRL in the immediate µ-TBS (p > 0.05). Adhesives with at least 1 wt.% of PHMGH presented better stability of µ-TBS. PHMGH-doped adhesives showed improved longitudinal µ-TBS compared to GCTRL (p < 0.05). Lower Streptococcus mutans biofilm formation was observed for PHMGH-doped adhesives (p < 0.05). There was lower viability of planktonic S. mutans in the media in contact with the samples when at least 1 wt.% of PHGMGH was incorporated (p < 0.05). The formulated adhesives showed no cytotoxicity against pulp cells (p > 0.05). CONCLUSIONS: The adhesive with 2 wt.% of PHMGH showed the highest antibacterial activity, without affecting the physicochemical properties and cytotoxicity, besides conferring stability for the dental adhesion. CLINICAL RELEVANCE: PHMGH, a positively charged polymer, conveyed antibacterial activity to dental adhesives. Furthermore, it did not negatively affect the essential physicochemical and biocompatibility properties of the adhesives. More importantly, the incorporation of PHMGH provided stability for the µ-TBS compared to the control group without this additive.

The brief methylprednisolone administration is crucial to mitigate cardiac dysfunction after myocardial infarction.

Acute myocardial infarction (AMI) is one of the major causes of heart failure and mortality. Glucocorticoids administration post-infarction has long been proposed, but it has shown conflicting results so far. This controversy may be associated with the glucocorticoid type and the period when it is administered. To elucidate these, the present aims to evaluate if the brief methylprednisolone acetate administration is determinant for heart adaptation after AMI. Male Wistar rats were divided into 3 groups: sham-operated (SHAM); infarcted (AMI); infarcted treated with methylprednisolone acetate (AMI+M). Immediately after surgery, the AMI+M group received a single dose of methylprednisolone acetate (40 mg/kg i.m.). After 56 days, the cardiac function was assessed and lungs, liver and heart were collected to determine rates of hypertrophy and congestion. Heart was used for oxidative stress and metalloproteinase activity analyses. Methylprednisolone acetate attenuated matrix metalloproteinase-2 activity, cardiac dilatation, and prevented the onset of pulmonary congestion, as well as avoided cardiac hypertrophy. Our data indicate that administration of methylprednisolone acetate shortly after AMI may be a therapeutic alternative for attenuation of detrimental ventricular remodeling.

Efficacy of topical non-steroidal immunomodulators in the treatment of oral lichen planus: a systematic review and meta-analysis.

OBJECTIVES: The aim of this systematic review was to assess the efficacy and safety of topical non-steroidal immunomodulators (TNSIs) for oral lichen planus (OLP) treatment. MATERIALS AND METHODS: A search strategy designed for this purpose retrieved 1156 references. After analysis of titles and abstracts, 75 studies were selected for full-text analysis. Only randomized controlled clinical trials were selected, resulting in 28 studies included for qualitative and quantitative analysis. RESULTS: The meta-analysis showed similar benefits in clinical response and symptom resolution between tacrolimus 0.1% and pimecrolimus 1% in comparison to topical steroids (TS). Pimecrolimus showed superior efficacy of clinical response but not for symptom resolution compared to placebo. Tacrolimus and pimecrolimus showed better performance preventing symptom relapse, while pimecrolimus also prevented clinical relapse better than TS. Cyclosporine was superior to placebo; however, TS showed better efficacy of clinical response. Thalidomide and retinoid were assessed in only one trial each, and both showed similar efficacy to TS. Rapamycin also presented similar clinical response to TS; however, the later showed greater reduction of symptoms. Mycophenolate mofetil 2% mucoadhesive was no better than placebo. No serious adverse effects have been reported. Cyclosporine showed a higher frequency and variety of adverse effects. CONCLUSIONS: Topical tacrolimus and pimecrolimus are safe and effective alternatives for OLP treatment. CLINICAL RELEVANCE: TS are usually the first choice for OLP treatment. Because some oral lesions may have a low response to treatment with TS, more topical therapeutic options, such as TNSIs, should be considered before systemic steroids are used.

Improvement in the chemical structure and biological activity of surface titanium after exposure to UVC light.

Ultraviolet (UV) irradiation has been proposed as a method to reverse the aging process of titanium. However, the intensity, exposure time and wavelength that provide the best results have not yet been determined. The objective of this study was to evaluate the effects of photocatalysis by ultraviolet C light on the time-dependent aging of titanium and to analyze the irradiated titanium for changes in structure and in vitro biological activity, with regard to different exposure times. A titanium photofunctionalization device was developed with characteristics different from those on the market. The sample was composed of titanium disks irradiated for different times of exposure to ultraviolet C light (0, 15, 30 and 60 min). The disks were tested for surface wettability (water contact angle), topography (scanning electron microscopy-SEM) and chemical composition (X-ray photoelectron spectroscopy), and effects on cell adhesion (cell culture and SEM) and cell viability by sulforhodamine B (SRB). Ultraviolet C treatment caused changes in titanium surface characteristics, such as increased wettability and removal of hydrocarbons from the surface after 15 min of exposure in the chamber developed. The biological characteristics of the material also appear to have changed, with improved cell adhesion and viability. Photofunctionalization of titanium proved to be effective for the treatment of aged surfaces, with significant modifications in the surface chemical structure and biological activity of the material.

The paradox of autophagy in Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by germline mutations in TSC1 or TSC2 genes, which leads to the hyperactivation of the mTORC1 pathway, an important negative regulator of autophagy. This leads to the development of hamartomas in multiple organs. The variability in symptoms presents a challenge for the development of completely effective treatments for TSC. One option is the treatment with mTORC1 inhibitors, which are targeted to block cell growth and restore autophagy. However, the therapeutic effect of rapamycin seems to be more efficient in the early stages of hamartoma development, an effect that seems to be associated with the paradoxical role of autophagy in tumor establishment. Under normal conditions, autophagy is directly inhibited by mTORC1. In situations of bioenergetics stress, mTORC1 releases the Ulk1 complex and initiates the autophagy process. In this way, autophagy promotes the survival of established tumors by supplying metabolic precursors during nutrient deprivation; paradoxically, excessive autophagy has been associated with cell death in some situations. In spite of its paradoxical role, autophagy is an alternative therapeutic strategy that could be explored in TSC. This review compiles the findings related to autophagy and the new therapeutic strategies targeting this pathway in TSC.

Oral, dental, and craniofacial features in chronic acid sphingomyelinase deficiency.

The aim of this study was to evaluate the oral, dental, and craniofacial features of individuals affected by the chronic forms of acid sphingomyelinase deficiency (ASMD). This study comprised a sample of adult and pediatric patients (n = 8) with chronic ASMD. The individuals underwent oral examinations to evaluate the occurrence of caries, as well as full-mouth periodontal examinations, to assess the occurrence and severity of periodontal diseases. Panoramic and profile radiographs were obtained to analyze dental conditions and craniofacial parameters. Participants also answered questionnaires to identify systemic impairment, parafunctional habits, and bruxism. Dental anomalies of size, shape, and number were found, with agenesis and microdontia being the predominant findings. The average of caries experience was 11.75 (±8.1). Only one patient had periodontal health and all adult individuals had periodontitis at different stages and degrees. Bruxism was found in 87.5% of the sample. The convex profile and maxillary and mandibular retrusion were the most relevant findings in the cephalometric analysis. It is concluded that individuals with chronic ASMD, in addition to several systemic manifestations, present significant modifications in their oral health, from a greater occurrence of dental anomalies, caries, periodontal disease, in addition to skeletal changes.