Ulcerative oral lesions: an overview of non-pharmacologic treatment options

Background and Objective: Ulcerative diseases frequently affect the oral cavity and are disabling conditions. The management is challenging, and traditional treatments are associated with potential side effects. Alternative non-pharmacologic strategies have become available to effectively manage these conditions. This review aims at providing a synthesis of the most common erosive-ulcerative oral diseases and an updated overview of the main non-pharmacologic options for their management, such as laser therapy, ozone applications, and photodynamic therapy. Methods: A narrative review was conducted by searching PubMed/MEDLINE for the most recent relevant systematic reviews or, alternatively, clinical trials or case reports. Results: Laser photobiomodulation therapy (PBMT), ozone therapy and photodynamic therapy (PDT) generally resulted in rapid relief of painful symptoms, reduced healing time and improved oral functions and patients’ quality of life. No major side-effects were reported. Regardless of the primary etiology, photodynamic therapy proved particularly effective in case of infections. Ozone was used in gaseous, ozonized water and oil formulations. The most used light sources were Nd:YAG, He:Ne, Er,Cr:YSGG, red and infrared diode lasers and LED for PBMT, while red diode lasers prevailed for PDT. The most common photosensitizers were methylene blue and toluidine blue O. Conclusions: There is growing evidence for an efficacy of PBMT, ozone and PDT for the treatment of ulcerative oral lesions, and therefore these approaches should be considered as valid non-pharmacologic strategies. However, due to the great heterogeneity of protocols, additional well-designed research to identify the best therapeutic protocols is needed. (www.actabiomedica.it)

Ozone Treatment for the Management of Caries in Primary Dentition: A Systematic Review of Clinical Studies

Dental caries in children is a frequent and debilitating condition, whose management is often challenging. The aim of this systematic review was to investigate the effectiveness of ozone applications for the treatment of caries in primary dentition. According to PRISMA guidelines, a systematic literature search was performed up to 6 January 2024. Clinical studies using ozone to treat caries of deciduous teeth were considered for inclusion. Out of the 215 records retrieved, seven studies were eventually included in the review, all of which used gaseous ozone. Four studies were judged at high risk of bias, two at low risk, and one of some concerns. The great heterogeneity of designs, outcomes, and protocols made it impossible to conduct a meta-analysis. Despite some limitations, the evidence yielded by the included studies suggests that ozone application, regardless of the protocol applied, is comparable to other interventions in terms of clinical outcomes and anti-bacterial activity, with no reported adverse effects and good patient acceptance. Therefore, ozone application may be a non-invasive approach to treat caries in primary dentition, especially in very young and poorly cooperative patients. Further standardized and rigorous studies are, however, needed to identify the best clinical protocols for this specific field

Rééducation Posturale Globale in musculoskeletal diseases: scientific evidence and clinical practice

SUMMARY Several studies on the treatment of musculoskeletal diseases with physiotherapy and clinical experiences on the basis of a method called Rééducation Posturale Globale (RPG), have highlighted the usefulness of this treatment. Although such treatment technique is commonly used in physical therapy practice, only few studies support its therapeutic effectiveness. Objective: To search the literature for evidence of RPG effectiveness, in order to identify the most appropriate therapeutic contexts for its use. Methods: A review of the literature through the following databases: PubMed, Embase, Cinahl, Pedro, and Medscape. The keywords used for the search in the databases are: Rééducation Posturale Globale, Souchard, Posture, and Manual Therapy. The following clinical studies were selected: randomized controlled studies, non-randomized controlled studies, observation studies, and case reports, in English, Spanish, Portuguese, and Italian. Results: Out of 18 studies found, 9 were analyzed: 2 randomized controlled studies, 2 non-randomized controlled studies, 3 non-controlled studies, and 2 case reports. Conclusions: The RPG method has been shown to be an effective treatment technique for musculoskeletal diseases, in particular for ankylosing spondylitis, acute and chronic low back pain, and lumbar discherniation. Although the scarcity of rigorous experimental trials on a large scale does not allow the drawing of undisputable conclusions, the results gathered up to now are an encouragement to carry on research in the field of conservative treatment

Early fluoride intake and Molar Incisor Hypomineralisation (MIH) defects: A systematic review and dose-response meta-analysis

Background: Excessive intake of fluoride has been implicated in the complex multifactorial etiology of hypomineralisation (MIH) defects. Objective: To study the possible effect of early exposure to fluoride on the risk of molar incisor hypomineralisation, also through a dose-response approach. Methods: Observational and clinical studies investigating the relation between fluoride exposure from any source or evaluating exposure biomarkers and MIH defects. PubMed MEDLINE, Embase and Web of Science databases were con-sulted up to December 1, 2023, using terms related to “fluoride”, “enamel defects” and “demarcated opacities”. We performed a meta-analysis comparing the highest versus lowest fluoride exposure using a random-effects model, and we quantitively assessed this relation using piece-wise linear meta-regression. Results: Thirteen studies were included in the meta-analysis, 12 of which were eligible for the dose-response analysis, all regarding exposure from fluoride in drinking water. Three of them specifically addressed MIH, while the remaining concerned “demarcated opacities”, yet with features attributable to MIH. Comparing the highest versus lowest water fluoride exposure categories, virtually no evidence of a fluoride effect was identified, with an overall odds ratio of 0.93 [95% confidence interval 0.60; 1.45]. The dose-response meta-regression showed a decreasing risk for MIH defects exposure up to 1 mg/L, whereas an increase in risk emerged at higher exposure levels. Conclusions: This meta-analysis suggests that early systemic exposure to fluoride may affect the occurrence of MIH defects differently depending on fluoride concentration. However, these results need to be evaluated with caution due to potential methodological limitations of the studies included. (www.actabiomedica.it)

The role of matrix metalloproteinases in periodontal disease

This review provides a detailed description of matrix metalloproteinases (MMPs), focusing on those that are known to have critical roles in bone and periodontal disease. Periodontal disease is an inflammatory process initiated by anaerobic bacteria, which promote the host immune response in the form of a complex network of molecular pathways involving proinflammatory mediators such as cytokines, growth factors, and MMPs. MMPs are a family of 23 endopeptidases, collectively capable of degrading virtually all extracellular matrix (ECM) components. This study critically discusses the available research concerning the involvement of the MMPs in periodontal disease development and progression and presents possible therapeutic strategies. MMPs participate in morphogenesis, physiological tissue turnover, and pathological tissue destruction. Alterations in the regulation of MMP activity are implicated in the manifestation of oral diseases, and MMPs comprise the most important pathway in tissue destruction associated with periodontal disease. MMPs can be considered a risk factor for periodontal disease, and measurements of MMP levels may be useful markers for early detection of periodontitis and as a tool to assess prognostic follow-ups. Detection and inhibition of MMPs could, therefore, be useful in periodontal disease prevention or be an essential part of periodontal disease therapy, which, considering the huge incidence of the disease, may greatly improve oral health globally

Influence of the activation mode on long-term bond strength and endogenous enzymatic activity of dual-cure resin cements

Objective: To investigate the long-term microtensile bond strength (µTBS), interfacial nanoleakage expression (NL), and adhesive stability of dual-cure resin cements with/out light activation to dentin. Materials and methods: Composite overlays (N = 20) were luted to deep dentin surfaces with RelyX Ultimate (RXU, 3M) or Variolink EstheticDC (VAR, Ivoclar-Vivadent). A universal adhesive was used for bonding procedures (iBond universal, Heraeus Kulzer). The resin cements were either self-cured (SC; 1 h at 37 °C) or dual-cured (DC; 20s light-cure followed by 15 min self-cure at 37 °C). Specimens were submitted to µTBS immediately (T0) or after 1 year of laboratory storage (T12). The fracture pattern was evaluated using scanning electron microscopy (SEM). Data were statistically analyzed with two-way ANOVA/Tukey test. Further, the NL was quantified and analyzed (chi-square test) and in situ zymography was performed to evaluate the endogenous enzymatic activity within the hybrid layer (HL) at T0 and T12 (Mann–Whitney test). The significance level for all statistical tests was set at p = 0.05. Results: DC resulted in higher bond strength and decreased fluorescence at the adhesive interface, irrespective of the material and the storage period (p < 0.05). Significantly lower bonding performances (p < 0.05) and higher endogenous enzymatic activity (p < 0.05) were observed within the HL at T12 compared to T0 in all tested groups. Conclusions: Light-curing the dual-cure resin cements, more than the cement materials, accounted for good bonding performances and higher HL stability over time when used with a universal adhesive. Clinical significance The curing condition influences the bonding performances of dual-cure resin cements to dentin when used with a universal adhesive

Updates on the CDK4/6 inhibitory strategy and combinations in breast cancer

Breast Cancer (BC) is the second most common type of cancer worldwide and displays the highest cancer-related mortality among women worldwide. Targeted therapies have revolutionized the way BC has been treated in recent decades, improving the life expectancies of millions of women. Among the different molecular pathways that have been of interest for the development of targeted therapies are the Cyclin-Dependent Kinases (CDK). CDK inhibitors are a class of molecules that already exist in nature and those belonging to the Cyclin dependent kinase inhibitors family INK4 that specifically inhibit CDK4/6 proteins. CDK4/6 inhibitors specifically block the transition from the G1 to the S phase of the cell cycle by dephosphorylation of the retinoblastoma tumor suppressor protein. In the past four years, the CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, received their first FDA approval for the treatment of Hormone Receptor (HR)-positive and Human Epidermal growth factor Receptor 2 (HER2)-negative breast cancer after showing significant improvements in progression-free survival in the PALOMA-1, MONALEESA-2 and the MONARCH-2 randomized clinical trials, respectively. After the encouraging results from these clinical trials, CDK4/6 inhibitors have also been investigated in other BC subtypes. In HER2-positive BC, a combination of CDK4/6 inhibitors with HER2-targeted therapies showed promise in preclinical studies and their clinical evaluation is ongoing. Moreover, in triple-negative BC, the efficacy of CDK4/6 inhibitors has been investigated in combination with other targeted therapies or immunotherapies. This review summarizes the molecular background and clinical efficacy of CDK4/6 inhibitors as single agents or in combination with other targeted therapies for the treatment of BC. Future directions for ongoing clinical trials and predictive biomarkers will be further debated

Glutaraldehyde-based desensitizers’ influence on bonding performances and dentin enzymatic activity of universal adhesives

Objectives: To evaluate the influence of two glutaraldehyde-based desensitizers (L: GLUMA Desensitizer, Heraeus Kulzer and G: GLUMA Desensitizer PowerGel) prior to the adhesive procedures on microtensile bond strength (μTBS) to dentin and endogenous enzymatic activity. Methods: Noncarious human third molars (N = 48) were cut to expose middle coronal dentin. Six experimental groups were formed according to the dentin pre-treatment (L or G) and the universal adhesives (IBU - iBond universal, Kulzer or AU - Adhese Universal, Ivoclar Vivadent) used in the self-etch mode (n = 8): 1) L/IBU; 2) G/IBU; 3) IBU; 4) L/AU; 5) G/AU; 6) AU. Specimens were cut into sticks and stressed until failure after 24 h (T0) or 1 yr of aging (T12). Additional 4 teeth were used for in situ zymography evaluation and data were statistically analyzed (α = 0.05). Results: Dentin pre-treatment, adhesive and aging statistically influenced bond strength and enzymatic activity (P<0.001). AU demonstrated higher bond strength values than IBU (P<0.001). The L resulted in higher bond strength compared to the G and control groups (P<0.001). aging statistically influenced bonding performance, especially when no dentin pre-treatment was performed (P<0.001). In situ zymography revealed that at baseline the control groups exhibited lower interfacial fluorescence compared to the experimental groups, irrespective of the adhesive used (P<0,001). However, after 1 yr of artificial storage, no differences were found among the groups (P>0.05). Conclusions: : Glutharldeadeyde-based products increased bond strength and determined a stabilization of the adhesive interface over time apparently not related to the MMPs inhibition. Clinical Significance: The results of this in vitro study suggest that the application of glutaraldehyde-based desensitizers prior to the adhesive procedures when associated with universal adhesives could result in increased bond strength and stabilization of the adhesive interface over time