Many uncertainties still surround the possible harmful effect of fluoride exposure on cognitive neurodevelopment in children. The aim of this systematic review and meta-analysis was to characterize this relation through a dose-response approach, by comparing the intelligence quotient (IQ) scores in the highest versus the lowest fluoride exposure category with a random-effects model, within a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1996 potentially relevant literature records, 33 studies were eligible for this review, 30 of which were also suitable for meta-analysis. The summary mean difference of IQ score, comparing highest versus lowest fluoride categories and considering all types of exposure, was -4.68 (95% confidence interval-CI -6.45; -2.92), with a value of -5.60 (95% CI -7.76; -3.44) for drinking water fluoride and -3.84 (95% CI -7.93; 0.24) for urinary fluoride. Dose-response analysis showed a substantially linear IQ decrease for increasing water fluoride above 1 mg/L, with -3.05 (95% CI -4.06; -2.04) IQ points per 1 mg/L up to 2 mg/L, becoming steeper above such level. A weaker and substantially linear decrease of -2.15 (95% CI -4.48; 0.18) IQ points with increasing urinary fluoride emerged above 0.28 mg/L (approximately reflecting a water fluoride content of 0.7 mg/L). The inverse association between fluoride exposure and IQ was particularly strong in the studies at high risk of bias, while no adverse effect emerged in the only study judged at low risk of bias. Overall, most studies suggested an adverse effect of fluoride exposure on children's IQ, starting at low levels of exposure. However, a major role of residual confounding could not be ruled out, thus indicating the need of additional prospective studies at low risk of bias to conclusively assess the relation between fluoride exposure and cognitive neurodevelopment.

Fluoride exposure may have various adverse health effects, including affecting thyroid function and disease risk, but the pattern of such relation is still uncertain. We systematically searched human studies assessing the relation between fluoride exposure and thyroid function and disease. We compared the highest versus the lowest fluoride category across these studies, and we performed a one-stage dose-response meta-analysis for aggregated data to explore the shape of the association. Most retrieved studies (27 of which with a cross-sectional design) were conducted in Asia and in children, assessing fluoride exposure through its concentrations in drinking water, urine, serum, or dietary intake. Twenty-four studies reported data on thyroid function by measuring thyroid-related hormones in blood (mainly thyroid-stimulating-hormone - TSH), 9 reported data on thyroid disease, and 4 on thyroid volume. By comparing the highest versus the lowest fluoride categories, overall mean TSH difference was 1.05 μIU/mL. Dose-response curve showed no change in TSH concentrations in the lowest water fluoride exposure range, while the hormone levels started to linearly increase around 2.5 mg/L, also dependending on the risk of bias of the included studies. The association between biomarkers of fluoride exposure and TSH was also positive, with little evidence of a threshold. Evidence for an association between fluoride exposure and blood concentrations of thyroid hormones was less evident, though there was an indication of inverse association with triiodothyronine. For thyroid disease, the few available studies suggested a positive association with goiter and with hypothyroidism in both children and adults. Overall, exposure to high-fluoride drinking water appears to non-linearly affect thyroid function and increase TSH release in children, starting above a threshold of exposure, and to increase the risk of some thyroid diseases.

This study aims to evaluate the effectiveness of the photobiomodulation therapy (PBMT) in the treatment of minor recurrent aphthous stomatitis (MiRAS) in children, in terms of pain relief, lesion size reduction and the parental satisfaction of the therapy. This randomized controlled study was carried out on 60 children with clinical diagnosis of MiRAS. Patients were randomized into two groups: group A receiving laser therapy and group B receiving sham therapy (placebo). Laser therapy (diode laser, λ: 645 nm) was administered on day 1 (T0) for three consecutive days. Patients were evaluated also on day 4 (T1), on day 7 (T2) and on day 10 (T3). Oral aphthous lesions size was assessed through a periodontal probe to measure the diameter length (mm); pain was evaluated through the Visual Analogue Scale (VAS); parental satisfaction was assessed through a questionnaire. The difference in the reduction of ulcers diameters between the two groups resulted statistically significant at T1 and at T2 (p<0.05). A statistically significant difference in pain reduction between two groups was found at T1 (p<0.05). No statistically significant difference between the two groups of parents was found as concerns the parental acceptance of the procedure and the discomfort for the need of multiple appointments. PBMT is to be considered effective in the treatment of MiRAS in children and well- accepted by the parents of the children themselves.

At low medically‑relevant concentrations, ozone serves as an oxidant with a wide spectrum of antimicrobial activity and the ability to promote healing and reduce inflammation. Despite providing therapeutic benefits in a range of diseases, certain adverse effects and contraindications of ozone treatment must be considered. These are primarily related to toxicity from inhalation and systemic types of administration and can be avoided by following relevant guidelines and recommendations. Ozone therapy has been implemented in a number of fields of dentistry and the most commonly used formulations for the oral cavity are gaseous ozone, ozonized water and ozonized oil. The biological mechanisms underlying the molecular effects of ozone have been increasingly reported, but currently remain largely unknown. The aim of the present review was to provide an overview of the mechanisms involved in ozone interaction with dental tissues. The present review focused on relevant evidence regarding the effect of ozone on dental tissues, including periodontal structures, dental cells, enamel and dentine, considering in vitro studies in addition to animal and human studies. A variety of biological mechanisms acting through multiple biochemical target pathways were reported to be responsible for the therapeutic effects of ozone. The main beneficial effects of ozone occurred in the following domains: antimicrobial activity, remineralization and microstructural changes of hard dental tissues, immunomodulation and biostimulation of dental and periodontal cells. Additional research could provide further insights into the use of ozone, increase its use for broader clinical applications and assist in the selection of targeted protocols.

Background and objectives: Attention deficit hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder characterized by two dimensions: inattentiveness and hyperactivity/impulsivity. ADHD may be the result of complex interactions between genetic, biological and environmental factors possibly including fluoride exposure. Materials and methods: A literature search was performed on 31 March 2023 in the following databases: PubMed, Embase and Web of Science. We defined the following inclusion criteria according to the PECOS statement: a healthy child and adolescent population (P), fluoride exposure of any type (E), comparison with low or null exposure (C), ADHD spectrum disorder (O), and ecological, cross-sectional, case–control and cohort studies (S). Results: We found eight eligible records corresponding to seven different studies investigating the effect of fluoride exposure on children and adolescents. One study had a cohort design and one a case–control one, while five were cross-sectional. Only three studies applied validated questionnaires for the purpose of ADHD diagnosis. As regards exposure assessment, levels of fluoride in urine and tap water were, respectively used in three and two studies, while two used both. Three studies reported a positive association with ADHD risk, all assessing exposure through fluoride levels. By using urinary fluoride, conversely, a positive correlation with inattention, internalizing symptoms, cognitive and psychosomatic problems was found in three studies, but no relation was found in the other one. Conclusions: The present review suggests that early exposure to fluoride may have neurotoxic effects on neurodevelopment affecting behavioral, cognitive and psychosomatic symptoms related to ADHD diagnosis. However, due to the heterogeneity of the studies included, current evidence does not allow to conclusively confirm that fluoride exposure is specifically linked to ADHD development.