Recent Advances in Remineralization Therapies for Caries Lesions.

Remineralization of caries lesions is naturally achieved by salivary ions, and it can be enhanced by external factors or elements such as fluoride. Numerous studies have demonstrated the remineralizing efficacy of fluoride therapies as well as the limitations with some groups of the population. Consequently, developing new remineralization therapies to close this gap in efficacy has been a priority for the last 2 decades. In this review, we summarize and briefly discuss some of the latest advances in remineralization therapies. Most new therapies try to enhance the effect of fluoride by adding other potentially active ingredients to the formulation, such as calcium, phosphate, stannous, xylitol, and arginine. Other remineralization strategies have focused on creating remineralizing scaffolds within the lesions (e.g., self-assembling peptides). While several of the new remineralization strategies have progressed significantly in recent years, for most of them, the evidence is still insufficient to assess their true clinical potential.

The effect of inoculum source and fluid shear force on the development of in vitro oral multispecies biofilms.

AIMS: Saliva has been previously used as an inoculum for in vitro oral biofilm studies. However, the microbial community profile of saliva is markedly different from hard- and soft-tissue-associated oral biofilms. Here, we investigated the changes in the biofilm architecture and microbial diversity of in vitro oral biofilms developed from saliva, tongue or plaque-derived inocula under different salivary shear forces. METHODS AND RESULTS: Four inoculum types (saliva, bacteria harvested from the tongue, toothbrush and curette-harvested plaque) were collected and pooled. Biofilms (n ≥ 15) were grown for 20 h in cell-free human saliva flowing at three different shear forces. Stained biofilms were imaged using a confocal laser scanning microscope. Biomass, thickness and roughness were determined by image analysis and bacterial community composition analysed using Ion Torrent. All developed biofilms showed a significant reduction in observed diversity compared with their respective original inoculum. Shear force altered biofilm architecture of saliva and curette-collected plaque and community composition of saliva, tongue and curette-harvested plaque. CONCLUSIONS: Different intraoral inocula served as precursors of in vitro oral polymicrobial biofilms which can be influenced by shear. SIGNIFICANCE AND IMPACT OF THE STUDY: Inoculum selection and shear force are key factors to consider when developing multispecies biofilms within in vitro models.

Teledentistry and mHealth for Promotion and Prevention of Oral Health: A Systematic Review and Meta-analysis.

The dental profession has experienced a dramatic acceleration in the use of communication systems and information-based technologies over recent years, originating new paradigms for the prevention and promotion of oral health. The purpose of this systematic review was to determine the effect of teledentistry-based (telematic) strategies, reported in randomized controlled trials and quasi-randomized trials, with a focus on oral health prevention and promotion-related outcomes in patients of all ages. We searched Medline via PubMed, SCOPUS, and Web of Science from inception until August 2020, regardless of the language of publication. We selected studies for inclusion and conducted data extraction, assessed risk of bias (Cochrane tool), and evaluated the certainty of the evidence (GRADE approach) in duplicate and independently. Out of 898 potentially eligible references, we selected 43 for full-text screening, of which 19 studies proved eligible: 18 randomized controlled trials and 1 quasi-randomized study. Virtual interventions were mostly asynchronous via apps (n = 9), text messages (n = 9), or computer-aided learning (n = 1). The use of teledentistry as compared with conventional strategies may result in a large reduction in the plaque index (standardized mean difference, -1.18; 95% CI, -1.54 to -0.82; I2 = 92%; low certainty) and will likely result in a large reduction in the gingival index (standardized mean difference, -2.17; 95% CI, -3.15 to -1.19; I2 = 97%; moderate certainty) and in the incidence of white spot lesions (risk ratio, 0.48; 95% CI, 0.35 to 0.66; I2 = 0%; moderate certainty), with an increased effect over time. Evidence suggests that teledentistry, particularly mHealth (messages and apps), is a promising clinical tool for preventing and promoting oral health, especially under the accelerated virtualization of dentistry. Future studies should include a broader spectrum of the population, including adults and elders, to better inform policy and implementation of teledentistry (PROSPERO: CRD42020192685).

Human Vascular Microphysiological System for in vitro Drug Screening.

In vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400-800 µM diameters were made by embedding human neonatal dermal fibroblasts or human bone marrow-derived mesenchymal stem cells in dense collagen gel. TEBVs were mechanically strong enough to allow endothelialization and perfusion at physiological shear stresses within 3 hours after fabrication. After 1 week of perfusion, TEBVs exhibited endothelial release of nitric oxide, phenylephrine-induced vasoconstriction, and acetylcholine-induced vasodilation, all of which were maintained up to 5 weeks in culture. Vasodilation was blocked with the addition of the nitric oxide synthase inhibitor L-N(G)-Nitroarginine methyl ester (L-NAME). TEBVs elicited reversible activation to acute inflammatory stimulation by TNF-α which had a transient effect upon acetylcholine-induced relaxation, and exhibited dose-dependent vasodilation in response to caffeine and theophylline. Treatment of TEBVs with 1 µM lovastatin for three days prior to addition of Tumor necrosis factor - α (TNF-α) blocked the injury response and maintained vasodilation. These results indicate the potential to develop a rapidly-producible, endothelialized TEBV for microphysiological systems capable of producing physiological responses to both pharmaceutical and immunological stimuli.

Relationship between physical activity and markers of oxidative stress in independent community-living elderly individuals.

The aim of the present study was to examine the relationship between objective data of physical activity and markers of oxidative stress in older men and women. Participants were old adults, aged≥60years (61 women and 34 men) who were all capable of performing basic daily activities by themselves and lived on their own. To describe physical activity we used objective data measured by accelerometers which record active and sedentary periods during everyday life for five days. Determination of oxidative stress was conducted from three perspectives: determination plasma total antioxidant status (TAS), plasma antioxidant enzyme activities, i.e., glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD), and membrane lipid peroxidation (TBARS). In the group of women, those who met physical activity recommendations (WR) had lower level of TAS. In addition, the moderate to vigorous physical activity (MVPA) was negatively correlated with TAS. Simultaneously, MVPA was correlated with increase in the GPx antioxidant enzyme activity, and the counts per minute were positively correlated with CAT activity. In the group of men, the cpm and the MVPA were negatively correlated with lipid peroxidation while lifestyle physical activity was positively correlated with CAT activity. These findings suggest that MVPA in the elderly although it is related to a decrease in the TAS in women, induces adaptive increase in antioxidant enzyme activity and decreases lipid peroxidation in both women and men. These results suggest that at this time of life, it is not only the amount of physical activity performed that is important but also its intensity.

Awareness, attitudes and behaviour of teenagers to sunlight.

Most campaigns for the prevention of skin cancer have detected more new cases and decreased the number of advanced cancers. Since the incidence of skin cancer continues to increase, however, we believe that primary prevention is the best way to control it. It must be kept in mind that sunlight exposure is the main changeable risk factor for skin cancer and that this exposure is most significant in childhood and adolescence. Our aim in this study was to evaluate the need for a campaign and design one if necessary. We therefore proposed to determine the level of awareness and the behaviour of students with respect to sunlight exposure. We surveyed 628 teenage students from 9 high schools in the city of Granada (Spain). The questions were grouped into four sections: 1. Relationship Sun and Skin, 2. Relationship Sun and Environment, 3. Relationship Sun and Health, 4. Evaluation of Attitudes and Behaviour. More than 60% of the students gave satisfactory answers with regard to awareness, in contrast to the responses for attitudes and behaviour. Prevention campaigns for students are definitely necessary, keeping in mind in their design that a high level of awareness does not translate into healthy habits with regard to sunlight. Intervention to change behaviour patterns should be the main goal of primary prevention campaigns.

Lipid raft disarrangement as a result of neuropathological progresses: a novel strategy for early diagnosis?

Lipid rafts are the preferential site of numerous membrane signaling proteins which are involved in neuronal functioning and survival. These proteins are organized in multiprotein complexes, or signalosomes, in close contact with lipid classes particularly represented in lipid rafts (i.e. cholesterol, sphingolipids and saturated fatty acids), which may contribute to physiological responses leading to neuroprotection. Increasing evidence indicates that alteration of lipid composition in raft structures as a consequence of neuropathologies, such as Alzheimer's disease (AD) and Parkinson's disease (PD), causes a dramatic increase in lipid raft order. These phenomena may correlate with perturbation of signalosome activities, likely contributing to neurodegenerative progression. Interestingly, significant disruption of stable raft microenvironments has been already observed in the first stages of either AD or PD, suggesting that these alterations may represent early events in the neuropathological development. In this regard, the search for biochemical markers, such as specific metabolic products altered in the brain at the first steps of the disease, presently represents an important challenge for early diagnostic strategies. Alterations of these biomarkers may be reflected in either plasma or cerebrospinal fluid, thus representing a potential strategy to predict an accurate diagnosis. We propose that pathologically-linked lipid raft markers may be interesting candidates to be explored at this level, although it has not been studied so far to what extent alteration of different signalosome components may be reflected in peripheral fluids. In this mini-review, we will discuss on relevant aspects of lipid rafts that contribute to the modulation of neuropathological events related to AD and PD. An interesting hypothesis is that anomalies on raft biomarkers measured at peripheral fluids might mirror the lipid raft pathology observed in early stages of AD and PD.

Oestrogens as modulators of neuronal signalosomes and brain lipid homeostasis related to protection against neurodegeneration.

Oestrogens trigger several pathways at the plasma membrane that exert beneficial actions against neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Part of these actions takes place in lipid rafts, which are membrane domains with a singular protein and lipid composition. These microdomains also represent a preferential site for signalling protein complexes, or signalosomes. A plausible hypothesis is that the dynamic interaction of signalosomes with different extracellular ligands may be at the basis of neuronal maintenance against different neuropathologies. Oestrogen receptors are localised in neuronal lipid rafts, taking part of macromolecular complexes together with a voltage-dependent anion channel (VDAC), and other molecules. Oestradiol binding to its receptor at this level enhances neuroprotection against amyloid-ß degeneration through the activation of different signal transduction pathways, including VDAC gating modulation. Moreover, part of the stability and functionality of signalling platforms lays on the distribution of lipid hallmarks in these microstructures, which modulate membrane physicochemical properties, thus favouring molecular interactions. Interestingly, recent findings indicate a potential role of oestrogens in the preservation of neuronal membrane physiology related to lipid homeostasis. Thus, oestrogens and docosahexaenoic acid may act synergistically to stabilise brain lipid structure by regulating neuronal lipid biosynthetic pathways, suggesting that part of the neuroprotective effects elicited by oestrogens occur through mechanisms aimed at preserving lipid homeostasis. Overall, oestrogen mechanisms of neuroprotection may occur not only by its interaction with neuronal protein targets through nongenomic and genomic mechanisms, but also through its participation in membrane architecture stabilisation via 'lipostatic' mechanisms.

1,25-Dihydroxyvitamin D3 protects HL60 cells against apoptosis but down-regulates the expression of the bcl-2 gene.

Exposure of myeloid leukemia cells to analogs of vitamin D results in monocytic-like maturation of several variants of these cells. We report here that brief treatment of HL60 cells with differentiation-inducing concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) makes these cells resistant to cell death by apoptosis. Resistance was studied by using the calcium inophore A23187 and the cancer chemotherapeutic drugs 1-beta-D-arabinocytosine and etoposide. Apoptosis was detected by the characteristic morphology under light microscopic examination, presence of DNA "ladders" on agarose gel electrophoresis, DNA fragmentation by filter elution assay, and the "apoptotic index" obtained by comparison of damage to mitochondrial and nuclear genes on Southern blots. The protective effect of 1,25(OH)2D3 treatment was apparent before the phenotypic evidence of differentiation and before altered traverse of the cell cycle could be detected. Northern and Western blot analysis showed that the expression of bcl-2 proto-oncogene was rapidly reduced by 1,25(OH)2D3, which excludes the involvement of this gene in the protective effect. The rapidity of the protective effect of 1,25(OH)2D3 is consistent with the hypothesis that the activation of the monocytic differentiation program is sufficient to interfere with programs that lead to cell death by apoptosis.