Ecological Therapeutic Opportunities for Oral Diseases

The three main oral diseases of humans, that is, caries, periodontal diseases, and oral candidiasis, are associated with microbiome shifts initiated by changes in the oral environment and/or decreased effectiveness of mucosal immune surveillance. In this review, we discuss the role that microbial-based therapies may have in the control of these conditions. Most investigations on the use of microorganisms for management of oral disease have been conducted with probiotic strains with some positive but very discrete clinical outcomes. Other strategies such as whole oral microbiome transplantation or modification of community function by enrichment with health-promoting indigenous oral strains may offer more promise, but research in this field is still in its infancy. Any microbial-based therapeutics for oral conditions, however, are likely to be only one component within a holistic preventive strategy that should also aim at modification of the environmental influences responsible for the initiation and perpetuation of microbiome shifts associated with oral dysbiosis

Achieving the Way for Automated Segmentation of Nuclei in Cancer Tissue Images through Morphology-Based Approach: a Quantitative Evaluation

In this paper we address the problem of nuclear segmentation in cancer tissue images, that is critical for specific protein activity quantification and for cancer diagnosis and therapy. We present a fully automated morphology-based technique able to perform accurate nuclear segmentations in images with heterogeneous staining and multiple tissue layers and we compare it with an alternate semi-automated method based on a well established segmentation approach, namely active contours. We discuss active contours’ limitations in the segmentation of immunohistochemical images and we demonstrate and motivate through extensive experiments the better accuracy of our fully automated approach compared to various active contours implementations

Effect of Zinc Supplementation on Growth of Low Birth Weight Infants Aged 1–6 Mo in Ardabil, Iran

Objective To assess the effect of zinc supplementation on growth of low birth weight (LBW) infants aged 1–6 mo. Methods LBW infants were enrolled at birth and randomly assigned to receive 5 mg elemental Zn per day (n=45) or placebo (n=45) until 6 mo of age. They were followed monthly for information on compliance; anthropometric measurements were performed monthly. Results After randomization, 5 infants from zinc group and 9 from placebo group were excluded. At 6 mo of age, significantly greater weight gains were observed in the zinc than in the placebo group (4995±741g in zinc group vs. 3896±865 g in placebo group, p = 0.036). Length gain during the study period improved in zinc group (16.9±8.2 cm vs. 15.1±4.1 cm, p = 0.039); after zinc supplementation head circumference were increased (8.7±1.4 cm vs.7.4± 1.5 cm p<0.001). In male infants, total weight gain and height and head circumference gain were higher in the zinc than in the placebo group. However, only head circumference change was statistically significant. A similar trend was observed among female infants, but these differences were not statistically significant. There was no significant relation between breast-feeding status and the main outcome variables. Conclusions Infants in the present study showed improve¬ments in growth rate, but more studies are required in this field to confirm this fact

Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis.

BACKGROUND: Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues. RESULTS: Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity. CONCLUSIONS: Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis

Fermion Pairing Dynamics in the Relativistic Scalar Plasma

Using many-body techniques we obtain the time-dependent Gaussian approximation for interacting fermion-scalar field models. This method is applied to an uniform system of relativistic spin-1/2 fermion field coupled, through a Yukawa term, to a scalar field in 3+1 dimensions, the so-called quantum scalar plasma model. The renormalization for the resulting Gaussian mean-field equations, both static and dynamical, are examined and initial conditions discussed. We also investigate solutions for the gap equation and show that the energy density has a single minimum.Comment: 21 pages, latex, 4 postscript figures, new sections, some literary changes, notation corrections, accepted for publication in Phys. Rev

A cross-species interaction with a symbiotic commensal enables cell-density-dependent growth and in vivo virulence of an oral pathogen

Recent studies describe in detail the shifts in composition of human-associated polymicrobial communities from health to disease. However, the specific processes that drive the colonization and overgrowth of pathogens within these communities remain incompletely understood. We used in vitro culture systems and a disease-relevant mouse model to show that population size, which determines the availability of an endogenous diffusible small molecule, limits the growth, colonization, and in vivo virulence of the human oral pathogen Porphyromonas gingivalis. This bacterial pathogen overcomes the requirement for an endogenous cue by utilizing a cell-density dependent, growth-promoting, soluble molecule provided by the symbiotic early colonizer Veillonella parvula, but not produced by other commensals tested. Our work shows that exchange of cell-density-dependent diffusible cues between specific early and late colonizing species in a polymicrobial community drives microbial successions, pathogen colonization and disease development, representing a target process for manipulation of the microbiome towards the healthy state

Metabolic effects of diets differing in glycaemic index depend on age and endogenous GIP

Aims/hypothesis High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling. Methods Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr −/− ) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20–26 weeks of intervention, n = 8–10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake. Results Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, p < 0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (p < 0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr −/− vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity. Conclusions/interpretation The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial

Why be down in the mouth? Three decades of research in oral microbiology

The document attached has been archived with permission from the Australian Dental Association. An external link to the publisher's copy is included.This paper describes some of the work done in the author's laboratory over the past 35 years. The research covers the following areas: the physiology of oral streptococci and their interactions; the physiology of some Gram-negative anaerobes and their interactions in relation to periodontal diseases; preventing the major dental diseases; and the future of oral microbiology.AH Roger

Methodological approaches to assess body-weight regulation and aetiology of obesity

Obesity, which is becoming one of the major health hazards in developed and developing societies, results from a long-term positive energy balance. Body-weight regulation and stability depend on an axis with three interrelated components: food intake, energy expenditure and adipogenesis, although there are still many unknown features concerning fuel homeostasis and energy balance. Biochemical processes are interconnected, and a separate consideration of each component is often useful for methodological purposes and to achieve a better understanding of the whole system. Thus, many different experimental approaches can be applied by using laboratory animals, cell culture or human subjects to unravel the molecular mechanisms which participate in body-weight regulation. Thus, both in vitro (cellular and subcellular models) and in vivo methods have dramatically increased our knowledge of weight control. Several strategies in obesity research are reported here, exploiting the opportunities of the molecular era as well as novel whole-body approaches, which will impact on the development of new targets for obesity management and prevention