Fluoride and oral health

The discovery during the first half of the 20th century of the link between natural fluoride, adjusted fluoride levels in drinking water and reduced dental caries prevalence proved to be a stimulus for worldwide on-going research into the role of fluoride in improving oral health. Epidemiological studies of fluoridation programmes have confirmed their safety and their effectiveness in controlling dental caries. Major advances in our knowledge of how fluoride impacts the caries process have led to the development, assessment of effectiveness and promotion of other fluoride vehicles including salt, milk, tablets, toothpaste, gels and varnishes. In 1993, the World Health Organization convened an Expert Committee to provide authoritative information on the role of fluorides in the promotion of oral health throughout the world (WHO TRS 846, 1994). This present publication is a revision of the original 1994 document, again using the expertise of researchers from the extensive fields of knowledge required to successfully implement complex interventions such as the use of fluorides to improve dental and oral health. Financial support for research into the development of these new fluoride strategies has come from many sources including government health departments as well as international and national grant agencies. In addition, the unique role which industry has played in the development, formulation, assessment of effectiveness and promotion of the various fluoride vehicles and strategies is noteworthy. This updated version of ‘Fluoride and Oral Health’ has adopted an evidence-based approach to its commentary on the different fluoride vehicles and strategies and also to its recommendations. In this regard, full account is taken of the many recent systematic reviews published in peer reviewed literature

Cloning of a gene (SR-A1), encoding for a new member of the human Ser/Arg-rich family of pre-mRNA splicing factors: overexpression in aggressive ovarian cancer

By using the positional cloning gene approach, we were able to identify a novel gene encoding for a serine/arginine-rich protein, which appears to be the human homologue of the rat A1 gene. We named this new gene SR-A1. Members of the SR family of proteins have been shown to interact with the C-terminal domain (CTD) of the large subunit of RNA polymerase II and participate in pre-mRNA splicing. We have localized the SR-A1 gene between the known genes IRF3 and RRAS on chromosome 19q13.3. The novel gene spans 16.7 kb of genomic sequence and it is formed of 11 exons and 10 intervening introns. The SR-A1 protein is composed of 1312 amino acids, with a molecular mass of 139.3 kDa and a theoretical isoelectric point of 9.31. The SR-A1 protein contains an SR-rich domain as well as a CTD-binding domain present only in a subset of SR-proteins. Through interactions with the pre-mRNA and the CTD domain of the Polymerase II, SR proteins have been shown to regulate alternative splicing. The SR-A1 gene is expressed in all tissues tested, with highest levels found in fetal brain and fetal liver. Our data suggest that this gene is overexpressed in a subset of ovarian cancers which are clinically more aggressive. Studies with the steroid hormone receptor-positive breast and prostate carcinoma cell lines ZR-75-1, BT-474 and LNCaP, respectively, suggest that SR-A1 is constitutively expressed. Furthermore, the mRNA of the SR-A1 gene in these cell lines appears to increase by estrogens, androgens and glucocorticoids, and to a lesser extend by progestins. © 2001 Cancer Research Campaign http://www.bjcancer.co

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Induction of Heme Oxygenase-1 Can Halt and Even Reverse Renal Tubule-Interstitial Fibrosis

Background: The tubule-interstitial fibrosis is the hallmark of progressive renal disease and is strongly associated with inflammation of this compartment. Heme-oxygenase-1 (HO-1) is a cytoprotective molecule that has been shown to be beneficial in various models of renal injury. However, the role of HO-1 in reversing an established renal scar has not yet been addressed. Aim: We explored the ability of HO-1 to halt and reverse the establishment of fibrosis in an experimental model of chronic renal disease. Methods: Sprague-Dawley male rats were subjected to unilateral ureteral obstruction (UUO) and divided into two groups: non-treated and Hemin-treated. To study the prevention of fibrosis, animals were pre-treated with Hemin at days -2 and -1 prior to UUO. To investigate whether HO-1 could reverse established fibrosis, Hemin therapy was given at days 6 and 7 post-surgery. After 7 and/or 14 days, animals were sacrificed and blood, urine and kidney tissue samples were collected for analyses. Renal function was determined by assessing the serum creatinine, inulin clearance, proteinuria/creatininuria ratio and extent of albuminuria. Arterial blood pressure was measured and fibrosis was quantified by Picrosirius staining. Gene and protein expression of pro-inflammatory and pro-fibrotic molecules, as well as HO-1 were performed. Results: Pre-treatment with Hemin upregulated HO-1 expression and significantly reduced proteinuria, albuminuria, inflammation and pro-fibrotic protein and gene expressions in animals subjected to UUO. Interestingly, the delayed treatment with Hemin was also able to reduce renal dysfunction and to decrease the expression of pro-inflammatory molecules, all in association with significantly reduced levels of fibrosis-related molecules and collagen deposition. Finally, TGF-beta protein production was significantly lower in Hemin-treated animals. Conclusion: Treatment with Hemin was able both to prevent the progression of fibrosis and to reverse an established renal scar. Modulation of inflammation appears to be the major mechanism behind HO-1 cytoprotection.Fundacao de Amparo Pesquisa do Estado de Sao Paulo-FAPESP[07/07139-3]Coordenaco de Aperfeioamento de Pessoal de Nivel Superior-CAPESInstituto Nacional de Ciencia e Tecnologia de Complexos Fluidos (INCT)Conselho Nacional de Desenvolvimento Cientifico e Tecnologico-CNP

Global Priorities for Conserving the Evolutionary History of Sharks, Rays, and Chimaeras

In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints. Chondrichthyans are by far the most evolutionarily distinct of all major radiations of jawed vertebrates—the average species embodies 26 million years of unique evolutionary history. With this metric, we identify 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets for conservation prioritization. On average, threatened chondrichthyans are more evolutionarily distinct—further motivating improved conservation, fisheries management and trade regulation to avoid significant pruning of the chondrichthyan tree of life

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators

Aquaporin water channels in the nervous system.

The aquaporins (AQPs) are plasma membrane water-transporting proteins. AQP4 is the principal member of this protein family in the CNS, where it is expressed in astrocytes and is involved in water movement, cell migration and neuroexcitation. AQP1 is expressed in the choroid plexus, where it facilitates cerebrospinal fluid secretion, and in dorsal root ganglion neurons, where it tunes pain perception. The AQPs are potential drug targets for several neurological conditions. Astrocytoma cells strongly express AQP4, which may facilitate their infiltration into the brain, and the neuroinflammatory disease neuromyelitis optica is caused by AQP4-specific autoantibodies that produce complement-mediated astrocytic damage

Species-Area Relationships Are Controlled by Species Traits

The species-area relationship (SAR) is one of the most thoroughly investigated empirical relationships in ecology. Two theories have been proposed to explain SARs: classical island biogeography theory and niche theory. Classical island biogeography theory considers the processes of persistence, extinction, and colonization, whereas niche theory focuses on species requirements, such as habitat and resource use. Recent studies have called for the unification of these two theories to better explain the underlying mechanisms that generates SARs. In this context, species traits that can be related to each theory seem promising. Here we analyzed the SARs of butterfly and moth assemblages on islands differing in size and isolation. We tested whether species traits modify the SAR and the response to isolation. In addition to the expected overall effects on the area, traits related to each of the two theories increased the model fit, from 69% up to 90%. Steeper slopes have been shown to have a particularly higher sensitivity to area, which was indicated by species with restricted range (slope  = 0.82), narrow dietary niche (slope  = 0.59), low abundance (slope  = 0.52), and low reproductive potential (slope  = 0.51). We concluded that considering species traits by analyzing SARs yields considerable potential for unifying island biogeography theory and niche theory, and that the systematic and predictable effects observed when considering traits can help to guide conservation and management actions