State of the science on controversial topics: orthodontic therapy and gingival recession (a report of the Angle Society of Europe 2013 meeting).

BACKGROUND: Controversy exists in the literature between the role of orthodontic treatment and gingival recession. Whilst movement of teeth outside the alveolar bone has been reported as a risk factor for gingival recession, others have found no such association. FINDINGS: The Angle Society of Europe devoted a study day to explore the evidence surrounding these controversies. The aim of the day was for a panel of experts to evaluate the current evidence base in relation to either the beneficial or detrimental effects of orthodontic treatment on the gingival tissue. CONCLUSIONS: There remains a relatively weak evidence base for the role of orthodontic treatment and gingival recession and thus a need to undertake a risk assessment and appropriate consent prior to the commencement of treatment. In further prospective, well designed trials are needed

Deletion of PTH Rescues Skeletal Abnormalities and High Osteopontin Levels in Klotho−/− Mice

Maintenance of normal mineral ion homeostasis is crucial for many biological activities, including proper mineralization of the skeleton. Parathyroid hormone (PTH), Klotho, and FGF23 have been shown to act as key regulators of serum calcium and phosphate homeostasis through a complex feedback mechanism. The phenotypes of Fgf23−/− and Klotho−/− (Kl−/−) mice are very similar and include hypercalcemia, hyperphosphatemia, hypervitaminosis D, suppressed PTH levels, and severe osteomalacia/osteoidosis. We recently reported that complete ablation of PTH from Fgf23−/− mice ameliorated the phenotype in Fgf23−/−/PTH−/− mice by suppressing serum vitamin D and calcium levels. The severe osteomalacia in Fgf23−/− mice, however, persisted, suggesting that a different mechanism is responsible for this mineralization defect. In the current study, we demonstrate that deletion of PTH from Kl−/− (Kl−/−/PTH−/− or DKO) mice corrects the abnormal skeletal phenotype. Bone turnover markers are restored to wild-type levels; and, more importantly, the skeletal mineralization defect is completely rescued in Kl−/−/PTH−/− mice. Interestingly, the correction of the osteomalacia is accompanied by a reduction in the high levels of osteopontin (Opn) in bone and serum. Such a reduction in Opn levels could not be observed in Fgf23−/−/PTH−/− mice, and these mice showed sustained osteomalacia. This significant in vivo finding is corroborated by in vitro studies using calvarial osteoblast cultures that show normalized Opn expression and rescued mineralization in Kl−/−/PTH−/− mice. Moreover, continuous PTH infusion of Kl−/− mice significantly increased Opn levels and osteoid volume, and decreased trabecular bone volume. In summary, our results demonstrate for the first time that PTH directly impacts the mineralization disorders and skeletal deformities of Kl−/−, but not of Fgf23−/− mice, possibly by regulating Opn expression. These are significant new perceptions into the role of PTH in skeletal and disease processes and suggest FGF23-independent interactions of PTH with Klotho

Localization and function of the renal calcium-sensing receptor

The ability to monitor changes in the ionic composition of the extracellular environment is a crucial feature that has evolved in all living organisms. The cloning and characterization of the extracellular calcium-sensing receptor (CaSR) from the mammalian parathyroid gland in the early 1990s provided the first description of a cellular, ion-sensing mechanism. This finding demonstrated how cells can detect small, physiological variations in free ionized calcium (Ca 2+) in the extracellular fluid and subsequently evoke an appropriate biological response by altering the secretion of parathyroid hormone (PTH) that acts on PTH receptors expressed in target tissues, including the kidney, intestine, and bone. Aberrant Ca 2+ sensing by the parathyroid glands, as a result of altered CaSR expression or function, is associated with impaired divalent cation homeostasis. CaSR activators that mimic the effects of Ca 2+ (calcimimetics) have been designed to treat hyperparathyroidism, and CaSR antagonists (calcilytics) are in development for the treatment of hypercalciuric disorders. The kidney expresses a CaSR that might directly contribute to the regulation of many aspects of renal function in a PTH-independent manner. This Review discusses the roles of the renal CaSR and the potential impact of pharmacological modulation of the CaSR on renal function

Genes in the Ureteric Budding Pathway: Association Study on Vesico-Ureteral Reflux Patients

Vesico-ureteral reflux (VUR) is the retrograde passage of urine from the bladder to the urinary tract and causes 8.5% of end-stage renal disease in children. It is a complex genetic developmental disorder, in which ectopic embryonal ureteric budding is implicated in the pathogenesis. VUR is part of the spectrum of Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). We performed an extensive association study for primary VUR using a two-stage, case-control design, investigating 44 candidate genes in the ureteric budding pathway in 409 Dutch VUR patients. The 44 genes were selected from the literature and a set of 567 single nucleotide polymorphisms (SNPs) capturing their genetic variation was genotyped in 207 cases and 554 controls. The 14 SNPs with p<0.005 were included in a follow-up study in 202 cases and 892 controls. Of the total cohort, ∼50% showed a clear-cut primary VUR phenotype and ∼25% had both a duplex collecting system and VUR. We also looked for association in these two extreme phenotype groups. None of the SNPs reached a significant p-value. Common genetic variants in four genes (GREM1, EYA1, ROBO2 and UPK3A) show a trend towards association with the development of primary VUR (GREM1, EYA1, ROBO2) or duplex collecting system (EYA1 and UPK3A). SNPs in three genes (TGFB1, GNB3 and VEGFA) have been shown to be associated with VUR in other populations. Only the result of rs1800469 in TGFB1 hinted at association in our study. This is the first extensive study of common variants in the genes of the ureteric budding pathway and the genetic susceptibility to primary VUR

Lactobacillus fermentum ME-3 – an antimicrobial and antioxidative probiotic

The paper lays out the short scientific history and characteristics of the new probiotic Lactobacillus fermentum strain ME-3 DSM-14241, elaborated according to the regulations of WHO/FAO (2002). L. fermentum ME-3 is a unique strain of Lactobacillus species, having at the same time the antimicrobial and physiologically effective antioxidative properties and expressing health-promoting characteristics if consumed. Tartu University has patented this strain in Estonia (priority June 2001, patent in 2006), Russia (patent in 2006) and the USA (patent in 2007). The paper describes the process of the identification and molecular typing of this probiotic strain of human origin, its deposition in an international culture collection, and its safety assessment by laboratory tests and testing on experimental animals and volunteers. It has been established that L. fermentum strain ME-3 has double functional properties: antimicrobial activity against intestinal pathogens and high total antioxidative activity (TAA) and total antioxidative status (TAS) of intact cells and lysates, and it is characterized by a complete glutathione system: synthesis, uptake and redox turnover. The functional efficacy of the antimicrobial and antioxidative probiotic has been proven by the eradication of salmonellas and the reduction of liver and spleen granulomas in Salmonella Typhimurium-infected mice treated with the combination of ofloxacin and L. fermentum strain ME-3. Using capsules or foodstuffs enriched with L. fermentum ME-3, different clinical study designs (including double-blind, placebo-controlled, crossover studies) and different subjects (healthy volunteers, allergic patients and those recovering from a stroke), it has been shown that this probiotic increased the antioxidative activity of sera and improved the composition of the low-density lipid particles (LDL) and post-prandial lipids as well as oxidative stress status, thus demonstrating a remarkable anti-atherogenic effect. The elaboration of the probiotic L. fermentum strain ME-3 has drawn on wide international cooperative research and has taken more than 12 years altogether. The new ME-3 probiotic-containing products have been successfully marketed and sold in Baltic countries and Finland

Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis

Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.info:eu-repo/semantics/publishedVersio

Location-specific modeling for optimizing wildlife management on crop farms

In order to guide conservation and restoration of wildlife in agricultural areas research is needed into the trade-off between wildlife and agricultural production and income. This study presents a location-specific model for optimizing wildlife management on crop farms using integer programming. The model is applied to crop farming in the Netherlands. Most important outcome is a wildlife-cost frontier at the farm level. Model results show that rotating wildlife conservation practices across the farm is economically more attractive than fixed-location practices. Opportunities for use of the insights provided by model results by both policy makers and farmers are analyzed