The management of an endodontically abscessed tooth: patient health state utility, decision-tree and economic analysis

<p>Abstract</p> <p>Background</p> <p>A frequent encounter in clinical practice is the middle-aged adult patient complaining of a toothache caused by the spread of a carious infection into the tooth's endodontic complex. Decisions about the range of treatment options (conventional crown with a post and core technique (CC), a single tooth implant (STI), a conventional dental bridge (CDB), and a partial removable denture (RPD)) have to balance the prognosis, utility and cost. Little is know about the utility patients attach to the different treatment options for an endontically abscessed mandibular molar and maxillary incisor. We measured patients' dental-health-state utilities and ranking preferences of the treatment options for these dental problems.</p> <p>Methods</p> <p>Forty school teachers ranked their preferences for conventional crown with a post and core technique, a single tooth implant, a conventional dental bridge, and a partial removable denture using a standard gamble and willingness to pay. Data previously reported on treatment prognosis and direct "out-of-pocket" costs were used in a decision-tree and economic analysis</p> <p>Results</p> <p>The Standard Gamble utilities for the restoration of a mandibular 1st molar with either the conventional crown (CC), single-tooth-implant (STI), conventional dental bridge (CDB) or removable-partial-denture (RPD) were 74.47 [± 6.91], 78.60 [± 5.19], 76.22 [± 5.78], 64.80 [± 8.1] respectively (p < 0.05). Their respective Willingness-to-Pay ($CDN) were 1,782.05 [± 361.42], 1,871.79 [± 349.44], 1,605.13 [± 348.10], 1,351.28 [± 368.62] (p < 0.05).</p> <p>The standard gamble utilities for the restoration of a maxillary central incisor with a CC, STI, CDB and RPD were 88.50 [± 6.12], 90.68 [± 3.41], 89.78 [± 3.81] and 91.10 [± 3.57] respectively (p > 0.05). Their respective willingness-to-pay ($CDN) were: 1,782.05 [± 361.42], 1,871.79 [± 349.44], 1,605.13 [± 348.10] and 1,351.28 [± 368.62]. A statistical difference was found between the utility of treating a maxillary central incisor and mandibular 1st-molar (p < 0.05).</p> <p>The expected-utility-value for a 5-year prosthetic survival was highest for the CDB and the STI treatment of an abscessed mandibular molar (74.75 and 71.47 respectively) and maxillary incisor (86.24 and 84.91 respectively). This held up to a sensitivity analysis when the success of root canal therapy and the risk of damage to the adjacent tooth were varied. The RPD for both the molar and incisor was the favored treatment based on a cost-utility (3.85 and 2.74 CND$per year of tooth saved respectively) and cost-benefit analysis (0.92 to 0.60 CND$ of cost per $ of benefit, respectively) for a prosthetic clinical survival of 5-years.</p> <p>Conclusion</p> <p>The position of the abscessed tooth and the amount of insurance coverage influences the utility and rank assigned by patients to the different treatment options. STI and CDB have optimal EUVs for a 5-year survival outcome, and RPD has significantly lower cost providing the better cost:benefit ratio.</p

Diseased muscles that lack dystrophin or laminin-α2 have altered compositions and proliferation of mononuclear cell populations

BACKGROUND: Multiple types of mononucleate cells reside among the multinucleate myofibers in skeletal muscles and these mononucleate cells function in muscle maintenance and repair. How neuromuscular disease might affect different types of muscle mononucleate cells had not been determined. In this study, therefore, we examined how two neuromuscular diseases, dystrophin-deficiency and laminin-α2-deficiency, altered the proliferation and composition of different subsets of muscle-derived mononucleate cells. METHODS: We used fluorescence-activated cell sorting combined with bromodeoxyuridine labeling to examine proliferation rates and compositions of mononuclear cells in diseased and healthy mouse skeletal muscle. We prepared mononucleate cells from muscles of mdx (dystrophin-deficient) or Lama2(-/- )(laminin-α2-deficient) mice and compared them to cells from healthy control muscles. We enumerated subsets of resident muscle cells based on Sca-1 and CD45 expression patterns and determined the proliferation of each cell subset in vivo by BrdU incorporation. RESULTS: We found that the proliferation and composition of the mononucleate cells in dystrophin-deficient and laminin-α2-deficient diseased muscles are different than in healthy muscle. The mdx and Lama2(-/- )muscles showed similar significant increases in CD45(+ )cells compared to healthy muscle. Changes in proliferation, however, differed between the two diseases with proliferation increased in mdx and decreased in Lama2(-/- )muscles compared to healthy muscles. In particular, the most abundant Sca-1(-)/CD45(- )subset, which contains muscle precursor cells, had increased proliferation in mdx muscle but decreased proliferation in Lama2(-/- )muscles. CONCLUSION: The similar increases in CD45(+ )cells, but opposite changes in proliferation of muscle precursor cells, may underlie aspects of the distinct pathologies in the two diseases

Identification, Isolation and Expansion of Myoendothelial Cells Involved in Leech Muscle Regeneration

Adult skeletal muscle in vertebrates contains myoendothelial cells that express both myogenic and endothelial markers, and which are able to differentiate into myogenic cells to contribute to muscle regeneration. In spite of intensive research efforts, numerous questions remain regarding the role of cytokine signalling on myoendothelial cell differentiation and muscle regeneration. Here we used Hirudo medicinalis (Annelid, leech) as an emerging new model to study myoendothelial cells and muscle regeneration. Although the leech has relative anatomical simplicity, it shows a striking similarity with vertebrate responses and is a reliable model for studying a variety of basic events, such as tissue repair. Double immunohistochemical analysis were used to characterize myoendothelial cells in leeches and, by injecting in vivo the matrigel biopolymer supplemented with the cytokine Vascular Endothelial Growth Factor (VEGF), we were able to isolate this specific cell population expressing myogenic and endothelial markers. We then evaluated the effect of VEGF on these cells in vitro. Our data indicate that, similar to that proposed for vertebrates, myoendothelial cells of the leech directly participate in myogenesis both in vivo and in vitro, and that VEGF secretion is involved in the recruitment and expansion of these muscle progenitor cells

NOA1 Functions in a Temperature-Dependent Manner to Regulate Chlorophyll Biosynthesis and Rubisco Formation in Rice

NITRIC OXIDE-ASSOCIATED1 (NOA1) encodes a circularly permuted GTPase (cGTPase) known to be essential for ribosome assembly in plants. While the reduced chlorophyll and Rubisco phenotypes were formerly noticed in both NOA1-supressed rice and Arabidopsis, a detailed insight is still necessary. In this study, by using RNAi transgenic rice, we further demonstrate that NOA1 functions in a temperature-dependent manner to regulate chlorophyll and Rubisco levels. When plants were grown at 30°C, the chlorophyll and Rubisco levels in OsNOA1-silenced plants were only slightly lower than those in WT. However, at 22°C, the silenced plants accumulated far less chlorophyll and Rubisco than WT. It was further revealed that the regulation of chlorophyll and Rubisco occurs at the anabolic level. Etiolated WT seedlings restored chlorophyll and Rubisco accumulations readily once returned to light, at either 30°C or 15°C. Etiolated OsNOA1-silenced plants accumulated chlorophyll and Rubisco to normal levels only at 30°C, and lost this ability at low temperature. On the other hand, de-etiolated OsNOA1-silenced seedlings maintained similar levels of chlorophyll and Rubisco as WT, even after being shifted to 15°C for various times. Further expression analyses identified several candidate genes, including OsPorA (NADPH: protochlorophyllide oxidoreductase A), OsrbcL (Rubisco large subunit), OsRALyase (Ribosomal RNA apurinic site specific lyase) and OsPuf4 (RNA-binding protein of the Puf family), which may be involved in OsNOA1-regulated chlorophyll biosynthesis and Rubisco formation. Overall, our results suggest OsNOA1 functions in a temperature-dependent manner to regulate chlorophyll biosynthesis, Rubisco formation and plastid development in rice

Role of Serine Racemase in Behavioral Sensitization in Mice after Repeated Administration of Methamphetamine

BACKGROUND: The N-methyl-D-aspartate (NMDA) receptors play a role in behavioral abnormalities observed after administration of the psychostimulant, methamphetamine (METH). Serine racemase (SRR) is an enzyme which synthesizes D-serine, an endogenous co-agonist of NMDA receptors. Using Srr knock-out (KO) mice, we investigated the role of SRR on METH-induced behavioral abnormalities in mice. METHODOLOGY/PRINCIPAL FINDINGS: Evaluations of behavior in acute hyperlocomotion, behavioral sensitization, and conditioned place preference (CPP) were performed. The role of SRR on the release of dopamine (DA) in the nucleus accumbens after administration of METH was examined using in vivo microdialysis technique. Additionally, phosphorylation levels of ERK1/2 proteins in the striatum, frontal cortex and hippocampus were examined using Western blot analysis. Acute hyperlocomotion after a single administration of METH (3 mg/kg) was comparable between wild-type (WT) and Srr-KO mice. However, repeated administration of METH (3 mg/kg/day, once daily for 5 days) resulted in behavioral sensitization in WT, but not Srr-KO mice. Pretreatment with D-serine (900 mg/kg, 30 min prior to each METH treatment) did not affect the development of behavioral sensitization after repeated METH administration. In the CPP paradigm, METH-induced rewarding effects were demonstrable in both WT and Srr-KO mice. In vivo microdialysis study showed that METH (1 mg/kg)-induced DA release in the nucleus accumbens of Srr-KO mice previously treated with METH was significantly lower than that of the WT mice previously treated with METH. Interestingly, a single administration of METH (3 mg/kg) significantly increased the phosphorylation status of ERK1/2 in the striatum of WT, but not Srr-KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest first, that SRR plays a role in the development of behavioral sensitization in mice after repeated administration of METH, and second that phosphorylation of ERK1/2 by METH may contribute to the development of this sensitization as seen in WT but not Srr-KO mice

Uncovering of major genetic factors generating naturally occurring variation in heading date among Asian rice cultivars

To dissect the genetic factors controlling naturally occurring variation of heading date in Asian rice cultivars, we performed QTL analyses using F2 populations derived from crosses between a japonica cultivar, Koshihikari, and each of 12 cultivars originating from various regions in Asia. These 12 diverse cultivars varied in heading date under natural field conditions in Tsukuba, Japan. Transgressive segregation was observed in 10 F2 combinations. QTL analyses using multiple crosses revealed a comprehensive series of loci involved in natural variation in flowering time. One to four QTLs were detected in each cross combination, and some QTLs were shared among combinations. The chromosomal locations of these QTLs corresponded well with those detected in other studies. The allelic effects of the QTLs varied among the cross combinations. Sequence analysis of several previously cloned genes controlling heading date, including Hd1, Hd3a, Hd6, RFT1, and Ghd7, identified several functional polymorphisms, indicating that allelic variation at these loci probably contributes to variation in heading date. Taken together, the QTL and sequencing results indicate that a large portion of the phenotypic variation in heading date in Asian rice cultivars could be generated by combinations of different alleles (possibly both loss- and gain-of-function) of the QTLs detected in this study

Homoplastic microinversions and the avian tree of life

Background: Microinversions are cytologically undetectable inversions of DNA sequences that accumulate slowly in genomes. Like many other rare genomic changes (RGCs), microinversions are thought to be virtually homoplasyfree evolutionary characters, suggesting that they may be very useful for difficult phylogenetic problems such as the avian tree of life. However, few detailed surveys of these genomic rearrangements have been conducted, making it difficult to assess this hypothesis or understand the impact of microinversions upon genome evolution. Results: We surveyed non-coding sequence data from a recent avian phylogenetic study and found substantially more microinversions than expected based upon prior information about vertebrate inversion rates, although this is likely due to underestimation of these rates in previous studies. Most microinversions were lineage-specific or united well-accepted groups. However, some homoplastic microinversions were evident among the informative characters. Hemiplasy, which reflects differences between gene trees and the species tree, did not explain the observed homoplasy. Two specific loci were microinversion hotspots, with high numbers of inversions that included both the homoplastic as well as some overlapping microinversions. Neither stem-loop structures nor detectable sequence motifs were associated with microinversions in the hotspots. Conclusions: Microinversions can provide valuable phylogenetic information, although power analysis indicate

Repression of Flowering by the miR172 Target SMZ

The flowering repressors SMZ and FLM, members of the AP-2 and MADS domain transcription factor families, unexpectedly work together to regulate flowering time via their effects on expression of the FT gene

GmFT2a, a Soybean Homolog of FLOWERING LOCUS T, Is Involved in Flowering Transition and Maintenance

BACKGROUND: Flowering reversion can be induced in soybean (Glycine max L. Merr.), a typical short-day (SD) dicot, by switching from SD to long-day (LD) photoperiods. This process may involve florigen, putatively encoded by FLOWERING LOCUS T (FT) in Arabidopsis thaliana. However, little is known about the potential function of soybean FT homologs in flowering reversion. METHODS: A photoperiod-responsive FT homologue GmFT (renamed as GmFT2a hereafter) was cloned from the photoperiod-sensitive cultivar Zigongdongdou. GmFT2a gene expression under different photoperiods was analyzed by real-time quantitative PCR. In situ hybridization showed direct evidence for its expression during flowering-related processes. GmFT2a was shown to promote flowering using transgenic studies in Arabidopsis and soybean. The effects of photoperiod and temperature on GmFT2a expression were also analyzed in two cultivars with different photoperiod-sensitivities. RESULTS: GmFT2a expression is regulated by photoperiod. Analyses of GmFT2a transcripts revealed a strong correlation between GmFT2a expression and flowering maintenance. GmFT2a transcripts were observed continuously within the vascular tissue up to the shoot apex during flowering. By contrast, transcripts decreased to undetectable levels during flowering reversion. In grafting experiments, the early-flowering, photoperiod-insensitive stock Heihe27 promotes the appearance of GmFT2a transcripts in the shoot apex of scion Zigongdongdou under noninductive LD conditions. The photothermal effects of GmFT2a expression diversity in cultivars with different photoperiod-sensitivities and a hypothesis is proposed. CONCLUSION: GmFT2a expression is associated with flowering induction and maintenance. Therefore, GmFT2a is a potential target gene for soybean breeding, with the aim of increasing geographic adaptation of this crop

Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk

An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmenting thrombosis risk. Current long-term therapies to prevent arterial occlusion in diabetes are focussed on anti-platelet agents, a strategy that fails to address the contribution of coagulation proteins to the enhanced thrombotic milieu. Moreover, antiplatelet treatment is associated with bleeding complications, particularly with newer agents and more aggressive combination therapies, questioning the safety of this approach. Therefore, to safely control thrombosis risk in diabetes, an alternative approach is required with the fibrin network representing a credible therapeutic target. In the current review, we address diabetes-specific mechanistic pathways responsible for hypofibrinolysis including the role of clot structure, defects in the fibrinolytic system and increased incorporation of anti-fibrinolytic proteins into the clot. Future anti-thrombotic therapeutic options are discussed with special emphasis on the potential advantages of modulating incorporation of the anti-fibrinolytic proteins into fibrin networks. This latter approach carries theoretical advantages, including specificity for diabetes, ability to target a particular protein with a possible favourable risk of bleeding. The development of alternative treatment strategies to better control residual thrombosis risk in diabetes will help to reduce vascular events, which remain the main cause of mortality in this condition