Search

Objective: This in situ study evaluated the effect of high-fluoride dentifrice (5000 μg F−/g) and fluoride-containing bonding composite resin on enamel demineralization adjacent to orthodontic brackets. Methods: Ten volunteers wore palatal appliances containing bovine enamel blocks with metallic brackets bonded with fluoride-free or fluoride-containing composite resin. During three phases of 14 days each, three dentifrices with different fluoride concentrations (0, 1100, and 5000 μg F−/g) were tested. The cariogenic challenge consisted of 20% sucrose solution dripped 8x/day onto the dental blocks. At the end of each phase, biofilm formed was collected for fluoride analysis. Cross section hardness was performed in enamel blocks, and the lesion area was calculated. Data were analyzed by two-way ANOVA followed by Tukey post hoc test (α = 5%). Results: The only signicant factor for all the variables under study was the dentifrice. Smaller lesion area and higher fluoride concentration on biofilm were found in 5000 μg F−/g group, irrespective of bonding composite resin (p < 0.001). Neither bracket-bonding composite resin nor the interaction between the factors was statistically significant (p > 0.05) for all the variables. Conclusion: High-fluoride dentifrice is effective in reducing demineralization on enamel adjacent to orthodontic brackets, while the fluoride-containing bonding composite resin does not influence it. Clinical Significance: Since high-fluoride dentifrice was able to reduce demineralization adjacent to brackets, it can be an option to caries management in orthodontics patients. [ABSTRACT FROM AUTHOR]

Purpose:To review the management of pregnancy after an unexplained stillbirth.Epidemiology:Approximately 1 in 200 pregnancies will end in stillbirth, of which about one-third will remain unexplained. Unexplained stillbirth is the largest single contributor to perinatal mortality. Subsequent pregnancies do not appear to have an increased risk of stillbirth, but are characterized by increased rates of intervention (induction of labor, elective cesarean section) and iatrogenic adverse outcomes (low birth weight, prematurity, emergency cesarean section and post-partum hemorrhage).Conclusions:There is no level-one evidence to guide management in this situation. Pre-pregnancy counseling is very important to detect and correct potential risk factors such as obesity, smoking and maternal disease. As timely delivery is the mainstay of management, early accurate determination of gestational age is vital. There is controversy regarding the pattern of surveillance, but evidence exists only for ultrasound and not for regular non-stress testing, nor formal fetal movement charting. There is an urgent need for more studies in this important area. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via a link at the top of the paper. [ABSTRACT FROM AUTHOR]

To evaluate whether a recombinant serine protease inhibitor (rBmTI-A) modulates inflammation in an experimental model of chronic allergic lung inflammation. Balb/c mice were divided into four groups: SAL (saline), OVA (sensitized with ovalbumin), SAL + rBmTI-A (control treated with rBmTI-A) and OVA + rBmTI-A (sensitized with ovalbumin and treated with rBmTI-A). The animals received an intraperitoneal injection of saline or ovalbumin, according to the group. The groups received inhalation with saline or ovalbumin and were treated with rBmTI-A or saline by nasal instillation. After 29 days, we evaluated the respiratory mechanics; bronchoalveolar lavage fluid (BALF); cytokines; MMP-9, TIMP-1; eosinophils; collagen and elastic fibre expression in the airways; and the trypsin-like, MMP-1, and MMP-9 lung tissue proteolytic activity. Treatment with rBmTI-A reduced the trypsin-like proteolytic activity, the elastance and resistance maximum response, the polymorphonuclear cells, IL-5, IL-10, IL-13 and IL-17A in the BALF, the expression of IL-5, IL-13, IL-17, CD4+, MMP-9, TIMP-1, eosinophils, collagen and elastic fibres in the airways of the OVA + rBmTI-A group compared to the OVA group (p < 0.05). rBmTI-A attenuated bronchial hyperresponsiveness, inflammation and remodelling in this experimental model of chronic allergic pulmonary inflammation. This inhibitor may serve as a potential therapeutic tool for asthma treatment. [ABSTRACT FROM AUTHOR]

Purpose: Umbilical hernia is a common complication in patients with cirrhosis. Early studies have reported a high morbidity and mortality associated with hernia repair. The traditional approach has been to non-operatively manage umbilical hernias in patients with cirrhosis. There are emerging data suggesting that an elective repair is a preferable approach. This study examined the outcomes of umbilical hernia repair in patients with advanced liver disease and compared this with a control group of non-cirrhotic patients.Methods: Prospective data were collected regarding the outcome of umbilical hernia repairs performed between 2004 and 2013 at the Austin Hospital, Melbourne, Australia. Outcomes at 90 days were compared between patients with and without cirrhosis.Results: 79 patients with cirrhosis and 249 controls were analysed. Of the patients with cirrhosis, 9% were classified as Child-Pugh A, 61% were Child-Pugh B and 30% were Child-Pugh C. Emergency repairs for complicated hernias was undertaken in 18% of the cirrhosis population and 10% in controls (P = 0.10). Post-operative complications occurred more commonly in patients with cirrhosis (26%) compared with controls (11%) (P < 0.01). Emergency hernia repairs were associated with a higher complication rate in both patients with cirrhosis (62%) and controls (20%) (P = 0.01). There was no significant difference in the rate of hernia recurrence as assessed by clinical examination between patients with cirrhosis (2.7%) and controls (6.8%) (P = 0.17) nor in 90-day mortality between patients with cirrhosis (n = 1, 1.3%) and the controls (n = 0) (P = 0.43).Conclusions: Within the limitations of a small study cohort and therefore an underpowered study, elective surgical repair of umbilical hernias in patients with cirrhosis, including decompensated cirrhosis, may not be associated with a significant increase in mortality when compared to a control cohort. Whilst complications are higher in cirrhotic patients, there is no difference in the rate of hernia recurrence. Emergency repairs of umbilical hernias are associated with a high complication rate in cirrhotic patients. [ABSTRACT FROM AUTHOR]

The article presents an obituary for Kenneth Cranston, dentist and cricket captain.

Recent findings link metabolic transformation of cancer cells to aberrant functions of mitochondrial uncoupling proteins (UCPs). By inducing proton leak, UCPs interfere with mitochondrial synthesis of adenosine 5'-triphosphate, which is also a key determinant of glycolytic pathways. In addition, UCP suppress the generation of superoxide, a byproduct of mitochondrial electron transport and a major source of oxidative stress. The near ubiquitous UCP2 becomes highly abundant in some cancers and may advance metabolic reprogramming, further disrupt tumour suppression, and promote chemoresistance. Here we review current evidence to suggest that inhibition of mitochondrial uncoupling may eliminate these responses and reveal novel anti-cancer strategies. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is associated with chronic and progressive lung disease and is closely related to increased morbidity and mortality in cystic fibrosis (CF) patients. Hypermutable (HPM) P. aeruginosa isolates have been described in these patients and are usually associated with antibiotic resistance. This study aimed to investigate the occurrence of carbapenem resistance and hypermutable phenotype in 179 P. aeruginosa isolates from 8 chronically CF patients assisted at two reference centers in Rio de Janeiro, Brazil. Using disk diffusion test, non-susceptible (NS) rates higher than 40% were observed for imipenem, amikacin, and gentamicin. A total of 79 isolates (44.1%), 71 (39.6%), and 8 (4.4%) were classified as carbapenem-resistant (CR resistance to at least one carbapenem), multidrug-resistant (MDR), and extensively drug-resistant (XDR), respectively. Minimal inhibitory concentration was determined for 79 CR P. aeruginosa and showed the following variations: 4 and 128 μg/mL to imipenem, 4 and 64 µg/mL to meropenem, and 4 and ≥ 32 µg/mL to doripenem. We have found only four (2.23%) HPM isolates from 4 patients. Analyzing the genetic relationship among the HPM isolates, 3 pulsed-field gel electrophoresis/pulsotypes (D, M, and J) were observed. Only M pulsotype was recovered from two patients in different years. Polymerase chain reaction screening for blaGES, blaIMP, blaKPC, blaNDM, blaOXA-48, blaSPM, and blaVIM genes was performed for all CR isolates and none of them were positive. Our results demonstrate a high occurrence of CR and MDR P. aeruginosa of CF patients follow-up in both centers studied, while the presence of HPM is still unusual. [ABSTRACT FROM AUTHOR]

Prolonged exposure to hyperoxia has deleterious effects on the lung, provoking both inflammation and alveolar injury. The elements of hyperoxic injury, which result in high rates of lethality in experimental models, are thought to include multicellular immune responses. To characterize these alterations in immune cell populations, we performed time-of-flight mass cytometry (CyTOF) analysis of CD45-expressing immune cells in whole lung parenchyma and the bronchoalveolar space of mice, exposed to 48 hours of hyperoxia together with normoxic controls. At the tested time point, hyperoxia exposure resulted in decreased abundance of immunoregulatory populations (regulatory B cells, myeloid regulatory cells) in lung parenchyma and markedly decreased proliferation rates of myeloid regulatory cells, monocytes and alveolar macrophages. Additionally, hyperoxia caused a shift in the phenotype of alveolar macrophages, increasing proportion of cells with elevated CD68, CD44, CD11c, PD-L1, and CD205 expression levels. These changes occurred in the absence of histologically evident alveolar damage and abundance of neutrophils in the parenchyma or alveolar space did not change at these time points. Collectively, these findings demonstrate that pulmonary response to hyperoxia involves marked changes in specific subsets of myeloid and lymphoid populations. These findings have important implications for therapeutic targeting in acute lung injury. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that inhibition of bromodomain and extra-terminal (BET) epigenetic readers may have clinical utility against acute myeloid leukemia (AML). Here we validate this hypothesis, demonstrating the efficacy of the BET inhibitor I-BET151 across a variety of AML subtypes driven by disparate mutations. We demonstrate that a common 'core' transcriptional program, which is HOX gene independent, is downregulated in AML and underlies sensitivity to I-BET treatment. This program is enriched for genes that contain 'super-enhancers', recently described regulatory elements postulated to control key oncogenic driver genes. Moreover, our program can independently classify AML patients into distinct cytogenetic and molecular subgroups, suggesting that it contains biomarkers of sensitivity and response. We focus AML with mutations of the Nucleophosmin gene (NPM1) and show evidence to suggest that wild-type NPM1 has an inhibitory influence on BRD4 that is relieved upon NPM1c mutation and cytosplasmic dislocation. This leads to the upregulation of the core transcriptional program facilitating leukemia development. This program is abrogated by I-BET therapy and by nuclear restoration of NPM1. Finally, we demonstrate the efficacy of I-BET151 in a unique murine model and in primary patient samples of NPM1c AML. Taken together, our data support the use of BET inhibitors in clinical trials in AML. [ABSTRACT FROM AUTHOR]

Small molecule inhibition of the BET family of proteins, which bind acetylated lysines within histones, has been shown to have a marked therapeutic benefit in pre-clinical models of mixed lineage leukemia (MLL) fusion protein-driven leukemias. Here, we report that I-BET151, a highly specific BET family bromodomain inhibitor, leads to growth inhibition in a human erythroleukemic (HEL) cell line as well as in erythroid precursors isolated from polycythemia vera patients. One of the genes most highly downregulated by I-BET151 was LMO2, an important oncogenic regulator of hematopoietic stem cell development and erythropoiesis. We previously reported that LMO2 transcription is dependent upon Janus kinase 2 (JAK2) kinase activity in HEL cells. Here, we show that the transcriptional changes induced by a JAK2 inhibitor (TG101209) and I-BET151 in HEL cells are significantly over-lapping, suggesting a common pathway of action. We generated JAK2 inhibitor resistant HEL cells and showed that these retain sensitivity to I-BET151. These data highlight I-BET151 as a potential alternative treatment against myeloproliferative neoplasms driven by constitutively active JAK2 kinase. [ABSTRACT FROM AUTHOR]

Extracellular nucleotides might influence aspects of the biology of reproduction in that ATP affects smooth muscle contraction, participates in steroidogenesis and spermatogenesis, and also regulates transepithelial transport, as in oviducts. Activation of cellular nucleotide purinergic receptors is influenced by four plasma membrane-bound members of the ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) family, namely NTPDase1, NTPDase2, NTPDase3, and NTPDase8 that differ in their ecto-enzymatic properties. The purpose of this study was to characterize the expression profile of the membrane-bound NTPDases in the murine female and male reproductive tracts by immunological techniques (immunolabelling, Western blotting) and by enzymatic assays, in situ and on tissue homogenates. Other than the expected expression on vascular endothelial and smooth muscle cells, NTPDase1 was also detected in Sertoli cells and interstitial macrophages in testes, in ovarian granulosa cells, and in apical cells from epididymal epithelium. NTPDase2 was largely expressed by cells in the connective tissue; NTPDase3 in secretory epithelia, and finally, NTPDase8 was not detected in any of the tissues studied here. In addition, NTPDase6 was putatively detected in Golgi-phase acrosome vesicles of round spermatids. This descriptive study suggests close regulation of extracellular nucleotide levels in the genital tract by NTPDases that may impact specific biological functions. [ABSTRACT FROM AUTHOR]

Thrombotic microangiopathy (TM) is a serious complication of bone marrow transplantation (BMT) that resembles thrombotic thrombocytopenic purpura (TTP). In attempting to achieve hematopoietic cell chimerism in the pig-to-baboon model, we have observed TM following infusion of high doses (>1010 cells/kg) of porcine peripheral blood mobilized progenitor cells (PBPC) into baboons. We performed investigations to analyze the pathobiology of this TM and to test therapeutic interventions to ameliorate it. PBPC were obtained by leukapheresis of cytokine-stimulated swine. The initial observations were made in two baboons that underwent a non-myeloablative regimen (NMR) prior to PBPC transplantation (TX) (group 1). We then studied three experimental groups. Group 2 (n = 2) received NMR without PBPC TX. Group 3 (n = 2) received PBPC TX alone. Group 4 (n = 6) received NMR + PBPC TX combined with prostacyclin, low-dose heparin, methylprednisolone, and cyclosporine was replaced by anti-CD40L mAb in five cases. Baboons in groups 1 and 3 developed severe thrombocytopenia (<10 000/mm3), intravascular hemolysis with schistocytosis (>10/high powered field (hpf)), increase in plasma lactate dehydrogenase (LDH) (2500–9000 U/l), transient neurologic changes, renal insufficiency, and purpura. Autopsy on two baboons confirmed extensive platelet thrombi in the microcirculation, and, similar to clinical BMT-associated TM/TTP, no unusually large vWF multimers or changes in vWF protease activity were observed in the plasma of baboons with TM. In group 2, self-limited thrombocytopenia occurred for 10–15 days following NMR. Group 4 baboons developed thrombocytopenia (<20 000/mm3) rarely requiring platelet transfusion, minimal schistocytosis (<3/hpf), minor increase in LDH (<1000 U/l), with no clinical sequelae. We conclude that high-dose porcine PBPC infusion into baboons induces a microangiopathic state with vWF biochemical parameters... [ABSTRACT FROM AUTHOR]

This research provides the first evidence of dispersal of bryophytes and associated microorganisms through ingestion by a highly mobile vertebrate vector, the spectacled flying fox ( Pteropus conspicillatus). Bryophyte fragments were found in faeces collected at four P. conspicillatus’ camps in the Wet Tropics bioregion, northeastern Australia. These fragments were viable when grown in culture; live invertebrates and other organisms were also present. Our study has significantly increased understanding of the role of flying foxes as dispersal vectors in tropical forests. [ABSTRACT FROM AUTHOR]