Bonded versus banded first molar attachments: a randomized controlled clinical trial

OBJECTIVE: To compare the clinical failure rates of bonded first molar tubes with those of cemented bands during fixed appliance therapy. DESIGN: Prospective randomized controlled clinical trial. SETTING: Two UK hospital orthodontic clinics, February 2001-December 2004. PARTICIPANTS: Hospital waiting list patients needing fixed appliances (n = 110). METHOD: Patients were randomly allocated to two groups. Experimental group patients (n = 55) received single first molar tubes (n = 181) bonded with a no-mix chemically cured composite (Rely-A-Bond) after a 30-second etch. Control group patients (n = 55) were treated with bands (n = 186) cemented with Intact glass ionomer cement (GIC). First-time failures were recorded together with the time of failure. All patients were followed to the end or discontinuation of treatment. RESULTS: First-time failures: bands = 18.8%; bonds = 33.7 %. Bonded tubes were more likely to fail [RR 2.4; 95% CI (1.4, 4.1)] compared with bands. Experimental group patients also had more bracket failures (P = 0.009), when analysed at patient level. CONCLUSION: First molar tubes bonded with Rely-A-Bond composite showed a significantly higher first-time failure rate than bands cemented with Intact GIC.     

Long-term clinical evaluation of bracket failure with a self-etching primer: a randomized controlled trial

OBJECTIVE: A long-term comparison of the failure rates of orthodontic brackets bonded with either a self-etching primer (SEP) or conventional etch and primer (AE). DESIGN: Prospective randomized controlled clinical trial. SETTING: UK district general hospital with one operator, 2003-6. PARTICIPANTS: Hospital waiting list patients needing fixed appliances (n=60). METHOD: Experimental (SEP) group patients (n=30) received pre-adjusted edgewise brackets (n=438) bonded with Transbond Plus following manufacturer's instructions. Control (AE) group patients (n=30, brackets n=433) were bonded using a 15-second conventional etch and primer (Transbond XT). In both groups brackets were light-cured for 20 seconds. First-time bond failures were recorded with the time of failure. Bracket bonding time was recorded. All patients were followed to the end or discontinuation of treatment. RESULTS: Bracket failure rates: SEP=4.8%, AE=3.5%, P=0.793. Mean placement time per bracket (seconds): SEP=75.5 (+/-6.7; 95% CI=72.9, 78.0), AE=97.7 (+/-9.1; 95% CI=94.3, 101.2) P=0.000. CONCLUSION: There was no difference in the failure rates of brackets bonded with either Transbond Plus SEP or conventional AE using Transbond XT paste. Bonding with SEP was significantly faster than using conventional AE.     

Sagittal curvature of total knee replacements predicts in vivo kinematics

BACKGROUND: It is known that in vivo kinematics after total knee replacement is influenced by the design of the implant. The goal of this study was to show that the sagittal curvature of two different knee prostheses differing in geometric design predicts their in vivo motion behavior. METHODS: Three-dimensional tibio-femoral displacements of two prosthesis designs (single radius vs. dual radius) were measured during knee extension under weight bearing conditions by in vivo video fluoroscopy. Finite helical axes were computed to represent the tibio-femoral motions. Angular deviation alpha and the spatial localization deviation delta were used to characterize the motions. Angular deviation is the angle between each incremental finite helical axis and the medio-lateral axis of the femoral component of the prosthesis. The spatial localization deviation is the distance between each finite helical axis and the center of the femoral component of the prosthesis. Statistical comparisons were performed using the median and the interquartile range of the angular deviation and the spatial localization deviation. FINDINGS: The single-radius design showed finite helical axes concentrated at a single axis near to the medio-lateral axis of the femoral component. The angular and spatial localization deviation of the dual radius design were larger compared to the single radius design, exhibiting finite helical axes varying between two axes. INTERPRETATION: Video fluoroscopy in combination with finite helical axis analysis proved to be suitable methods to evaluate the in vivo kinematical behavior of total knee arthroplasty, which can be useful for implant designers. Knowledge of in vivo kinematics can also provide surgeons with more background information about the total knee arthroplasty models they implant.     

H7N7 Avian Influenza Virus Mutation from Low to High Pathogenicity on a Layer Chicken Farm in the UK

Avian influenza virus (AIV) subtypes H5 and H7 are capable of mutating from low to high pathogenicity strains, causing high mortality in poultry with significant economic losses globally. During 2015, two outbreaks of H7N7 low pathogenicity AIV (LPAIV) in Germany, and one each in the United Kingdom (UK) and The Netherlands occurred, as well as single outbreaks of H7N7 high pathogenicity AIV (HPAIV) in Germany and the UK. Both HPAIV outbreaks were linked to precursor H7N7 LPAIV outbreaks on the same or adjacent premises. Herein, we describe the clinical, epidemiological, and virological investigations for the H7N7 UK HPAIV outbreak on a farm with layer chickens in mixed free-range and caged units. H7N7 HPAIV was identified and isolated from clinical samples, as well as H7N7 LPAIV, which could not be isolated. Using serological and molecular evidence, we postulate how the viruses spread throughout the premises, indicating potential points of incursion and possible locations for the mutation event. Serological and mortality data suggested that the LPAIV infection preceded the HPAIV infection and afforded some clinical protection against the HPAIV. These results document the identification of a LPAIV to HPAIV mutation in nature, providing insights into factors that drive its manifestation during outbreaks.     

Provider type influences adherence to lifestyle changes in chronic pancreatitis

Background/Objectives: Alcohol and smoking cessation are recommended in chronic pancreatitis. The aim of this study is to measure the rates of alcohol and smoking cessation counselling among providers and adherence to recommendations.MethodsRetrospective cohort study of chronic pancreatitis patients at a tertiary hospital. Provider types were defined as primary care (PCP), gastroenterologist, or pancreas specialist. Pairwise comparisons and multivariable analysis were conducted to assess the relation between provider type and smoking/alcohol cessation.ResultsOf 256 patients with chronic pancreatitis, 142 (55.5%) consumed alcohol and 130 (91.5%) were advised to stop. Alcohol cessation was advised to 88.9, 96.0 and 92.5% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively. Sixty-one patients (46.9%) were compliant with the recommendation: 31.3, 44.0 and 54.1% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, others nonsignificant). In multivariable analysis, patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation compared to those followed by PCP (OR = 4.31, CI 1.52–12.20, p = 0.006). Smoking cessation was advised to all the 127 current smokers (100%). Fifty-six (44.1%) were compliant with the recommendation: 24.1, 58.3 and 47.3% of patients followed by PCP, gastroenterologists and pancreas specialists, respectively (Pairwise comparisons PCP vs Pancreas: p = 0.03, PCP vs. Gastroenterologist: p = 0.01, others nonsignificant). Multivariable analysis did not confirm this finding.ConclusionsThe majority of providers counsel for alcohol/smoking cessation. Less than half the patients follow the recommendations. Patients followed by pancreas specialists were more likely to adhere to alcohol cessation recommendation.     

Combination therapy of established cancer using a histone deacetylase inhibitor and a TRAIL receptor agonist

Histone deacetylase inhibitors (HDACi) and agents such as recombinant tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and agonistic anti-TRAIL receptor (TRAIL-R) antibodies are anticancer agents that have shown promise in preclinical settings and in early phase clinical trials as monotherapies. Although HDACi and activators of the TRAIL pathway have different molecular targets and mechanisms of action, they share the ability to induce tumor cell-selective apoptosis. The ability of HDACi to induce expression of TRAIL-R death receptors 4 and 5 (DR4/DR5), and induce tumor cell death via the intrinsic apoptotic pathway provides a molecular rationale to combine these agents with activators of the TRAIL pathway that activate the alternative (death receptor) apoptotic pathway. Herein, we demonstrate that the HDACi vorinostat synergizes with the mouse DR5-specific monoclonal antibody MD5-1 to induce rapid and robust tumor cell apoptosis in vitro and in vivo. Importantly, using a preclinical mouse breast cancer model, we show that the combination of vorinostat and MD5-1 is safe and induces regression of established tumors, whereas single agent treatment had little or no effect. Functional analyses revealed that rather than mediating enhanced tumor cell apoptosis via the simultaneous activation of the intrinsic and extrinsic apoptotic pathways, vorinostat augmented MD5-1-induced apoptosis concomitant with down-regulation of the intracellular apoptosis inhibitor cellular-FLIP (c-FLIP). These data demonstrate that combination therapies involving HDACi and activators of the TRAIL pathway can be efficacious for the treatment of cancer in experimental mouse models.     

Perturbations in the erythroid marrow progenitor cell pools may play a role in the augmentation of HbF by 5-azacytidine

In vivo observations on the kinetics of F cells and of fetal hemoglobin (HbF) synthesis and in vitro studies of erythroid progenitors, their number, and the gamma-gene expression in their progeny were carried out in baboons (Papio cynocephalus) treated with 5-azacytidine. Maximum effect on the increase of HbF production in vivo was observed only when an expanded erythroid marrow population was present. In these animals, as well as in normal animals, treatment resulted in a significant reduction of the late erythroid progenitor cell pools (erythroid clusters and erythroid colony-forming units, CFU-E) in the marrow. This reduction was more pronounced among those progenitors grown in the absence of added erythropoietin, and it was followed by a rebound a few days after treatment cessation, reflecting the accumulation of regenerating progenitors. An early increase in the in vitro synthesis of HbF in erythroid clusters and CFU-E colonies was observed. This increase was further documented at the cellular level, with immunofluorescent labeling of colonies with monoclonal anti-gamma- globin chain antibodies. In contrast to the findings in late progenitors, the number of erythroid burst-forming unit (BFU-E) colonies and the synthesis of HbF in these colonies was not influenced significantly by 5-azacytidine treatment. It is proposed that the toxic effects of 5-azacytidine on late progenitors, leading to faster mobilization of earlier progenitors to the next more mature compartment, play a role in the in vivo augmentation of HbF synthesis by this drug. This perturbation in the progenitor cell population kinetics and the presumed hypomethylation of the surviving differentiating cells may act synergistically to produce a maximum HbF response after 5-azacytidine treatment.     

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.