Biological and Mechanical Evaluation of Novel Prototype Dental Composites.

The breakdown of the polymeric component of contemporary composite dental restorative materials compromises their longevity, while leachable compounds from these materials have cellular consequences. Thus, a new generation of composite materials needed to be designed to have a longer service life and ensure that any leachable compounds are not harmful to appropriate cell lines. To accomplish this, we have developed concurrent thiol-ene-based polymerization and allyl sulfide-based addition-fragmentation chain transfer chemistries to afford cross-linked polymeric resins that demonstrate low shrinkage and low shrinkage stress. In the past, the filler used in dental composites mainly consisted of glass, which is biologically inert. In several of our prototype composites, we introduced fluorapatite (FA) crystals, which resemble enamel crystals and are bioactive. These novel prototype composites were benchmarked against similarly filled methacrylate-based bisphenol A diglycidyl ether dimethacrylate / triethylene glycol dimethacrylate (bisGMA/TEGDMA) composite for their cytotoxicity, mechanical properties, biofilm formation, and fluoride release. The leachables at pH 7 from all the composites were nontoxic to dental pulp stem cells. There was a trend toward an increase in total toughness of the glass-only-filled prototype composites as compared with the similarly filled bisGMA/TEGDMA composite. Other mechanical properties of the glass-only-filled prototype composites were comparable to the similarly filled bisGMA/TEGDMA composite. Incorporation of the FA reduced the mechanical properties of the prototype and bisGMA/TEGDMA composite. Biofilm mass and colony-forming units per milliliter were reduced on the glass-only-filled prototype composites as compared with the glass-only-filled bisGMA/TEGDMA composite and were significantly reduced by the addition of FA to all composites. Fluoride release at pH 7 was greatest after 24 h for the bisGMA/TEGDMA glass + FA composite as compared with the similarly filled prototypes, but overall the F- release was marginal and not at a concentration to affect bacterial metabolism.

Quality control in public participation assessments of water quality: the OPAL Water Survey.

BACKGROUND: Public participation in scientific data collection is a rapidly expanding field. In water quality surveys, the involvement of the public, usually as trained volunteers, generally includes the identification of aquatic invertebrates to a broad taxonomic level. However, quality assurance is often not addressed and remains a key concern for the acceptance of publicly-generated water quality data. The Open Air Laboratories (OPAL) Water Survey, launched in May 2010, aimed to encourage interest and participation in water science by developing a 'low-barrier-to-entry' water quality survey. During 2010, over 3000 participant-selected lakes and ponds were surveyed making this the largest public participation lake and pond survey undertaken to date in the UK. But the OPAL approach of using untrained volunteers and largely anonymous data submission exacerbates quality control concerns. A number of approaches were used in order to address data quality issues including: sensitivity analysis to determine differences due to operator, sampling effort and duration; direct comparisons of identification between participants and experienced scientists; the use of a self-assessment identification quiz; the use of multiple participant surveys to assess data variability at single sites over short periods of time; comparison of survey techniques with other measurement variables and with other metrics generally considered more accurate. These quality control approaches were then used to screen the OPAL Water Survey data to generate a more robust dataset. RESULTS: The OPAL Water Survey results provide a regional and national assessment of water quality as well as a first national picture of water clarity (as suspended solids concentrations). Less than 10 % of lakes and ponds surveyed were 'poor' quality while 26.8 % were in the highest water quality band. CONCLUSIONS: It is likely that there will always be a question mark over untrained volunteer generated data simply because quality assurance is uncertain, regardless of any post hoc data analyses. Quality control at all stages, from survey design, identification tests, data submission and interpretation can all increase confidence such that useful data can be generated by public participants.

The effect of acute respiratory distress syndrome on long-term survival.

Despite a great deal of information about the risk factors, prognostic variables, and hospital mortality in the acute respiratory distress syndrome (ARDS), very little is known about the long-term outcomes of patients with this syndrome. We conducted a prospective, matched, parallel cohort study with the goals of describing the survival of patients with ARDS after hospital discharge and comparing the long-term survival of patients with ARDS and that of a group of matched controls. The study involved 127 patients with ARDS associated with trauma or sepsis and 127 controls matched for risk factor (trauma or sepsis) and severity of illness who survived to hospital discharge. Time until death was used as the outcome measure. Survival was associated with age, risk factor for ARDS, and comorbidity. There was no difference in the long-term mortality rate for ARDS patients and that of matched controls (hazard ratio for ARDS: 1.00; 95% confidence interval: 0.47 to 2.09) after controlling for age, risk factor for ARDS, comorbidity, and severity of illness. We conclude that if sepsis or trauma patients survive to hospital discharge, ARDS does not increase their risk of subsequent death. Older patients, patients with sepsis, and patients with comorbidities, regardless of the presence of ARDS, have a higher risk of death after hospital discharge. For the purposes of clinical prognosis and cost-effectiveness analysis, the long-term survival of patients with ARDS can be modeled on the basis of age, underlying risk factor for ARDS, and comorbidity.

Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients.

CONTEXT: Health-related quality of life (HRQL) is reduced in patients who survive acute respiratory distress (ARDS), but whether this decline in HRQL is caused by ARDS or other aspects of the patient's illness or injury is unknown. OBJECTIVE: To determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS. DESIGN: Prospective, matched, parallel cohort study. SETTING: A 411-bed municipal medical and regional level I trauma center. PATIENTS: Seventy-three pairs of ARDS survivors and severity-matched controls with the clinical risk factors for ARDS of sepsis and trauma admitted between January 1, 1994, and July 30, 1996. MAIN OUTCOME MEASURES: The HRQL of ARDS survivors and controls, assessed by generic and pulmonary disease-specific HRQL instruments (Medical Outcomes Study 36-Item Short Form Health Survey, Standard Form [SF-36] and St George's Respiratory Questionnaire [SGRQ], respectively). RESULTS: Clinically meaningful and statistically significant reductions in HRQL scores of ARDS survivors (n = 73) were seen in 7 of 8 SF-36 domains and 3 of 3 SGRQ domains compared with matched controls (P<.001 for all reductions). The largest decrements in the HRQL were seen in physical function and pulmonary symptoms and limitations. Analysis of trauma-matched pairs (n = 46) revealed significant reductions in 7 of 8 SF-36 domains (P< or =.02) and 3 of 3 SGRQ domains (P< or =.003). Analysis of sepsis-matched pairs (n = 27) revealed significant reductions in 6 of 8 SF-36 domains (P< or =.05) and 3 of 3 SGRQ domains (P< or =.002). CONCLUSIONS: Survivors of ARDS have a clinically significant reduction in HRQL that appears to be caused exclusively by ARDS and its sequelae. Reductions were primarily noted in physical functioning and pulmonary disease-specific domains.

Flavones. 2. Synthesis and structure-activity relationship of flavodilol and its analogues, a novel class of antihypertensive agents with catecholamine depleting properties.

(3-Phenyl-7-flavonoxy)propanolamines have been shown to exhibit antihypertensive activity in spontaneously hypertensive rats. Although they are structurally similar to classical beta-adrenergic blocking compounds, their activity is not due to inhibition of beta-adrenoceptors. In the present study, a series of simple flavonoxypropanolamines was prepared to further explore the structural requirements for the antihypertensive effect of these compounds. A structure-activity relationship of these derivatives indicates that the position of the oxypropanolamine side chain, the hydroxy group of the side chain, steric bulkiness and length of N substituents, degree of the N-substitution, phenyl group at the 2-position of the chromone nucleus, and substituents of the phenyl group or B ring of the flavone play significant roles in imparting pharmacological effects. In addition, there is a good correlation between the antihypertensive activity and depletion of myocardial norepinephrine. Of these analogues tested, the most effective one was flavodilol. Only the 8-substituted analogue 6 was found to be a beta-antagonist. Flavodilol was chosen for in-depth pharmacological, toxicological, and clinical evaluation.

Flavones. 1. Synthesis and antihypertensive activity of (3-phenylflavonoxy)propanolamines without beta-adrenoceptor antagonism.

The synthesis of a series of (3-phenylflavonoxy)propanolamines is described. These compounds were evaluated for potential antihypertensive activity in spontaneously hypertensive rats, as well as for in vivo and in vitro evidence of beta-adrenoceptor antagonism. Some of the compounds of this series exhibited effective antihypertensive properties but did not antagonize beta-adrenergic receptors. These active compounds represent a unique series of effective antihypertensive agents that, despite possessing structural characteristics typical of beta-blockers, does not have beta-adrenergic receptor blocking activity.