Unmethylated Insulin DNA Is Elevated After Total Pancreatectomy With Islet Autotransplantation: Assessment of a Novel Beta Cell Marker.

Beta cell death may occur both after islet isolation and during infusion back into recipients undergoing total pancreatectomy with islet autotransplantation (TPIAT) for chronic pancreatitis. We measured the novel beta cell death marker unmethylated insulin (INS) DNA in TPIAT recipients before and immediately after islet infusion (n = 21) and again 90 days after TPIAT, concurrent with metabolic functional assessments (n = 25). As expected, INS DNA decreased after pancreatectomy (p = 0.0002). All TPIAT recipients had an elevated unmethylated INS DNA ratio in the first hours following islet infusion. In four samples (three patients), INS DNA was also assessed immediately after islet isolation and again before islet infusion to assess the impact of the isolation process: Unmethylated and methylated INS DNA fractions both increased over this interval, suggesting death of beta cells and exocrine tissue before islet infusion. Higher glucose excursion with mixed-meal tolerance testing was associated with persistently elevated INS DNA at day 90. In conclusion, we observed universal early elevations in the beta cell death marker INS DNA after TPIAT, with pronounced elevations in the islet supernatant before infusion, likely reflecting beta cell death induced by islet isolation. Persistent posttransplant elevation of INS DNA predicted greater hyperglycemia at 90 days.

Sitagliptin Treatment After Total Pancreatectomy With Islet Autotransplantation: A Randomized, Placebo-Controlled Study.

Insulin independence after total pancreatectomy and islet autotransplant (TPIAT) for chronic pancreatitis is limited by a high rate of postprocedure beta cell apoptosis. Endogenous glucagon-like peptide-1 and glucose-dependent insulinotropic peptide, which are increased by dipeptidyl peptidase 4 inhibitor therapy (sitagliptin) may protect against beta cell apoptosis. To determine the effect of sitagliptin after TPIAT, 83 adult TPIAT recipients were randomized to receive sitagliptin (n = 54) or placebo (n = 29) for 12 months after TPIAT. At 12 and 18 months after TPIAT, participants were assessed for insulin independence; metabolic testing was performed with mixed meal tolerance testing and frequent sample intravenous glucose tolerance testing. Insulin independence did not differ between the sitagliptin and placebo groups at 12 months (42% vs. 45%, p = 0.82) or 18 months (36% vs. 44%, p = 0.48). At 12 months, insulin dose was 9.0 (standard error 1.7) units/day and 7.9 (2.2) units/day in the sitagliptin and placebo groups, respectively (p = 0.67) and at 18 months 10.3 (1.9) and 7.1 (2.6) units/day, respectively (p = 0.32). Hemoglobin A1c levels and insulin secretory measures were similar in the two groups, as were adverse events. In conclusion, sitagliptin could be safely administered but did not improve metabolic outcomes after TPIAT.

Oral complications at 6 months after radiation therapy for head and neck cancer.

OBJECTIVE: To examine oral complications 6 months after modern radiation therapy (RT) for head and neck cancer (HNC). METHODS: Prospective multicenter cohort study of patients with HNC receiving intensity-modulated radiation therapy or more advanced RT. Stimulated whole salivary flow, maximal mouth opening, oral mucositis, oral pain, oral health-related quality of life (OH-QOL), and oral hygiene practices were measured in 372 subjects pre-RT and 216 subjects at 6 months from the start of RT. RESULTS: Mean stimulated whole salivary flow declined from 1.09 to 0.47 ml/min at 6 months (p < .0001). Mean maximal mouth opening reduced from 45.58 to 42.53 mm at 6 months (p < .0001). 8.1% of subjects had some oral mucositis at 6 months, including 3.8% with oral ulceration. Mean overall pain score was unchanged. OH-QOL was reduced at 6 months, with changes related to dry mouth, sticky saliva, swallowing solid foods, and sense of taste (p ≤ .0001). At 6 months, there was greater frequency of using dental floss and greater proportion using supplemental fluoride (p < .0001). CONCLUSIONS: Despite advances in RT techniques, patients with HNC experience oral complications 6 months after RT, with resulting negative impacts on oral function and quality of life.

Characterization of priority substances in effluents from an integrated steelworks in the United Kingdom.

In the Water Framework Directive, a list of priority substances that are deemed to be persistent, toxic, and liable to bioaccumulate have been identified. Within this list, a range of polycyclic aromatic hydrocarbons (PAHs) and certain trace metals are relevant to the steel industry. This study summarizes work carried out by Tata Steel Europe (Rotherham, U.K.) to characterize the emissions of PAHs and trace metals from wastewater streams at one of its main integrated steelworks in the United Kingdom over a 3-year period (2010 to 2012). The emissions inventory revealed that PAH emissions to water were almost entirely attributable to the cokemaking process, with emissions factors ranging from 20 to 55 mg/tonne of coke. Furthermore, analysis of the PAH distribution in coke oven effluents revealed that medium- and high-molecular-weight PAHs were associated with the suspended solids (particle-bound). Regarding trace metals, both ironmaking and steelmaking processes were the most important emission sources.

Nanoscale magnetic sensing with an individual electronic spin in diamond.

Detection of weak magnetic fields with nanoscale spatial resolution is an outstanding problem in the biological and physical sciences. For example, at a distance of 10 nm, the spin of a single electron produces a magnetic field of about 1 muT, and the corresponding field from a single proton is a few nanoteslas. A sensor able to detect such magnetic fields with nanometre spatial resolution would enable powerful applications, ranging from the detection of magnetic resonance signals from individual electron or nuclear spins in complex biological molecules to readout of classical or quantum bits of information encoded in an electron or nuclear spin memory. Here we experimentally demonstrate an approach to such nanoscale magnetic sensing, using coherent manipulation of an individual electronic spin qubit associated with a nitrogen-vacancy impurity in diamond at room temperature. Using an ultra-pure diamond sample, we achieve detection of 3 nT magnetic fields at kilohertz frequencies after 100 s of averaging. In addition, we demonstrate a sensitivity of 0.5 muT Hz(-1/2) for a diamond nanocrystal with a diameter of 30 nm.

Environment-assisted precision measurement.

We describe a method to enhance the sensitivity of precision measurements that takes advantage of the environment of a quantum sensor to amplify the response of the sensor to weak external perturbations. An individual qubit is used to sense the dynamics of surrounding ancillary qubits, which are in turn affected by the external field to be measured. The resulting sensitivity enhancement is determined by the number of ancillas that are coupled strongly to the sensor qubit; it does not depend on the exact values of the coupling strengths and is resilient to many forms of decoherence. The method achieves nearly Heisenberg-limited precision measurement, using a novel class of entangled states. We discuss specific applications to improve clock sensitivity using trapped ions and magnetic sensing based on electronic spins in diamond.

Robust decoupling techniques to extend quantum coherence in diamond.

We experimentally demonstrate over 2 orders of magnitude increase in the room-temperature coherence time of nitrogen-vacancy centers in diamond by implementing decoupling techniques. We show that equal pulse spacing decoupling performs just as well as nonperiodic Uhrig decoupling and also allows us to take advantage of revivals in the echo to explore the longest coherence times. At short times, we can extend the coherence of particular quantum states out from T2*=2.7 µs out to an effective T2>340 µs. For preserving arbitrary states we show the experimental importance of using pulse sequences that compensate the imperfections of individual pulses for all input states through judicious choice of the phase of the pulses. We use these compensated sequences to enhance the echo revivals and show a coherence time of over 1.6 ms in ultrapure natural abundance 13C diamond.

Opportunities for improving medication use and monitoring in gout.

PURPOSE: To study patterns and predictors of medication use and laboratory monitoring in gout. METHODS: In a cohort of veterans with a diagnosis of gout prescribed allopurinol, colchicine or probenecid, quality of care was assessed by examining adherence to the following evidence-based recommendations: (1) whether patients starting a new allopurinol prescription (a) received continuous allopurinol, (b) received colchicine prophylaxis, (c) achieved the target uric acid level of

A pilot study of the association between cariogenic oral bacteria and preterm birth.

OBJECTIVES: We examined the associations between preterm birth and low birth weight and maternal caries history, maternal periodontal status, and salivary levels of mutans streptococci and Lactobacilli. DESIGN: This study was a matched case-control study in women during their pregnancy or up to 8 weeks after delivery. SUBJECTS AND METHODS: Thirty-four women delivering before 37 weeks gestation were recruited along with 73 term controls matched for age and race/ethnicity. Demographic and obstetric information was collected from questionnaires and medical records and oral examinations along with commercial salivary tests were completed within the study groups. MAIN OUTCOME MEASURES: The main outcome variables were the preterm birth and low birth weight status. The independent variables measured were the salivary levels of Lactobacilli and mutans streptococci and the caries and periodontal status of the subjects. RESULTS: The odds ratio comparing low levels of bacteria in preterm mothers and controls was statistically significant for Lactobacilli (odds ratio (OR) = 3.45, 95% confidence interval (CI) = 1.27 to 10.00) and almost significant for mutans streptococci (OR = 2.63, 95% CI = 0.95 to 8.33). Clinical caries and periodontal disease measures did not differ significantly between groups. CONCLUSION: Within the limitation of our study, low levels of Lactobacilli in saliva were found to be associated with preterm birth.

Parental attitudes on restorative materials as factors influencing current use in pediatric dentistry.

PURPOSE: The purpose of this study was to determine pediatric dentists' current practices and the perceptions about parents' opinions and how those parental preferences regarding dental materials influence dentists' practices. METHODS: A questionnaire was sent to 500 randomly selected active members of the American Academy of Pediatric Dentistry. Twenty-five items queried demographics, use of restorative materials, perceptions of parents' attitudes towards materials, and dentists' reactions to parents' concerns. RESULTS: The survey response rate was 61%. Parental concerns about materials in decreasing order were: (1) esthetics; (2) cost; (3) toxicity; and (4) durability. Parents' greatest concerns about stainless steel crowns were: (1) esthetics; and (2) cost. Among respondents, 43% followed parental preferences when challenged, and 28% currently never use amalgam. Amalgam use and the dentists' perception of parental challenge were each related to the socioeconomic status of the practice population, with lower socioeconomic practices feeling less parental challenge than higher socioeconomic practices and being more likely to use amalgam than "white" filling materials (P = .001). CONCLUSIONS: Mercury concerns occur more frequently with higher than lower socioeconomic status parents (P = .002). Stainless steel crowns are challenged based on esthetics and cost. When confronted, many pediatric dentists (43%) follow parental preferences, even when that action is contrary to their initial clinical judgment.

Effect of adhesive systems and bevel on enamel margin integrity in primary and permanent teeth.

PURPOSE: This study compared the effectiveness of self-etch and total-etch adhesive systems in bonding to the beveled and nonbeveled margins of primary and permanent teeth. METHODS: This in vitro, factorial-designed study allowed evaluation of 3 factors: (1) tooth type; (2) presence of a bevel; and (3) adhesive type. Two preparations, each including a beveled and nonbeveled margin, were completed on buccal surfaces of 60 extracted molars (30 primary and 30 permanent). Preparations were randomly assigned to self-etch or a total-etch adhesive system and restored with resin composite. After thermocycling, teeth were stained with silver nitrate, sectioned, and measured for microleakage. Statistical analysis used a repeated measures analysis of variance. RESULTS: Beveled margins had less microleakage than nonbeveled margins for primary and permanent teeth (P < .001). Total-etch had less microleakage than self-etch adhesives on primary (53% less, P < .001) and on permanent teeth (22% less, P = .01). Self-etch had considerably more microleakage when enamel margins were not beveled. Comparably less microleakage, however, was found for total-etch and self-etch in restorations with beveled margins. CONCLUSIONS: Total-etch adhesive and beveled margins resulted in the least microleakage. Margin beveling has a greater effect in minimizing microleakage than the type of adhesive used.

Self-reported oral health perceptions of Somali adults in Minnesota: a pilot study.

OBJECTIVE: To assess self-reported oral health perceptions and associated factors in an adult Somali population living in Minnesota, USA. METHODS: We analysed data from a cross-sectional study of Somali adults aged 18 to 65+ years attending a dental school clinic for care. A comprehensive oral examination was performed by the dental school outreach team on all patients who attended a 2-week designated Somali dental clinic. Adults who consented were given an oral health questionnaire to collect information on sociodemographics, marital status, language preference and self-rated oral and general health. We performed summary statistics and differences between proportions using Fisher's exact test and a comparison of means using one-way anova or a two-sample t-test. RESULTS: The sample consisted of 53 adults, 75% of whom were females. About 49% of subjects reported poor/fair oral health and 38% reported poor/fair general health. Seventy-four percent rated their access to dental care as poor/fair and 83% reported that they did not have a regular source of dental care. Self-rated oral health was significantly associated with marital status (P < 0.05) and self-rated general health (P < 0.01) using Fisher's exact test. CONCLUSION: A substantial proportion of Somali adults rated their oral health and access to dental care as poor/fair. These findings suggest that this population would benefit from improved access to oral health care and culturally appropriate oral health education and promotion programs.

Randomized effectiveness study of four therapeutic strategies for TMJ closed lock.

For individuals with temporomandibular joint (TMJ) disc displacement without reduction with limited mouth opening (closed lock), interventions vary from minimal treatment to surgery. In a single-blind trial, 106 individuals with TMJ closed lock were randomized among medical management, rehabilitation, arthroscopic surgery with post-operative rehabilitation, or arthroplasty with post-operative rehabilitation. Evaluations at baseline, 3, 6, 12, 18, 24, and 60 months used the Craniomandibular Index (CMI) and Symptom Severity Index (SSI) for jaw function and TMJ pain respectively. Using an intention-to-treat analysis, we observed no between-group difference at any follow-up for CMI (p > or = 0.33) or SSI (p > or = 0.08). Both outcomes showed within-group improvement (p < 0.0001) for all groups. The findings of this study suggest that primary treatment for individuals with TMJ closed lock should consist of medical management or rehabilitation. The use of this approach will avoid unnecessary surgical procedures.

Longitudinal Stability of Common TMJ Structural Disorders.

The longitudinal course of temporomandibular joint (TMJ) disc displacement (DD) and degenerative joint disease (DJD) has never been conclusively described with magnetic resonance imaging and computed tomography, respectively. This 8-y observational study's objective was to assess the longitudinal stability of DD and DJD among 401 subjects. The Validation Project provided baseline measures; follow-up was performed in the TMJ Impact Project. With magnetic resonance imaging, 2 radiologists rendered a consensus diagnosis of normal/indeterminate, DD with reduction, or DD without reduction. Computed tomography consensus diagnoses included normal/indeterminate, grade 1 DJD, or grade 2 DJD. Radiologist reliability was assessed by kappa; a Hui-Walter model was used to estimate, after accounting for diagnostic disagreement, the frequency of diagnostic progression and reversal. Permutation tests were used to test the statistical influence of concurrent baseline diagnoses on diagnostic changes at follow-up. Of 789 baseline joint-specific soft tissue diagnoses of DD, 598 (76%) joints showed no change; 109 (14%) demonstrated progression; and 82 (10%) had reversal. Of 794 joints with baseline joint-specific hard tissue diagnoses of DJD, progression was observed in 122 (15%) joints, no change in 564 (71%), and reversal in 108 (14%). Radiologist reliability (kappa) was 0.73 (95% CI, 0.64 to 0.83) for DD and 0.76 (95% CI, 0.68 to 0.83) for DJD. After accounting for the influence of diagnostic disagreement, progression of hard tissue diagnoses in the right TMJ occurred in 15.2% of subjects (95% CI, 10.5% to 20.8%) and reversal in 8.3% (95% CI, 4.9% to 12.3%); results were similar for soft tissue diagnoses and the left TMJ. Concurrent baseline soft tissue diagnoses were associated with hard tissue diagnostic changes at follow-up ( P < 0.0001). Baseline hard tissue diagnoses showed no statistical association with soft tissue changes at follow-up ( P = 0.11). Longitudinally, 76% of baseline TMJ soft tissue diagnoses and 71% of the baseline hard tissue diagnoses remained stable. Diagnostic reversal and progression were confirmed for both soft and hard tissues.

Temporomandibular joint disorders' impact on pain, function, and disability.

The aim of this study was to determine the association between more advanced stages of temporomandibular joint (TMJ) intra-articular disorders ("TMJ intra-articular status"), representing a transition from normal joint structure to TMJ disc displacement with and without reduction (DDwR and DDwoR) to degenerative joint disease (DJD), and patient-reported outcomes of jaw pain, function, and disability ("TMD impact"). This cross-sectional study included 614 cases from the RDC/TMD Validation Project with at least one temporomandibular disorder (TMD) diagnosis. TMJ intra-articular status was determined by 3 blinded, calibrated radiologists using magnetic resonance imaging and computed tomography as one of normal joint structure, DDwR, DDwoR, or DJD, representing the subject's most advanced TMJ diagnosis. TMD impact was conceptualized as a latent variable consisting of 1) pain intensity (Characteristic Pain Index from the Graded Chronic Pain Scale [GCPS]), 2) jaw function (Jaw Functional Limitation Scale), and 3) disability (Disability Points from GCPS). A structural equation model estimated the association of TMJ intra-articular status with the latent measure TMD impact as a correlation coefficient in all TMD cases (n = 614) and in cases with a TMD pain diagnosis (n = 500). The correlations between TMJ intra-articular status and TMD impact were 0.05 (95% confidence interval [CI], -0.04 to 0.13) for all TMD cases and 0.07 (95% CI, -0.04 to 0.17) for cases with a pain diagnosis, which are neither statistically significant nor clinically relevant. Conceptualizing worsening of TMJ intra-articular disorders as 4 stages and characterizing impact from TMD as a composite of jaw pain, function, and disability, this cross-sectional study found no clinically significant association. Models of TMJ intra-articular status other than ours (normal structure → DDwR → DDwoR → DJD) should be explored.

Rating the quality of evidence for clinical practice guidelines.

This article describes the system for rating the quality of medical evidence developed and used during creation of the Agency for Health Care Policy and Research-sponsored heart failure guideline. Previous approaches to rating evidence were not designed for use in the setting of clinical practice guidelines. The present system is based on the tenet that flaws in research design are serious to the extent they threaten the validity of the results of studies. A taxonomy of major and minor flaws based on that tenet was developed for randomized controlled trials and for cohort and medical registry studies. The use of the system is described in the context of two difficult clinical issues considered by the Panel: the role of coronary artery revascularization and the use of metoprolol.

SYM-2081 a kainate receptor antagonist reduces allodynia and hyperalgesia in a freeze injury model of neuropathic pain.

Cold-freeze injury at -4 degrees C to the rat sciatic nerve produces mechanical allodynia and thermal hyperalgesia [M.A. Kleive, P.S. Jungbluth, J.A. Uhlenkamp, K.C. Kajander, Cold injury to rat sciatic nerve induces thermal hyperalgesia or analgesia, 8th World Congress on Pain, Vancouver, BC, Canada, August 1996 (Abstract).]. The NMDA receptor, an excitatory amino acid (EAA) receptor, appears to be involved in the development of allodynia and hyperalgesia following nerve injury. The role, if any, of the kainate receptor, another EAA receptor, remains unknown. In the current study, we evaluated whether (2S,4R)-4-methylglutamic acid (SYM-2081), a recently developed kainate receptor antagonist, attenuates increased responsiveness following cold injury to the sciatic nerve. During baseline testing, Sprague-Dawley rats were evaluated for frequency of withdrawal from von Frey filaments and latency of withdrawal from a radiant thermal source. Animals were then anesthetized, the left sciatic nerve was exposed, and the nerve was cooled to -4 degrees C for 15 min (n=24). For control rats (n=24), all procedures were identical except that the nerve was maintained at 37 degrees C. Testing resumed on the third day following surgery. On the fifth post-operative day, SYM-2081 (150 or 100 mg/kg), fentanyl citrate (0. 04 mg/kg) or vehicle was injected intraperitoneally. Injury to the rat sciatic nerve induced a significant increase in withdrawal frequency and a significant decrease in withdrawal latency (ANOVA, p<0.05). SYM-2081 and fentanyl significantly reduced these responses (p<0.05). These results suggest that kainate and opioid receptors are involved in the mechanical allodynia and thermal hyperalgesia that develop following cold injury to the sciatic nerve.

Accuracy of a system for creating 3D computer models of dental arches.

Three-dimensional imaging of dental tissues will have a major impact in dentistry if the images are accurate. The purpose of this study was to measure the accuracy and precision of a system for creating three-dimensional images of dental arches. Using vinyl polysiloxane impression materials and improved dental stone, we made 10 stone casts of a "dental" standard with known dimensions. The impressions and casts were scanned by means of a Comet 100 optical scanner. Custom software created three-dimensional images (computer models) from the scanned data. Accuracy was defined as the average of the absolute differences between the computer models and the standard. Precision was the standard deviation of accuracy over 10 repeated measures. Software processing improved the accuracy of the scanner data. Accuracy +/- precision for the casts and impressions was 0.024 +/- 0.002 mm and 0.013 +/- 0.003 mm, respectively. The system produced computer models with sufficient accuracy for clinical application.

Nominal shear or fracture mechanics in the assessment of composite-dentin adhesion?

This study addresses the anticipated problem of discriminating among high-performing dentin adhesives. The simplicity of the nominal shear bond test, despite being heavily criticized, has made it a routine procedure for the determination of bonding efficacy. A fracture mechanics approach has been suggested as a better assessment of bonding efficacy (Versluis et al., 1997). However, experimental complexity is a major limitation. It is hypothesized that a new, simplified interfacial fracture toughness test (Lin, 1994) will evaluate bonding agents differently if compared with the traditional shear bond test. Therefore, the objective of this study was to compare the performances of six dentin bonding agents subjected to the interfacial fracture toughness test (critical plane strain energy release rate) or to the nominal shear bond test (shear bond strength). Their performances were also characterized by scanning electron micrography of the fracture surfaces for evidence of dentin cohesive failure. Statistical analyses showed only marginal differences between these determinants of the two tests. However, when the analysis was applied only to the materials that had 100% frequency of dentin cohesive failure in shear testing, which also had high bonding efficacy, the difference in adhesive strengths between the two tests became significant. The reliability of the nominal shear test is questioned when dentin cohesive failure occurs, which usually is associated with high bonding efficacy. Since it is expected that bonding efficacy will increase further, the interfacial fracture toughness test is the preferred methodology to distinguish among high-performing dentin adhesives.

No heritability of temporomandibular joint signs and symptoms.

The causes of temporomandibular joint (TMJ)-related signs and symptoms are largely unknown. We tested the hypotheses that these signs and symptoms, as well as oral parafunctional habits, are substantially heritable. Questionnaire and clinical data were collected from 494 twins, including pairs of reared-apart and reared-together monozygotic (MZ) and dizygotic (DZ) twins. A history of joint-area pain, joint noises, and clenching and grinding habits was scored as present or absent. Twenty-nine percent of the population experienced at least one sign or symptom. Nearly one-quarter of subjects clenched or ground their teeth, and 8.7% reported a history of joint-area pain. Pain was associated with clenching, grinding, and joint noises. MZ twins were no more similar than DZ twins for any outcome, suggesting that genetic factors do not influence these traits in the population. Reared-together MZ twins were no more similar than reared-apart MZ twins, suggesting a negligible effect of the family environment on these outcomes. Environmental factors unique to each twin appeared to be the major determinants of variation in this population.