Measuring orthodontic treatment impact: Description or judgment, challenge or result.

INTRODUCTION: Determination of improvement in orthodontic treatment may depend on the measurement method used and the purpose. METHODS: Improvement after orthodontic treatment (from T1 to T2 [beginning to end of treatment]) was assessed 3 ways from a set of 98 patient records: (1) calculated by subtracting judges' assessments at T2 from T1 for records presented in random order, (2) judged as a holistic impression viewing T1 and T2 records side by side, and (3) determined from proxies (American Board of Orthodontics Discrepancy Index, the American Board of Orthodontics Objective Grading System, and the Peer Assessment Rating index). RESULTS: High levels of intramethod consistency were observed, with intraclass correlation coefficient clustering around an intraclass correlation coefficient of 0.900, and distributions were normal. Calculated and judged improvements correlated at r = 0.606. Calculated or judged improvements were correlated at a lower level with proxies. Calculated improvement was significantly associated with "challenge" (T1) scores and judged improvement associated with "results" (T2) scores. Common method bias was observed, with higher correlations among similar indexes than among indexes at the same time that used various methods. Relative to differences in Peer Assessment Rating scores, calculated improvement overestimated low scores and underestimated high ones. The same effect, but statistically greater, was observed using direct judgment of improvement. CONCLUSIONS: These findings are consistent with decision science and measurement theory. In some circumstances, such as third-party reimbursement and research, operationally defined measures of occlusion are appropriate. In practice, the determination of occlusion and improvement are best performed by judgment that naturally corrects for biases in proxies and incorporates background information.

Novel methods for the analysis of toxicants in bronchoalveolar lavage fluid samples from e-cigarette, or vaping, product use-associated lung injury cases: Selected petroleum distillates.

RATIONALE: Over 2700 e-cigarette, or vaping, product use-associated lung injury (EVALI) cases were reported to the Centers for Disease Control and Prevention (CDC) during August 2019-February 2020. Bronchoalveolar lavage (BAL) fluid samples from 51 EVALI and 99 non-EVALI cases were analyzed for toxicants including petroleum distillates. We describe a novel method to measure petroleum distillates in BAL fluid using gas chromatography-mass spectrometry (GC/MS). METHODS: n-Hexane, n-heptane, n-octane, methylcyclopentane, and cyclohexane were measured in BAL fluid specimens by headspace solid-phase microextraction/GC/MS. We created and characterized BAL fluid pools from non-EVALI individuals to determine assay accuracy, precision, linearity, limits of detection (LODs), and analytical specificity. All measurements were conducted in accordance with the rigorous method validation procedures of CDC's Division of Laboratory Sciences. RESULTS: Matrix validation experiments showed that calibration curves in BAL fluid and saline had similar slopes, with differences less than 5%. Assay precision ranged from 1.98% to 18%. In addition, the LODs for the five analytes ranged from 0.05 to 0.10 µg/L, and their linearity was confirmed with R2 values >0.99. The analysis of selected petroleum distillates in BAL fluid analysis was shown to be comparable with their analysis in blood in which the 95th percentiles are below detection. CONCLUSIONS: We developed and validated a method to quantify petroleum distillates in BAL fluid specimens using GC/MS. The assay provided precise and accurate analyses of EVALI and non-EVALI BAL fluid specimens in support of CDC's EVALI response. This method is applicable to the determination of a broad range of volatile organic compounds in BAL fluid specimens.

Vitamin E Acetate in Bronchoalveolar-Lavage Fluid Associated with EVALI.

BACKGROUND: The causative agents for the current national outbreak of electronic-cigarette, or vaping, product use-associated lung injury (EVALI) have not been established. Detection of toxicants in bronchoalveolar-lavage (BAL) fluid from patients with EVALI can provide direct information on exposure within the lung. METHODS: BAL fluids were collected from 51 patients with EVALI in 16 states and from 99 healthy participants who were part of an ongoing study of smoking involving nonsmokers, exclusive users of e-cigarettes or vaping products, and exclusive cigarette smokers that was initiated in 2015. Using the BAL fluid, we performed isotope dilution mass spectrometry to measure several priority toxicants: vitamin E acetate, plant oils, medium-chain triglyceride oil, coconut oil, petroleum distillates, and diluent terpenes. RESULTS: State and local health departments assigned EVALI case status as confirmed for 25 patients and as probable for 26 patients. Vitamin E acetate was identified in BAL fluid obtained from 48 of 51 case patients (94%) in 16 states but not in such fluid obtained from the healthy comparator group. No other priority toxicants were found in BAL fluid from the case patients or the comparator group, except for coconut oil and limonene, which were found in 1 patient each. Among the case patients for whom laboratory or epidemiologic data were available, 47 of 50 (94%) had detectable tetrahydrocannabinol (THC) or its metabolites in BAL fluid or had reported vaping THC products in the 90 days before the onset of illness. Nicotine or its metabolites were detected in 30 of 47 of the case patients (64%). CONCLUSIONS: Vitamin E acetate was associated with EVALI in a convenience sample of 51 patients in 16 states across the United States. (Funded by the National Cancer Institute and others.).

A comparison of haemostatic biomarkers during low-risk patients undergoing cardiopulmonary bypass using either conventional centrifugal cell salvage or the HemoSep device.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass (CPB) is associated with a coagulopathy due to haemodilution, thrombocytopenia and platelet dysfunction and the activation of coagulation and fibrinolysis, despite the use of large doses of unfractionated heparin. Conventional red cell salvage may exacerbate post-operative bleeding as plasma containing haemostatic factors is discarded. We hypothesized that a novel cell salvage device (HemoSep) may attenuate haemostatic changes associated with red cell salvage. We studied haemostatic markers following autologous transfusion from conventional cell salvage or the HemoSep device. METHODS: This randomised, controlled trial compared haemostatic markers in patients undergoing coronary artery bypass grafting or aortic valve replacement who received autologous blood returned from cell salvage (control) or HemoSep (study). Blood samples were taken pre-operatively, end of CPB, post-transfusion of salvaged blood and 3 hours post-operatively and analysed for full blood count (FBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, D-dimer and endogenous thrombin potential (ETP). RESULTS: Fifty-four patients were recruited (n=28 control, n=26 study). Processed blood volume for transfusion was significantly (p<0.001) higher in the HemoSep group. In the HemoSep group, the PT was shorter (18.7±0.3 vs 19.9±0.3 sec; p<0.05) post-operatively and the aPTT was longer (48.6±3.8 vs 37.3±1.0 sec; p<0.01) following autologous transfusion. In the control group, D-dimer and ETP levels were higher (1903±424 vs.1088±151; p<0.05 and 739±46 vs. 394±60; p<0.001, respectively) following autologous transfusion. CONCLUSIONS: Although centrifuged cell salvage is known to adequately haemoconcentrate and remove unwanted substrates and bacteriological contamination, the process can exacerbate coagulopathy. The HemoSep device demonstrated some increase in haemostatic markers when used in low-risk cardiac surgery patients.

Evaluating centralized technical assistance as an implementation strategy to improve cancer prevention and control.

PURPOSE: In 2015-2016, the Comprehensive Cancer Control National Partnership provided technical assistance workshops to support 22 cancer coalitions in increasing human papillomavirus (HPV) vaccination uptake and increasing colorectal cancer (CRC) screening in their local communities. As national efforts continue to invest in providing technical assistance, there is a current gap in understanding its use as a strategy to accelerate implementation of evidence-based interventions (EBIs) for cancer prevention. The objective of this study was to evaluate the impact of technical assistance on the participants' knowledge, attitudes, and skills for implementing EBIs in their local context and enhancing state team collaboration. METHODS: Data were collected August-November 2017 using web-based questionnaires from 44 HPV workshop participants and 66 CRC workshop participants. RESULTS: Both HPV vaccination and CRC screening workshop participants reported changes in knowledge, attitudes, and skills related to implementing EBIs in their local state context. Several participants reported increased abilities in communicating and coordinating with partners in their states and utilizing additional implementation strategies to increase HPV vaccination uptake and CRC screening rates. CONCLUSIONS: Findings from this study suggest that providing technical assistance to members of comprehensive cancer control coalitions is useful in promoting collaborations and building capacity for implementing EBIs for cancer prevention and control.

Serotonin Receptor 1A (HTR1A), a Novel Regulator of GnRH Neuronal Migration in Chick Embryo.

The hypothalamic GnRH neurons are a small group of cells that regulate the reproductive axis. These neurons are specified within the olfactory placode, delaminate from this structure, and then migrate to enter the forebrain before populating the hypothalamus. We have used microarray technology to analyze the transcriptome of the olfactory placode at a number of key time points for GnRH ontogeny using the chick embryo. This resulted in the identification of a large number of genes whose expression levels change significantly over this period. This repertoire includes those genes that are known to be important for GnRH neuronal development as well as many novel genes, such as the serotonin receptor 1A, HTR1A. We find that HTR1A is expressed in the region of the olfactory placode that generates GnRH neurons. We further show that when this receptor is inactivated using a selective HTR1A antagonist as well as a gene knockdown approach using RNAi, this resulted in delayed migration causing the GnRH neurons to stall just outside the forebrain. These findings implicate HTR1A as being important for GnRH neuronal migration from the olfactory placode to the forebrain. Our study thus extends the repertoire of genes involved in GnRH neuron biology and thus identifies new candidate genes that can be screened for in patients who do not show mutations in any of the previously identified hypogonadotrophic hypogonadism/Kallmann syndrome genes.

Effects of nutritional supplementation on periodontal parameters, carotenoid antioxidant levels, and serum C-reactive protein.

Few studies have focused on the role of nutrition in periodontal disease. The purpose of this trial was to determine the effect of a nutritional supplement on gingival inflammation, bleeding, probing depth, clinical attachment level, carotenoid antioxidant level, and C-reactive protein. The test supplement, consisting of a standard multivitamin formula, as well as several phytonutrients associated with antiinflammatory/antioxidant effects, provided modest benefits in reducing inflammation; however, further studies with larger populations and longer intervention are warranted.

Gentlemen.

The gentleman, with the help of his friends, takes responsibility for living at a high standard. Four historical examples are used to illustrate this point: Cicero, Castiglione, Lord Chesterfield, and Adam Smith. These lives span the period from the last half of the century before Christ to the last half of the eighteenth century. Gentlemen of that status are rare today, but the legacy of values, self-image, friendships, manners, and speech remain. These are especially a legacy of the professions.

Picogram measurement of volatile n-alkanes (n-hexane through n-dodecane) in blood using solid-phase microextraction to assess nonoccupational petroleum-based fuel exposure.

We describe here a new method for the analysis of alkanes ( n-hexane, n-heptane, n-octane, n-nonane, n-decane, n-undecane, and n-dodecane) in blood using headspace solid-phase microextraction gas chromatography/mass spectrometry. This method is used to measure picogram per milliliter levels of n-alkanes in blood that may result from nonoccupational exposure to alkanes and other volatile nonpolar compounds from common sources such as petroleum-based fuel. This alkane signature is useful in distinguishing typical fuel biomarkers (e.g., benzene and toluene) from other confounding exposure sources such as cigarette smoke. Development of this method required special attention to sample handling as alkanes are not highly soluble in aqueous matrixes and exist as ubiquitous compounds found in many laboratory materials and the environment. In particular, significant n-hexane contamination ( approximately 0.4 ng/mL) occurred from collecting blood samples in vacutainers. This residue was removed by boiling the vacutainer stoppers in methanol followed by vacuum baking. For all the alkanes, the calculated accuracy demonstrated for the water-based standards ranged from 3.3% to 17% as deduced from the difference of the lowest and middle standards from the curve fit. Quality control data among runs over a 10 month period were found to vary from 14% to -29%, with a few exceptions. The resulting quantification limits for n-hexane through n-decane ranged from 0.069 to 0.132 ng/mL. In the analysis of 1200 blood samples from people with no known occupational exposure, median blood levels for all n-alkanes were below these quantification limits. n-Hexane levels above the method detection limit were, however, found in 1.3% of the samples.

Tissue interactions in the developing chick diencephalon.

BACKGROUND: The developing vertebrate brain is patterned first by global signalling gradients that define crude anteroposterior and dorsoventral coordinates, and subsequently by local signalling centres (organisers) that refine cell fate assignment within pre-patterned regions. The interface between the prethalamus and the thalamus, the zona limitans intrathalamica (ZLI), is one such local signalling centre that is essential for the establishment of these major diencephalic subdivisions by secreting the signalling factor Sonic hedgehog. Various models for ZLI formation have been proposed, but a thorough understanding of how this important local organiser is established is lacking. RESULTS: Here, we describe tissue explant experiments in chick embryos aimed at characterising the roles of different forebrain areas in ZLI formation. We found that: the ZLI becomes specified unexpectedly early; flanking regions are required for its characteristic morphogenesis; ZLI induction can occur independently from ventral tissues; interaction between any prechordal and epichordal neuroepithelial tissue anterior to the midbrain-hindbrain boundary is able to generate a ZLI; and signals from the dorsal diencephalon antagonise ZLI formation. We further show that a localised source of retinoic acid in the dorsal diencephalon is a likely candidate to mediate this inhibitory signal. CONCLUSION: Our results are consistent with a model where planar, rather than vertical, signals position the ZLI at early stages of neural development and they implicate retinoic acid as a novel molecular cue that determines its dorsoventral extent.

Myocardial protection with oxygenated esmolol cardioplegia during prolonged normothermic ischemia in the rat.

OBJECTIVE: We previously showed that arrest with multidose infusions of high-dose (1 mmol/L) esmolol (an ultra-short-acting beta-blocker) in oxygenated Krebs-Henseleit buffer (esmolol cardioplegia) provided complete myocardial protection after 40 minutes of normothermic (37 degrees C) global ischemia in isolated rat hearts. In this study we investigated the importance of oxygenation for protection with esmolol cardioplegia, compared it with that of St Thomas' Hospital cardioplegia, and determined the protective efficacy of multidose esmolol cardioplegia for extended ischemic durations. METHODS: Isolated rat hearts (n = 6/group) were perfused in the Langendorff mode at constant pressure (75 mm Hg) with oxygenated Krebs-Henseleit bicarbonate buffer at 37 degrees C. The first part of the first study had four groups: (i) multidose (every 15 minutes) oxygenated (95% oxygen/5% carbon dioxide) Krebs-Henseleit buffer during 60 minutes of global ischemia, (ii) multidose deoxygenated (95% nitrogen/5% carbon dioxide) Krebs-Henseleit buffer during 60 minutes of global ischemia, (iii) multidose oxygenated esmolol cardioplegia during 60 minutes of global ischemia, and (iv) multidose deoxygenated esmolol cardioplegia during 60 minutes of global ischemia. The second part of the first study had three groups: (v) multidose St Thomas' Hospital solution during 60 minutes of global ischemia, (vi) multidose oxygenated St Thomas' Hospital solution during 60 minutes of global ischemia, and (vii) multidose oxygenated esmolol cardioplegia during 60 minutes of global ischemia. In the second study, hearts were randomly assigned to 60, 75, 90, or 120 minutes of global ischemia and at each ischemic duration were subjected to multidose oxygenated constant flow or constant pressure infusion of (i) Krebs-Henseleit buffer (constant flow), (ii) Krebs-Henseleit buffer (constant pressure), (iii) esmolol cardioplegia (constant flow), or (iv) esmolol cardioplegia (constant pressure). All hearts were reperfused for 60 minutes, and recovery of function was measured. RESULTS: Multidose infusion of oxygenated esmolol cardioplegia completely protected the hearts (97% +/- 5%) after 60 minutes of 37 degrees C global ischemia. Deoxygenated esmolol cardioplegia was significantly less protective (45% +/- 8%). Oxygenation of St Thomas' Hospital solution did not alter its protective efficacy in this study (70% +/- 4% vs 69% +/- 7%). Infusion of esmolol cardioplegia at constant pressure provided complete protection for 60, 75, and 90 minutes (104% +/- 5%, 95% +/- 5%, and 95% +/- 3%, respectively), whereas protection with constant-flow esmolol cardioplegic infusion was significantly decreased at ischemic durations longer than 60 minutes. This decrease in efficacy of constant-flow esmolol cardioplegia was associated with increasing coronary perfusion pressure leading to myocardial injury. CONCLUSIONS: Oxygenation of esmolol cardioplegia (Krebs-Henseleit buffer plus 1.0 mmol/L esmolol) was essential for optimal myocardial protection. Multidose infusion of oxygenated esmolol cardioplegia provided good myocardial protection during extended periods of normothermic ischemia. Esmolol cardioplegia may provide an efficacious alternative to hyperkalemia.