Has Choosing Wisely® affected rates of dual-energy X-ray absorptiometry use?

UNLABELLED: Reducing overuse of tests such as dual-energy X-ray absorptiometry (DXA) scans in younger women is an important quality issue. We evaluated trends in DXA ordering before and after Choosing Wisely recommendations were released. We found no significant difference in ordering trends suggesting that other initiatives are needed to change behavior. INTRODUCTION: Reducing overuse of tests such as dual-energy X-ray absorptiometry (DXA) scans in younger women is an important quality issue, but trends in care are difficult to change. We evaluated (1) trends in DXA ordering before and after the Choosing Wisely recommendation release and (2) patterns of key characteristics that indicate a potentially appropriate DXA scan order. METHODS: We performed a retrospective longitudinal analysis of electronic health record data at a multi-specialty, ambulatory care network of 34 practices across Maryland and Washington, DC. Since the Choosing Wisely DXA recommendation was released April 2012, the study periods were April-December 2011 (pre-initiative) and April-December 2012 (post-initiative). Women between 50 and 64 years with primary care encounters, and primary care providers who saw ten or more women in the study population in both pre and post periods were included. RESULTS: For 42,320 eligible patients, the mean provider ordering rate was 2.6 % pre-initiative and 2.0 % post-initiative; there was no significant difference in trend over time. Over 70 % of the population had no characteristics associated with potentially appropriate DXA ordering. Low body mass index, current smoker status, and osteopenia were the most common characteristics indicating potentially appropriate DXA orders. Patients with any of these three characteristics had DXA ordering rates between 3-20 %. CONCLUSIONS: The trend in provider ordering rates of DXA scans did not decrease after the release of the DXA Choosing Wisely recommendation. Targeted initiatives addressing providers with high ordering rates will be needed to change behavior.

Mineralogical and petrological investigations of lunar samples.

Fragments of igneous rocks and breccias, and one coarse-grained rock with thin sections, have been studied. Minerals found include pyroxene, plagioclase, olivine, ilmenite, troilite, ulvöspinel, native iron, cristobalite, tridymite, alkali feldspar, apatite, and quartz. Textures are described and interpreted. Among features revealed by optical, microprobe, x-ray diffraction, and electron microscope methods are extreme zoning and unmixing in pyroxene grains, compositional variations in ilmenites, and effects of shock metamorphism. Some trace elements were determined by x-ray fluorescence analysis.

Parasympathetic effects on electrophysiologic properties of cardiac ventricular tissue.

The physiologic importance of parasympathetic influence on the sinoatrial and atrioventricular nodes is well established, but the importance of parasympathetic modulation of ventricular function remains controversial. Recognized effects of muscarinic cholinergic stimulation on ventricular automaticity and ventricular repolarization, the ability of muscarinic cholinergic agonists to antagonize catecholamine effects in the ventricle and proposed mechanisms for these effects are described. Anatomic studies have demonstrated a great abundance of cholinergic nerve endings in association with the ventricular conducting system. Stimulation of the vagus nerve or addition of muscarinic cholinergic agonists suppresses ventricular automaticity in most species and antagonizes isoproterenol-induced action potential shortening and isoproterenol-restored slow response action potentials. In vivo, interactions between the parasympathetic and sympathetic nervous systems occur at multiple levels. Muscarinic cholinergic agonists inhibit release of norepinephrine from sympathetic nerve terminals, inhibit catecholamine-stimulated adenylate cyclase activity and alter cyclic guanosine monophosphate (GMP) and possibly cyclic adenosine monophosphate (AMP) levels. Evidence is also presented that, in vivo, parasympathetic effects on ventricular electrical function might influence the pathophysiologic milieu responsible for initiation or termination of certain ventricular arrhythmias. Vagal influences appear to be protective against certain digitalis-induced arrhythmias and protective in certain experimental acute myocardial infarctions. In human beings, there appears to be tonic vagal tone in the ventricle and vagal stimulation terminates certain types of ventricular tachycardia. The evidence presented supports a physiologic role of parasympathetic stimulation in altering ventricular electrical function.

Repression of the prolactin promoter: a functional consequence of the heterodimerization between Pit-1 and Pit-1 beta.

The POU-homeodomain transcription factor Pit-1 is required for the differentiation of the anterior pituitary cells and the expression of their hormone products. Pit-1beta, an alternate splicing isoform, has diametrically different outcomes when it is expressed in different cell types. Pit-1beta acts as a transcriptional repressor of prolactin (PRL) and growth hormone genes in pituitary cells, and as a transcriptional activator in non-pituitary cells. In order to explore these differences, we: (1) identified the transcriptional cofactors necessary for reconstitution of repression in non-pituitary cells; (2) tested the effect of the beta-domain on heterodimerization with Pit-1 and physical interaction with the co-activator CREB binding protein (CBP); and (3) determined the beta-domain sidechain chemistry requirements for repression. Co-expression of both Pit-1 isoforms reconstituted the repression of the PRL promoter in non-pituitary cells. The beta-domain allowed heterodimerization with Pit-1 but blocked physical interaction with CBP, and specific chemical properties of the beta-domain beyond hydrophobicity were dispensable. These data strongly suggest that Pit-1beta represses hormone gene expression by heterodimerizing with Pit-1 and interfering with the assembly of the Pit-1-CBP complex required for PRL promoter activity in pituitary cells.

Pit-1beta reduces transcription and CREB-binding protein recruitment in a DNA context-dependent manner.

Many transcription factors are expressed as multiple isoforms with distinct effects on the regulation of gene expression, and the functional consequences of structural differences between transcription factor isoforms may allow for precise control of gene expression. The pituitary transcription factor isoforms Pit-1 and Pit-1beta differentially regulate anterior pituitary hormone gene expression. Pit-1 is required for the development of and appropriate hormone expression by anterior pituitary somatotrophs and lactotrophs. Pit-1beta differs structurally from Pit-1 by the splice-insertion of the 26-residue beta-domain in the trans-activation domain, and it differs functionally from Pit-1 in that it represses expression of the prolactin promoter in a cell-type specific manner. In order to identify signal and promoter context requirements for repression by Pit-1beta, we examined its function in the presence of physiological regulatory signals as well as wild-type and mutant Pit-1-dependent target promoters. Here, we demonstrate that Pit-1beta impairs recruitment of cAMP response element-binding protein (CREB)-binding protein to the promoters that it represses. In addition, we show that repression of target promoter activity, reduction in promoter histone acetylation, and decrease of CREB-binding protein recruitment all depend on promoter context. These findings provide a mechanism for promoter-specific repression by Pit-1beta.

Accuracy of Deoxynucleotide Incorporation by Soybean Chloroplast DNA Polymerases Is Independent of the Presence of a 3[prime] to 5[prime] Exonuclease.

DNA polymerase was purified from soybean (Glycine max) chloroplasts that were actively replicating DNA. The main form (form I) of the enzyme was associated with a low level of 3[prime] to 5[prime] exonuclease activity throughout purification, although the ratio of exonuclease to polymerase activity decreased with each successive purification step. A second form (form II) of DNA polymerase, which elutes from DEAE-cellulose at a higher salt concentration than form I, was devoid of any exonuclease activity. To assess the potential function of the 3[prime] to 5[prime] exonuclease in proofreading, the fidelity of deoxynucleotide incorporation was measured for form I DNA polymerase throughout purification. Despite the steadily decreasing ratio of 3[prime] to 5[prime] exonuclease to polymerase activity, the extent of misincorporation by form I enzyme remained unchanged during the final purification steps, suggesting that the exonuclease did not contribute to the accuracy of DNA synthesis by this polymerase. Fidelity of form I DNA polymerase, when compared with that of form II, revealed a higher level of misincorporation for form I enzyme, a finding that is consistent with the exonuclease playing little or no role in exonucleolytic proofreading.

Partial purification and characterization of the DNA polymerase from the cyanelles of Cyanophora paradoxa.

A DNA polymerase was partially purified and characterized from the photosynthetic organelles (cyanelles) of the protist, Cyanophora paradoxa. While cyanelles have several cyanobacterial features, such as a lysozyme-sensitive cell wall, unstacked thylakoids and light harvesting phycobilisomes, their genome size and structure resemble those of chloroplasts, suggesting that cyanelles occupy a unique intermediate position between chloroplasts and their phylogenetic ancestors, the cyanobacteria. When comparing the biochemical characteristics of the cyanelle DNA polymerase to those of its counterparts from higher plant chloroplasts and from a cyanobacterium, it is clear that the cyanelle enzyme resembles chloroplast DNA polymerases which are eukaryotic gamma-type enzymes.

Intravenous leiomyomatosis of the uterus with extension into the heart.

A 42 year old woman presented with impaired filling of the right atrium and right ventricle two years after removal of uterine leiomyomas. At the time of hysterectomy, intravenous leiomyomatosis was noted, with extension of the tumor into the inferior vena cava. The tumor subsequently extended into the right atrium and coronary sinus, and protruded through the tricuspid orifice. It was successfully removed from the heart, and proved to be histologically benign.

The role of the autonomic central nervous system in mediating and modifying the action of cardiac antiarrhythmic drugs.

The autonomic nervous system, particularly the sympathetic nervous system, plays an important role in initiating or perpetuating cardiac arrhythmias in various animal models and presumably also in man. The parasympathetic and sympathetic nervous systems interact in a complex manner in regulating the electrophysiologic properties of cardiac tissues. To the extent that a given arrhythmia is influenced by autonomic tone, the alteration in autonomic tone produced by an antiarrhythmic drug will modify the effects of the antiarrhythmic drug. Several antiarrhythmic drugs that are known to have direct electrophysiologic effects on cardiac tissues also reduce efferent sympathetic nerve activity by acting in the CNS. This centrally mediated effect on sympathetic activity likely plays an important role in the antiarrhythmic effects of these drugs. Other antiarrhythmic drugs interact directly with autonomic receptors on cardiac tissues in addition to producing their direct electrophysiological effects. The electrophysiologic effects of such antiarrhythmic drugs that interact with autonomic receptors are qualitatively modified by the magnitude and nature of the prevailing autonomic tone. These interactions between the autonomic nervous system and antiarrhythmic drugs must be kept in mind when the mechanism of action of these drugs is considered.

Detection of human IL-2 in normal and inflamed dental pulps.

Irreversible pulpitis has been associated with an increase in the number of pulpal T-cells. Interleukin-2 (IL-2) stimulates T-cell proliferation and signals the release of other proinflammatory mediators associated with connective tissue degradation. IL-2 has been suggested to be a useful marker of pathologic inflammatory activity in periodontal and systemic disease conditions. The purpose of this study was to analyze normal and inflamed dental pulps for the presence of immunoreactive IL-2 (iIL-2). Normal healthy pulpal tissue was obtained from 17 impacted third molars and inflamed samples were obtained from 12 symptomatic carious molars clinically diagnosed with irreversible pulpitis. Pulpal tissues were collected, prepared, and analyzed for histological status and iIL-2 concentration by a modified ELISA technique. iIL-2 was detected in all vital pulpal tissues. A t-test revealed significant differences in iIL-2 concentrations when inflamed pulpal tissues were compared to normal healthy samples (T = -2.75, p < 0.05). These results suggest that iIL-2 may serve as a marker of pathologic inflammatory activity in irreversible pulpitis.

The electrophysiologic basis for cardiac electrical activity: normal and abnormal.

The participation of several more-or-less independent electrophysiologic and structural phenomena may be required to generate and maintain a cardiac arrhythmia. Until these phenomena are better understood, therapy of these disorders will remain largely empirical.

Pharmacology and therapeutic role of inorganic nitrite and nitrate in vasodilatation.

Nitrite has emerged as an important bioactive molecule that can be biotransformed to nitric oxide (NO) related metabolites in normoxia and reduced to NO under hypoxic and acidic conditions to exert vasodilatory effects and confer a variety of other benefits to the cardiovascular system. Abundant research is currently underway to understand the mechanisms involved and define the role of nitrite in health and disease. In this review we discuss the impact of nitrite and dietary nitrate on vascular function and the potential therapeutic role of nitrite in acute heart failure.

Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma.

AIMS: Vascular perfusion may be impaired in primary open-angle glaucoma (POAG); thus, we evaluated a panel of markers in vascular tone-regulating genes in relation to POAG. METHODS: We used Illumina 660W-Quad array genotype data and pooled P-values from 3108 POAG cases and 3430 controls from the combined National Eye Institute Glaucoma Human Genetics Collaboration consortium and Glaucoma Genes and Environment studies. Using information from previous literature and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, we compiled single-nucleotide polymorphisms (SNPs) in 186 vascular tone-regulating genes. We used the 'Pathway Analysis by Randomization Incorporating Structure' analysis software, which performed 1000 permutations to compare the overall pathway and selected genes with comparable randomly generated pathways and genes in their association with POAG. RESULTS: The vascular tone pathway was not associated with POAG overall or POAG subtypes, defined by the type of visual field loss (early paracentral loss (n=224 cases) or only peripheral loss (n=993 cases)) (permuted P≥0.20). In gene-based analyses, eight were associated with POAG overall at permuted P<0.001: PRKAA1, CAV1, ITPR3, EDNRB, GNB2, DNM2, HFE, and MYL9. Notably, six of these eight (the first six listed) code for factors involved in the endothelial nitric oxide synthase activity, and three of these six (CAV1, ITPR3, and EDNRB) were also associated with early paracentral loss at P<0.001, whereas none of the six genes reached P<0.001 for peripheral loss only. DISCUSSION: Although the assembled vascular tone SNP set was not associated with POAG, genes that code for local factors involved in setting vascular tone were associated with POAG.

Relationships between postweaning residual feed intake in heifers and forage use, body composition, feeding behavior, physical activity, and heart rate of pregnant beef females.

The objectives of this study were to determine if residual feed intake (RFI) classification of beef heifers affected efficiency of forage utilization, body composition, feeding behavior, heart rate, and physical activity of pregnant females. Residual feed intake was measured in growing Bonsmara heifers for 2 yr (n=62 and 53/yr), and heifers with the lowest (n=12/yr) and highest (n=12/yr) RFI were retained for breeding. Of the 48 heifers identified as having divergent RFI, 19 second-parity and 23 first-parity females were used in the subsequent pregnant-female trial. Pregnant females were fed a chopped hay diet (ME=2.11 Mcal kg(-1) DM) in separate pens equipped with GrowSafe bunks to measure individual intake and feeding behavior. Body weights were measured at 7-d intervals and BCS and ultrasound measurements of 12th-rib fat depth, rump fat depth, and LM area obtained on d 0 and 77. Heart rate and physical activity were measured for 7 consecutive d. First-parity females had lower (P<0.05) initial BW, BW gain, and initial hip height and tended (P=0.07) to have lower DMI compared to second-parity females. Females with low RFI as heifers consumed 17% less (P<0.01) forage compared to females with high RFI as heifers but maintained the same BW, BW gain, and body composition. Likewise, RFI classification did not affect calving date. An interaction (P=0.04) between heifer RFI classification and parity was found for calf birth weight. Calves from first-parity low-RFI females were lighter at birth (P<0.01) than calves from high-RFI females, but RFI classification did not affect BW of calves born to second-parity females. Residual feed intake classification did not affect bunk visit frequency, but low-RFI females spent 26% less time (P<0.01) at the bunk compared to high-RFI females. First-parity females had more (P<0.05) daily step counts and greater lying-bout frequencies compared to second-parity females, but physical activity was not affected by RFI classification. Heart rates of females classified as low RFI were 7% lower (P=0.03) compared to high-RFI females. Heifer postweaning RFI but not G:F or residual gain were positively correlated with forage intake (r=0.38) and RFI (r=0.42) of pregnant females. Results indicate that heifers identified as having low postweaning RFI have greater efficiency of forage utilization as pregnant females, with minimal impacts on growth, body composition, calving date, and calf birth BW, compared to their high-RFI counterparts.

Technical note: Evaluation of bimodal distribution models to determine meal criterion in heifers fed a high-grain diet.

Meals are clusters of feedbunk visit (BV) events that are differentiated from the next meal by a nonfeeding interval that is longer compared with the nonfeeding intervals within a meal. The longest nonfeeding interval considered to be part of a meal is defined as the meal criterion. The objective of this study was to determine which combination of 2 probability density functions [(PDF): Gaussian normal (G), Weibull (W), Log-Normal, Gamma, and Gumbel] used in a bimodal distribution model had the best fit of nonfeeding interval data collected in beef heifers. Feeding behavior traits (572,627 total BV events) were measured in 119 heifers fed a high-grain diet (3.08 Mcal ME/kg DM), using a GrowSafe system for 66 d. The frequency and duration of BV events averaged 75 ± 15 events/d and 73.0 ± 22.3 min/d, respectively. The bimodal PDF combinations were fitted to the log(10)-transformed interval lengths between BV events for each animal, using R mixdist package (2.13). The Akaike Information Criterion (AIC) was used to assess goodness of fit of the 25 bimodal PDF combinations. The PDF model with the least AIC value was selected as the best fit for each individual. A χ(2) analysis of the selected best PDF distribution across individuals revealed that 78.2% of the heifers best fit were G-W or W-W PDF models. The likelihood probability estimates were calculated from the average AIC deviation of each model from the standard G-G model. The G-W likelihood probability estimate was greater (P = 0.001) than the W-W combination (0.997 vs. 0.727). Our analysis indicated the G-W model had a statistically better fit and is most likely the best approach to define meal criterion in beef heifers fed high-grain diets.