Intervention to promote adolescents' communication and engagement in diabetes clinic encounters: A pilot randomized controlled trial.

AIM: To conduct a pilot randomized trial of an intervention to improve adolescent question-asking and provider education during paediatric diabetes visits. METHODS: Adolescents aged 11 to 17 with type 1 diabetes and their parents were enrolled from two urban tertiary paediatric clinics. Adolescents were randomised to the intervention group or control group. Adolescent consultations were audio-recorded, their HbA1c level was recorded, and they completed surveys after three clinic appointments. The intervention group completed a question prompt list and watched a video on a tablet with their parents before meeting their doctor and completed a short evaluation after each visit. RESULTS: Six consultant endocrinologists and ninety-nine adolescents and their parents participated. The intervention increased adolescents' question asking and provider education in diabetes encounters. Total patient question-asking across the 3 consultations and a higher baseline HbA1c at time one was significantly associated with HbA1c at time three. CONCLUSIONS: Question prompt lists and an educational video are useful tools to increase adolescents' question-asking and communication between adolescents and their providers. PRACTICE IMPLICATIONS: Interventions that encourage adolescents' question-asking in healthcare encounters may lead to more meaningful providers-adolescents' communication and tailored education. Interventions to improve professionals' listening, communication and educational skills are also required.

Reduced expression of glucocorticoid-inducible genes GILZ and SGK-1: high IL-6 levels are associated with reduced hippocampal volumes in major depressive disorder.

Neuroplasticity may have a core role in the pathophysiology of major depressive disorder (MDD), a concept supported by experimental studies that found that excessive cortisol secretion and/or excessive production of inflammatory cytokines impairs neuronal plasticity and neurogenesis in the hippocampus. The objective of this study was to examine how changes in the glucocorticoid and inflammatory systems may affect hippocampal volumes in MDD. A multimodal approach with structural neuroimaging of hippocampus and amygdala, measurement of peripheral inflammatory proteins interleukin (IL)-6 and C-reactive protein (CRP), glucocorticoid receptor (GR) mRNA expression, and expression of glucocorticoid-inducible genes (glucocorticoid-inducible genes Leucin Zipper (GILZ) and glucocorticoid-inducible kinase-1 (SGK-1)) was used in 40 patients with MDD and 43 healthy controls (HC). Patients with MDD showed smaller hippocampal volumes and increased inflammatory proteins IL-6 and CRP compared with HC. Childhood maltreatment was associated with increased CRP. Patients with MDD, who had less expression of the glucocorticoid-inducible genes GILZ or SGK-1 had smaller hippocampal volumes. Regression analysis showed a strong positive effect of GILZ and SGK-1 mRNA expression, and further inverse effects of IL-6 concentration, on hippocampal volumes. These findings suggest that childhood maltreatment, peripheral inflammatory and glucocorticoid markers and hippocampal volume are interrelated factors in the pathophysiology of MDD. Glucocorticoid-inducible genes GILZ and SGK-1 might be promising candidate markers for hippocampal volume changes relevant for diseases like MDD. Further studies need to explore the possible clinical usefulness of such a blood biomarker, for example, for diagnosis or prediction of therapy response.

The discovery of indoxacarb: oxadiazines as a new class of pyrazoline-type insecticides.

The evolution of the insecticidal pyrazoline moiety that was originally discovered in 1972 has led to the discovery of a new crop insecticide, indoxacarb, which is the first commercialized pyrazoline-type sodium-channel blocker. Both monocyclic and fused-tricyclic pyrazolines and pyridazines, as well as structurally related semicarbazones were examined prior to the discovery of analogous tricyclic oxadiazines which had similarly high activity as well as favorable environmental dissipation rates and low toxicity to non-target organisms. The eventual leading candidate, DPX-JW062, was originally obtained as a racemic molecule, but a chiral synthesis was developed which produces material that is 50% ee in the insecticidal (+)-S-enantiomer (DPX-MP062, indoxacarb).

Recombination signal sequences restrict chromosomal V(D)J recombination beyond the 12/23 rule.

The genes encoding the variable regions of lymphocyte antigen receptors are assembled from variable (V), diversity (D) and joining (J) gene segments. V(D)J recombination is initiated by the recombinase activating gene (RAG)-1 and -2 proteins, which introduce DNA double-strand breaks between the V, D and J segments and their flanking recombination signal sequences (RSSs). Generally expressed DNA repair proteins then carry out the joining reaction. The conserved heptamer and nonamer sequences of the RSSs are separated by non-conserved spacers of 12 or 23 base pairs (forming 12-RSSs and 23-RSSs). The 12/23 rule, which is mediated at the level of RAG-1/2 recognition and cutting, specifies that V(D)J recombination occurs only between a gene segment flanked by a 12-RSS and one flanked by a 23-RSS. Vbeta segments are appended to DJbeta rearrangements, with little or no direct Vbeta to Jbeta joining, despite 12/23 compatibility of Vbeta 23-RSSs and Jbeta12-RSSs. Here we use embryonic stem cells and mice with a modified T-cell receptor (TCR)beta locus containing only one Dbeta (Dbeta1) gene segment and one Jbeta (Jbeta1) gene cluster to show that the 5' Dbeta1 12-RSS, but not the Jbeta1 12-RSSs, targets rearrangement of a diverse Vbeta repertoire. This targeting is precise and position-independent. This additional restriction on V(D)J recombination has important implications for the regulation of variable region gene assembly and repertoire development.

Mechanisms that direct ordered assembly of T cell receptor beta locus V, D, and J gene segments.

T cell receptor (TCR) beta variable region genes are assembled in progenitor T cells from germ-line Vbeta, Dbeta, and Jbeta segments via an ordered two-step process in which Dbeta to Jbeta rearrangements occur on both alleles before appendage of a Vbeta to a preexisting DJbeta complex. Direct joining of Vbeta segments to nonrearranged Dbeta or Jbeta segments, while compatible with known restrictions on the V(D)J recombination mechanism, are infrequent within the endogenous TCRbeta locus. We have analyzed mechanisms that mediate ordered Vbeta, Dbeta, and Jbeta assembly via an approach in which TCRbeta minilocus recombination substrates were introduced into embryonic stem cells and then analyzed for rearrangement in normal thymocytes by recombinase-activating gene 2-deficient blastocyst complementation. These analyses demonstrated that Vbeta segments are preferentially targeted for rearrangement to Dbeta as opposed to Jbeta segments. In addition, we further demonstrated that Vbeta segments can be appended to nonrearranged endogenous Dbeta segments in which we have eliminated the ability of Dbeta segments to join to Jbeta segments. Our findings are discussed in the context of the mechanisms that regulate the ordered assembly and utilization of V, D, and J segments.

Anomalous origin of the right coronary artery from the left anterior descending coronary artery.

A 77-year-old male presented with a recent posterior myocardial infarction for coronary angiography. This angiogram revealed a rare, previously unreported anomalous origin of the right coronary artery from the proximal left anterior descending coronary artery distal to the first major diagonal branch.

Bilateral functioning Vineberg grafts. A 25-year follow-up.

This report describes a 25-year follow-up of angiographically proven bilateral functioning Vineberg grafts. This represents the longest angiographic follow-up found in the literature. The relevance of these grafts in present-day revascularization procedures is discussed.

Dollars, dilemmas, and the deliverance of care: strategies to promote ethical awareness.

In the face of fiscal restraints, shrinking resources, and a bottom line emphasis, the imperative question is how home care agencies and hospices can promote ethical practice, awareness, and concern. By establishing an ethics committee and encouraging discussions on ethical dilemmas, home care and hospice providers can ensure that dollars do not overshadow care delivery.

Case studies in reconciling ethical differences.

Life-sustaining and end-of-life issues have a significant impact on both hospice and home care providers. Reaching consensus is difficult when families and caregivers hold differing opinions and emotions. Exemplary case consultations can serve as guides to reconciliations that promote mercy, prevent misery, and integrate morality.

Flecainide therapy in patients treated for supraventricular tachycardia with near normal left ventricular function.

Concerns about the safety and efficacy of class IC antiarrhythmic agents have arisen as a result of the recent CAST data. We reviewed records of 175 consecutive patients treated with flecainide between July 1, 1988 and July 5, 1989. One hundred ten patients with normal or mildly impaired left ventricular function and symptomatic supraventricular arrhythmias were identified. Follow-up data were obtained on 102 patients for a mean of 14 months. The average duration of flecainide therapy was 13 months. Tachyarrhythmias treated included atrial fibrillation/flutter, atrioventricular reentry, and atrioventricular nodal reentry. Flecainide provided effective antiarrhythmic therapy in 62% of the patients and was discontinued in 38% of the patients. Left atrial size did not predict treatment failure. Two patients developed proarrhythmic events (nonsustained ventricular tachycardia). There were no deaths during the follow-up period. In conclusion, flecainide provides safe and effective therapy for supraventricular tachyarrhythmias in patients with normal or mildly impaired left ventricular function.

Aneurysmal saphenous vein graft presenting as an anterior mediastinal mass.

A 58-year-old male presented with an anterior mediastinal mass which was found to be secondary to an aneurysmal dilatation of the saphenous vein graft to his circumflex artery. This represents an unusual presentation of an aneurysmally dilated saphenous vein graft.

An evaluation of a short-term chronic effluent toxicity test using sheepshead minnow (Cyprinodon variegatus) larvae.

In response to recent changes in National Pollutant Discharge Elimination System (NPDES) permit regulations, rapid (7-day) static renewal toxicity tests have been developed to detect chronic (sublethal and lethal) effect concentrations of municipal and industrial effluents on freshwater and marine/estuarine organisms. This paper evaluates results from short-term (7-day) chronic effluent tests measuring effects on the growth and survival of the larvae of estuarine sheepshead minnow (Cyprinodon variegatus). Growth was the more sensitive endpoint in 52% of the effluent tests; survival was most sensitive in 7% of the tests. Growth and survival were equally sensitive endpoints in 26% of the tests, while there was no effect on either endpoint at the highest test concentration in 15% of the tests. Four short-term chronic tests were conducted concurrently with early life stage (ELS) tests using a common effluent. Effect concentrations were generally (two of three) within one dilution (a factor of three). Comparison of short-term chronic and ELS tests were also conducted with reference single chemicals and the results were slightly better than the effluent comparisons. A series of ten intralaboratory tests and seven interlaboratory tests were conducted to assess the variability among tests results. Toxicity in these tests varied by no more than one test concentration interval. We concluded that this sheepshead minnow test is suitable to estimate chronic values for complex effluents discharged to marine/estuarine environments within the NPDES permit regulations.