Digital Genome-Wide ncRNA Expression, Including SnoRNAs, across 11 Human Tissues Using PolyA-Neutral Amplification

Non-coding RNAs (ncRNAs) are an essential class of molecular species that have been difficult to monitor on high throughput platforms due to frequent lack of polyadenylation. Using a polyadenylation-neutral amplification protocol and next-generation sequencing, we explore ncRNA expression in eleven human tissues. ncRNAs 7SL, U2, 7SK, and HBII-52 are expressed at levels far exceeding mRNAs. C/D and H/ACA box snoRNAs are associated with rRNA methylation and pseudouridylation, respectively: spleen expresses both, hypothalamus expresses mainly C/D box snoRNAs, and testes show enriched expression of both H/ACA box snoRNAs and RNA telomerase TERC. Within the snoRNA 14q cluster, 14q(I-6) is expressed at much higher levels than other cluster members. More reads align to mitochondrial than nuclear tRNAs. Many lincRNAs are actively transcribed, particularly those overlapping known ncRNAs. Within the Prader-Willi syndrome loci, the snoRNA HBII-85 (group I) cluster is highly expressed in hypothalamus, greater than in other tissues and greater than group II or III. Additionally, within the disease locus we find novel transcription across a 400,000 nt span in ovaries. This genome-wide polyA-neutral expression compendium demonstrates the richness of ncRNA expression, their high expression patterns, their function-specific expression patterns, and is publicly available

Physician Compensation from Salary and Quality of Diabetes Care

OBJECTIVE: To examine the association between physician-reported percent of total compensation from salary and quality of diabetes care. DESIGN: Cross-sectional analysis. PARTICIPANTS: Physicians (n = 1248) and their patients with diabetes mellitus (n = 4200) enrolled in 10 managed care plans. MEASUREMENTS: We examined the associations between physician-reported percent compensation from salary and processes of care including receipt of dilated eye exams and foot exams, advice to take aspirin, influenza immunizations, and assessments of glycemic control, proteinuria, and lipid profile, intermediate outcomes such as adequate control of hemoglobin A1c, lipid levels, and systolic blood pressure levels, and satisfaction with provider communication and perceived difficulty getting needed care. We used hierarchical logistic regression models to adjust for clustering at the health plan and physician levels, as well as for physician and patient covariates. We adjusted for plan as a fixed effect, meaning we estimated variation between physicians using the variance within a particular health plan only, to minimize confounding by other unmeasured health plan variables. RESULTS: In unadjusted analyses, patients of physicians who reported higher percent compensation from salary (>90%) were more likely to receive 5 of 7 diabetes process measures and more intensive lipid management and to have an HbA1c<8.0% than patients of physicians who reported lower percent compensation from salary (<10%). However, these associations did not persist after adjustment. CONCLUSIONS: Our findings suggest that salary, as opposed to fee-for-service compensation, is not independently associated with diabetes processes and intermediate outcomes

Assessing childhood maltreatment and mental health correlates of disordered eating profiles in a nationally representative sample of English females

PURPOSE: Previous research suggests that childhood maltreatment is associated with the onset of eating disorders (ED). In turn, EDs are associated with alternative psychopathologies such as depression and posttraumatic stress disorder (PTSD), and with suicidality. Moreover, it has been reported that various ED profiles may exist. The aim of the current study was to examine the profiles of disordered eating and the associations of these with childhood maltreatment and with mental health psychopathology. METHODS: The current study utilised a representative sample of English females (N = 4206) and assessed for the presence of disordered eating profiles using Latent Class Analysis. Multinomial logistic regression was implemented to examine the associations of childhood sexual and physical abuse with the disordered eating profiles and the associations of these with PTSD, depression and suicidality. RESULTS: Results supported those of previous findings in that we found five latent classes of which three were regarded as disordered eating classes. Significant relationships were found between these and measures of childhood trauma and mental health outcomes. CONCLUSIONS: Childhood sexual and physical abuse increased the likelihood of membership in disordered eating classes and these in turn increased the likelihood of adverse mental health and suicidal outcomes

Consumer Preference for Dinoprostone Vaginal Gel Using Stated Preference Discrete Choice Modelling

Objective: To assess consumer preference for two methods of induction of labour using stated preference discrete choice modelling. The methods of induction were artificial rupture of the membranes (ARM) plus oxytocin and dinoprostone (prostaglandin E2) vaginal gel, followed by oxytocin if necessary. Methods: Consumer preference was measured in terms of willingness to pay for each of the attributes. These attributes were the method of administration, place of care, length of time from induction to delivery, need for epidural anaesthetic, type of delivery and cost. Levels were assigned to each of the attributes. Pregnant women attending a public hospital antenatal clinic were asked to read a description of the two methods and then to choose between them in 18 different scenarios in which the levels of the attributes were varied. Results: Women were willing to pay 11 Australian dollars ($A) for a 1$A55 for every 1 hour reduction in the length of time from induction to delivery. For a 1% reduction in the chance of needing an epidural anaesthetic or Caesarean section, women expressed a willingness to pay of $A20 and$A90, respectively. All estimates were obtained in 1998 and expressed in Australian dollars ($A1 =$US0.63). Conclusion: Women valued the less invasive method of administration of the gel and the associated greater freedom of movement during labour. However, they valued the shorter time from induction to delivery associated with ARM plus oxytocin more highly. A policy which allows women access to the gel for up to two doses would accommodate this consumer preference.Abortifacients, Dinoprostone, Labour-induction, Oxytocin, Pharmacoeconomics, Pregnancy, Willingness-to-pay

Physicians' perspectives on communication and decision making in clinical encounters for treatment of latent tuberculosis infection

The aim of the study was to explore the views of tuberculosis (TB) physicians on treatment of latent TB infection (LTBI), focusing on decision making and communication in clinical practice. 20 Australian TB physicians participated in a semistructured interview in person or over the telephone. Interviews were recorded, transcribed and analysed thematically. The study identified challenges that physicians face when discussing treatment for LTBI with patients. These included difficulties explaining the concept of latency (in particular to patients from culturally and linguistically diverse backgrounds) and providing guidance to patients while still framing treatment decisions as a choice. Tailored estimates of the risk of developing TB and the risk of developing an adverse effect from LTBI treatment were considered the most important information for decision making and discussion with patients. Physicians acknowledged that there is a significant amount of unwarranted treatment variation, which they attributed to the lack of evidence about the risk–benefit balance of LTBI treatment in certain scenarios and guidelines that refer to the need for case-by-case decision making in many instances. In order to successfully implement LTBI treatment at a clinical level, consideration should be given to research on how to best address communication challenges arising in clinical encounters

RAGE and TLRs: relatives, friends or neighbours?

The innate immune system forms the first line of protection against infectious and non-infectious tissue injury. Cells of the innate immune system detect pathogen-associated molecular patterns or endogenous molecules released as a result of tissue injury or inflammation through various innate immune receptors, collectively termed pattern-recognition receptors. Members of the Toll-like receptor (TLR) family of pattern-recognition receptors have well established roles in the host immune response to infection, while the receptor for advanced glycation end products (RAGE) is a pattern-recognition receptor predominantly involved in the recognition of endogenous molecules released in the context of infection, physiological stress or chronic inflammation. RAGE and TLRs share common ligands and signaling pathways, and accumulating evidence points towards their co-operative interaction in the host immune response. At present however, little is known about the mechanisms that result in TLR versus RAGE signalling or RAGE-TLR cross-talk in response to their shared ligands. Here we review what is known in relation to the physicochemical basis of ligand interactions between TLRs and RAGE, focusing on three shared ligands of these receptors: HMGB1, S100A8/A9 and LPS. Our aim is to discuss what is known about differential ligand interactions with RAGE and TLRs and to highlight important areas for further investigation so that we may better understand the role of these receptors and their relationship in host defense

Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

Abstract Background Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.</p