Renin-Angiotensin-Aldosterone System, Glucose Metabolism and Incident Type 2 Diabetes Mellitus: MESA.

Background Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross-sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance ( IR ), β-cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Methods and Results Homeostatic model assessment of IR ( HOMA 2- IR ) and HOMA 2-β were used to estimate IR and β-cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti-diabetic medication use at follow-up. Linear regression was used to examine cross-sectional associations of aldosterone with fasting plasma glucose, HOMA 2- IR and HOMA 2-β; Cox regression was used to estimate hazard ratios ( HR ) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non-Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log-aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA 2- IR and 6% higher HOMA 2-β ( P<0.01). A 1- SD increase in log-aldosterone was associated with a 44% higher risk of incident diabetes mellitus ( P<0.01) with the greatest increase of 142% ( P<0.01) observed in Chinese Americans ( P for interaction=0.09 versus other ethnicities). Similar cross-sectional findings for log-plasma renin activity existed, but log-plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Conclusions Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation

Medial Femoral Condyle Vascularized Bone Graft for Treatment of Midshaft Clavicle Recalcitrant Nonunion With Use of the Transverse Cervical Artery as an Anastomosis.

Vascularized medial femoral condyle bone grafts have been reported to be a reliable treatment for recalcitrant bony nonunions of the extremities. Although clavicle fracture nonunions are rare after treatment with open reduction internal fixation, symptomatic nonunions can be a challenge. The medial femoral condyle vascularized bone graft has been described as a treatment option for clavicle nonunions with the thoracoacromial trunk as the recipient anastomosis site. This case illustrates how the transverse cervical artery and accompanying veins can be used as an anastomosis when the thoracoacromial trunk is inaccessible because of previous surgical- and infection-related scaring. At the final follow-up, the patient had returned to full duty and resumed competitive triathlons. Radiographs demonstrated complete healing of clavicle fracture

Transcriptional profiling of C57 and DBA strains of mice in the absence and presence of morphine

BACKGROUND: The mouse C57BL/6 (C57) and DBA/2J (DBA) inbred strains differ substantially in many aspects of their response to drugs of abuse. The development of microarray analyses represents a genome-wide method for measuring differences across strains, focusing on expression differences. In the current study, we carried out microarray analysis in C57 and DBA mice in the nucleus accumbens of drug-naïve and morphine-treated animals. RESULTS: We identified mRNAs with altered expression between the two strains. We validated the mRNA expression changes of several such mRNAs, including Gnb1, which has been observed to be regulated by several drugs of abuse. In addition, we validated alterations in the enzyme activity of one mRNA product, catechol-O-methyltransferase (Comt). Data mining of expression and behavioral data indicates that both Gnb1 and Comt expression correlate with aspects of drug response in C57/DBA recombinant inbred strains. Pathway analysis was carried out to identify pathways showing significant alterations as a result of treatment and/or due to strain differences. These analyses identified axon guidance genes, particularly the semaphorins, as showing altered expression in the presence of morphine, and plasticity genes as showing altered expression across strains. Pathway analysis of genes showing strain by treatment interaction suggest that the phosphatidylinositol signaling pathway may represent an important difference between the strains as related to morphine exposure. CONCLUSION: mRNAs with differing expression between the two strains could potentially contribute to strain-specific responses to drugs of abuse. One such mRNA is Comt and we hypothesize that altered expression of Comt may represent a potential mechanism for regulating the effect of, and response to, multiple substances of abuse. Similarly, a role for Gnb1 in responses to multiple drugs of abuse is supported by expression data from our study and from other studies. Finally, the data support a role for semaphorin signaling in morphine effects, and indicate that altered expression of genes involved in phosphatidylinositol signaling and plasticity might also affect the altered drug responses in the two strains

The association of ideal cardiovascular health with incident type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis

Levels of ideal cardiovascular health (ICH) and incident type 2 diabetes mellitus have not been examined in a multiethnic population. We assessed the total and race/ethnicity-specific incidence of diabetes based on American Heart Association (AHA) ICH components

Searching for C ii Emission from the First Sample of z ∼ 6 O i Absorption-associated Galaxies with the Atacama Large Millimeter/submillimeter Array

We report the first statistical analyses of [C ii ] and dust continuum observations in six strong O i absorber fields at the end of the reionization epoch obtained by the Atacama Large Millimeter/submillimeter Array (ALMA). Combined with one [C ii ] emitter reported in Wu et al., we detect one O i -associated [C ii ] emitter in six fields. At redshifts of O i absorbers in nondetection fields, no emitters are brighter than our detection limit within impact parameters of 50 kpc and velocity offsets between ±200 km s ^−1 . The averaged [C ii ]-detection upper limit is 50 kpc) and having larger outflow velocities within ±600 km s ^−1 . If these detections are confirmed in the future, then the mechanism of pushing metals at larger distances with higher velocities needs to be further explored from the theoretical side

Planck-Scale Unification and Dynamical Symmetry Breaking

We explore the possibility of unification of gauge couplings near the Planck scale in models of extended technicolor. We observe that models of the form G X SU(3)_c X SU(2)_L X U(1)_Y cannot be realized, due to the presence of massless neutral Goldstone bosons (axions) and light charged pseudo-Goldstone bosons; thus, unification of the known forces near the Planck scale cannot be achieved. The next simplest possibility, G X SU(4)_{PS} X SU(2)_L X U(1)_{T_{3R}}, cannot lead to unification of the Pati-Salam and weak gauge groups near the Planck scale. However, superstring theory provides relations between couplings at the Planck scale without the need for an underlying grand-unified gauge group, which allows unification of the SU(4)$_{PS}$ and SU(2)$_L$ couplings.Comment: LaTeX, 12 pages, FERMILAB-PUB-93/262-

Message framing to inform cancer prevention pricing interventions in the UK and USA: a factorial experiment, 2019

Objectives: To advance understanding of how message framing can be used to maximise public support across different pricing policies for alcohol, tobacco and sugary drinks/foods that prevent consumption of cancer-causing products. Design: We designed a 3×4×3 randomised factorial experiment to test responses to messages with three pricing policies, four message frames and three products. Setting: Online survey panel (Qualtrics) in 2019. Participants: Adults (N=1850) from the UK and USA. Interventions: Participants randomly viewed one of 36 separate messages that varied by pricing policy (increasing taxes, getting rid of price discounts, getting rid of low-cost products), four frames and product (alcohol, tobacco, sugary drinks/foods). Primary and secondary outcome measures: We assessed the relationship between the message characteristics and four dependent variables. Three were related to policy support: (1) increasing taxes on the product mentioned in the message, (2) getting rid of price discounts and special offers on the product mentioned in the message and (3) getting rid of low-cost versions of the product mentioned in the message. One was related to reactance, a psychological response to having one’s freedom limited. Results: We found no effect for pricing policy in the message. Frames regarding children and reducing cancer risk moderated some outcomes, showing promise for real-world use. We found differences in support by product and reactance with greatest support and least reactance for tobacco policies, less support and more reactance for alcohol policies, and the least support and most reactance for sugary drinks/foods policies. Conclusions: Cancer prevention efforts using policy interventions can be informed by the message framing literature. Our results offer insights for cancer prevention advocacy efforts across the UK and USA and highlight that tax versus non-tax approaches to increasing the cost of cancer-causing products result in similar responses from consumers

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Consumer Bankruptcy Update

Materials from the Consumer Bankruptcy Update presentations held by UK/CLE in December 2000