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Mirmalek-Sani SH, Orlando G, McQuilling JP, Pareta R, Mack DL, Salvatori M, Farney AC, Stratta RJ, Atala A, Opara EC, Soker S.
Biomaterials. 2013 Jul ;34(22):5488-95.
PMID: 23583038
Emergent technologies of regenerative medicine have the potential to overcome the limitations of organ transplantation by supplying tissues and organs bioengineered in the laboratory. Pancreas bioengineering requires a scaffold that approximates the biochemical, spatial and vascular relationships of the native extracellular matrix (ECM). We describe the generation of a whole organ, three-dimensional pancreas scaffold using acellular porcine pancreas. Imaging studies confirm that our protocol effectively removes cellular material while preserving ECM proteins and the native vascular tree. The scaffold was seeded with human stem cells and porcine pancreatic islets, demonstrating that the decellularized pancreas can support cellular adhesion and maintenance of cell functions. These findings advance the field of regenerative medicine towards the development of a fully functional, bioengineered pancreas capable of establishing and sustaining euglycemia and may be used for transplantation to cure diabetes mellitus.
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Sun X, Kang Y, Bao J, Zhang Y, Yang Y, Zhou X.
Biomaterials. 2013 Jul ;34(21):4971-81.
PMID: 23566802
Osteogenetic microenvironment is a complex constitution in which extracellular matrix (ECM) molecules, stem cells and growth factors each interact to direct the coordinate regulation of bone tissue development. Importantly, angiogenesis improvement and revascularization are critical for osteogenesis during bone tissue regeneration processes. In this study, we developed a three-dimensional (3D) multi-scale system model to study cell response to growth factors released from a 3D biodegradable porous calcium phosphate (CaP) scaffold. Our model reconstructed the 3D bone regeneration system and examined the effects of pore size and porosity on bone formation and angiogenesis. The results suggested that scaffold porosity played a more dominant role in affecting bone formation and angiogenesis compared with pore size, while the pore size could be controlled to tailor the growth factor release rate and release fraction. Furthermore, a combination of gradient VEGF with BMP2 and Wnt released from the multi-layer scaffold promoted angiogenesis and bone formation more readily than single growth factors. These results demonstrated that the developed model can be potentially applied to predict vascularized bone regeneration with specific scaffold and growth factors.
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Kokkonen EW, Davis SA, Lin HC, Dabade TS, Feldman SR, Fleischer AB.
J Am Med Inform Assoc. 2013 Jun 1;20(e1):e33-e38.
PMID: 23538721
OBJECTIVE: To assess differences in the use of electronic medical records (EMRs) among medical specialties and practice settings. METHODS: A cross-sectional retrospective study using nationally representative data from the National Ambulatory Medical Care Survey for the period 2003-2010 was performed. Bivariate and multivariate analyzes compared EMR use among physicians of 14 specialties and assessed variation by practice setting. Differences in EMR use by geographic region, patient characteristics, and physician office settings were also assessed. RESULTS: Bivariate and multivariate analysis demonstrated increased EMR use from 2003 to 2010, with 16% reporting at least partial use in 2003, rising to 52% in 2010 (p<0.001). Cardiologists, orthopedic surgeons, urologists, and family/general practitioners had higher frequencies of EMR use whereas psychiatrists, ophthalmologists, and dermatologists had the lowest EMR use. Employed physicians had higher EMR uptake than physicians who owned their practice (48% vs 31%, p<0.001). EMR uptake was lower among solo practitioners (23%) than non-solo practitioners (42%, p<0.001). Practices owned by Health Maintenance Organizations had higher frequencies of EMR use (83%) than practices owned by physicians, community health centers, or academic centers (all <45%, p<0.001). Patient demographics did not affect EMR use (p>0.05). CONCLUSIONS: Uptake of EMR is increasing, although it is significantly slower in dermatology, ophthalmology, and psychiatry. Solo practitioners and owners of a practice have low frequencies of EMR use compared with non-solo practitioners and those who do not own their practice. Despite incentives for EMR adoption, physicians should carefully weigh which, if any, EMR to adopt in their practices.
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Bura KS, Lord C, Marshall S, McDaniel A, Thomas G, Warrier M, Zhang J, Davis MA, Sawyer JK, Shah R, Wilson MD, Dikkers A, Tietge UJ, Collet X, Rudel LL, Temel RE, Brown JM.
J Lipid Res. 2013 Jun ;54(6):1567-77.
PMID: 23564696
Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the nonbiliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.
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Chen R, Daining CP, Sun H, Fraser R, Stokes SL, Leitges M, Gnegy ME.
J Neurochem. 2013 Jun ;125(5):663-672.
PMID: 23458603
The strength and duration of extracellular dopamine concentrations are regulated by the presynaptic dopamine transporter (DAT) and dopamine D2 autoreceptors (D2autoRs). There is a functional interaction between these two proteins. Activation of D2autoRs increases DAT trafficking to the surface whereas disruption of this interaction compromises activities of both proteins and alters dopaminergic transmission. Previously we reported that DAT expression and activity are subject to modulation by protein kinase Cβ (PKCβ). Here, we further demonstrate that PKCβ is integral for the interaction between DAT and D2autoR. Inhibition or absence of PKCβ abolished the communication between DAT and D2autoR. In mouse striatal synaptosomes and transfected N2A cells, the D2autoR-stimulated membrane insertion of DAT was abolished by PKCβ inhibition. Moreover, D2autoR-stimulated DAT trafficking is mediated by a PKCβ-extracellular signal-regulated kinase signaling cascade where PKCβ is upstream of extracellular signal-regulated kinase. The increased surface DAT expression upon D2autoR activation resulted from enhanced DAT recycling as opposed to reduced internalization. Further, PKCβ promoted accelerated DAT recycling. Our study demonstrates that PKCβ critically regulates D2autoR-activated DAT trafficking and dopaminergic signaling. PKCβ is a potential drug target for correcting abnormal extracellular dopamine levels in diseases such as drug addiction and schizophrenia.
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Czoty PW, Martelle SE, Gould RW, Nader MA.
J Pharmacol Exp Ther. 2013 Jun ;345(3):374-82.
PMID: 23579044
It has been hypothesized that drugs that serve as substrates for dopamine (DA) and norepinephrine (NE) transporters may be more suitable medications for cocaine dependence than drugs that inhibit DA and NE uptake by binding to transporters. Previous studies have shown that the DA/NE releaser d-amphetamine can decrease cocaine self-administration in preclinical and clinical studies. The present study examined the effects of methylphenidate (MPD), a DA uptake inhibitor, for its ability to decrease cocaine self-administration under conditions designed to reflect clinically relevant regimens of cocaine exposure and pharmacotherapy. Each morning, rhesus monkeys pressed a lever to receive food pellets under a fixed-ratio 50 schedule of reinforcement; cocaine was self-administered under a progressive-ratio schedule of reinforcement in the evening. After cocaine (0.003-0.56 mg/kg per injection, i.v.) dose-response curves were determined, self-administration sessions were suspended and MPD (0.003-0.0056 mg/kg per hour, i.v.; or 1.0-9.0 mg/kg p.o., b.i.d.) was administered for several weeks. A cocaine self-administration session was conducted every 7 days. When a MPD dose was reached that either persistently decreased cocaine self-administration or produced disruptive effects, the cocaine dose-effect curve was re-determined. In most cases, MPD treatment either produced behaviorally disruptive effects or increased cocaine self-administration; it took several weeks for these effects to dissipate. These data are consistent with the largely negative results of clinical trials with MPD. In contrast to the positive effects with the monoamine releaser d-amphetamine under identical conditions, these results do not support use of monoamine uptake inhibitors like MPD as a medication for cocaine dependence.
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Yamaleyeva LM, Neves LA, Coveleskie K, Diz DI, Gallagher PE, Brosnihan KB.
Placenta. 2013 Jun ;34(6):497-502.
PMID: 23602334
We investigated the expression of angiotensin receptors in early pregnancy and established whether normal pregnancy or preeclampsia alters the expression and distribution of the uteroplacental AT1R, AT2R and mas/AT1-7R at late gestation.
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Bellavia L, Dumond JF, Perlegas A, Bruce King S, Kim-Shapiro DB.
Nitric Oxide. 2013 May 31;31():38-47.
PMID: 23545404
Angeli's salt (Na2N2O3) decomposes into nitroxyl (HNO) and nitrite (NO2(-)), compounds of physiological and therapeutic interest for their impact on biological signaling both through nitric oxide and nitric oxide independent pathways. Both nitrite and HNO oxidize oxygenated hemoglobin to methemoglobin. Earlier work has shown that HNO catalyzes the reduction of nitrite by deoxygenated hemoglobin. In this work, we have shown that HNO accelerates the oxidation of oxygenated hemoglobin by NO2(-). We have demonstrated this HNO mediated acceleration of the nitrite/oxygenated hemoglobin reaction with oxygenated hemoglobin being in excess to HNO and nitrite (as would be found under physiological conditions) by monitoring the formation of methemoglobin in the presence of Angeli's salt with and without added NO2(-). In addition, this acceleration has been demonstrated using the HNO donor 4-nitrosotetrahydro-2H-pyran-4-yl pivalate, a water-soluble acyloxy nitroso compound that does not release NO2(-) but generates HNO in the presence of esterase. This HNO donor was used both with and without NO2(-) and acceleration of the NO2(-) induced formation of methemoglobin was observed. We found that the acceleration was not substantially affected by catalase, superoxide dismutase, c-PTIO, or IHP, suggesting that it is not due to formation of extramolecular peroxide, NO2 or H2O2, or to modulation of allosteric properties. In addition, we found that the acceleration is not likely to be related to HNO binding to free reduced hemoglobin, as we found HNO binding to reduced hemoglobin to be much weaker than has previously been proposed. We suggest that the mechanism of the acceleration involves local propagation of autocatalysis in the nitrite-oxygenated Hb reaction. This acceleration of the nitrite oxyhemoglobin reaction could affect studies aimed at understanding physiological roles of HNO and perhaps nitrite and use of these agents in therapeutics such as hemolytic anemias, heart failure, and ischemia reperfusion injury.
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Del Gaizo A, Silva AC, Lam-Himlin DM, Allen BC, Leyendecker J, Kawashima A.
Insights Imaging. 2013 May 19. [Epub ahead of print]
PMID: 23686749
Solid urethral and peri-urethral lesions are rare and encompass benign and malignant aetiologies. A diagnosis without imaging is often challenging secondary to non-specific clinical symptoms and overlapping findings at the time of physical examination. Magnetic resonance (MR) imaging may be helpful in confirming a diagnosis while providing anatomical detail and delineating disease extent. This article reviews the normal MR anatomy of the male and female urethra, the MR appearance of solid primary and secondary urethral lesions, and the MR appearance of solid urethral lesion mimics. Teaching points • MRI is an important imaging technique in the evaluation of the spectrum of solid urethral lesions.• With excellent soft tissue resolution, MR is accurate in staging primary urethral carcinoma.• Disruption of the zonal anatomy of the female urethral wall indicates peri-urethral extension.• Be aware of benign urethral lesions, particularly those that may mimic solid urethral masses.
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Rejeski WJ, Marsh AP, Anton S, Chen SH, Church T, Gill TM, Guralnik JM, Glynn NW, King AC, Rushing J, Ip EH.
J Gerontol A Biol Sci Med Sci. 2013 May 17. [Epub ahead of print]
PMID: 23685766
BACKGROUND: The measurement of mobility is essential to both aging research and clinical practice. A newly developed self-report measure of mobility, the mobility assessment tool-short form (MAT-sf), uses video animations to improve measurement accuracy/precision. Using a large baseline data set, we recalibrated the items, evaluated the extent to which older patients' self-efficacy (i.e., confidence) for walking was related to MAT-sf scores beyond their actual 400-m walk time, and assessed the relationship of the MAT-sf with body mass index and other clinical variables. METHODS: The analyses employed baseline data from the Lifestyle Interventions and Independence for Elders Study. RESULTS: Item recalibration demonstrated that the MAT-sf scoring algorithm was robust. In an analysis with 400-m walk time and self-efficacy regressed on the MAT-sf, both variables shared unique variance with the MAT-sf (p < .001). The MAT-sf was inversely related to several comorbidities, most notably hypertension and arthritis (p < .001), and scores were lowest when body mass index ≥ 35kg/m(2). Finally, MAT-sf scores were directly related to Short Physical Performance Battery scores, inversely related to difficulty with activities of daily living (p < .001) and higher for men than for women (p < .001). CONCLUSIONS: The findings extend the validity and clinical utility of this innovative tool for assessing self-reported mobility in older adults. Longitudinal data on the MAT-sf from the Lifestyle Interventions and Independence for Elders Study will enable us to evaluate the relative contributions of self-report and performance-based measures of mobility on important health outcomes.
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Shah SA, Kambur T, Chan C, Herrington DM, Liu K, Shah SJ.
Am J Cardiol. 2013 May 16. [Epub ahead of print]
PMID: 23683953
Whether autonomic dysfunction predates the development of symptomatic heart failure (HF) or is simply a consequence of severe HF is unknown. We hypothesized that reduced heart rate variability (a marker of abnormal autonomic function) at baseline is associated with incident HF in subjects free of clinically recognized cardiovascular disease. In the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based study of subclinical cardiovascular disease in adults aged 45 to 84 years, we measured the heart rate variability using a standard 30-second, 12-lead electrocardiogram to measure the standard deviation of normal-to-normal intervals (SDNN) and the root mean square of successive differences in RR intervals (RMSSD). During a median follow-up of 7.6 years, 95 participants developed HF (incidence rate 2.7/1,000 person-years). After adjusting for age, gender, and ethnicity, the hazard ratio for incident HF stratified by the RMSSD tertile was 2.4 (95% confidence interval 1.4 to 4.2) for the lowest tertile and 1.7 (95% confidence interval 1.0 to 3.2) for the middle tertile (highest tertile was the referent group; p for trend <0.001). The inverse association between the RMSSD and incident HF persisted after adjustment for additional covariates, including diabetes, systolic blood pressure, heart rate, subclinical atherosclerosis, left ventricular end-systolic volume, interim myocardial infarction, and high-sensitivity C-reactive protein (p for trend = 0.009). A similarly significant inverse association was also observed for SDNN. In conclusion, baseline autonomic dysfunction was a risk factor for the development of HF in a multiethnic cohort. These population-based findings implicate autonomic dysfunction in the pathogenesis of HF, and decreased short-term heart rate variability might be a novel form of stage B (asymptomatic) HF.
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Palmer NR, Geiger AM, Felder TM, Lu L, Case LD, Weaver KE.
Am J Public Health. 2013 May 16. [Epub ahead of print]
PMID: 23678936
Objectives. We examined racial/ethnic disparities in health care receipt among a nationally representative sample of male cancer survivors. Methods. We identified men aged 18 years and older from the 2006-2010 National Health Interview Survey who reported a history of cancer. We assessed health care receipt in 4 self-reported measures: primary care visit, specialist visit, flu vaccination, and pneumococcal vaccination. We used hierarchical logistic regression modeling, stratified by age (< 65 years vs ≥ 65 years). Results. In adjusted models, older African American and Hispanic survivors were approximately twice as likely as were non-Hispanic Whites to not see a specialist (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.19, 2.68 and OR = 2.09; 95% CI = 1.18, 3.70, respectively), not receive the flu vaccine (OR = 2.21; 95% CI = 1.45, 3.37 and OR = 2.20; 95% CI = 1.21, 4.01, respectively), and not receive the pneumococcal vaccine (OR = 2.24; 95% CI = 1.54, 3.24 and OR = 3.10; 95% CI = 1.75, 5.51, respectively). Conclusions. Racial/ethnic disparities in health care receipt are evident among older, but not younger, cancer survivors, despite access to Medicare. These survivors may be less likely to see specialists, including oncologists, and receive basic preventive care. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e8. doi:10.2105/AJPH.2012.301096).
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Weaver KE, Palmer N, Lu L, Case LD, Geiger AM.
Cancer Causes Control. 2013 May 16. [Epub ahead of print]
PMID: 23677333
PURPOSE: Rural US adults have increased risk of poor outcomes after cancer, including increased cancer mortality. Rural-urban differences in health behaviors have been identified in the general population and may contribute to cancer health disparities, but have not yet been examined among US survivors. We examined rural-urban differences in health behaviors among cancer survivors and associations with self-reported health and health-related unemployment. METHODS: We identified rural (n = 1,642) and urban (n = 6,162) survivors from the cross-sectional National Health Interview Survey (2006-2010) and calculated the prevalence of smoking, physical activity, overweight/obesity, and alcohol consumption. Multivariable models were used to examine the associations of fair/poor health and health-related unemployment with health behaviors and rural-urban residence. RESULTS: The prevalence of fair/poor health (rural 36.7 %, urban 26.6 %), health-related unemployment (rural 18.5 %, urban 10.6 %), smoking (rural 25.3 %, urban 15.8 %), and physical inactivity (rural 50.7 %, urban 38.7 %) was significantly higher in rural survivors (all p < .05); alcohol consumption was lower (rural 46.3 %, urban 58.6 %), and there were no significant differences in overweight/obesity (rural 65.4 %, urban 62.6 %). All health behaviors were significantly associated with fair/poor health and health-related unemployment in both univariate and multivariable models. After adjustment for behaviors, rural survivors remained more likely than urban survivors to report fair/poor health (OR = 1.21, 95 % CI 1.03-1.43) and health-related unemployment (OR = 1.49, 95 % CI 1.18-1.88). CONCLUSIONS: Rural survivors may need tailored, accessible health promotion interventions to address health-compromising behaviors and improve outcomes after cancer.
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Andersson KE.
Curr Urol Rep. 2013 May 16. [Epub ahead of print]
PMID: 23677692
The new information generated over the last decade on the physiology/pharmacology of the normal bladder and on the pathophysiology of the overactive bladder has resulted in the introduction of a new therapeutic principle, β3-adrenoceptor (AR) agonism, and the approval of mirabegron, a selective agonist at β3-ARs. It may be asked in what respects the β3-AR agonists as a group, and mirabegron in particular, differ from the antimuscarinics, and what can clinically be gained by the β3-AR agonists. In this short review, the mechanisms of action, clinical efficacy, and adverse effect profiles of the two groups of drugs are compared and discussed.
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Cartwright MS, Walker FO.
Muscle Nerve. 2013 May 16. [Epub ahead of print]
PMID: 23681885
Neuromuscular ultrasound involves the use of high-resolution ultrasound to image the peripheral nervous system of patients with suspected neuromuscular diseases. It complements electrodiagnostic studies well by providing anatomic information regarding nerves, muscles, vessels, tendons, ligaments, bones, and other structures that cannot be obtained with nerve conduction studies and electromyography. Neuromuscular ultrasound has been studied closely over the past 10 years and has been used most often in the assessment of entrapment neuropathies. This review focuses on the use of neuromuscular ultrasound in 4 of the most common entrapment neuropathies: carpal tunnel syndrome, ulnar neuropathy at the elbow and wrist, and fibular neuropathy at the knee. © 2013 Wiley Periodicals, Inc.
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Gustafson CJ, Feldman SR, Quandt SA, Isom S, Chen H, Spears CR, Arcury TA.
Int J Dermatol. 2013 May 15. [Epub ahead of print]
PMID: 23675774
BACKGROUND: Skin conditions are common among Latino migrant farm workers. Although many skin conditions are related to occupational exposures, poor housing conditions may also contribute to skin ailments in migrant farm workers. OBJECTIVES: To evaluate the association between housing conditions and skin conditions among Latino migrant farm workers. MATERIALS AND METHODS: A cross-sectional study design using interview questionnaires, home inspections, and environmental sampling was implemented to document housing quality of farm worker camps/homes and the prevalence of self-reported skin conditions in Latino migrant farm workers. Interviews were completed with 371 farm workers residing in 186 of the 226 camps (camp response rate 82.3%). RESULTS: Self-reported pruritus (31%), rash (25%), scaling (12%), blisters (11%), and ingrown nails (10%) were common among the participants. Pruritus was more likely to be reported by farm workers living in dwellings without air-conditioning (P < 0.05). Rash was associated with dwellings reported to have a low humidity (P < 0.05). Scaling was more likely to be reported by farm workers living in dwellings with indoor temperatures in the thermal discomfort range (P < 0.05). No statistically significant associations were detected for indoor allergens and self-reported skin ailments among migrant farm workers. CONCLUSIONS: Skin conditions are common among migrant farm workers in North Carolina. The quality of housing conditions, particularly hot, dry indoor thermal environment, demonstrated significant associations with pruritus, rash, and scaling. The impact of housing characteristics on pruritus and blisters was greatest in new migrant farm workers. Further research is needed to delineate additional housing factors that could cause or exacerbate skin diseases in farm workers.
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Amoah S, Holbrook BC, Yammani RD, Alexander-Miller MA.
J Immunol. 2013 May 15;190(10):5020-9.
PMID: 23589620
Generating and maintaining a robust CD8(+) T cell response in the face of high viral burden is vital for host survival. Further, balancing the differentiation of effectors along the memory precursor effector cell pathway versus the short-lived effector cell (SLEC) pathway may be critical in controlling the outcome of virus infection with regard to clearance and establishing protection. Although recent studies have identified several factors that have the capacity to regulate effector CD8(+) T cell differentiation-for example, inflammatory cytokines-we are far from a complete understanding of how cells choose the memory precursor effector cell versus SLEC fate following infection. In this study, we have modulated the infectious dose of the poxvirus vaccinia virus as an approach to modulate the environment present during activation and expansion of virus-specific effector cells. Surprisingly, in the face of a high virus burden, the number of SLECs was decreased. This decrease was the result of increased natural regulatory T cells (Tregs) generated by high viral burden, as depletion of these cells restored SLECs. Our data suggest Treg modulation of differentiation occurs via competition for IL-2 during the late expansion period, as opposed to the time of T cell priming. These findings support a novel model wherein modulation of the Treg response as a result of high viral burden regulates late-stage SLEC number.
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Divers J, Núñez M, High KP, Murea M, Rocco MV, Ma L, Bowden DW, Hicks PJ, Spainhour M, Ornelles DA, Kleiboeker SB, Duncan K, Langefeld CD, Turner J, Freedman BI.
Kidney Int. 2013 May 15. [Epub ahead of print]
PMID: 23677244
Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.Kidney International advance online publication, 15 May 2013; doi:10.1038/ki.2013.173.
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Sukumar P, Maloney G, Muday GK.
Plant Physiol. 2013 May 15. [Epub ahead of print]
PMID: 23677937
Adventitious roots emerge from aerial plant tissues and the induction of these roots is essential for clonal propagation of agriculturally important plant species. This process has received extensive study in horticultural species, but much less focus in genetically tractable model species. We have explored the role of auxin transport in this process in Arabidopsis thaliana seedlings in which adventitious root initiation was induced by excising roots from low light grown hypocotyls. Inhibition of auxin transport from the shoot apex abolishes adventitious root formation under these conditions. Root excision was accompanied by a rapid increase in radioactive IAA transport and its accumulation in the hypocotyl above the point of excision where adventitious roots emerge. Local increases in auxin-responsive gene expression were also observed above the site of excision, using auxin responsive reporters, pIAA2:GUS, pGH3:GUS, and pDR5:GUS. These changes in auxin accumulation preceded cell division events, monitored by pCYCB1:GUS, and adventitious root initiation. We examined excision-induced adventitious root formation in auxin influx and efflux mutants, including aux1, pin1, pin2, pin3, and pin7, with the most profound reductions observed in abcb19. An ABCB19 overexpression line forms more adventitious roots than wild-type in intact seedlings. Examination of transcriptional and translational fusions between ABCB19 and GFP indicates that excision locally induced the accumulation of ABCB19 transcript and protein that is temporally and spatially linked to local IAA accumulation leading to adventitious root formation. These experiments are consistent with localized synthesis of ABCB19 protein leading to enhanced IAA transport and local IAA accumulation driving adventitious root formation.
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O'Neal WT, Efird JT, Anderson CA, Kindell LC, O'Neal JB, Bruce Ferguson T, Randolph Chitwood W, Kypson AP.
Heart Lung Circ. 2013 May 14. [Epub ahead of print]
PMID: 23683716
BACKGROUND: Previous studies examining the influence of prior percutaneous coronary intervention (PCI) on long-term survival after coronary artery bypass grafting (CABG) have reported conflicting results. The purpose of this study was to further examine the influence of prior PCI on long-term survival after CABG at a large tertiary referral heart institute. METHODS: Long-term survival between 1992 and 2011 was compared in non-emergent CABG cases with and without prior PCI. Hazard ratios (HR) and 95% confidence intervals (CI) were computed using a Cox regression model. RESULTS: A total of 2532 (19%) patients had prior PCI before CABG (n=13,354). The median follow-up for study participants was 8.1 years. The median survival for patients with and without prior PCI was 15 years and 14 years, respectively (p<0.0001). Long-term survival was similar between patients with and without prior PCI after adjusting for age, sex, race, hypertension, coronary artery disease severity, congestive heart failure, and prior stroke (adjusted HR=0.99, 95%CI=0.91-1.06). CONCLUSION: Findings from outcomes research are important in the planning of appropriate postoperative patient care. Our study provides additional evidence that prior PCI is not a significant predictor of long-term survival after CABG.
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