Recent Stanford Publications in PubMedSubscribe to Recent Stanford Publications in PubMed
- Physical Activity versus Cardiorespiratory Fitness: Two (Partly) Distinct Components of Cardiovascular Health?DeFina LF, Haskell WL, Willis BL, Barlow CE, Finley CE, Levine BD, Cooper KHProg Cardiovasc Dis
- Physical Activity and Cardiorespiratory Fitness as Major Markers of Cardiovascular Risk: Their Independent and Interwoven Importance to Health Status.Myers J, McAuley P, Lavie C, Despres JP, Arena R, Kokkinos PProg Cardiovasc Dis
- More than 10 Million Steps in the Right Direction: Results from the First American Heart Association Scientific Sessions Walking Challenge.Harrington RA, Arena R, Després JP, Ciarochi A, Croll E, Bloch KD, Committee for Scientific Sessions Programming and the Global Congress on Physical Activity, American Heart Association Scientific Sessions 2013Prog Cardiovasc Dis
- Nanoelectronic circuits based on two-dimensional atomic layer crystals.Lee S, Zhong ZNanoscale
- Primary Amine Stabilization of a Dicopper(III) Bis(μ-oxo) Species: Modeling the Ligation in pMMO.Citek C, Lin BL, Phelps TE, Wasinger EC, Stack TDJ Am Chem Soc
- Effect of humic acid on the sorption of perfluorooctane sulfonate (PFOS) and perfluorobutane sulfonate (PFBS) on boehmite.Wang F, Shih K, Leckie JOChemosphere
- The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy.Patel MA, Kim JE, Ruzevick J, Li G, Lim MCancers (Basel)
- Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains.Mostafavi S, Ortiz-Lopez A, Bogue MA, Hattori K, Pop C, Koller D, Mathis D, Benoist C, The Immunological Genome Consortium, Blair DA, Dustin ML, Shinton SA, Hardy RR, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LLJ Immunol
- Modeling and Simulation of Viscous Electro-Active Polymers.Vogel F, Göktepe S, Steinmann P, Kuhl EEur J Mech A Solids
- The Living Heart Project: A robust and integrative simulator for human heart function.Baillargeon B, Rebelo N, Fox DD, Taylor RL, Kuhl EEur J Mech A Solids
- A Predominantly Visual Subdivision of The Right Temporo-Parietal Junction (vTPJ).Horiguchi H, Wandell BA, Winawer JCereb Cortex
- p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma.Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM, Wang D, Redmond KP, Shenouda G, Trotti A, Raben D, Gillison ML, Jordan RC, Le QTJ Clin Oncol
- Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states.Overton KW, Spencer SL, Noderer WL, Meyer T, Wang CLProc Natl Acad Sci U S A
- A fluorescence-activated cell sorting-based strategy for rapid isolation of high-lipid Chlamydomonas mutants.Terashima M, Freeman ES, Jinkerson RE, Jonikas MCPlant J
- Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats.Drummond ES, Dawson LF, Finch PM, Li W, Guo TZ, Kingery WS, Drummond PDNeuroscience
- Editorial Comment: ABJS Carl T. Brighton Workshop on Implant Wear and Tribocorrosion of Total Joint Replacements.Goodman SB, Wright TMClin Orthop Relat Res
- A call to arms: new approaches to an old heart failure problem.Abnousi F, Yock P, Heidenreich PJ Card Fail
- Challenges and Priorities for Research: A Report From the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) Working Group on Thrombosis in Pediatric Cardiology and Congenital Heart Disease.McCrindle BW, Li JS, Manlhiot C, Tweddell JS, Giglia TM, Massicotte MP, Monagle P, Krishnamurthy R, Mahaffey KW, Michelson AD, Verdun N, Almond CS, Newburger JW, Brandão LR, Esmon CT, Manco-Johnson MJ, Ichord R, Ortel TL, Chan AK, Portman R, Rose M, Strony J, Kaltman JRCirculation
- Essential is Not Irreplaceable: Fitness Dynamics of Experimental E. coli RNase P RNA Heterologous Replacement.Loveland JL, Rice J, Turrini PC, Lizotte-Waniewski M, Dorit RLJ Mol Evol
- A Caulobacter MreB mutant with irregular cell shape exhibits compensatory widening to maintain a preferred surface area to volume ratio.Harris LK, Dye NA, Theriot JAMol Microbiol
- 44-h ambulatory blood pressure monitoring: revealing the true burden of hypertension in pediatric hemodialysis patients.Haskin O, Wong CJ, McCabe L, Begin B, Sutherland SM, Chaudhuri APediatr Nephrol
- Cell recruitment by amnion chorion grafts promotes neovascularization.Maan ZN, Rennert RC, Koob TJ, Januszyk M, Li WW, Gurtner GCJ Surg Res
- Task-evoked substantia nigra hyperactivity associated with prefrontal hypofunction, prefrontonigral disconnectivity and nigrostriatal connectivity predicting psychosis severity in medication naïve first episode schizophrenia.Yoon JH, Westphal AJ, Minzenberg MJ, Niendam T, Ragland JD, Lesh T, Solomon M, Carter CSSchizophr Res
- Epilepsy: Pregnancy in women with epilepsy-risks and management.Meador KJNat Rev Neurol
- Topical fentanyl stimulates healing of ischemic wounds in diabetic rats.Gupta M, Poonawala T, Farooqui M, Ericson ME, Gupta KJ Diabetes
- Telomere length and cortisol reactivity in children of depressed mothers.Gotlib IH, LeMoult J, Colich NL, Foland-Ross LC, Hallmayer J, Joormann J, Lin J, Wolkowitz OMMol Psychiatry
- Processing Scalar Implicature: A Constraint-Based Approach.Degen J, Tanenhaus MKCogn Sci
- Vascular access cannulation practices and outcomes.Besarab A, Kumbar LKidney Int
- Fauna in decline: global assessments.Mooney H, Tallis HScience
- Urodynamics for postprostatectomy incontinence: when are they helpful and how do we use them?Jura YH, Comiter CVUrol Clin North Am
- DNA damage-specific deubiquitination regulates Rad18 functions to suppress mutagenesis.Zeman MK, Lin JR, Freire R, Cimprich KAJ Cell Biol
- Direct kinetochore-spindle pole connections are not required for chromosome segregation.Sikirzhytski V, Magidson V, Steinman JB, He J, Le Berre M, Tikhonenko I, Ault JG, McEwen BF, Chen JK, Sui H, Piel M, Kapoor TM, Khodjakov AJ Cell Biol
- Covalent agonists for studying G protein-coupled receptor activation.Weichert D, Kruse AC, Manglik A, Hiller C, Zhang C, Hübner H, Kobilka BK, Gmeiner PProc Natl Acad Sci U S A
- Alteration of the lipid profile in lymphomas induced by MYC overexpression.Eberlin LS, Gabay M, Fan AC, Gouw AM, Tibshirani RJ, Felsher DW, Zare RNProc Natl Acad Sci U S A
- Treatment of 4T1 metastatic breast cancer with combined hypofractionated irradiation and autologous T-cell infusion.Filatenkov A, Baker J, Müller AM, Ahn GO, Kohrt H, Dutt S, Jensen K, Dejbakhsh-Jones S, Negrin RS, Shizuru JA, Engleman EG, Strober SRadiat Res
- ACR appropriateness Criteria® advanced stage endometrial cancer.Elshaikh MA, Yashar CM, Wolfson AH, Cardenes HR, Erickson B, Jhingran A, Jolly S, Kidd E, Lee LJ, Mayr NA, Moore D, Rao GG, Small W, Varia MA, Wahl AO, Yuh W, Gaffney DK, Expert Panel on Radiation Oncology-Gynecology:Am J Clin Oncol
- Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs.Zheng GX, Do BT, Webster DE, Khavari PA, Chang HYNat Struct Mol Biol
- A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy.Cohen JE, Purcell BP, MacArthur JW, Mu A, Shudo Y, Patel JB, Brusalis CM, Trubelja A, Fairman AS, Edwards BB, Davis MS, Hung G, Hiesinger W, Atluri P, Margulies KB, Burdick JA, Woo YJCirc Heart Fail
- Use of transmission electron microscopy to identify nanocrystals of challenging protein targets.Stevenson HP, Makhov AM, Calero M, Edwards AL, Zeldin OB, Mathews II, Lin G, Barnes CO, Santamaria H, Ross TM, Soltis SM, Khosla C, Nagarajan V, Conway JF, Cohen AE, Calero GProc Natl Acad Sci U S A
- Large-scale comparison of science teaching methods sends clear message.Wieman CEProc Natl Acad Sci U S A
- Toward an improved definition of acute-on-chronic liver failure.Jalan R, Yurdaydin C, Bajaj JS, Acharya SK, Arroyo V, Lin HC, Gines P, Kim WR, Kamath PS, World Gastroenterology Organization Working PartyGastroenterology
- Assessment of elastin deficit in a Marfan mouse aneurysm model using an elastin-specific magnetic resonance imaging contrast agent.Okamura H, Pisani LJ, Dalal AR, Emrich F, Dake BA, Arakawa M, Onthank DC, Cesati RR, Robinson SP, Milanesi M, Kotek G, Smit H, Connolly AJ, Adachi H, McConnell MV, Fischbein MPCirc Cardiovasc Imaging
- New American Heart Association/American College of Cardiology guidelines on cardiovascular risk: when will fitness get the recognition it deserves?Myers JMayo Clin Proc
- Mucociliary clearance and submucosal gland secretion in the ex vivo ferret trachea.Jeong JH, Joo NS, Hwang PH, Wine JJAm J Physiol Lung Cell Mol Physiol
- Outcomes after coronary artery calcium and other cardiovascular biomarker testing among asymptomatic medicare beneficiaries.Shreibati JB, Baker LC, McConnell MV, Hlatky MACirc Cardiovasc Imaging
- Advancing adsorption and membrane separation processes for the gigaton carbon capture challenge.Wilcox J, Haghpanah R, Rupp EC, He J, Lee KAnnu Rev Chem Biomol Eng
- Postapproval outcomes of juxtarenal aortic aneurysms treated with the Zenith fenestrated endovascular graft.Vemuri C, Oderich GS, Lee JT, Farber MA, Fajardo A, Woo EY, Cayne N, Sanchez LAJ Vasc Surg
- Response to letter to the editor regarding "Application of principal component analysis in clinical gait research".Federolf P, Boyer K, Andriacchi TJ Biomech
- What drives the comparative effectiveness of biologics vs. methotrexate in rheumatoid arthritis? Meta-regression and graphical inspection of suspected clinical factors.Kanters S, Druyts E, Mills EJ, Thorlund KRheumatology (Oxford)
- Response to letter regarding article, "Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention".Fearon WF, Low AF, Yong AC, McGeoch R, Berry C, Shah MG, Ho M, Kim HS, Loh JP, Oldroyd KGCirculation
- A novel electron gun for inline MRI-linac configurations.Constantin DE, Holloway L, Keall PJ, Fahrig RMed Phys
- Dose reduction using a dynamic, piecewise-linear attenuator.Hsieh SS, Fleischmann D, Pelc NJMed Phys
- The potential of positron emission tomography for intratreatment dynamic lung tumor tracking: a phantom study.Yang J, Yamamoto T, Mazin SR, Graves EE, Keall PJMed Phys
- Monitoring the immune competence of cancer patients to predict outcome.Chang S, Kohrt H, Maecker HTCancer Immunol Immunother
- Evolution of a unique anatomical precision in angiosperm leaf venation lifts constraints on vascular plant ecology.Zwieniecki MA, Boyce CKProc Biol Sci
- Comprehensive review of surgeries for obstructive sleep apnea syndrome.Camacho M, Certal V, Capasso RBraz J Otorhinolaryngol
- Hyperuricaemia: the unintended consequence of insulin resistance/compensatory hyperinsulinaemia. Philanthropy gone awry.Knowles JW, Reaven GJ Intern Med
- Do physiatric procedures represent a value or liability?Furman MB, Melvin JL, Kennedy DJPM R
- Environmental variability counteracts priority effects to facilitate species coexistence: evidence from nectar microbes.Tucker CM, Fukami TProc Biol Sci
- Slow wave activity is reliably low in sleepwalkers: response to Pressman et al. letter to the editor.Cartwright R, Guilleminault CJ Clin Sleep Med
- Use of Medicare data to identify coronary heart disease outcomes in the Women's Health Initiative.Hlatky MA, Ray RM, Burwen DR, Margolis KL, Johnson KC, Kucharska-Newton A, Manson JE, Robinson JG, Safford MM, Allison M, Assimes TL, Bavry AA, Berger J, Cooper-DeHoff RM, Heckbert SR, Li W, Liu S, Martin LW, Perez MV, Tindle HA, Winkelmayer WC, Stefanick MLCirc Cardiovasc Qual Outcomes
- Strategies to predict, measure, and improve psychosocial treatment adherence.Gearing RE, Townsend L, Elkins J, El-Bassel N, Osterberg LHarv Rev Psychiatry
- A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.Deng C, He X, Hsueh AJPLoS One
- Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.Zech M, Nübling G, Castrop F, Jochim A, Schulte EC, Mollenhauer B, Lichtner P, Peters A, Gieger C, Marquardt T, Vanier MT, Latour P, Klünemann H, Trenkwalder C, Diehl-Schmid J, Perneczky R, Meitinger T, Oexle K, Haslinger B, Lorenzl S, Winkelmann JPLoS One
- Extensive differences in gene expression between symbiotic and aposymbiotic cnidarians.Lehnert EM, Mouchka ME, Burriesci MS, Gallo ND, Schwarz JA, Pringle JRG3 (Bethesda)
- Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.Li L, Khush K, Hsieh SC, Ying L, Luikart H, Sigdel T, Roedder S, Yang A, Valantine H, Sarwal MMPLoS One
- The comorbidity of sleep apnea and mood, anxiety, and substance use disorders among obese military veterans within the Veterans Health Administration.Babson KA, Del Re AC, Bonn-Miller MO, Woodward SHJ Clin Sleep Med
- Renewing US medical students' interest in primary care: bridging the role model gap.Teng VC, Lin SYPostgrad Med J
- The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation.Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC, Goddard M, Hammond EH, Leone O, Marboe C, Miller D, Neil D, Rassl D, Revelo MP, Rice A, Rene Rodriguez E, Stewart S, Tan CD, Winters GL, West L, Mehra MR, Angelini AJ Heart Lung Transplant
- Cardiac arrhythmias and conduction defects in systemic sclerosis.Vacca A, Meune C, Gordon J, Chung L, Proudman S, Assassi S, Nikpour M, Rodriguez-Reyna TS, Khanna D, Lafyatis R, Matucci-Cerinic M, Distler O, Allanore Y, Scleroderma Clinical Trial Consortium Cardiac SubcommitteeRheumatology (Oxford)
- Gamete-type dependent crossover interference levels in a defined region of Caenorhabditis elegans chromosome V.Gabdank I, Fire AZG3 (Bethesda)
- Outcomes of transcatheter and surgical aortic valve replacement in high-risk patients with aortic stenosis and left ventricular dysfunction: results from the Placement of Aortic Transcatheter Valves (PARTNER) trial (cohort A).Elmariah S, Palacios IF, McAndrew T, Hueter I, Inglessis I, Baker JN, Kodali S, Leon MB, Svensson L, Pibarot P, Douglas PS, Fearon WF, Kirtane AJ, Maniar HS, Passeri JJ, PARTNER InvestigatorsCirc Cardiovasc Interv
- Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU.Axelrod DM, Anglemyer AT, Sherman-Levine SF, Zhu A, Grimm PC, Roth SJ, Sutherland SMPediatr Crit Care Med
- Pre-operative health status and outcomes after continuous-flow left ventricular assist device implantation.Flint KM, Matlock DD, Sundareswaran KS, Lindenfeld J, Spertus JA, Farrar DJ, Allen LAJ Heart Lung Transplant
- Patient access to medical devices-what about Japan, the second largest medical device market?Ikeno F, Ikeda K, Uchida TCardiovasc Interv Ther
- A conversation with Leonard and Leonore Herzenberg.Herzenberg LA, Herzenberg LA, Roederer MAnnu Rev Physiol
- Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.Schröder CM, Primeau MM, Hallmayer JF, Lazzeroni LC, Hubbard JT, O'Hara RInt J Geriatr Psychiatry
- Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention.Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, Ho MY, Kim HS, Loh JP, Oldroyd KGCirculation
- Numerous protein-bound solutes are cleared by the kidney with high efficiency.Sirich TL, Aronov PA, Plummer NS, Hostetter TH, Meyer TWKidney Int
- Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC).Chen C, Fee W, Chen J, Chan C, Khong B, Hara W, Goffinet D, Li D, Le QTAm J Clin Oncol
- Exposure to violence in relation to depressive symptoms among male and female adolescent students in Cambodia.Yi S, Poudel KC, Yasuoka J, Yi S, Palmer PH, Jimba MSoc Psychiatry Psychiatr Epidemiol
Physical Activity versus Cardiorespiratory Fitness: Two (Partly) Distinct Components of Cardiovascular Health?
Prog Cardiovasc Dis. 2014 Sep 27;
Authors: DeFina LF, Haskell WL, Willis BL, Barlow CE, Finley CE, Levine BD, Cooper KH
Physical activity (PA) and cardiorespiratory fitness (CRF) both have inverse relationships to cardiovascular (CV) morbidity and mortality. Recent position papers and guidelines have identified the important role of both of these factors in CV health. The benefits of PA and CRF in the prevention of CV disease and risk factors are reviewed. In addition, assessment methodology and utilization in the research and clinical arenas are discussed. Finally, the benefits, methodology, and utilization are compared and contrasted to better understand the two (partly) distinct components and their impact on CV health.
PMID: 25269066 [PubMed - as supplied by publisher]
Physical Activity and Cardiorespiratory Fitness as Major Markers of Cardiovascular Risk: Their Independent and Interwoven Importance to Health Status.
Prog Cardiovasc Dis. 2014 Sep 27;
Authors: Myers J, McAuley P, Lavie C, Despres JP, Arena R, Kokkinos P
The evolution from hunting and gathering to agriculture, followed by industrialization, has had a profound effect on human physical activity (PA) patterns. Current PA patterns are undoubtedly the lowest they have been in human history, with particularly marked declines in recent generations, and future projections indicate further declines around the globe. Non-communicable health problems that afflict current societies are fundamentally attributable to the fact that PA patterns are markedly different than those for which humans were genetically adapted. The advent of modern statistics and epidemiological methods has made it possible to quantify the independent effects of cardiorespiratory fitness (CRF) and PA on health outcomes. Based on more than five decades of epidemiological studies, it is now widely accepted that higher PA patterns and levels of CRF are associated with better health outcomes. This review will discuss the evidence supporting the premise that PA and CRF are independent risk factors for cardiovascular disease (CVD) as well as the interplay between both PA and CRF and other CVD risk factors. A particular focus will be given to the interplay between CRF, metabolic risk and obesity.
PMID: 25269064 [PubMed - as supplied by publisher]
More than 10 Million Steps in the Right Direction: Results from the First American Heart Association Scientific Sessions Walking Challenge.
Prog Cardiovasc Dis. 2014 Sep 27;
Authors: Harrington RA, Arena R, Després JP, Ciarochi A, Croll E, Bloch KD, Committee for Scientific Sessions Programming and the Global Congress on Physical Activity, American Heart Association Scientific Sessions 2013
In 2013, the Global Congress theme at the American Heart Association (AHA) Annual Scientific Sessions was Physical Activity (PA). As a key component of the Congress, iHealth working in collaboration with AHA provided a Bluetooth-enabled wireless PA and sleep tracker to up to 2,000 Scientific Sessions attendees. Approximately 1,850 Scientific Sessions attendees registered for, received an PA tracker and participated in the Walking Challenge. More than 10 million steps were walked by participants (10,703,504) during the 2.5days of the Walking Challenge. This translates into almost 6000 miles walked (5976.3 miles) and 656,716 calories burned by participants during the Challenge. The Global Congress of PA held at Scientific Sessions 2013 not only extensively reviewed the science of PA as a powerful/independent and, most importantly, modifiable cardiovascular risk factor, but it also provided evidence from a fun and entertaining challenge that PA as a risk behavior can be assessed and targeted. We just took 10 million steps in the right direction. Join us and make your steps count!
PMID: 25269063 [PubMed - as supplied by publisher]
Nanoelectronic circuits based on two-dimensional atomic layer crystals.
Nanoscale. 2014 Sep 30;
Authors: Lee S, Zhong Z
Since the discovery of graphene and related forms of two-dimensional (2D) atomic layer crystals, numerous studies have reported on the fundamental material aspects, such as the synthesis, the physical properties, and the electrical properties on the transistor level. With the advancement in large-area synthesis methods, system level integration to exploit the unique applications of these materials is close at hand. The main purpose of this review is to focus on the current progress and the prospect of circuits and systems based on 2D material that go beyond the single-transistor level studies. Both analog and digital circuits based on graphene and related 2D atomic layer crystals will be discussed.
PMID: 25268929 [PubMed - as supplied by publisher]
Primary Amine Stabilization of a Dicopper(III) Bis(μ-oxo) Species: Modeling the Ligation in pMMO.
J Am Chem Soc. 2014 Sep 30;
Authors: Citek C, Lin BL, Phelps TE, Wasinger EC, Stack TD
Here we report the formation of the first examples of dicopper(III) bis(μ-oxo) complexes ligated by the primary amines, propylenediamine, and N,N,-dimethyl propylenediamine. Stabilization of these new compounds is effected at -125 °C by "core capture"- introduction of exogenous ligand to a preformed dicopper(III) bis(μ-oxo) complex supported by the peralkylated tetramethyl propylenediamine. Primary amine ligation in these compounds matches the single primary amine coordination of the putative active site of particulate methane monooxygenase (pMMO) and polysaccharide monooxygenase. Reactivity studies presented here show primary amine ligated cores are competent oxidants, capable of activating C-H bonds by an H-atom abstraction mechanism. Trends in spectroscopy, structure, and reactivity provide hints to the potential role of primary amine ligation in pMMO: increased substrate accessibility to the redox active orbitals of the Cu2O2 core and greater stabilization of the oxidant without attenuation of oxidizing power.
PMID: 25268334 [PubMed - as supplied by publisher]
Effect of humic acid on the sorption of perfluorooctane sulfonate (PFOS) and perfluorobutane sulfonate (PFBS) on boehmite.
Chemosphere. 2014 Sep 27;118C:213-218
Authors: Wang F, Shih K, Leckie JO
The sorption of PFOS and PFBS on boehmite was significantly retarded by the competitive sorption of humic acid (HA), implying that PFOS and PFBS are likely more mobile in water and groundwater systems enriched with HA. The sorption behavior of PFOS and PFBS on the HA-modified boehmite surface were also found to differ due to their different chain lengths. For a partially HA-modified boehmite surface, the isotherm study showed that PFOS had a much higher maximum sorption capacity than PFBS and that PFOS might possess additional surface interactions besides electrostatic interaction. For a HA-saturated boehmite, a linear sorption isotherm was found for PFOS while nearly no PFBS sorption was observed. This indicates that sorption behavior between PFOS and the sorbed HA on boehmite was dominated by hydrophobic interactions, instead of electrostatic interaction. In addition, a conceptual model combining hydrophobic and electrostatic interaction was established to explain the sorption behavior of PFOS and PFBS on HA-modified boehmite. Finally, the results revealed that the sorption of PFOS and PFBS on HA-modified boehmite is pH-dependent. The neutralization of negative sites on HA-modified boehmite reduced the electrostatic repulsion and enhanced the partitioning of PFBS on the sorbed HA.
PMID: 25268321 [PubMed - as supplied by publisher]
The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy.
Cancers (Basel). 2014;6(4):1953-1985
Authors: Patel MA, Kim JE, Ruzevick J, Li G, Lim M
The current standard of care for glioblastoma (GBM) is maximal surgical resection with adjuvant radiotherapy and temozolomide (TMZ). As the 5-year survival with GBM remains at a dismal <10%, novel therapies are needed. Immunotherapies such as the dendritic cell (DC) vaccine, heat shock protein vaccines, and epidermal growth factor receptor (EGFRvIII) vaccines have shown encouraging results in clinical trials, and have demonstrated synergistic effects with conventional therapeutics resulting in ongoing phase III trials. Chemoradiation has been shown to have synergistic effects when used in combination with immunotherapy. Cytotoxic ionizing radiation is known to trigger pro-inflammatory signaling cascades and immune activation secondary to cell death, which can then be exploited by immunotherapies. The future of GBM therapeutics will involve finding the place for immunotherapy in the current treatment regimen with a focus on developing strategies. Here, we review current GBM therapy and the evidence for combination of immune checkpoint inhibitors, DC and peptide vaccines with the current standard of care.
PMID: 25268164 [PubMed - as supplied by publisher]
Variation and Genetic Control of Gene Expression in Primary Immunocytes across Inbred Mouse Strains.
J Immunol. 2014 Sep 29;
Authors: Mostafavi S, Ortiz-Lopez A, Bogue MA, Hattori K, Pop C, Koller D, Mathis D, Benoist C, The Immunological Genome Consortium, Blair DA, Dustin ML, Shinton SA, Hardy RR, Shay T, Regev A, Cohen N, Brennan P, Brenner M, Kim F, Rao TN, Wagers A, Heng T, Ericson J, Rothamel K, Ortiz-Lopez A, Mathis D, Benoist C, Kreslavsky T, Fletcher A, Elpek K, Bellemare-Pelletier A, Malhotra D, Turley S, Miller J, Brown B, Merad M, Gautier EL, Jakubzick C, Randolph GJ, Monach P, Best AJ, Knell J, Goldrath A, Jojic V, Koller D, Laidlaw D, Collins J, Gazit R, Rossi DJ, Malhotra N, Sylvia K, Kang J, Bezman NA, Sun JC, Min-Oo G, Kim CC, Lanier LL
To determine the breadth and underpinning of changes in immunocyte gene expression due to genetic variation in mice, we performed, as part of the Immunological Genome Project, gene expression profiling for CD4(+) T cells and neutrophils purified from 39 inbred strains of the Mouse Phenome Database. Considering both cell types, a large number of transcripts showed significant variation across the inbred strains, with 22% of the transcriptome varying by 2-fold or more. These included 119 loci with apparent complete loss of function, where the corresponding transcript was not expressed in some of the strains, representing a useful resource of "natural knockouts." We identified 1222 cis-expression quantitative trait loci (cis-eQTL) that control some of this variation. Most (60%) cis-eQTLs were shared between T cells and neutrophils, but a significant portion uniquely impacted one of the cell types, suggesting cell type-specific regulatory mechanisms. Using a conditional regression algorithm, we predicted regulatory interactions between transcription factors and potential targets, and we demonstrated that these predictions overlap with regulatory interactions inferred from transcriptional changes during immunocyte differentiation. Finally, comparison of these and parallel data from CD4(+) T cells of healthy humans demonstrated intriguing similarities in variability of a gene's expression: the most variable genes tended to be the same in both species, and there was an overlap in genes subject to strong cis-acting genetic variants. We speculate that this "conservation of variation" reflects a differential constraint on intraspecies variation in expression levels of different genes, either through lower pressure for some genes, or by favoring variability for others.
PMID: 25267973 [PubMed - as supplied by publisher]
Modeling and Simulation of Viscous Electro-Active Polymers.
Eur J Mech A Solids. 2014 11;48:112-128
Authors: Vogel F, Göktepe S, Steinmann P, Kuhl E
Electro-active materials are capable of undergoing large deformation when stimulated by an electric field. They can be divided into electronic and ionic electro-active polymers (EAPs) depending on their actuation mechanism based on their composition. We consider electronic EAPs, for which attractive Coulomb forces or local re-orientation of polar groups cause a bulk deformation. Many of these materials exhibit pronounced visco-elastic behavior. Here we show the development and implementation of a constitutive model, which captures the influence of the electric field on the visco-elastic response within a geometrically non-linear finite element framework. The electric field affects not only the equilibrium part of the strain energy function, but also the viscous part. To adopt the familiar additive split of the strain from the small strain setting, we formulate the governing equations in the logarithmic strain space and additively decompose the logarithmic strain into elastic and viscous parts. We show that the incorporation of the electric field in the viscous response significantly alters the relaxation and hysteresis behavior of the model. Our parametric study demonstrates that the model is sensitive to the choice of the electro-viscous coupling parameters. We simulate several actuator structures to illustrate the performance of the method in typical relaxation and creep scenarios. Our model could serve as a design tool for micro-electro-mechanical systems, microfluidic devices, and stimuli-responsive gels such as artificial skin, tactile displays, or artificial muscle.
PMID: 25267881 [PubMed - as supplied by publisher]
The Living Heart Project: A robust and integrative simulator for human heart function.
Eur J Mech A Solids. 2014 11;48:38-47
Authors: Baillargeon B, Rebelo N, Fox DD, Taylor RL, Kuhl E
The heart is not only our most vital, but also our most complex organ: Precisely controlled by the interplay of electrical and mechanical fields, it consists of four chambers and four valves, which act in concert to regulate its filling, ejection, and overall pump function. While numerous computational models exist to study either the electrical or the mechanical response of its individual chambers, the integrative electro-mechanical response of the whole heart remains poorly understood. Here we present a proof-of-concept simulator for a four-chamber human heart model created from computer topography and magnetic resonance images. We illustrate the governing equations of excitation-contraction coupling and discretize them using a single, unified finite element environment. To illustrate the basic features of our model, we visualize the electrical potential and the mechanical deformation across the human heart throughout its cardiac cycle. To compare our simulation against common metrics of cardiac function, we extract the pressure-volume relationship and show that it agrees well with clinical observations. Our prototype model allows us to explore and understand the key features, physics, and technologies to create an integrative, predictive model of the living human heart. Ultimately, our simulator will open opportunities to probe landscapes of clinical parameters, and guide device design and treatment planning in cardiac diseases such as stenosis, regurgitation, or prolapse of the aortic, pulmonary, tricuspid, or mitral valve.
PMID: 25267880 [PubMed - as supplied by publisher]
A Predominantly Visual Subdivision of The Right Temporo-Parietal Junction (vTPJ).
Cereb Cortex. 2014 Sep 29;
Authors: Horiguchi H, Wandell BA, Winawer J
A multiplicity of sensory and cognitive functions has been attributed to the large cortical region at the temporo-parietal junction (TPJ). Using functional MRI, we report that a small region lateralized within the right TPJ responds robustly to certain simple visual stimuli ("vTPJ"). The vTPJ was found in all right hemispheres (n = 7), posterior to the auditory cortex. To manipulate stimuli and attention, subjects were presented with a mixture of visual and auditory stimuli in a concurrent block design in 2 experiments: (1) A simple visual stimulus (a grating pattern modulating in mean luminance) elicited robust responses in the vTPJ, whether or not the subject attended to vision and(2) a drifting low-contrast dartboard pattern of constant mean luminance evoked robust responses in the vTPJ when it was task-relevant (visual task), and smaller responses when it was not (auditory task). The results suggest a focal, visually responsive region within the right TPJ that is powerfully driven by certain visual stimuli (luminance fluctuations), and that can be driven by other visual stimuli when the subject is attending. The precise localization of this visually responsive region is helpful in segmenting the TPJ and to better understand its role in visual awareness and related disorders such as extinction and neglect.
PMID: 25267856 [PubMed - as supplied by publisher]
p16 Protein Expression and Human Papillomavirus Status As Prognostic Biomarkers of Nonoropharyngeal Head and Neck Squamous Cell Carcinoma.
J Clin Oncol. 2014 Sep 29;
Authors: Chung CH, Zhang Q, Kong CS, Harris J, Fertig EJ, Harari PM, Wang D, Redmond KP, Shenouda G, Trotti A, Raben D, Gillison ML, Jordan RC, Le QT
PURPOSE: Although p16 protein expression, a surrogate marker of oncogenic human papillomavirus (HPV) infection, is recognized as a prognostic marker in oropharyngeal squamous cell carcinoma (OPSCC), its prevalence and significance have not been well established in cancer of the oral cavity, hypopharynx, or larynx, collectively referred as non-OPSCC, where HPV infection is less common than in the oropharynx.
PATIENTS AND METHODS: p16 expression and high-risk HPV status in non-OPSCCs from RTOG 0129, 0234, and 0522 studies were determined by immunohistochemistry (IHC) and in situ hybridization (ISH). Hazard ratios from Cox models were expressed as positive or negative, stratified by trial, and adjusted for clinical characteristics.
RESULTS: p16 expression was positive in 14.1% (12 of 85), 24.2% (23 of 95), and 19.0% (27 of 142) and HPV ISH was positive in 6.5% (six of 93), 14.6% (15 of 103), and 6.9% (seven of 101) of non-OPSCCs from RTOG 0129, 0234, and 0522 studies, respectively. Hazard ratios for p16 expression were 0.63 (95% CI, 0.42 to 0.95; P = .03) and 0.56 (95% CI, 0.35 to 0.89; P = .01) for progression-free (PFS) and overall survival (OS), respectively. Comparing OPSCC and non-OPSCC, patients with p16-positive OPSCC have better PFS and OS than patients with p16-positive non-OPSCC, but patients with p16-negative OPSCC and non-OPSCC have similar outcomes.
CONCLUSION: Similar to results in patients with OPSCC, patients with p16-negative non-OPSCC have worse outcomes than patients with p16-positive non-OPSCC, and HPV may also have a role in outcome in a subset of non-OPSCC. However, further development of a p16 IHC scoring system in non-OPSCC and improvement of HPV detection methods are warranted before broad application in the clinical setting.
PMID: 25267748 [PubMed - as supplied by publisher]
Basal p21 controls population heterogeneity in cycling and quiescent cell cycle states.
Proc Natl Acad Sci U S A. 2014 Sep 29;
Authors: Overton KW, Spencer SL, Noderer WL, Meyer T, Wang CL
Phenotypic heterogeneity within a population of genetically identical cells is emerging as a common theme in multiple biological systems, including human cell biology and cancer. Using live-cell imaging, flow cytometry, and kinetic modeling, we showed that two states-quiescence and cell cycling-can coexist within an isogenic population of human cells and resulted from low basal expression levels of p21, a Cyclin-dependent kinase (CDK) inhibitor (CKI). We attribute the p21-dependent heterogeneity in cell cycle activity to double-negative feedback regulation involving CDK2, p21, and E3 ubiquitin ligases. In support of this mechanism, analysis of cells at a point before cell cycle entry (i.e., before the G1/S transition) revealed a p21-CDK2 axis that determines quiescent and cycling cell states. Our findings suggest a mechanistic role for p21 in generating heterogeneity in both normal tissues and tumors.
PMID: 25267623 [PubMed - as supplied by publisher]
A fluorescence-activated cell sorting-based strategy for rapid isolation of high-lipid Chlamydomonas mutants.
Plant J. 2014 Sep 29;
Authors: Terashima M, Freeman ES, Jinkerson RE, Jonikas MC
There is significant interest in farming algae for the direct production of biofuels and valuable lipids. Chlamydomonas reinhardtii is the leading model system for studying lipid metabolism in green algae, but current methods for isolating mutants with perturbed lipid content in this organism are slow and tedious. Here, we present the Chlamydomonas High Lipid Sorting (CHiLiS) strategy, which enables enrichment of high-lipid mutants by fluorescence-activated cell sorting (FACS) of pooled mutants stained with the lipid-sensitive dye Nile Red. This method only takes five weeks from mutagenesis to mutant isolation. We developed a staining protocol that allows quantitation of lipid content while preserving cell viability. We improved separation of high-lipid mutants from wild-type by using each cell's chlorophyll fluorescence as an internal control. We initially demonstrated 20-fold enrichment of the known high-lipid mutant sta1 from a mixture of sta1 and wild-type cells. We then applied CHiLiS to sort thousands of high-lipid cells from a pool of ~60,000 mutants. Flow cytometry analysis of 24 individual mutants isolated by this approach revealed that ~50% showed a reproducible high lipid phenotype. We further characterized 9 of the mutants with highest lipid content by flame ionization detection and mass spectrometry lipidomics. All mutants analyzed had higher triacylglycerol content and perturbed whole-cell fatty-acid composition. One arbitrarily chosen mutant was evaluated by microscopy, revealing larger lipid droplets than wild-type. The unprecedented throughput of CHiLiS opens the door to a systems-level understanding of green algal lipid biology by enabling genome-saturating isolation of mutants in key genes. This article is protected by copyright. All rights reserved.
PMID: 25267488 [PubMed - as supplied by publisher]
Increased bilateral expression of α1-adrenoceptors on peripheral nerves, blood vessels and keratinocytes does not account for pain or neuroinflammatory changes after distal tibia fracture in rats.
Neuroscience. 2014 Sep 26;
Authors: Drummond ES, Dawson LF, Finch PM, Li W, Guo TZ, Kingery WS, Drummond PD
In certain forms of nerve injury and inflammation, noradrenaline augments pain via actions on up-regulated α1-adrenoceptors (α1-AR). The aim of this study was to use immunohistochemistry to examine α1-AR expression on peripheral neurons, cutaneous blood vessels and keratinocytes after distal tibia fracture and cast immobilization, a model of complex regional pain syndrome type 1. We hypothesized that there would be increased α1-AR expression on neurons and keratinocytes in the injured limb in comparison to the contralateral unaffected limb after distal tibia fracture, in association with inflammatory changes and pain. α1-AR expression was increased on plantar keratinocytes, dermal blood vessels and peripheral nerve fibres at 16 weeks after injury both in the fractured and contralateral uninjured limb. Similar changes were seen in controls whose limb had been immobilised in a cast for 4 weeks but not fractured. Neurofilament 200 (NF200), a marker of myelinated neurons, and calcitonin gene-related peptide (CGRP), a neuropeptide involved in neuro-inflammatory signalling, decreased 4 weeks after fracture and casting but then increased at the 16-week time point. As some of these changes were also detected in the contralateral hind limb, they probably were triggered by a systemic response to fracture and casting. Soon after the cast was removed, intraplantar injections of the α1-AR antagonist prazosin released local vasoconstrictor tone but had no effect on pain behaviours. However, systemic injection of prazosin inhibited behavioural signs of pain, suggesting that fracture and/or casting triggered an up-regulation of α1-ARs in central nociceptive pathways that augmented pain. Together, these findings indicate that α1-AR expression increases in the hind limbs after distal tibia fracture and cast immobilisation. However, these peripheral increases do not contribute directly to residual pain.
PMID: 25267387 [PubMed - as supplied by publisher]
Editorial Comment: ABJS Carl T. Brighton Workshop on Implant Wear and Tribocorrosion of Total Joint Replacements.
Clin Orthop Relat Res. 2014 Sep 30;
Authors: Goodman SB, Wright TM
PMID: 25267269 [PubMed - as supplied by publisher]
A call to arms: new approaches to an old heart failure problem.
J Card Fail. 2014 Sep 26;
Authors: Abnousi F, Yock P, Heidenreich P
Heart failure with preserved ejection fraction is often thought of as "the other half" of all heart failure. It is similar to heart failure with reduced ejection fraction in incidence, prevalence, morbidity, mortality, and cost, yet there is still not a single therapy - device, pharmaceutical, or otherwise - that has shown any benefit in reducing hospitalization or mortality. However, after years of failed pharmaceutical trials, researchers are now branching out to investigate whether answers may lie in device based treatment.
PMID: 25267078 [PubMed - as supplied by publisher]
Challenges and Priorities for Research: A Report From the National Heart, Lung, and Blood Institute (NHLBI)/National Institutes of Health (NIH) Working Group on Thrombosis in Pediatric Cardiology and Congenital Heart Disease.
Circulation. 2014 Sep 30;130(14):1192-203
Authors: McCrindle BW, Li JS, Manlhiot C, Tweddell JS, Giglia TM, Massicotte MP, Monagle P, Krishnamurthy R, Mahaffey KW, Michelson AD, Verdun N, Almond CS, Newburger JW, Brandão LR, Esmon CT, Manco-Johnson MJ, Ichord R, Ortel TL, Chan AK, Portman R, Rose M, Strony J, Kaltman JR
PMID: 25266860 [PubMed - in process]
Essential is Not Irreplaceable: Fitness Dynamics of Experimental E. coli RNase P RNA Heterologous Replacement.
J Mol Evol. 2014 Sep 30;
Authors: Loveland JL, Rice J, Turrini PC, Lizotte-Waniewski M, Dorit RL
While critical cellular components-such as the RNA moiety of bacterial ribonuclease P-can sometimes be replaced with a highly divergent homolog, the cellular response to such perturbations is often unexpectedly complex. RNase P is a ubiquitous and essential ribonucleoprotein involved in the processing of multiple RNA substrates, including tRNAs, small non-coding RNAs and intergenic operons. In Bacteria, RNase P RNAs have been subdivided-based on their secondary and tertiary structures-into two major groups (A and B), each with a distinct phylogenetic distribution. Despite the vast phylogenetic and structural gap that separates the two RNase P RNA classes, previous work suggested their interchangeability. Here, we explore in detail the functional and fitness consequences of replacing the endogenous Type-A Escherichia coli RNase P RNA with a Type-B homolog derived from Bacillus subtilis, and show that E. coli cells forced to survive with a chimeric RNase P as their sole source of RNase P activity exhibit extremely variable responses. The chimeric RNase P alters growth rates-used here as an indirect measure of fitness-in unpredictable ways, ranging from 3- to 20-fold reductions in maximal growth rate. The transcriptional behavior of cells harboring the chimeric RNAse P is also perturbed, affecting the levels of at least 79 different transcripts. Such transcriptional plasticity represents an important mechanism of transient adaptation which, when coupled with the emergence and eventual fixation of compensatory mutations, enables the cells to overcome the disruption of this tightly coevolving ribonucleoprotein.
PMID: 25266807 [PubMed - as supplied by publisher]
A Caulobacter MreB mutant with irregular cell shape exhibits compensatory widening to maintain a preferred surface area to volume ratio.
Mol Microbiol. 2014 Sep 30;
Authors: Harris LK, Dye NA, Theriot JA
Rod-shaped bacteria typically elongate at a uniform width. To investigate the genetic and physiological determinants involved in this process, we studied a mutation in the morphogenetic protein MreB in Caulobacter crescentus that gives rise to cells with a variable-width phenotype, where cells have regions that are both thinner and wider than wild-type. During growth, individual cells develop a balance of wide and thin regions, and mutant MreB dynamically localizes to poles and thin regions. Surprisingly, the surface area to volume ratio of these irregularly-shaped cells is, on average, very similar to wild-type. We propose that, while mutant MreB localizes to thin regions and promotes rod-like growth there, wide regions develop as a compensatory mechanism, allowing cells to maintain a wild-type-like surface area to volume ratio. To support this model, we have shown that cell widening is abrogated in growth conditions that promote higher surface area to volume ratios, and we have observed individual cells with high ratios return to wild-type levels over several hours by developing wide regions, suggesting that compensation can take place at the level of individual cells.
PMID: 25266768 [PubMed - as supplied by publisher]
44-h ambulatory blood pressure monitoring: revealing the true burden of hypertension in pediatric hemodialysis patients.
Pediatr Nephrol. 2014 Sep 26;
Authors: Haskin O, Wong CJ, McCabe L, Begin B, Sutherland SM, Chaudhuri A
BACKGROUND: The blood pressure (BP) burden is high in pediatric hemodialysis (HD) patients and adversely affects prognosis. The aim of this study was to examine whether 44-h ambulatory BP monitoring (ABPM) provides additional relevant BP data compared with 24-h ABPM.
METHODS: ABPM was initiated at the end of the mid-week dialysis run in 13 stable pediatric HD patients and continued until the next run for 44 h. Day 1 was defined as the initial 24-h ABPM and Day 2 as the time period after that until the next dialysis run. All patients had an echocardiogram to calculate the left ventricular mass index (LVMI).
RESULTS: A higher percentage of patients were diagnosed with hypertension from the 44-h ABPM than from the 24-h ABPM. All BP indexes and loads (except nighttime diastolic load) were significantly higher on Day 2 than on Day 1. Patients with BP loads of ≥25 % on 44-h ABPM had significantly higher LVMI than those patients with normal BP loads. No such association was found with 24-h ABPM and LVMI. Higher interdialytic weight gain was associated with higher Day-2 nighttime systolic BP load.
CONCLUSIONS: The 44-h ABPM provides more information than the 24-h ABPM in terms of diagnosing and assessing the true burden of hypertension in pediatric HD patients. Elevated BP loads from 44-h ABPM correlate with a higher LVMI on the echocardiogram.
PMID: 25266709 [PubMed - as supplied by publisher]
Cell recruitment by amnion chorion grafts promotes neovascularization.
J Surg Res. 2014 Sep 1;
Authors: Maan ZN, Rennert RC, Koob TJ, Januszyk M, Li WW, Gurtner GC
BACKGROUND: Nonhealing wounds are a significant health burden. Stem and progenitor cells can accelerate wound repair and regeneration. Human amniotic membrane has demonstrated efficacy in promoting wound healing, though the underlying mechanisms remain unknown. A dehydrated human amnion chorion membrane (dHACM) was tested for its ability to recruit hematopoietic progenitor cells to a surgically implanted graft in a murine model of cutaneous ischemia.
METHODS: dHACM was subcutaneously implanted under elevated skin (ischemic stimulus) in either wild-type mice or mice surgically parabiosed to green fluorescent protein (GFP) + reporter mice. A control acellular dermal matrix, elevated skin without an implant, and normal unwounded skin were used as controls. Wound tissue was harvested and processed for histology and flow cytometric analysis.
RESULTS: Implanted dHACMs recruited significantly more progenitor cells compared with controls (*P < 0.05) and displayed in vivo SDF-1 expression with incorporation of CD34 + progenitor cells within the matrix. Parabiosis modeling confirmed the circulatory origin of recruited cells, which coexpressed progenitor cell markers and were localized to foci of neovascularization within implanted matrices.
CONCLUSIONS: In summary, dHACM effectively recruits circulating progenitor cells, likely because of stromal derived factor 1 (SDF-1) expression. The recruited cells express markers of "stemness" and localize to sites of neovascularization, providing a partial mechanism for the clinical efficacy of human amniotic membrane in the treatment of chronic wounds.
PMID: 25266600 [PubMed - as supplied by publisher]
Task-evoked substantia nigra hyperactivity associated with prefrontal hypofunction, prefrontonigral disconnectivity and nigrostriatal connectivity predicting psychosis severity in medication naïve first episode schizophrenia.
Schizophr Res. 2014 Sep 26;
Authors: Yoon JH, Westphal AJ, Minzenberg MJ, Niendam T, Ragland JD, Lesh T, Solomon M, Carter CS
The widely cited prefrontal dysfunction - excess subcortical dopamine model of schizophrenia posits that prefrontal deficits give rise to cognitive impairments and the disinhibition of subcortical dopamine release underlying psychosis. While this has been one of the most influential schizophrenia models, only a handful of studies have provided evidence supporting it directly in patients with schizophrenia. We previously demonstrated task-evoked substantia nigra hyperactivity in the context of prefrontal hypofunction and prefrontonigral functional disconnectivity. In addition, nigrostriatal functional connectivity was identified as a potential marker of psychosis. Because patients in this prior study had chronic schizophrenia and were treated with antipsychotics, in the present study we tested whether these findings were confounded by illness chronicity and medication effects by seeking to reproduce these findings in an independent sample of antipsychotic naïve, first episode (FE) patients. We compared event-related fMRI activations from 12 FE patients with 15 demographically matched healthy control subjects during cognitive testing. We found substantia nigra hyperactivity associated with prefrontal hypofunction and prefrontonigral functional disconnectivity, as well as the magnitude of nigrostriatal functional connectivity positively correlating with severity of psychosis. This study adds to the body of evidence supporting the prefrontal-dopamine model of schizophrenia and further validates nigrostriatal functional connectivity as a marker of psychosis.
PMID: 25266549 [PubMed - as supplied by publisher]
Epilepsy: Pregnancy in women with epilepsy-risks and management.
Nat Rev Neurol. 2014 Sep 30;
Authors: Meador KJ
PMID: 25266298 [PubMed - as supplied by publisher]
Topical fentanyl stimulates healing of ischemic wounds in diabetic rats.
J Diabetes. 2014 Sep 30;
Authors: Gupta M, Poonawala T, Farooqui M, Ericson ME, Gupta K
BACKGROUND: Topically applied opioids promote angiogenesis and healing of ischemic wounds in rats. We examined if topical fentanyl stimulates wound healing in diabetic rats by stimulating growth-promoting signaling, angiogenesis, lymphangiogenesis and nerve regeneration.
METHODS: We used Zucker diabetic fatty rats that develop obesity and diabetes on a high fat diet due to a mutation in the Leptin receptor. Fentanyl blended with hydrocream was applied topically on ischemic wounds twice daily, and wound closure was analyzed regularly. Wound histology was analyzed by hematoxylin and eosin staining. Angiogenesis, lymphangiogenesis, nerve fibers and phospho-PDGFR-β were visualized by CD31-, lymphatic vessel endothelium-1, protein gene product 9.5- and anti-phospho PDGFR-β-immunoreactivity, respectively. Nitric oxide synthase (NOS) and PDGFR-β signaling were analyzed using Western immunoblotting.
RESULTS: Fentanyl significantly promoted wound closure as compared to PBS. Histology scores were significantly higher in fentanyl-treated wounds, indicative of increased granulation tissue formation, reduced edema and inflammation, and increased matrix deposition. Fentanyl treatment resulted in increased wound angiogenesis, lymphatic vasculature, nerve fibers, nitric oxide, NOS and PDGFR-β signaling as compared to PBS. Phospho PDGFR-β co-localized with CD31 co-staining for vasculature.
CONCLUSIONS: Topically applied fentanyl promotes closure of ischemic wounds in diabetic rats. Increased angiogenesis, lymphangiogenesis, peripheral nerve regeneration, NO and PDGFR-β signaling are associated with fentanyl-induced tissue remodeling and wound healing.
PMID: 25266258 [PubMed - as supplied by publisher]
Telomere length and cortisol reactivity in children of depressed mothers.
Mol Psychiatry. 2014 Sep 30;
Authors: Gotlib IH, LeMoult J, Colich NL, Foland-Ross LC, Hallmayer J, Joormann J, Lin J, Wolkowitz OM
A growing body of research demonstrates that individuals diagnosed with major depressive disorder (MDD) are characterized by shortened telomere length, which has been posited to underlie the association between depression and increased instances of medical illness. The temporal nature of the relation between MDD and shortened telomere length, however, is not clear. Importantly, both MDD and telomere length have been associated independently with high levels of stress, implicating dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and anomalous levels of cortisol secretion in this relation. Despite these associations, no study has assessed telomere length or its relation with HPA-axis activity in individuals at risk for depression, before the onset of disorder. In the present study, we assessed cortisol levels in response to a laboratory stressor and telomere length in 97 healthy young daughters of mothers either with recurrent episodes of depression (i.e., daughters at familial risk for depression) or with no history of psychopathology. We found that daughters of depressed mothers had shorter telomeres than did daughters of never-depressed mothers and, further, that shorter telomeres were associated with greater cortisol reactivity to stress. This study is the first to demonstrate that children at familial risk of developing MDD are characterized by accelerated biological aging, operationalized as shortened telomere length, before they had experienced an onset of depression; this may predispose them to develop not only MDD but also other age-related medical illnesses. It is critical, therefore, that we attempt to identify and distinguish genetic and environmental mechanisms that contribute to telomere shortening.Molecular Psychiatry advance online publication, 30 September 2014; doi:10.1038/mp.2014.119.
PMID: 25266121 [PubMed - as supplied by publisher]
Processing Scalar Implicature: A Constraint-Based Approach.
Cogn Sci. 2014 Sep 30;
Authors: Degen J, Tanenhaus MK
Three experiments investigated the processing of the implicature associated with some using a "gumball paradigm." On each trial, participants saw an image of a gumball machine with an upper chamber with 13 gumballs and an empty lower chamber. Gumballs then dropped to the lower chamber and participants evaluated statements, such as "You got some of the gumballs." Experiment 1 established that some is less natural for reference to small sets (1, 2, and 3 of the 13 gumballs) and unpartitioned sets (all 13 gumballs) compared to intermediate sets (6-8). Partitive some of was less natural than simple some when used with the unpartitioned set. In Experiment 2, including exact number descriptions lowered naturalness ratings for some with small sets but not for intermediate size sets and the unpartitioned set. In Experiment 3, the naturalness ratings from Experiment 2 predicted response times. The results are interpreted as evidence for a Constraint-Based account of scalar implicature processing and against both two-stage, Literal-First models and pragmatic Default models.
PMID: 25265993 [PubMed - as supplied by publisher]
Vascular access cannulation practices and outcomes.
Kidney Int. 2014 Oct;86(4):671-3
Authors: Besarab A, Kumbar L
Vascular access cannulation practices such as the dialysis prescription for blood pump flow and dialysis duration vary significantly among countries. Choice of needle gauge and cannulation practice with the needle in terms of direction relative to the flow stream and rotation after insertion are dictated in part by practicalities but appear to be mostly the result of 'cultural' practices within dialysis centers. Prospective studies of cannulation are needed to improve access outcomes.
PMID: 25265949 [PubMed - in process]
Fauna in decline: global assessments.
Science. 2014 Aug 22;345(6199):885
Authors: Mooney H, Tallis H
PMID: 25146278 [PubMed - indexed for MEDLINE]
Urodynamics for postprostatectomy incontinence: when are they helpful and how do we use them?
Urol Clin North Am. 2014 Aug;41(3):419-27, viii
Authors: Jura YH, Comiter CV
Urodynamics is indicated for the evaluation of postprostatectomy incontinence unless an artificial urinary sphincter placement is the preferred option, as in cases of severe incontinence, prior radiation, or previous male sling or artificial urinary sphincter placement--when male sling is unlikely to achieve efficacy. Urodynamics should be performed only when there is a question it can answer that would affect treatment choice or outcome. Urodynamic findings of detrusor underactivity, overactivity, and reduced compliance are important considerations in deciding how best to treat postprostatectomy incontinence.
PMID: 25063598 [PubMed - indexed for MEDLINE]
DNA damage-specific deubiquitination regulates Rad18 functions to suppress mutagenesis.
J Cell Biol. 2014 Jul 21;206(2):183-97
Authors: Zeman MK, Lin JR, Freire R, Cimprich KA
Deoxyribonucleic acid (DNA) lesions encountered during replication are often bypassed using DNA damage tolerance (DDT) pathways to avoid prolonged fork stalling and allow for completion of DNA replication. Rad18 is a central E3 ubiquitin ligase in DDT, which exists in a monoubiquitinated (Rad18•Ub) and nonubiquitinated form in human cells. We find that Rad18 is deubiquitinated when cells are treated with methyl methanesulfonate or hydrogen peroxide. The ubiquitinated form of Rad18 does not interact with SNF2 histone linker plant homeodomain RING helicase (SHPRH) or helicase-like transcription factor, two downstream E3 ligases needed to carry out error-free bypass of DNA lesions. Instead, it interacts preferentially with the zinc finger domain of another, nonubiquitinated Rad18 and may inhibit Rad18 function in trans. Ubiquitination also prevents Rad18 from localizing to sites of DNA damage, inducing proliferating cell nuclear antigen monoubiquitination, and suppressing mutagenesis. These data reveal a new role for monoubiquitination in controlling Rad18 function and suggest that damage-specific deubiquitination promotes a switch from Rad18•Ub-Rad18 complexes to the Rad18-SHPRH complexes necessary for error-free lesion bypass in cells.
PMID: 25023518 [PubMed - indexed for MEDLINE]
Direct kinetochore-spindle pole connections are not required for chromosome segregation.
J Cell Biol. 2014 Jul 21;206(2):231-43
Authors: Sikirzhytski V, Magidson V, Steinman JB, He J, Le Berre M, Tikhonenko I, Ault JG, McEwen BF, Chen JK, Sui H, Piel M, Kapoor TM, Khodjakov A
Segregation of genetic material occurs when chromosomes move to opposite spindle poles during mitosis. This movement depends on K-fibers, specialized microtubule (MT) bundles attached to the chromosomes' kinetochores. A long-standing assumption is that continuous K-fibers connect every kinetochore to a spindle pole and the force for chromosome movement is produced at the kinetochore and coupled with MT depolymerization. However, we found that chromosomes still maintained their position at the spindle equator during metaphase and segregated properly during anaphase when one of their K-fibers was severed near the kinetochore with a laser microbeam. We also found that, in normal fully assembled spindles, K-fibers of some chromosomes did not extend to the spindle pole. These K-fibers connected to adjacent K-fibers and/or nonkinetochore MTs. Poleward movement of chromosomes with short K-fibers was uncoupled from MT depolymerization at the kinetochore. Instead, these chromosomes moved by dynein-mediated transport of the entire K-fiber/kinetochore assembly. Thus, at least two distinct parallel mechanisms drive chromosome segregation in mammalian cells.
PMID: 25023516 [PubMed - indexed for MEDLINE]
Covalent agonists for studying G protein-coupled receptor activation.
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10744-8
Authors: Weichert D, Kruse AC, Manglik A, Hiller C, Zhang C, Hübner H, Kobilka BK, Gmeiner P
Structural studies on G protein-coupled receptors (GPCRs) provide important insights into the architecture and function of these important drug targets. However, the crystallization of GPCRs in active states is particularly challenging, requiring the formation of stable and conformationally homogeneous ligand-receptor complexes. Native hormones, neurotransmitters, and synthetic agonists that bind with low affinity are ineffective at stabilizing an active state for crystallogenesis. To promote structural studies on the pharmacologically highly relevant class of aminergic GPCRs, we here present the development of covalently binding molecular tools activating Gs-, Gi-, and Gq-coupled receptors. The covalent agonists are derived from the monoamine neurotransmitters noradrenaline, dopamine, serotonin, and histamine, and they were accessed using a general and versatile synthetic strategy. We demonstrate that the tool compounds presented herein display an efficient covalent binding mode and that the respective covalent ligand-receptor complexes activate G proteins comparable to the natural neurotransmitters. A crystal structure of the β2-adrenoreceptor in complex with a covalent noradrenaline analog and a conformationally selective antibody (nanobody) verified that these agonists can be used to facilitate crystallogenesis.
PMID: 25006259 [PubMed - indexed for MEDLINE]
Alteration of the lipid profile in lymphomas induced by MYC overexpression.
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10450-5
Authors: Eberlin LS, Gabay M, Fan AC, Gouw AM, Tibshirani RJ, Felsher DW, Zare RN
Overexpression of the v-myc avian myelocytomatosis viral oncogene homolog (MYC) oncogene is one of the most commonly implicated causes of human tumorigenesis. MYC is known to regulate many aspects of cellular biology including glucose and glutamine metabolism. Little is known about the relationship between MYC and the appearance and disappearance of specific lipid species. We use desorption electrospray ionization mass spectrometry imaging (DESI-MSI), statistical analysis, and conditional transgenic animal models and cell samples to investigate changes in lipid profiles in MYC-induced lymphoma. We have detected a lipid signature distinct from that observed in normal tissue and in rat sarcoma-induced lymphoma cells. We found 104 distinct molecular ions that have an altered abundance in MYC lymphoma compared with normal control tissue by statistical analysis with a false discovery rate of less than 5%. Of these, 86 molecular ions were specifically identified as complex phospholipids. To evaluate whether the lipid signature could also be observed in human tissue, we examined 15 human lymphoma samples with varying expression levels of MYC oncoprotein. Distinct lipid profiles in lymphomas with high and low MYC expression were observed, including many of the lipid species identified as significant for MYC-induced animal lymphoma tissue. Our results suggest a relationship between the appearance of specific lipid species and the overexpression of MYC in lymphomas.
PMID: 24994904 [PubMed - indexed for MEDLINE]
Treatment of 4T1 metastatic breast cancer with combined hypofractionated irradiation and autologous T-cell infusion.
Radiat Res. 2014 Aug;182(2):163-9
Authors: Filatenkov A, Baker J, Müller AM, Ahn GO, Kohrt H, Dutt S, Jensen K, Dejbakhsh-Jones S, Negrin RS, Shizuru JA, Engleman EG, Strober S
The goal of this study was to determine whether a combination of local tumor irradiation and autologous T-cell transplantation can effectively treat metastatic 4T1 breast cancer in mice. BALB/c mice were injected subcutaneously with luciferase-labeled 4T1 breast tumor cells and allowed to grow for 21 days, at which time metastases appeared in the lungs. Primary tumors were treated at that time with 3 daily fractions of 20 Gy of radiation each. Although this approach could eradicate primary tumors, tumors in the lungs grew progressively. We attempted to improve efficacy of the radiation by adding autologous T-cell infusions. Accordingly, T cells were purified from the spleens of tumor-bearing mice after completion of irradiation and cryopreserved. Cyclophosphamide was administered thereafter to induce lymphodepletion, followed by T-cell infusion. Although the addition of cyclophosphamide to irradiation did not improve survival or reduce tumor progression, the combination of radiation, cyclophosphamide and autologous T-cell infusion induced durable remissions and markedly improved survival. We conclude that the combination of radiation and autologous T-cell infusion is an effective treatment for metastatic 4T1 breast cancer.
PMID: 24992165 [PubMed - indexed for MEDLINE]
ACR appropriateness Criteria® advanced stage endometrial cancer.
Am J Clin Oncol. 2014 Aug;37(4):391-6
Authors: Elshaikh MA, Yashar CM, Wolfson AH, Cardenes HR, Erickson B, Jhingran A, Jolly S, Kidd E, Lee LJ, Mayr NA, Moore D, Rao GG, Small W, Varia MA, Wahl AO, Yuh W, Gaffney DK, Expert Panel on Radiation Oncology-Gynecology:
OBJECTIVES: Patients with advanced stage endometrial carcinoma constitute a heterogeneous group of patients with different stages, tumor histologic types, and involved sites. Hysterectomy, bilateral salpingo-ophorectomy, and surgical staging are the cornerstone of surgical management in these patients. The optimal adjuvant therapy is yet to be established. An expert panel was convened to reach consensus on the most appropriate management options in this group of patients.
METHODS: The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.
RESULTS: Four clinical variants were developed to address common scenarios in the management of women with advanced-stage endometrial carcinoma. Group members reached consensus on the appropriateness of specific evaluation and treatment approaches with numerical ratings.
CONCLUSIONS: In combining available medical literature and expert opinions, this manuscript may serve as an aid for other practitioners in the appropriate management of women with advanced-stage endometrial carcinoma.
PMID: 24977691 [PubMed - indexed for MEDLINE]
Dicer-microRNA-Myc circuit promotes transcription of hundreds of long noncoding RNAs.
Nat Struct Mol Biol. 2014 Jul;21(7):585-90
Authors: Zheng GX, Do BT, Webster DE, Khavari PA, Chang HY
Long noncoding RNAs (lncRNAs) are important regulators of cell fate, yet little is known about mechanisms controlling lncRNA expression. Here we show that transcription is quantitatively different for lncRNAs and mRNAs--as revealed by deficiency of Dicer (Dcr), a key RNase that generates microRNAs (miRNAs). Dcr loss in mouse embryonic stem cells led unexpectedly to decreased levels of hundreds of lncRNAs. The canonical Dgcr8-Dcr-miRNA pathway is required for robust lncRNA transcriptional initiation and elongation. Computational and genetic epistasis analyses demonstrated that Dcr activation of the oncogenic transcription factor cMyc is partly responsible for lncRNA expression. A quantitative metric of mRNA-lncRNA decoupling revealed that Dcr and cMyc differentially regulate lncRNAs versus mRNAs in diverse cell types and in vivo. Thus, numerous lncRNAs may be modulated as a class in development and disease, notably where Dcr and cMyc act.
PMID: 24929436 [PubMed - indexed for MEDLINE]
A bioengineered hydrogel system enables targeted and sustained intramyocardial delivery of neuregulin, activating the cardiomyocyte cell cycle and enhancing ventricular function in a murine model of ischemic cardiomyopathy.
Circ Heart Fail. 2014 Jul;7(4):619-26
Authors: Cohen JE, Purcell BP, MacArthur JW, Mu A, Shudo Y, Patel JB, Brusalis CM, Trubelja A, Fairman AS, Edwards BB, Davis MS, Hung G, Hiesinger W, Atluri P, Margulies KB, Burdick JA, Woo YJ
BACKGROUND: Neuregulin-1β (NRG) is a member of the epidermal growth factor family possessing a critical role in cardiomyocyte development and proliferation. Systemic administration of NRG demonstrated efficacy in cardiomyopathy animal models, leading to clinical trials using daily NRG infusions. This approach is hindered by requiring daily infusions and off-target exposure. Therefore, this study aimed to encapsulate NRG in a hydrogel to be directly delivered to the myocardium, accomplishing sustained localized NRG delivery.
METHODS AND RESULTS: NRG was encapsulated in hydrogel, and release over 14 days was confirmed by ELISA in vitro. Sprague-Dawley rats were used for cardiomyocyte isolation. Cells were stimulated by PBS, NRG, hydrogel, or NRG-hydrogel (NRG-HG) and evaluated for proliferation. Cardiomyocytes demonstrated EdU (5-ethynyl-2'-deoxyuridine) and phosphorylated histone H3 positivity in the NRG-HG group only. For in vivo studies, 2-month-old mice (n=60) underwent left anterior descending coronary artery ligation and were randomized to the 4 treatment groups mentioned. Only NRG-HG-treated mice demonstrated phosphorylated histone H3 and Ki67 positivity along with decreased caspase-3 activity compared with all controls. NRG was detected in myocardium 6 days after injection without evidence of off-target exposure in NRG-HG animals. At 2 weeks, the NRG-HG group exhibited enhanced left ventricular ejection fraction, decreased left ventricular area, and augmented borderzone thickness.
CONCLUSIONS: Targeted and sustained delivery of NRG directly to the myocardial borderzone augments cardiomyocyte mitotic activity, decreases apoptosis, and greatly enhances left ventricular function in a model of ischemic cardiomyopathy. This novel approach to NRG administration avoids off-target exposure and represents a clinically translatable strategy in myocardial regenerative therapeutics.
PMID: 24902740 [PubMed - indexed for MEDLINE]
Use of transmission electron microscopy to identify nanocrystals of challenging protein targets.
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8470-5
Authors: Stevenson HP, Makhov AM, Calero M, Edwards AL, Zeldin OB, Mathews II, Lin G, Barnes CO, Santamaria H, Ross TM, Soltis SM, Khosla C, Nagarajan V, Conway JF, Cohen AE, Calero G
The current practice for identifying crystal hits for X-ray crystallography relies on optical microscopy techniques that are limited to detecting crystals no smaller than 5 μm. Because of these limitations, nanometer-sized protein crystals cannot be distinguished from common amorphous precipitates, and therefore go unnoticed during screening. These crystals would be ideal candidates for further optimization or for femtosecond X-ray protein nanocrystallography. The latter technique offers the possibility to solve high-resolution structures using submicron crystals. Transmission electron microscopy (TEM) was used to visualize nanocrystals (NCs) found in crystallization drops that would classically not be considered as "hits." We found that protein NCs were readily detected in all samples tested, including multiprotein complexes and membrane proteins. NC quality was evaluated by TEM visualization of lattices, and diffraction quality was validated by experiments in an X-ray free electron laser.
PMID: 24872454 [PubMed - indexed for MEDLINE]
Large-scale comparison of science teaching methods sends clear message.
Proc Natl Acad Sci U S A. 2014 Jun 10;111(23):8319-20
Authors: Wieman CE
PMID: 24853505 [PubMed - indexed for MEDLINE]
Toward an improved definition of acute-on-chronic liver failure.
Gastroenterology. 2014 Jul;147(1):4-10
Authors: Jalan R, Yurdaydin C, Bajaj JS, Acharya SK, Arroyo V, Lin HC, Gines P, Kim WR, Kamath PS, World Gastroenterology Organization Working Party
PMID: 24853409 [PubMed - indexed for MEDLINE]
Assessment of elastin deficit in a Marfan mouse aneurysm model using an elastin-specific magnetic resonance imaging contrast agent.
Circ Cardiovasc Imaging. 2014 Jul;7(4):690-6
Authors: Okamura H, Pisani LJ, Dalal AR, Emrich F, Dake BA, Arakawa M, Onthank DC, Cesati RR, Robinson SP, Milanesi M, Kotek G, Smit H, Connolly AJ, Adachi H, McConnell MV, Fischbein MP
BACKGROUND: Ascending aortic dissection and rupture remain a life-threatening complication in patients with Marfan syndrome. The extracellular matrix provides strength and elastic recoil to the aortic wall, thereby preventing radial expansion. We have previously shown that ascending aortic aneurysm formation in Marfan mice (Fbn1(C1039G/+)) is associated with decreased aortic wall elastogenesis and increased elastin breakdown. In this study, we test the feasibility of quantifying aortic wall elastin content using MRI with a gadolinium-based elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) mice.
METHODS AND RESULTS: Ascending aorta elastin content was measured in 32-week-old Fbn1(C1039G/+) mice and wild-type (n=9 and n=10, respectively) using 7-T MRI with a T1 mapping sequence. Significantly lower enhancement (ie, lower R1 values, where R1=1/T1) was detected post-elastin-specific magnetic resonance contrast agent in Fbn1(C1039G/+) compared with wild-type ascending aortas (1.15±0.07 versus 1.36±0.05; P<0.05). Post-elastin-specific magnetic resonance contrast agent R1 values correlated with ascending aortic wall gadolinium content directly measured by inductively coupled mass spectroscopy (P=0.006).
CONCLUSIONS: Herein, we demonstrate that MRI with elastin-specific magnetic resonance contrast agent accurately measures elastin bound gadolinium within the aortic wall and detects a decrease in aortic wall elastin in Marfan mice compared with wild-type controls. This approach has translational potential for noninvasively assessing aneurysm tissue changes and risk, as well as monitoring elastin content in response to therapeutic interventions.
PMID: 24814820 [PubMed - indexed for MEDLINE]
New American Heart Association/American College of Cardiology guidelines on cardiovascular risk: when will fitness get the recognition it deserves?
Mayo Clin Proc. 2014 Jun;89(6):722-6
Authors: Myers J
PMID: 24809757 [PubMed - indexed for MEDLINE]
Mucociliary clearance and submucosal gland secretion in the ex vivo ferret trachea.
Am J Physiol Lung Cell Mol Physiol. 2014 Jul 1;307(1):L83-93
Authors: Jeong JH, Joo NS, Hwang PH, Wine JJ
In many species submucosal glands are an important source of tracheal mucus, but the extent to which mucociliary clearance (MCC) depends on gland secretion is unknown. To explore this relationship, we measured basal and agonist-stimulated MCC velocities in ex vivo tracheas from adult ferrets and compared the velocities with previously measured rates of ferret glandular mucus secretion (Cho HJ, Joo NS, Wine JJ. Am J Physiol Lung Cell Mol Physiol 299: L124-L136, 2010). Stimulated MCC velocities (mm/min, means ± SE for 10- to 35-min period poststimulation) were as follows: 1 μM carbachol: 19.1 ± 3.3 > 10 μM phenylephrine: 15.3 ± 2.4 ≈ 10 μM isoproterenol: 15.0 ± 1.9 ≈ 10 μM forskolin: 14.6 ± 3.1 > 1 μM vasoactive intestinal peptide (VIP): 10.2 ± 2.2 >> basal (t15): 1.8 ± 0.3; n = 5-10 for each condition. Synergistic stimulation of MCC was observed between low concentrations of carbachol (100 nM) and isoproterenol (300 nM). Bumetanide inhibited carbachol-stimulated MCC by ~70% and abolished the increase in MCC stimulated by forskolin + VIP, whereas HCO3 (-)-free solutions did not significantly inhibit MCC to either intracellular Ca(2+) concentration or intracellular cAMP concentration ([cAMP]i)-elevating agonists. Stimulation and inhibition of MCC and gland secretion differed in several respects: most importantly, elevating [cAMP]i increased MCC much more effectively than expected from its effects on gland secretion, and bumetanide almost completely inhibited [cAMP]i-stimulated MCC while it had a smaller effect on gland secretion. We conclude that changes in glandular fluid secretion are complexly related to MCC and discuss possible reasons for this.
PMID: 24793168 [PubMed - indexed for MEDLINE]
Outcomes after coronary artery calcium and other cardiovascular biomarker testing among asymptomatic medicare beneficiaries.
Circ Cardiovasc Imaging. 2014 Jul;7(4):655-62
Authors: Shreibati JB, Baker LC, McConnell MV, Hlatky MA
BACKGROUND: Biomarkers improve cardiovascular disease (CVD) risk prediction, but their comparative effectiveness in clinical practice is not known. We sought to compare the use, spending, and clinical outcomes in asymptomatic Medicare beneficiaries evaluated for CVD with coronary artery calcium (CAC) or other cardiovascular risk markers.
METHODS AND RESULTS: We used a 20% sample of 2005 to 2011 Medicare claims to identify fee-for-service beneficiaries aged ≥65.5 years with no CVD claims in the previous 6 months. We matched patients with CAC with patients who received high-sensitivity C-reactive protein (hs-CRP; n=8358) or lipid screening (n=6250) using propensity-score methods. CAC was associated with increased noninvasive cardiac testing within 180 days (hazard ratio, 2.22, 95% confidence interval, 1.68-2.93, P<0.001, versus hs-CRP; hazard ratio, 4.30, 95% confidence interval, 3.04-6.06, P<0.001, versus lipid screening) and increased coronary angiography and revascularization. During 3-year follow-up, CAC was associated with higher CVD-related spending ($6525 versus $4432 for hs-CRP, P<0.001; and $6500 versus $3073 for lipid screening, P<0.001) and fewer CVD-related events when compared with hs-CRP (hazard ratio, 0.74, 95% confidence interval, 0.58-0.94, P=0.017) but not compared with lipid screening (hazard ratio, 0.84, 95% confidence interval, 0.64-1.11, P=0.23).
CONCLUSIONS: CAC testing among asymptomatic Medicare beneficiaries was associated with increased use of cardiac tests and procedures, higher spending, and slightly improved clinical outcomes when compared with hs-CRP testing.
PMID: 24777939 [PubMed - indexed for MEDLINE]
Advancing adsorption and membrane separation processes for the gigaton carbon capture challenge.
Annu Rev Chem Biomol Eng. 2014;5:479-505
Authors: Wilcox J, Haghpanah R, Rupp EC, He J, Lee K
Reducing CO2 in the atmosphere and preventing its release from point-source emitters, such as coal and natural gas-fired power plants, is a global challenge measured in gigatons. Capturing CO2 at this scale will require a portfolio of gas-separation technologies to be applied over a range of applications in which the gas mixtures and operating conditions will vary. Chemical scrubbing using absorption is the current state-of-the-art technology. Considerably less attention has been given to other gas-separation technologies, including adsorption and membranes. It will take a range of creative solutions to reduce CO2 at scale, thereby slowing global warming and minimizing its potential negative environmental impacts. This review focuses on the current challenges of adsorption and membrane-separation processes. Technological advancement of these processes will lead to reduced cost, which will enable subsequent adoption for practical scaled-up application.
PMID: 24702296 [PubMed - indexed for MEDLINE]
Postapproval outcomes of juxtarenal aortic aneurysms treated with the Zenith fenestrated endovascular graft.
J Vasc Surg. 2014 Aug;60(2):295-300
Authors: Vemuri C, Oderich GS, Lee JT, Farber MA, Fajardo A, Woo EY, Cayne N, Sanchez LA
OBJECTIVE: The objective of this study was to evaluate postapproval outcomes of patients with juxtarenal aortic aneurysms treated with the Zenith fenestrated endovascular graft (Cook Inc, Bloomington, Ind).
METHODS: We reviewed clinical data of consecutive patients treated with the Zenith fenestrated endovascular graft in the United States at seven institutions with early commercial access from July 2012 to December 2012. Clinical outcomes and compliance to anatomic guidelines were compared with results of the U.S. fenestrated trial (USFT).
RESULTS: Fifty-seven patients were treated. There were significantly more (P < .05) patients with coronary artery disease, myocardial infarction, and preoperative renal insufficiency than in the USFT. Thirty-six patients (63.2%) did not meet the USFT anatomic criteria of a >4-mm infrarenal neck, and there were significantly more mesenteric stents (13 vs 0; P < .05) used in this group than in the USFT, reflecting the higher anatomic complexity of these patients. The total operative time was 250.2 ± 14.8 minutes, the fluoroscopy time was 68.9 ± 4.47 minutes, and the average volume of contrast material was 108.6 ± 5.6 mL. Technical success was 100% in regard to aneurysm exclusion, although the left renal fenestration was not able to be aligned in two patients, and one patient had a kinked renal stent that was successfully restented. During this time period, there were a total of 10 endoleaks, of which two were type III and eight were type II.
CONCLUSIONS: Despite higher rates of comorbidities and more challenging anatomy, early 30-day outcomes of juxtarenal aortic aneurysms treated postapproval with the Zenith fenestrated endovascular graft compare well with USFT data. Future studies are needed to assess durability of this treatment modality as the technology diffuses and data mature.
PMID: 24680241 [PubMed - indexed for MEDLINE]
Response to letter to the editor regarding "Application of principal component analysis in clinical gait research".
J Biomech. 2014 Apr 11;47(6):1555-6
Authors: Federolf P, Boyer K, Andriacchi T
PMID: 24602290 [PubMed - indexed for MEDLINE]
What drives the comparative effectiveness of biologics vs. methotrexate in rheumatoid arthritis? Meta-regression and graphical inspection of suspected clinical factors.
Rheumatology (Oxford). 2014 Jul;53(7):1264-73
Authors: Kanters S, Druyts E, Mills EJ, Thorlund K
OBJECTIVE: The aim of this study was to explore which clinical factors and patient characteristics are associated with the magnitude of comparative efficacy between biologics vs. MTX in RA patients with inadequate response to MTX.
METHODS: We included randomized controlled trials assessing the efficacy of a biologic plus MTX vs. MTX alone. We examined several clinical factors and patient characteristics potentially associated with magnitude of response, measured as ACR20 (20% improvement in ACR criteria) and ACR50 (16-26 weeks). We employed meta-regression for formal estimates and statistical significance of effect modification. We produced regression and forest plots to further inspect potential associations.
RESULTS: For ACR50, a 1-year increment on the average patient disease duration was statistically significantly associated with a 16% relative increase in the pooled odds ratio (OR) estimate (P = 0.003). A 1-year increment in patient age and a 1 mg/week increment in MTX dose were marginally statistically significantly associated with a 9% (P = 0.056) and 22% (P = 0.092) relative increase in the OR. For ACR20, the average number of swollen and tender joints was marginally statistically associated with a 3% relative decrease. The associations for age and MTX dose appeared to be partly driven by significant negative associations between these two factors and the control group response.
CONCLUSION: Our analyses identified key variables associated with the magnitude of comparative effects for ACR outcomes. Our findings provide valuable insights for future trial designs and systematic reviews as well as decision-making and clinical practice.
PMID: 24599922 [PubMed - indexed for MEDLINE]
Response to letter regarding article, "Prognostic value of the index of microcirculatory resistance measured after primary percutaneous coronary intervention".
Circulation. 2014 Feb 18;129(7):e342
Authors: Fearon WF, Low AF, Yong AC, McGeoch R, Berry C, Shah MG, Ho M, Kim HS, Loh JP, Oldroyd KG
PMID: 24550557 [PubMed - indexed for MEDLINE]
A novel electron gun for inline MRI-linac configurations.
Med Phys. 2014 Feb;41(2):022301
Authors: Constantin DE, Holloway L, Keall PJ, Fahrig R
PURPOSE: This work introduces a new electron gun geometry capable of robust functioning in the presence of a high strength external magnetic field for axisymmetric magnetic resonance imaging (MRI)-linac configurations. This allows an inline MRI-linac to operate without the need to isolate the linear accelerator (linac) using a magnetic shield. This MRI-linac integration approach not only leaves the magnet homogeneity unchanged but also provides the linac flexibility to move along the magnet axis of symmetry if the source to target distance needs to be adjusted.
METHODS: Simple electron gun geometry modifications of a Varian 600 C electron gun are considered and solved in the presence of an external magnetic field in order to determine a set of design principles for the new geometry. Based on these results, a new gun geometry is proposed and optimized in the fringe field of a 0.5 T open bore MRI magnet (GE Signa SP). A computer model for the 6 MeV Varian 600 C linac is used to determine the capture efficiency of the new electron gun-linac system in the presence of the fringe field of the same MRI scanner. The behavior of the new electron gun plus the linac system is also studied in the fringe fields of two other magnets, a 1.0 T prototype open bore magnet and a 1.5 T GE Conquest scanner.
RESULTS: Simple geometrical modifications of the original electron gun geometry do not provide feasible solutions. However, these tests show that a smaller transverse cathode diameter with a flat surface and a slightly larger anode diameter could alleviate the current loss due to beam interactions with the anode in the presence of magnetic fields. Based on these findings, an initial geometry resembling a parallel plate capacitor with a hole in the anode is proposed. The optimization procedure finds a cathode-anode distance of 5 mm, a focusing electrode angle of 5°, and an anode drift tube length of 17.1 mm. Also, the linac can be displaced with ± 15 cm along the axis of the 0.5 T magnet without capture efficiency reduction below the experimental value in zero field. In this range of linac displacements, the electron beam generated by the new gun geometry is more effectively injected into the linac in the presence of an external magnetic field, resulting in approximately 20% increase of the target current compared to the original gun geometry behavior at zero field. The new gun geometry can generate and accelerate electron beams in external magnetic fields without current loss for fields higher than 0.11 T. The new electron-gun geometry is robust enough to function in the fringe fields of the other two magnets with a target current loss of no more than 16% with respect to the current obtained with no external magnetic fields.
CONCLUSIONS: In this work, a specially designed electron gun was presented which can operate in the presence of axisymmetric strong magnetic fringe fields of MRI magnets. Computer simulations show that the electron gun can produce high quality beams which can be injected into a straight through linac such as Varian 600 C and accelerated with more efficiency in the presence of the external magnetic fields. Also, the new configuration allows linac displacements along the magnet axis in a range equal to the diameter of the imaging spherical volume of the magnet under consideration. The new electron gun-linac system can function in the fringe field of a MRI magnet if the field strength at the cathode position is higher than 0.11 T. The capture efficiency of the linac depends on the magnetic field strength and the field gradient. The higher the gradient the better the capture efficiency. The capture efficiency does not degrade more than 16%.
PMID: 24506639 [PubMed - indexed for MEDLINE]
Dose reduction using a dynamic, piecewise-linear attenuator.
Med Phys. 2014 Feb;41(2):021910
Authors: Hsieh SS, Fleischmann D, Pelc NJ
PURPOSE: The authors recently proposed a dynamic, prepatient x-ray attenuator capable of producing a piecewise-linear attenuation profile customized to each patient and viewing angle. This attenuator was intended to reduce scatter-to-primary ratio (SPR), dynamic range, and dose by redistributing flux. In this work the authors tested the ability of the attenuator to reduce dose and SPR in simulations.
METHODS: The authors selected four clinical applications, including routine full field-of-view scans of the thorax and abdomen, and targeted reconstruction tasks for an abdominal aortic aneurysm and the pancreas. Raw data were estimated by forward projection of the image volume datasets. The dynamic attenuator was controlled to reduce dose while maintaining peak variance by solving a convex optimization problem, assuminga priori knowledge of the patient anatomy. In targeted reconstruction tasks, the noise in specific regions was given increased weighting. A system with a standard attenuator (or "bowtie filter") was used as a reference, and used either convex optimized tube current modulation (TCM) or a standard TCM heuristic. The noise of the scan was determined analytically while the dose was estimated using Monte Carlo simulations. Scatter was also estimated using Monte Carlo simulations. The sensitivity of the dynamic attenuator to patient centering was also examined by shifting the abdomen in 2 cm intervals.
RESULTS: Compared to a reference system with optimized TCM, use of the dynamic attenuator reduced dose by about 30% in routine scans and 50% in targeted scans. Compared to the TCM heuristics which are typically used withouta priori knowledge, the dose reduction is about 50% for routine scans. The dynamic attenuator gives the ability to redistribute noise and variance and produces more uniform noise profiles than systems with a conventional bowtie filter. The SPR was also modestly reduced by 10% in the thorax and 24% in the abdomen. Imaging with the dynamic attenuator was relatively insensitive to patient centering, showing a 17% increase in peak variance for a 6 cm shift of the abdomen, instead of an 82% increase in peak variance for a fixed bowtie filter.
CONCLUSIONS: A dynamic prepatient x-ray attenuator consisting of multiple wedges is capable of achieving substantial dose reductions and modest SPR reductions.
PMID: 24506631 [PubMed - indexed for MEDLINE]
The potential of positron emission tomography for intratreatment dynamic lung tumor tracking: a phantom study.
Med Phys. 2014 Feb;41(2):021718
Authors: Yang J, Yamamoto T, Mazin SR, Graves EE, Keall PJ
PURPOSE: This study aims to evaluate the potential and feasibility of positron emission tomography for dynamic lung tumor tracking during radiation treatment. The authors propose a center of mass (CoM) tumor tracking algorithm using gated-PET images combined with a respiratory monitor and investigate the geometric accuracy of the proposed algorithm.
METHODS: The proposed PET dynamic lung tumor tracking algorithm estimated the target position information through the CoM of the segmented target volume on gated PET images reconstructed from accumulated coincidence events. The information was continuously updated throughout a scan based on the assumption that real-time processing was supported (actual processing time at each frame ≈ 10 s). External respiratory motion and list-mode PET data were acquired from a phantom programmed to move with measured respiratory traces (external respiratory motion and internal target motion) from human subjects, for which the ground truth target position was known as a function of time. The phantom was cylindrical with six hollow sphere targets (10, 13, 17, 22, 28, and 37 mm in diameter). The measured respiratory traces consisted of two sets: (1) 1D-measured motion from ten healthy volunteers and (2) 3D-measured motion from four lung cancer patients. The authors evaluated the geometric accuracy of the proposed algorithm by quantifying estimation errors (Euclidean distance) between the actual motion of targets (1D-motion and 3D-motion traces) and CoM trajectories estimated by the proposed algorithm as a function of time.
RESULTS: The time-averaged error of 1D-motion traces over all trajectories of all targets was 1.6 mm. The error trajectories decreased with time as coincidence events were accumulated. The overall error trajectory of 1D-motion traces converged to within 2 mm in approximately 90 s. As expected, more accurate results were obtained for larger targets. For example, for the 37 mm target, the average error over all 1D-motion traces was 1.1 mm; and for the 10 mm target, the average error over all 1D-motion traces was 2.8 mm. The overall time-averaged error of 3D-motion traces was 1.6 mm, which was comparable to that of the 1D-motion traces. There were small variations in the errors between the 3D-motion traces, although the motion trajectories were very different. The accuracy of the estimates was consistent for all targets except for the smallest.
CONCLUSIONS: The authors developed an algorithm for dynamic lung tumor tracking using list-mode PET data and a respiratory motion signal, and demonstrated proof-of-principle for PET-guided lung tumor tracking. The overall tracking error in phantom studies is less than 2 mm.
PMID: 24506609 [PubMed - indexed for MEDLINE]
Monitoring the immune competence of cancer patients to predict outcome.
Cancer Immunol Immunother. 2014 Jul;63(7):713-9
Authors: Chang S, Kohrt H, Maecker HT
A new era of cancer immunotherapy has brought not only successful cancer vaccines but also immunomodulators, such as those that target checkpoint blockade in order to induce endogenous host immune responses. However, the immune system of cancer patients can be compromised through multiple means, including immune suppression by the tumor and by prior therapies such as chemotherapy and radiation. Therefore, a comprehensive means of assessing patient immunocompetence would seem helpful for determining whether patients are ready to benefit from immunotherapy, and perhaps even which immunotherapy might be most appropriate for them. Unfortunately, there are no standardized tests for immune competence, nor is there agreement on what to measure and what will be predictive of outcome. In this review, we will discuss the technologies and assays that might be most useful for this purpose. We argue for a comprehensive approach that should maximize the chances of developing predictive biomarkers for eventual clinical use.
PMID: 24487923 [PubMed - indexed for MEDLINE]
Evolution of a unique anatomical precision in angiosperm leaf venation lifts constraints on vascular plant ecology.
Proc Biol Sci. 2014 Mar 22;281(1779):20132829
Authors: Zwieniecki MA, Boyce CK
The main role of leaf venation is to supply water across the photosynthetic surface to keep stomata open and allow access to atmospheric CO2 despite evaporative demand. The optimal uniform delivery of water occurs when the distance between veins equals the depth of vein placement within the leaf away from the evaporative surface. As presented here, only angiosperms maintain this anatomical optimum across all leaf thicknesses and different habitats, including sheltered environments where this optimization need not be required. Intriguingly, basal angiosperm lineages tend to be underinvested hydraulically; uniformly high optimization is derived independently in the magnoliids, monocots and core eudicots. Gymnosperms and ferns, including available fossils, are limited by their inability to produce high vein densities. The common association of ferns with shaded humid environments may, in part, be a direct evolutionary consequence of their inability to produce hydraulically optimized leaves. Some gymnosperms do approach optimal vein placement, but only by virtue of their ability to produce thick leaves most appropriate in environments requiring water conservation. Thus, this simple anatomical metric presents an important perspective on the evolution and phylogenetic distribution of plant ecologies and further evidence that the vegetative biology of flowering plants-not just their reproductive biology-is unique.
PMID: 24478301 [PubMed - indexed for MEDLINE]
Comprehensive review of surgeries for obstructive sleep apnea syndrome.
Braz J Otorhinolaryngol. 2013 Nov-Dec;79(6):780-8
Authors: Camacho M, Certal V, Capasso R
UNLABELLED: There are several surgical treatment modalities utilized for obstructive sleep apnea syndrome (OSAS). OSAS can cause excessive daytime sleepiness as well as cardiovascular morbidity and mortality. Patients who fail medical management often seek surgical treatment.
OBJECTIVE: This paper reviews surgical treatment options for obstructive sleep apnea syndrome to include original descriptions as well as outcomes for snoring, apnea-hypopnea indices, and mortality benefits.
METHOD: A literature review was performed for OSAS surgical treatment options for soft tissue and skeletal surgeries. Articles with the original descriptions and surgical reviews are included for each procedure.
RESULTS: A total of twenty-eight surgical treatment modalities for OSAS were identified. Original article authors and year of description were obtained and presented. Polysomnographic data for apnea indices, apnea-hypopnea indices and mortality are presented.
CONCLUSION: There is a large amount of variability in outcomes for sleep surgeries, however, in order to maximize success and cure rates, multiple procedures are most often necessary. Sleep surgeons must get familiar with modern surgical concepts and techniques, and participate in multi-disciplinary care in order to maximize treatment outcomes.
PMID: 24474491 [PubMed - indexed for MEDLINE]
Hyperuricaemia: the unintended consequence of insulin resistance/compensatory hyperinsulinaemia. Philanthropy gone awry.
J Intern Med. 2014 Aug;276(2):196-8
Authors: Knowles JW, Reaven G
PMID: 24471887 [PubMed - indexed for MEDLINE]
Do physiatric procedures represent a value or liability?
PM R. 2014 Jan;6(1):85-91
Authors: Furman MB, Melvin JL, Kennedy DJ
PMID: 24439151 [PubMed - indexed for MEDLINE]
Environmental variability counteracts priority effects to facilitate species coexistence: evidence from nectar microbes.
Proc Biol Sci. 2014 Mar 7;281(1778):20132637
Authors: Tucker CM, Fukami T
The order of species arrival during community assembly can greatly affect species coexistence, but the strength of these effects, known as priority effects, appears highly variable across species and ecosystems. Furthermore, the causes of this variation remain unclear despite their fundamental importance in understanding species coexistence. Here, we show that one potential cause is environmental variability. In laboratory experiments using nectar-inhabiting microorganisms as a model system, we manipulated spatial and temporal variability of temperature, and examined consequences for priority effects. If species arrived sequentially, multiple species coexisted under variable temperature, but not under constant temperature. Temperature variability prevented extinction of late-arriving species that would have been excluded owing to priority effects if temperature had been constant. By contrast, if species arrived simultaneously, species coexisted under both variable and constant temperatures. We propose possible mechanisms underlying these results using a mathematical model that incorporates contrasting effects of microbial species on nectar pH and amino acids. Overall, our findings suggest that understanding consequences of priority effects for species coexistence requires explicit consideration of environmental variability.
PMID: 24430846 [PubMed - indexed for MEDLINE]
Slow wave activity is reliably low in sleepwalkers: response to Pressman et al. letter to the editor.
J Clin Sleep Med. 2014 Jan 15;10(1):113-5
Authors: Cartwright R, Guilleminault C
PMID: 24426832 [PubMed - indexed for MEDLINE]
Use of Medicare data to identify coronary heart disease outcomes in the Women's Health Initiative.
Circ Cardiovasc Qual Outcomes. 2014 Jan;7(1):157-62
Authors: Hlatky MA, Ray RM, Burwen DR, Margolis KL, Johnson KC, Kucharska-Newton A, Manson JE, Robinson JG, Safford MM, Allison M, Assimes TL, Bavry AA, Berger J, Cooper-DeHoff RM, Heckbert SR, Li W, Liu S, Martin LW, Perez MV, Tindle HA, Winkelmayer WC, Stefanick ML
BACKGROUND: Data collected as part of routine clinical practice could be used to detect cardiovascular outcomes in pragmatic clinical trials or clinical registry studies. The reliability of claims data for documenting outcomes is unknown.
METHODS AND RESULTS: We linked records of Women's Health Initiative (WHI) participants aged ≥65 years to Medicare claims data and compared hospitalizations that had diagnosis codes for acute myocardial infarction or coronary revascularization with WHI outcomes adjudicated by study physicians. We then compared the hazard ratios for active versus placebo hormone therapy based solely on WHI-adjudicated events with corresponding hazard ratios based solely on claims data for the same hormone trial participants. Agreement between WHI-adjudicated outcomes and Medicare claims was good for the diagnosis of myocardial infarction (κ, 0.71-0.74) and excellent for coronary revascularization (κ, 0.88-0.91). The hormone:placebo hazard ratio for clinical myocardial infarction was 1.31 (95% confidence interval, 1.03-1.67) based on WHI outcomes and 1.29 (95% confidence interval, 1.00-1.68) based on Medicare data. The hazard ratio for coronary revascularization was 1.09 (95% confidence interval, 0.88-1.35) based on WHI outcomes and 1.10 (95% confidence interval, 0.89-1.35) based on Medicare data. The differences between hazard ratios derived from WHI and Medicare data were not significant in 1000 bootstrap replications.
CONCLUSIONS: Medicare claims may provide useful data on coronary heart disease outcomes among patients aged ≥65 years in clinical research studies.
CLINICAL TRIALS REGISTRATION INFORMATION: URL: www.clinicaltrials.gov. Unique identifier: NCT00000611.
PMID: 24399330 [PubMed - indexed for MEDLINE]
Strategies to predict, measure, and improve psychosocial treatment adherence.
Harv Rev Psychiatry. 2014 Jan-Feb;22(1):31-45
Authors: Gearing RE, Townsend L, Elkins J, El-Bassel N, Osterberg L
Nonadherence to psychosocial and behavioral treatment is a significant public health problem that presents a barrier to recovery and effective treatment. An estimated 20% to 70% of individuals who initiate psychosocial mental health services discontinue treatment prior to clinicians' recommendations. Empirically supported, evidence-based, stand-alone or adjunctive psychosocial interventions treat an increasingly wide range of mental health conditions. A core assumption of most, if not all, interventions is that clients will fully and actively engage in the treatment protocol. Adherence to psychosocial treatment has received much less scientific attention, however, than adherence to medical treatment. Drawing extensively from existing research, this comprehensive review conceptualizes several types of psychosocial and behavioral treatment adherence, examines predictors of adherence to psychosocial treatment, summarizes measures of adherence, and describes existing interventions to enhance psychosocial treatment adherence.
PMID: 24394220 [PubMed - indexed for MEDLINE]
A single-nucleotide polymorphism of human neuropeptide s gene originated from Europe shows decreased bioactivity.
PLoS One. 2013;8(12):e83009
Authors: Deng C, He X, Hsueh AJ
Using accumulating SNP (Single-Nucleotide Polymorphism) data, we performed a genome-wide search for polypeptide hormone ligands showing changes in the mature regions to elucidate genotype/phenotype diversity among various human populations. Neuropeptide S (NPS), a brain peptide hormone highly conserved in vertebrates, has diverse physiological effects on anxiety, fear, hyperactivity, food intake, and sleeping time through its cognate receptor-NPSR. Here, we report a SNP rs4751440 (L(6)-NPS) causing non-synonymous substitution on the 6(th) position (V to L) of the NPS mature peptide region. L(6)-NPS has a higher allele frequency in Europeans than other populations and probably originated from European ancestors ~25,000 yrs ago based on haplotype analysis and Approximate Bayesian Computation. Functional analyses indicate that L(6)-NPS exhibits a significant lower bioactivity than the wild type NPS, with ~20-fold higher EC50 values in the stimulation of NPSR. Additional evolutionary and mutagenesis studies further demonstrate the importance of the valine residue in the 6(th) position for NPS functions. Given the known physiological roles of NPS receptor in inflammatory bowel diseases, asthma pathogenesis, macrophage immune responses, and brain functions, our study provides the basis to elucidate NPS evolution and signaling diversity among human populations.
PMID: 24386135 [PubMed - indexed for MEDLINE]
Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.
PLoS One. 2013;8(12):e82879
Authors: Zech M, Nübling G, Castrop F, Jochim A, Schulte EC, Mollenhauer B, Lichtner P, Peters A, Gieger C, Marquardt T, Vanier MT, Latour P, Klünemann H, Trenkwalder C, Diehl-Schmid J, Perneczky R, Meitinger T, Oexle K, Haslinger B, Lorenzl S, Winkelmann J
Niemann-Pick type C (NPC) disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95%) or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563), FTLD (n = 133) and PSP (n = 94), and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1%) and seven control subjects (0.8%), but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted.
PMID: 24386122 [PubMed - indexed for MEDLINE]
Extensive differences in gene expression between symbiotic and aposymbiotic cnidarians.
G3 (Bethesda). 2014 Feb;4(2):277-95
Authors: Lehnert EM, Mouchka ME, Burriesci MS, Gallo ND, Schwarz JA, Pringle JR
Coral reefs provide habitats for a disproportionate number of marine species relative to the small area of the oceans that they occupy. The mutualism between the cnidarian animal hosts and their intracellular dinoflagellate symbionts provides the nutritional foundation for coral growth and formation of reef structures, because algal photosynthesis can provide >90% of the total energy of the host. Disruption of this symbiosis ("coral bleaching") is occurring on a large scale due primarily to anthropogenic factors and poses a major threat to the future of coral reefs. Despite the importance of this symbiosis, the cellular mechanisms involved in its establishment, maintenance, and breakdown remain largely unknown. We report our continued development of genomic tools to study these mechanisms in Aiptasia, a small sea anemone with great promise as a model system for studies of cnidarian-dinoflagellate symbiosis. Specifically, we have generated de novo assemblies of the transcriptomes of both a clonal line of symbiotic anemones and their endogenous dinoflagellate symbionts. We then compared transcript abundances in animals with and without dinoflagellates. This analysis identified >900 differentially expressed genes and allowed us to generate testable hypotheses about the cellular functions affected by symbiosis establishment. The differentially regulated transcripts include >60 encoding proteins that may play roles in transporting various nutrients between the symbiotic partners; many more encoding proteins functioning in several metabolic pathways, providing clues regarding how the transported nutrients may be used by the partners; and several encoding proteins that may be involved in host recognition and tolerance of the dinoflagellate.
PMID: 24368779 [PubMed - indexed for MEDLINE]
Identification of common blood gene signatures for the diagnosis of renal and cardiac acute allograft rejection.
PLoS One. 2013;8(12):e82153
Authors: Li L, Khush K, Hsieh SC, Ying L, Luikart H, Sigdel T, Roedder S, Yang A, Valantine H, Sarwal MM
To test, whether 10 genes, diagnostic of renal allograft rejection in blood, are able to diagnose and predict cardiac allograft rejection, we analyzed 250 blood samples from heart transplant recipients with and without acute rejection (AR) and with cytomegalovirus (CMV) infection by QPCR. A QPCR-based logistic regression model was built on 5 of these 10 genes (AR threshold composite score >37% = AR) and tested for AR prediction in an independent set of 109 samples, where it correctly diagnosed AR with 89% accuracy, with no misclassifications for AR ISHLT grade 1b. CMV infection did not confound the AR score. The genes correctly diagnosed AR in a blood sample within 6 months prior to biopsy diagnosis with 80% sensitivity and untreated grade 1b AR episodes had persistently elevated scores until 6 months after biopsy diagnosis. The gene score was also correlated with presence or absence of cardiac allograft vasculopathy (CAV) irrespective of rejection grade. In conclusion, there is a common transcriptional axis of immunological trafficking in peripheral blood in both renal and cardiac organ transplant rejection, across a diverse recipient age range. A common gene signature, initially identified in the setting of renal transplant rejection, can be utilized serially after cardiac transplantation, to diagnose and predict biopsy confirmed acute heart transplant rejection.
PMID: 24358149 [PubMed - indexed for MEDLINE]
The comorbidity of sleep apnea and mood, anxiety, and substance use disorders among obese military veterans within the Veterans Health Administration.
J Clin Sleep Med. 2013;9(12):1253-8
Authors: Babson KA, Del Re AC, Bonn-Miller MO, Woodward SH
OBJECTIVES: To determine the relations between obstructive sleep apnea (OSA) diagnosis, the likelihood of being diagnosed with a psychological condition, among obese veterans, after accounting for severity of obesity and the correlated nature of patients within facility. We hypothesized that (1) individuals with a diagnosis of OSA would be more likely to receive a diagnosis of a (a) mood disorder and (b) anxiety disorder, but not (c) substance use disorder.
DESIGN: Cross-sectional retrospective database review of outpatient medical records between October 2009 and September 2010, conducted across all 140 Veterans Health Administration (VHA) facilities.
SETTING: The entire VA Health Care System.
PATIENTS OR PARTICIPANTS: Population-based sample of veterans with obesity (N = 2,485,658).
MAIN OUTCOME MEASURES: Physician- or psychologist-determined diagnosis of psychological conditions including mood, anxiety, and substance use disorders.
RESULTS: Using generalized linear mixed modeling, after accounting for the correlated nature of patients within facility and the severity of obesity, individuals with a diagnosis of sleep apnea had increased odds of receiving a mood disorder diagnosis (OR = 1.85; CI = 1.71-1.72; p < 0.001), anxiety disorder diagnosis (OR = 1.82; CI = 1.77-1.84; p < 0.001), but not a diagnosis of substance use disorder.
CONCLUSIONS: Among obese veterans within VA, OSA is associated with increased risk for having a mood and anxiety disorder, but not substance use disorder, with the strongest associations observed for posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). In addition, this relation remained after accounting for severity of BMI.
PMID: 24340286 [PubMed - indexed for MEDLINE]
Renewing US medical students' interest in primary care: bridging the role model gap.
Postgrad Med J. 2014 Jan;90(1059):1-2
Authors: Teng VC, Lin SY
PMID: 24336309 [PubMed - indexed for MEDLINE]
The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation.
J Heart Lung Transplant. 2013 Dec;32(12):1147-62
Authors: Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC, Goddard M, Hammond EH, Leone O, Marboe C, Miller D, Neil D, Rassl D, Revelo MP, Rice A, Rene Rodriguez E, Stewart S, Tan CD, Winters GL, West L, Mehra MR, Angelini A
During the last 25 years, antibody-mediated rejection of the cardiac allograft has evolved from a relatively obscure concept to a recognized clinical complication in the management of heart transplant patients. Herein we report the consensus findings from a series of meetings held between 2010-2012 to develop a Working Formulation for the pathologic diagnosis, grading, and reporting of cardiac antibody-mediated rejection. The diagnostic criteria for its morphologic and immunopathologic components are enumerated, illustrated, and described in detail. Numerous challenges and unresolved clinical, immunologic, and pathologic questions remain to which a Working Formulation may facilitate answers.
PMID: 24263017 [PubMed - indexed for MEDLINE]
Cardiac arrhythmias and conduction defects in systemic sclerosis.
Rheumatology (Oxford). 2014 Jul;53(7):1172-7
Authors: Vacca A, Meune C, Gordon J, Chung L, Proudman S, Assassi S, Nikpour M, Rodriguez-Reyna TS, Khanna D, Lafyatis R, Matucci-Cerinic M, Distler O, Allanore Y, Scleroderma Clinical Trial Consortium Cardiac Subcommittee
Signs and symptoms of arrhythmias or conduction defects are frequently reported in patients with SSc. These rhythm disorders may have several origins (i.e., related to primary heart involvement, pericardial disease, valvular regurgitation or pulmonary arterial hypertension) and may negatively affect the overall prognosis of these patients. It is therefore important to identify patients at high risk for cardiac arrhythmias with a complete cardiological evaluation and to identify the underlying heart disease, including SSc-related myocardial involvement. In addition, some therapeutic options in SSc patients may differ from those recommended in other populations.
PMID: 24241036 [PubMed - indexed for MEDLINE]
Gamete-type dependent crossover interference levels in a defined region of Caenorhabditis elegans chromosome V.
G3 (Bethesda). 2014 Jan;4(1):117-20
Authors: Gabdank I, Fire AZ
In certain organisms, numbers of crossover events for any single chromosome are limited ("crossover interference") so that double crossover events are obtained at much lower frequencies than would be expected from the simple product of independent single-crossover events. We present a number of observations during which we examined interference over a large region of Caenorhabditis elegans chromosome V. Examining this region for multiple crossover events in heteroallelic configurations with limited dimorphism, we observed high levels of crossover interference in oocytes with only partial interference in spermatocytes.
PMID: 24240780 [PubMed - indexed for MEDLINE]
Outcomes of transcatheter and surgical aortic valve replacement in high-risk patients with aortic stenosis and left ventricular dysfunction: results from the Placement of Aortic Transcatheter Valves (PARTNER) trial (cohort A).
Circ Cardiovasc Interv. 2013 Dec;6(6):604-14
Authors: Elmariah S, Palacios IF, McAndrew T, Hueter I, Inglessis I, Baker JN, Kodali S, Leon MB, Svensson L, Pibarot P, Douglas PS, Fearon WF, Kirtane AJ, Maniar HS, Passeri JJ, PARTNER Investigators
BACKGROUND: The Placement of Aortic Transcatheter Valves (PARTNER) trial demonstrated similar survival after transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively) in high-risk patients with symptomatic, severe aortic stenosis. The aim of this study was to evaluate the effect of left ventricular (LV) dysfunction on clinical outcomes after TAVR and SAVR and the impact of aortic valve replacement technique on LV function.
METHODS AND RESULTS: The PARTNER trial randomized high-risk patients with severe aortic stenosis to TAVR or SAVR. Patients were stratified by the presence of LV ejection fraction (LVEF) <50%. All-cause mortality was similar for TAVR and SAVR at 30-days and 1 year regardless of baseline LV function and valve replacement technique. In patients with LV dysfunction, mean LVEF increased from 35.7±8.5% to 48.6±11.3% (P<0.0001) 1 year after TAVR and from 38.0±8.0% to 50.1±10.8% after SAVR (P<0.0001). Higher baseline LVEF (odds ratio, 0.90 [95% confidence interval, 0.86, 0.95]; P<0.0001) and previous permanent pacemaker (odds ratio, 0.34 [95% confidence interval, 0.15, 0.81]) were independently associated with reduced likelihood of ≥10% absolute LVEF improvement by 30 days; higher mean aortic valve gradient was associated with increased odds of LVEF improvement (odds ratio, 1.04 per 1 mm Hg [95% confidence interval, 1.01, 1.08]). Failure to improve LVEF by 30 days was associated with adverse 1-year outcomes after TAVR but not SAVR.
CONCLUSIONS: In high-risk patients with severe aortic stenosis and LV dysfunction, mortality rates and LV functional recovery were comparable between valve replacement techniques. TAVR is a feasible alternative for patients with symptomatic severe aortic stenosis and LV dysfunction who are at high risk for SAVR.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00530894.
PMID: 24221391 [PubMed - indexed for MEDLINE]
Initial experience using aminophylline to improve renal dysfunction in the pediatric cardiovascular ICU.
Pediatr Crit Care Med. 2014 Jan;15(1):21-7
Authors: Axelrod DM, Anglemyer AT, Sherman-Levine SF, Zhu A, Grimm PC, Roth SJ, Sutherland SM
OBJECTIVE: To determine if aminophylline administration is associated with improved creatinine clearance and greater urine output in children with acute kidney injury in the cardiovascular ICU.
DESIGN: Single-center retrospective cohort study.
SETTING: Pediatric cardiovascular ICU, university-affiliated children's hospital.
PATIENTS: Children with congenital or acquired heart disease in the cardiovascular ICU who received aminophylline to treat oliguric acute kidney injury and fluid overload.
INTERVENTIONS: Patients received aminophylline after consultation with a pediatric nephrologist. Data were collected retrospectively over 7 days to assess if aminophylline was associated with improvement in creatinine clearance, urine output, and fluid overload.
MEASUREMENTS AND MAIN RESULTS: Thirty-one patients received 52 aminophylline courses. Over the 7-day study period, serum creatinine decreased from a mean of 1.13 ± 0.91 to 0.87 ± 0.83 mg/dL (-0.05 mg/dL/d, p < 0.001). A concomitant increase was seen in estimated glomerular filtration rate from a mean of 50.0 ± 30.0 to 70.6 ± 58.1 mL/min/1.73 m (+3.66 mL/min/1.73 m/d, p < 0.001). Average daily urine output increased by 0.22 mL/kg/hr (p < 0.001), and fluid overload decreased on average by 0.42% per day in the 7-day study period (p = 0.005). Although mean furosemide dose increased slightly (0.12 mg/kg/d, p = 0.01), hydrochlorothiazide dosing did not significantly change over the study period. There were no complications related to aminophylline administration.
CONCLUSIONS: Our study suggests that aminophylline therapy may be associated with significantly improved renal excretory function and may augment urine output in children who experience oliguric acute kidney injury in the cardiovascular ICU. Additionally, we did not identify any aminophylline-related side effects in this high-risk cardiac population. Future prospective studies are necessary to confirm the safety profile and to ensure that the beneficial effects are independent of other clinical interventions.
PMID: 24212284 [PubMed - indexed for MEDLINE]
Pre-operative health status and outcomes after continuous-flow left ventricular assist device implantation.
J Heart Lung Transplant. 2013 Dec;32(12):1249-54
Authors: Flint KM, Matlock DD, Sundareswaran KS, Lindenfeld J, Spertus JA, Farrar DJ, Allen LA
BACKGROUND: Health status predicts adverse outcomes in heart failure and cardiac surgery patients, but its prognostic value in left ventricular assist device (LVAD) placement is unknown.
METHODS: We examined the association of pre-operative health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), with survival and hospitalization after LVAD using the KCCQ score as a continuous variable and stratified by KCCQ score quartile plus missing KCCQ in 1,125 clinical trial participants who received the HeartMate II (Thoratec Corp, Pleasanton, CA) as destination therapy (n = 635) or bridge to transplantation (n = 490).
RESULTS: The mean pre-operative KCCQ score was 29.4 ± 18.7 among survivors (n = 719), and 27.1 ± 18.3 (n = 406) in those who died. In time-to-event analysis for all available follow-up using health status as a continuous variable, the pre-operative KCCQ score did not correlate with overall mortality after LVAD implantation (p = 0.178). Small absolute differences were seen between the pre-operative KCCQ quartile and 30-day survival (Q4 95% vs. Q1 89% vs. missing 87%; p = 0.0009 for trend), 180-day survival (Q4 83% vs. Q1 76% vs missing 79%; p = 0.060 for trend), and days hospitalized at 180 days (Q4 29.8 ± 25.6 vs. Q1 34.1 ± 27.1 vs. missing 36.5 ± 29.9 days; p = 0.009 for trend).
CONCLUSION: Our findings suggest that pre-operative health status has limited association with outcomes after LVAD implantation. Although these data require further study in a diverse population, mechanical circulatory support may represent a relatively unique clinical situation, distinct from heart failure and other cardiac surgeries, in which heart failure-specific health status measures may be largely reversed.
PMID: 24119729 [PubMed - indexed for MEDLINE]
Patient access to medical devices-what about Japan, the second largest medical device market?
Cardiovasc Interv Ther. 2014 Jan;29(1):1-3
Authors: Ikeno F, Ikeda K, Uchida T
Patients' access to innovative medical devices in Japan still shows the gap between the other countries. The cause of this device gap is researched from the prior published data. We searched the review time of new innovative devices by the Pharmaceuticals and Medical Devices Agency (PMDA) and the submission time lag compared with the US and EU from the prior published data. The average review time was 9.5 months and the total time from PMDA to introduction of the device to patients in Japan is almost similar to the US and the four European countries. However, the time lag of the file submission between Japan and the US was 2.42 years, on average, between 2001 and 2009. The review time for new innovative medical devices by the PMDA has been improving year after year. On the contrary, the pre-submission delay still exists in Japan.
PMID: 23975639 [PubMed - indexed for MEDLINE]
A conversation with Leonard and Leonore Herzenberg.
Annu Rev Physiol. 2014;76:1-20
Authors: Herzenberg LA, Herzenberg LA, Roederer M
Leonard and Leonore Herzenberg have left an indelible mark on the fields of immunology and cell biology, both in research and clinical aspects. They are perhaps best known for developing the technologies of fluorescence flow cytometry and hybridomas. Over six decades, they made a number of important and fundamental discoveries in lymphocyte biology by applying these technologies. During this era, they immersed themselves in the sociopolitical environment, interjecting scientific rationale into public discourse about McCarthyism, nuclear fallout, war, genetics, and other politically charged topics. Their unique philosophy has shaped their lives, their science, and ultimately the scientific community. In this Conversation, we explore some of these driving forces and the impact on the laboratory.
PMID: 23957332 [PubMed - indexed for MEDLINE]
Serotonin transporter polymorphism is associated with increased apnea-hypopnea index in older adults.
Int J Geriatr Psychiatry. 2014 Mar;29(3):227-35
Authors: Schröder CM, Primeau MM, Hallmayer JF, Lazzeroni LC, Hubbard JT, O'Hara R
RATIONALE: A functional polymorphism of the serotonin transporter gene (5-HTTLPR) has previously been related to upper airway pathology, but its contribution to obstructive sleep apnea (OSA), a highly prevalent sleep disorder in older adults, remains unclear.
OBJECTIVES: We aimed to investigate the relationship between apnea-hypopnea index (AHI) and genetic variations in the promoter region of the 5-HTTLPR in older adults.
METHODS: DNA samples from 94 community-dwelling older adults (57% female, mean age 72 ± 8) were genotyped for the 5-HTTLPR polymorphism. All participants were assessed in their homes with full ambulatory polysomnography in order to determine AHI and related parameters such as hypoxia, sleep fragmentation, and self-reported daytime sleepiness.
RESULTS: The 5-HTT l allele was significantly associated with AHI (p = 0.019), with l allele carriers displaying a higher AHI than s allele homozygotes. A single allele change in 5-HTTLPR genotype from s to l resulted in an increase of AHI by 4.46 per hour of sleep (95% CI, 0.75-8.17). The l allele was also associated with increased time during sleep spent at oxygen saturation levels below 90% (p = 0.014).
CONCLUSIONS: The observed significant association between the 5-HTTLPR l allele and severity of OSA in older adults suggests that the l allele may be important to consider when assessing for OSA in this age group. This association may also explain some of the observed variability among serotonergic pharmacological treatment studies for OSA, and 5-HTT genotype status may have to be taken into account in future therapeutic trials involving serotonergic agents.
PMID: 23754303 [PubMed - indexed for MEDLINE]
Prognostic value of the Index of Microcirculatory Resistance measured after primary percutaneous coronary intervention.
Circulation. 2013 Jun 18;127(24):2436-41
Authors: Fearon WF, Low AF, Yong AS, McGeoch R, Berry C, Shah MG, Ho MY, Kim HS, Loh JP, Oldroyd KG
BACKGROUND: Most methods for assessing microvascular function are not readily available in the cardiac catheterization laboratory. The aim of this study is to determine whether the Index of Microcirculatory Resistance (IMR), measured at the time of primary percutaneous coronary intervention, is predictive of death and rehospitalization for heart failure.
METHODS AND RESULTS: IMR was measured immediately after primary percutaneous coronary intervention in 253 patients from 3 institutions with the use of a pressure-temperature sensor wire. The primary end point was the rate of death or rehospitalization for heart failure. The prognostic value of IMR was compared with coronary flow reserve, TIMI myocardial perfusion grade, and clinical variables. The mean IMR was 40.3±32.5. Patients with an IMR >40 had a higher rate of the primary end point at 1 year than patients with an IMR ≤40 (17.1% versus 6.6%; P=0.027). During a median follow-up period of 2.8 years, 13.8% experienced the primary end point and 4.3% died. An IMR >40 was associated with an increased risk of death or rehospitalization for heart failure (hazard ratio [HR], 2.1; P=0.034) and of death alone (HR, 3.95; P=0.028). On multivariable analysis, independent predictors of death or rehospitalization for heart failure included IMR >40 (HR, 2.2; P=0.026), fractional flow reserve ≤0.8 (HR, 3.24; P=0.008), and diabetes mellitus (HR, 4.4; P<0.001). An IMR >40 was the only independent predictor of death alone (HR, 4.3; P=0.02).
CONCLUSIONS: An elevated IMR at the time of primary percutaneous coronary intervention predicts poor long-term outcomes.
PMID: 23681066 [PubMed - indexed for MEDLINE]
Numerous protein-bound solutes are cleared by the kidney with high efficiency.
Kidney Int. 2013 Sep;84(3):585-90
Authors: Sirich TL, Aronov PA, Plummer NS, Hostetter TH, Meyer TW
The kidney clears numerous solutes from the plasma; however, retention of these solutes causes uremic illness when the kidneys fail. We know remarkably little about which retained solutes are toxic and this limits our ability to improve dialysis therapies. To explore this, we employed untargeted mass spectrometry to identify solutes that are efficiently cleared by the kidney. High-resolution mass spectrometry detected 1808 features in the urine and plasma ultrafiltrate of 5 individuals with normal renal function. The estimated clearance rates of 1082 peaks were greater than the creatinine clearance indicating tubular secretion. Further analysis identified 90 features representing solutes with estimated clearance rates greater than the renal plasma flow. Quantitative mass spectrometry with stable isotope dilution confirmed that efficient clearance of these solutes is made possible by the combination of binding to plasma proteins and tubular secretion. Tandem mass spectrometry established the chemical identity of 13 solutes including hippuric acid, indoxyl sulfate, and p-cresol sulfate. These 13 efficiently cleared solutes were found to accumulate in the plasma of hemodialysis patients, with free levels rising to more than 20-fold normal for all but two of them. Thus, further analysis of solutes efficiently cleared by secretion in the native kidney may provide a potential route to the identification of uremic toxins.
PMID: 23636170 [PubMed - indexed for MEDLINE]
Salvage treatment for locally recurrent nasopharyngeal carcinoma (NPC).
Am J Clin Oncol. 2014 Aug;37(4):327-31
Authors: Chen C, Fee W, Chen J, Chan C, Khong B, Hara W, Goffinet D, Li D, Le QT
BACKGROUND: It is important to determine the outcomes of retreatment in patients with locally recurrent nasopharyngeal carcinoma.
METHODS: We reviewed the records of patients treated for local recurrence at Stanford and Shantou Universities. The end points were local relapse-free survival (LRFS) and overall survival after retreatment.
RESULTS: Fifty-six patients from Stanford and 98 from Shantou qualified. For the Stanford patients, 33 had surgery alone (S group), 12 had surgery plus radiotherapy±chemotherapy (CMT group), and 22 had radiotherapy±chemotherapy (RT Stanford group). All Shantou patients received radiotherapy±chemotherapy (RT Shantou group). The 5-year LRFS rates were: 57% for S group, 25% for CMT group, 53% for RT Stanford group, and 41% for RT Shantou group (P>0.05) for rT1-2 tumors; they were 29% for S group, 25% for CMT group, 39% for RT Stanford group, and 9% for RT Shantou group for rT3-4 tumors (P>0.05). For RT patients, 5-year overall survival rates were 49% for Stanford and 25% for Shantou patients (P=0.026).
CONCLUSIONS: Similar and durable LRFS rates were attained for both S and RT groups when stratified by rT-stage.
PMID: 23275273 [PubMed - indexed for MEDLINE]
Exposure to violence in relation to depressive symptoms among male and female adolescent students in Cambodia.
Soc Psychiatry Psychiatr Epidemiol. 2013 Mar;48(3):397-405
Authors: Yi S, Poudel KC, Yasuoka J, Yi S, Palmer PH, Jimba M
PURPOSE: In spite of the apparent increases in family and community violence, research into its effects on adolescent mental health has received limited attention in Cambodia. This study examines the association between exposure to violence and depressive symptoms among adolescents controlling for the effects of several factors in family and school domains.
METHODS: We randomly selected 993 male and 950 female students proportionally from 11 junior high schools and high schools in Battembang provincial city. Students were questioned about the violence to which they were subjected and which they witnessed in their family and community. The Asian adolescent depression scale was used to measure depressive symptoms.
RESULTS: In this study, 27.9% of male students and 21.5% of female students had been victimized in at least one case of family violence, while 18.0% of male and 5.8% of female students had been victimized in at least one case of community violence. After adjustment, increased levels of depressive symptoms were significantly associated with being the victim of or witnessing family or community violence among both male and female students. However, the positive association between the levels of depressive symptoms and being a witness to community violence was found only in female students.
CONCLUSIONS: Efforts to prevent depression in adolescent students should focus on reducing family and community violence; such efforts should also consider gender differences.
PMID: 22820619 [PubMed - indexed for MEDLINE]
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