Recent Stanford Publications in PubMed
- Reviewer Acknowledgement.Doe CQ, Harris W, Shen K, Wong RNeural Dev
- The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.Stanford SN, Sabra A, D'Silva L, Lawrence M, Morris RH, Storton S, Brown MR, Evans V, Hawkins K, Williams PR, Davidson SJ, Wani M, Potter JF, Evans PABMC Neurol
- Results of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis.Warren MS, Hughes SG, Singleton W, Yamashita M, Genovese MCArthritis Res Ther
- Green EP, Catalani C, Diero L, Carter EJ, Gardner A, Ndwiga C, Keny A, Owiti P, Israelski D, Biondich PTrials
- Copy number gain of granulin-epithelin precursor (GEP) at chromosome 17q21 associates with overexpression in human liver cancer.Yung MK, Lo KW, Yip CW, Chung GT, Tong CY, Cheung PF, Cheung TT, Poon RT, So S, Fan ST, Cheung STBMC Cancer
- Cell Signaling-Based Classifier Predicts Response to Induction Therapy in Elderly Patients with Acute Myeloid Leukemia.Cesano A, Willman CL, Kopecky KJ, Gayko U, Putta S, Louie B, Westfall M, Purvis N, Spellmeyer DC, Marimpietri C, Cohen AC, Hackett J, Shi J, Walker MG, Sun Z, Paietta E, Tallman MS, Cripe LD, Atwater S, Appelbaum FR, Radich JPPLoS One
- γ-Glutamyl transferase 7 is a novel regulator of glioblastoma growth.Bui TT, Nitta RT, Kahn SA, Razavi SM, Agarwal M, Aujla P, Gholamin S, Recht L, Li GBMC Cancer
- Critical role for prokineticin 2 in CNS autoimmunity.Abou-Hamdan M, Costanza M, Fontana E, Di Dario M, Musio S, Congiu C, Onnis V, Lattanzi R, Radaelli M, Martinelli V, Salvadori S, Negri L, Poliani PL, Farina C, Balboni G, Steinman L, Pedotti RNeurol Neuroimmunol Neuroinflamm
- Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty.Mitchelson AJ, Wilson CJ, Mihalko WM, Grupp TM, Manning BT, Dennis DA, Goodman SB, Tzeng TH, Vasdev S, Saleh KJBiomed Res Int
- popRange: a highly flexible spatially and temporally explicit Wright-Fisher simulator.McManus KFSource Code Biol Med
- An observational study of adults seeking emergency care in Cambodia.Yan LD, Mahadevan SV, Yore M, Pirrotta EA, Woods J, Somontha K, Sovannra Y, Raman M, Cornell E, Grundmann C, Strehlow MCBull World Health Organ
- Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.Rinkevich Y, Walmsley GG, Hu MS, Maan ZN, Newman AM, Drukker M, Januszyk M, Krampitz GW, Gurtner GC, Lorenz HP, Weissman IL, Longaker MTScience
- Infectious disease. Combating emerging viral threats.Bekerman E, Einav SScience
- Inhibition of cathepsin proteases attenuates migration and sensitizes aggressive N-Myc amplified human neuroblastoma cells to doxorubicin.Gangoda L, Keerthikumar S, Fonseka P, Edgington LE, Ang CS, Ozcitti C, Bogyo M, Parker BS, Mathivanan SOncotarget
- Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.Younger ST, Kenzelmann-Broz D, Jung H, Attardi LD, Rinn JLNucleic Acids Res
- Anterior Septal Reconstruction for Treatment of Severe Caudal Septal Deviation: Clinical Severity and Outcomes.Surowitz J, Lee MK, Most SPOtolaryngol Head Neck Surg
- RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures.Miao Z, Adamiak RW, Blanchet MF, Boniecki M, Bujnicki JM, Chen SJ, Cheng C, Chojnowski G, Chou FC, Cordero P, Cruz JA, Ferré-D'amaré AR, Das R, Ding F, Dokholyan NV, Dunin-Horkawicz S, Kladwang W, Krokhotin A, Lach G, Magnus M, Major F, Mann TH, Masquida B, Matelska D, Meyer M, Peselis A, Popenda M, Purzycka KJ, Serganov A, Stasiewicz J, Szachniuk M, Tandon A, Tian S, Wang J, Xiao Y, Xu X, Zhang J, Zhao P, Zok T, Westhof ERNA
- Intended and unintended effects of large-scale adverse event disclosure: a controlled before-after analysis of five large-scale notifications.Wagner TH, Taylor T, Cowgill E, Asch SM, Su P, Bokhour B, Durfee J, Martinello RA, Maguire E, Elwy ARBMJ Qual Saf
- Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles nanoparticles.Campbell D, Saenz R, Bharati IS, Seible D, Zhang L, Esener S, Messmer B, Larsson M, Messmer DBreast Cancer Res
- A call to include people with mental illness and substance use disorders alongside 'regular' smokers in smoking cessation research.Lembke A, Humphreys KTob Control
- Advances in Imaging Technologies in the Evaluation of High-Grade Bladder Cancer.Zlatev DV, Altobelli E, Liao JCUrol Clin North Am
- Multimorbidity and healthcare utilisation among high-cost patients in the US Veterans Affairs Health Care System.Zulman DM, Pal Chee C, Wagner TH, Yoon J, Cohen DM, Holmes TH, Ritchie C, Asch SMBMJ Open
- Biomechanical Evaluation of Capsulotomy, Capsulectomy, and Capsular Repair on Hip Rotation.Abrams GD, Hart MA, Takami K, Bayne CO, Kelly BT, Espinoza Orías AA, Nho SJArthroscopy
- Are adaptive randomised trials or non-randomised studies the best way to address the Ebola outbreak in west Africa?Lanini S, Zumla A, Ioannidis JP, Caro AD, Krishna S, Gostin L, Girardi E, Pletschette M, Strada G, Baritussio A, Portella G, Apolone G, Cavuto S, Satolli R, Kremsner P, Vairo F, Ippolito GLancet Infect Dis
- Racial Disparities in Postoperative Complications After Radical Nephrectomy: A Population-based Analysis.Chung BI, Leow JJ, Gelpi-Hammerschmidt F, Wang Y, Del Giudice F, De S, Chou EP, Song KH, Almario L, Chang SLUrology
- Special Commentary: Supporting Innovation for Safe and Effective Minimally Invasive Glaucoma Surgery: Summary of a Joint Meeting of the American Glaucoma Society and the Food and Drug Administration, Washington, DC, February 26, 2014.Caprioli J, Kim JH, Friedman DS, Kiang T, Moster MR, Parrish RK, Rorer EM, Samuelson T, Tarver ME, Singh K, Eydelman MBOphthalmology
- Emergent Salvage Direct Intrahepatic Portocaval Shunt Procedure for Acute Variceal Hemorrhage.Ward TJ, Techasith T, Louie JD, Hwang GL, Hofmann LV, Sze DYJ Vasc Interv Radiol
- Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine.Guven S, Lindsey JS, Poudel I, Chinthala S, Nickerson MD, Gerami-Naini B, Gurkan UA, Anchan RM, Demirci UStem Cells Transl Med
- A delicate balance: the cost effectiveness of new antiplatelet agents.Kazi DS, Hlatky MAJ Am Coll Cardiol
- Economic analysis of ticagrelor therapy from a U.S. perspective: results from the PLATO study.Cowper PA, Pan W, Anstrom KJ, Kaul P, Wallentin L, Davidson-Ray L, Nikolic E, Janzon M, Levin LÅ, Cannon CP, Harrington RA, Mark DBJ Am Coll Cardiol
- Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.French A, Bravery C, Smith J, Chandra A, Archibald P, Gold JD, Artzi N, Kim HW, Barker RW, Meissner A, Wu JC, Knowles JC, Williams D, García-Cardeña G, Sipp D, Oh S, Loring JF, Rao MS, Reeve B, Wall I, Carr AJ, Bure K, Stacey G, Karp JM, Snyder EY, Brindley DAStem Cells Transl Med
- Reply: Studies in fat grafting: part I. Effects of injection technique on in vitro fat viability and in vivo volume retention; and studies in fat grafting: part II. Effects of injection mechanics on material properties of fat.Wan DC, Gurtner GC, Longaker MTPlast Reconstr Surg
- Exercise induces stromal cell-derived factor-1α-mediated release of endothelial progenitor cells with increased vasculogenic function.Chang E, Paterno J, Duscher D, Maan ZN, Chen JS, Januszyk M, Rodrigues M, Rennert RC, Bishop S, Whitmore AJ, Whittam AJ, Longaker MT, Gurtner GCPlast Reconstr Surg
- Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation.Johansen JP, Diaz-Mataix L, Hamanaka H, Ozawa T, Ycu E, Koivumaa J, Kumar A, Hou M, Deisseroth K, Boyden ES, LeDoux JEProc Natl Acad Sci U S A
- Risk factors predictive of endogenous endophthalmitis among hospitalized patients with hematogenous infections in the United States.Vaziri K, Pershing S, Albini TA, Moshfeghi DM, Moshfeghi AAAm J Ophthalmol
- Anaerobic methane oxidation coupled to denitrification is the dominant methane sink in a deep lake.Deutzmann JS, Stief P, Brandes J, Schink BProc Natl Acad Sci U S A
- Double-stranded RNA under force and torque: similarities to and striking differences from double-stranded DNA.Lipfert J, Skinner GM, Keegstra JM, Hensgens T, Jager T, Dulin D, Köber M, Yu Z, Donkers SP, Chou FC, Das R, Dekker NHProc Natl Acad Sci U S A
- Beyond emotional benefits: physical activity and sedentary behaviour affect psychosocial resources through emotions.Hogan CL, Catalino LI, Mata J, Fredrickson BLPsychol Health
- Functional specialization of stomatal bHLHs through modification of DNA-binding and phosphoregulation potential.Davies KA, Bergmann DCProc Natl Acad Sci U S A
- Where are the women editors?Roberts LWAcad Psychiatry
- The critical need to diversify the clinical and academic workforce.Roberts LW, Maldonado Y, Coverdale JH, Balon R, Louie AK, Beresin EVAcad Psychiatry
- From school health to integrated health: expanding our children's public mental health system.Adelsheim SAcad Psychiatry
- Best practices in philanthropy in medical schools.Schiele MAcad Psychiatry
- Immunoglobulin and T cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplantation relapse and survival.Logan AC, Vashi N, Faham M, Carlton V, Kong K, Buño I, Zheng J, Moorhead M, Klinger M, Zhang B, Waqar A, Zehnder JL, Miklos DBBiol Blood Marrow Transplant
- Highly stretchable transistors using a microcracked organic semiconductor.Chortos A, Lim J, To JW, Vosgueritchian M, Dusseault TJ, Kim TH, Hwang S, Bao ZAdv Mater
- Janus kinase inhibitors and allogeneic stem cell transplantation for myelofibrosis.Gupta V, Gotlib J, Radich JP, Kröger NM, Rondelli D, Verstovsek S, Deeg HJBiol Blood Marrow Transplant
- Personalized normative feedback for depression symptoms: a qualitative pilot study of female undergraduates.Hom M, Heaney C, Koopman CAcad Psychiatry
- Comparing the utility of a novel neonatal resuscitation cart with a generic code cart using simulation: a randomised, controlled, crossover trial.Chitkara R, Rajani AK, Lee HC, Snyder Hansen SF, Halamek LPBMJ Qual Saf
Neural Dev. 2015;10(1):4
Authors: Doe CQ, Harris W, Shen K, Wong R
CONTRIBUTING REVIEWERS: The editors of Neural Development would like to thank all the reviewers who have contributed to the journal in Volume 9 (2014).
PMID: 25885854 [PubMed - as supplied by publisher]
The changes in clot microstructure in patients with ischaemic stroke and the effects of therapeutic intervention: a prospective observational study.
BMC Neurol. 2015;15(1):35
Authors: Stanford SN, Sabra A, D'Silva L, Lawrence M, Morris RH, Storton S, Brown MR, Evans V, Hawkins K, Williams PR, Davidson SJ, Wani M, Potter JF, Evans PA
BACKGROUND: Stroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (d f )) ex-vivo, real-time clot formation time (T GP ) and blood clot strength (elasticity at the gel point (G'GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention.
METHODS: In a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2-4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy.
RESULTS: 75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: d f (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G'GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in d f (p = 0.02), G'GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for d f (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values.
CONCLUSION: Patients with ischaemic stroke have denser and stronger clot structure as detected by d f and G'GP. The effect of thrombolysis on clot microstructure (d f ) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.
PMID: 25885595 [PubMed - as supplied by publisher]
Results of a proof of concept, double-blind, randomized trial of a second generation antisense oligonucleotide targeting high-sensitivity C-reactive protein (hs-CRP) in rheumatoid arthritis.
Arthritis Res Ther. 2015 Mar 19;17(1):80
Authors: Warren MS, Hughes SG, Singleton W, Yamashita M, Genovese MC
INTRODUCTION: This randomized, double-blind, phase II study evaluated the pharmacodynamics, safety and tolerability of ISIS 329993 (ISIS-CRPRx), an antisense oligonucleotide, in patients with active rheumatoid arthritis (RA).
METHODS: Patients with active RA of at least 6 months duration were randomized into 3 cohorts to receive ISIS-CRPRx (100 mg, 200 mg or 400 mg) or placebo (3 active:1 placebo within each cohort) via subcutaneous (SC) injection on Days 1, 3, 5 and 8 and then once weekly for the next 11 weeks. The effects of study treatment on high-sensitivity C-reactive protein (hs-CRP) level were evaluated. An exploratory analysis on disease activity was assessed via the American College of Rheumatology 20% improvement criteria (ACR20). Safety was evaluated via adverse events and laboratory measures.
RESULTS: Fifty-one patients received one of the following treatments: ISIS-CRPRx 100 mg, n = 12; 200 mg, n = 13, 400 mg, n = 14; placebo n = 12. In the ISIS-CRPRx treatment groups there were dose-dependent reductions in hs-CRP. At Day 36 the mean percent change from baseline was: placebo: -14.4%; ISIS-CRPRx 100 mg: -19.5%; 200 mg: -56.6% and 400 mg: -76.7%, (p = 0.0015 placebo compared to 400 mg). There were no differences between treatment groups and placebo in the ACR20 at Day 36 or Day 92. There were no serious infections and no elevations in liver function tests, lipids, creatinine or other lab abnormalities related to ISIS-CRPRx.
CONCLUSIONS: In this study, ISIS-CRPRx selectively reduced hs-CRP in a dose-dependent manner, and was well-tolerated in patients with RA. Its utility as a therapy in RA remains unclear.
TRIAL REGISTRATION: Clinicaltrials.gov NCT01414101 . Registered July 21, 2011.
PMID: 25885521 [PubMed - as supplied by publisher]
Trials. 2015 Apr 9;16(1):141
Authors: Green EP, Catalani C, Diero L, Carter EJ, Gardner A, Ndwiga C, Keny A, Owiti P, Israelski D, Biondich P
BACKGROUND: This document describes a research protocol for a study designed to estimate the impact of implementing a reminder system for medical providers on the use of isoniazid preventative therapy (IPT) for adults living with HIV in western Kenya. People living with HIV have a 5% to 10% annual risk of developing active tuberculosis (TB) once infected with TB bacilli, compared to a 5% lifetime risk in HIV-negative people with latent TB infection. Moreover, people living with HIV have a 20-fold higher risk of dying from TB. A growing body of literature suggests that IPT reduces overall TB incidence and is therefore of considerable benefit to patients and the larger community. However, in 2009, of the estimated 33 million people living with HIV, only 1.7 million (5%) were screened for TB, and about 85,000 (0.2%) were offered IPT.
METHODS/DESIGN: This study will examine the use of clinical decision-support reminders to improve rates of initiation of preventative treatment in a TB/HIV co-morbid population living in a TB endemic area. This will be a pragmatic, parallel-group, cluster-randomized superiority trial with a 1:1 allocation to treatment ratio. For the trial, 20 public medical facilities that use clinical summary sheets generated from an electronic medical records system will participate as clusters. All HIV-positive adult patients who complete an initial encounter at a study cluster and at least one return encounter during the study period will be included in the study cohort. The primary endpoint will be IPT prescription at 3 months post the initial encounter. We will conduct both individual-level and cluster-level analyses. Due to the nature of the intervention, the trial will not be blinded. This study will contribute to the growing evidence base for the use of electronic health interventions in low-resource settings to promote high-quality clinical care, health system optimization and positive patient outcomes.
TRIAL REGISTRATION: ClinicalTrials.gov NCT01934309, registered 29 August 2013.
PMID: 25885266 [PubMed - as supplied by publisher]
Copy number gain of granulin-epithelin precursor (GEP) at chromosome 17q21 associates with overexpression in human liver cancer.
BMC Cancer. 2015;15(1):264
Authors: Yung MK, Lo KW, Yip CW, Chung GT, Tong CY, Cheung PF, Cheung TT, Poon RT, So S, Fan ST, Cheung ST
BACKGROUND: Granulin-epithelin precursor (GEP), a secretory growth factor, demonstrated overexpression in various human cancers, however, mechanism remain elusive. Primary liver cancer, hepatocellular carcinoma (HCC), ranks the second in cancer-related death globally. GEP controlled growth, invasion, metastasis and chemo-resistance in liver cancer. Noted that GEP gene locates at 17q21 and the region has been frequently reported to be amplified in subset of HCC. The study aims to investigate if copy number gain would associate with GEP overexpression.
METHODS: Quantitative Microsatellite Analysis (QuMA) was used to quantify the GEP DNA copy number, and fluorescent in situ hybridization (FISH) was performed to consolidate the amplification status. GEP gene copy number, mRNA expression level and clinico-pathological features were analyzed.
RESULTS: GEP DNA copy number determined by QuMA corroborated well with the FISH data, and the gene copy number correlated with the expression levels (n = 60, r = 0.331, P = 0.010). Gain of GEP copy number was observed in 20% (12/60) HCC and associated with hepatitis B virus infection status (P = 0.015). In HCC with increased GEP copy number, tight association between GEP DNA and mRNA levels were observed (n = 12, r = 0.664, P = 0.019).
CONCLUSIONS: Gain of the GEP gene copy number was observed in 20% HCC and the frequency comparable to literatures reported on the chromosome region 17q. Increased gene copy number contributed to GEP overexpression in subset of HCC.
PMID: 25885205 [PubMed - as supplied by publisher]
Cell Signaling-Based Classifier Predicts Response to Induction Therapy in Elderly Patients with Acute Myeloid Leukemia.
PLoS One. 2015;10(4):e0118485
Authors: Cesano A, Willman CL, Kopecky KJ, Gayko U, Putta S, Louie B, Westfall M, Purvis N, Spellmeyer DC, Marimpietri C, Cohen AC, Hackett J, Shi J, Walker MG, Sun Z, Paietta E, Tallman MS, Cripe LD, Atwater S, Appelbaum FR, Radich JP
Single-cell network profiling (SCNP) data generated from multi-parametric flow cytometry analysis of bone marrow (BM) and peripheral blood (PB) samples collected from patients >55 years old with non-M3 AML were used to train and validate a diagnostic classifier (DXSCNP) for predicting response to standard induction chemotherapy (complete response [CR] or CR with incomplete hematologic recovery [CRi] versus resistant disease [RD]). SCNP-evaluable patients from four SWOG AML trials were randomized between Training (N = 74 patients with CR, CRi or RD; BM set = 43; PB set = 57) and Validation Analysis Sets (N = 71; BM set = 42, PB set = 53). Cell survival, differentiation, and apoptosis pathway signaling were used as potential inputs for DXSCNP. Five DXSCNP classifiers were developed on the SWOG Training set and tested for prediction accuracy in an independent BM verification sample set (N = 24) from ECOG AML trials to select the final classifier, which was a significant predictor of CR/CRi (area under the receiver operating characteristic curve AUROC = 0.76, p = 0.01). The selected classifier was then validated in the SWOG BM Validation Set (AUROC = 0.72, p = 0.02). Importantly, a classifier developed using only clinical and molecular inputs from the same sample set (DXCLINICAL2) lacked prediction accuracy: AUROC = 0.61 (p = 0.18) in the BM Verification Set and 0.53 (p = 0.38) in the BM Validation Set. Notably, the DXSCNP classifier was still significant in predicting response in the BM Validation Analysis Set after controlling for DXCLINICAL2 (p = 0.03), showing that DXSCNP provides information that is independent from that provided by currently used prognostic markers. Taken together, these data show that the proteomic classifier may provide prognostic information relevant to treatment planning beyond genetic mutations and traditional prognostic factors in elderly AML.
PMID: 25884949 [PubMed - as supplied by publisher]
γ-Glutamyl transferase 7 is a novel regulator of glioblastoma growth.
BMC Cancer. 2015;15(1):225
Authors: Bui TT, Nitta RT, Kahn SA, Razavi SM, Agarwal M, Aujla P, Gholamin S, Recht L, Li G
BACKGROUND: Glioblastoma (GBM) is the most malignant primary brain tumor in adults, with a median survival time of one and a half years. Traditional treatments, including radiation, chemotherapy, and surgery, are not curative, making it imperative to find more effective treatments for this lethal disease. γ-Glutamyl transferase (GGT) is a family of enzymes that was shown to control crucial redox-sensitive functions and to regulate the balance between proliferation and apoptosis. GGT7 is a novel GGT family member that is highly expressed in brain and was previously shown to have decreased expression in gliomas. Since other members of the GGT family were found to be altered in a variety of cancers, we hypothesized that GGT7 could regulate GBM growth and formation.
METHODS: To determine if GGT7 is involved in GBM tumorigenesis, we modulated GGT7 expression in two GBM cell lines (U87-MG and U138) and monitored changes in tumorigenicity in vitro and in vivo.
RESULTS: We demonstrated for the first time that GBM patients with low GGT7 expression had a worse prognosis and that 87% (7/8) of primary GBM tissue samples showed a 2-fold decrease in GGT7 expression compared to normal brain samples. Exogenous expression of GGT7 resulted in a 2- to 3-fold reduction in proliferation and anchorage-independent growth under minimal growth conditions (1% serum). Decreasing GGT7 expression using either short interfering RNA or short hairpin RNA consistently increased proliferation 1.5- to 2-fold. In addition, intracranial injections of U87-MG cells with reduced GGT7 expression increased tumor growth in mice approximately 2-fold, and decreased mouse survival. To elucidate the mechanism by which GGT7 regulates GBM growth, we analyzed reactive oxygen species (ROS) levels in GBM cells with modulated GGT7 expression. We found that enhanced GGT7 expression reduced ROS levels by 11-33%.
CONCLUSION: Our study demonstrates that GGT7 is a novel player in GBM growth and that GGT7 can play a critical role in tumorigenesis by regulating anti-oxidative damage. Loss of GGT7 may increase the cellular ROS levels, inducing GBM occurrence and growth. Our findings suggest that GGT7 can be a promising biomarker and a potential therapeutic target for GBM.
PMID: 25884624 [PubMed - as supplied by publisher]
Critical role for prokineticin 2 in CNS autoimmunity.
Neurol Neuroimmunol Neuroinflamm. 2015 Jun;2(3):e95
Authors: Abou-Hamdan M, Costanza M, Fontana E, Di Dario M, Musio S, Congiu C, Onnis V, Lattanzi R, Radaelli M, Martinelli V, Salvadori S, Negri L, Poliani PL, Farina C, Balboni G, Steinman L, Pedotti R
OBJECTIVE: To investigate the potential role of prokineticin 2 (PK2), a bioactive peptide involved in multiple biological functions including immune modulation, in CNS autoimmune demyelinating disease.
METHODS: We investigated the expression of PK2 in mice with experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis (MS), and in patients with relapsing-remitting MS. We evaluated the biological effects of PK2 on expression of EAE and on development of T-cell response against myelin by blocking PK2 in vivo with PK2 receptor antagonists. We treated with PK2 immune cells activated against myelin antigen to explore the immune-modulating effects of this peptide in vitro.
RESULTS: Pk2 messenger RNA was upregulated in spinal cord and lymph node cells (LNCs) of mice with EAE. PK2 protein was expressed in EAE inflammatory infiltrates and was increased in sera during EAE. In patients with relapsing-remitting MS, transcripts for PK2 were significantly increased in peripheral blood mononuclear cells compared with healthy controls, and PK2 serum concentrations were significantly higher. A PK2 receptor antagonist prevented or attenuated established EAE in chronic and relapsing-remitting models, reduced CNS inflammation and demyelination, and decreased the production of interferon (IFN)-γ and interleukin (IL)-17A cytokines in LNCs while increasing IL-10. PK2 in vitro increased IFN-γ and IL-17A and reduced IL-10 in splenocytes activated against myelin antigen.
CONCLUSION: These data suggest that PK2 is a critical immune regulator in CNS autoimmune demyelination and may represent a new target for therapy.
PMID: 25884014 [PubMed]
Biomaterial Hypersensitivity: Is It Real? Supportive Evidence and Approach Considerations for Metal Allergic Patients following Total Knee Arthroplasty.
Biomed Res Int. 2015;2015:137287
Authors: Mitchelson AJ, Wilson CJ, Mihalko WM, Grupp TM, Manning BT, Dennis DA, Goodman SB, Tzeng TH, Vasdev S, Saleh KJ
The prospect of biomaterial hypersensitivity developing in response to joint implant materials was first presented more than 30 years ago. Many studies have established probable causation between first-generation metal-on-metal hip implants and hypersensitivity reactions. In a limited patient population, implant failure may ultimately be related to metal hypersensitivity. The examination of hypersensitivity reactions in current-generation metal-on-metal knee implants is comparatively limited. The purpose of this study is to summarize all available literature regarding biomaterial hypersensitivity after total knee arthroplasty, elucidate overall trends about this topic in the current literature, and provide a foundation for clinical approach considerations when biomaterial hypersensitivity is suspected.
PMID: 25883940 [PubMed - as supplied by publisher]
popRange: a highly flexible spatially and temporally explicit Wright-Fisher simulator.
Source Code Biol Med. 2015;10:6
Authors: McManus KF
BACKGROUND: Sequencing and genotyping technology advancements have led to massive, growing repositories of spatially explicit genetic data and increasing quantities of temporal data (i.e., ancient DNA). These data will allow more complex and fine-scale inferences about population history than ever before; however, new methods are needed to test complex hypotheses.
RESULTS: This article presents popRange, a forward genetic simulator, which incorporates large-scale genetic data with stochastic spatially and temporally explicit demographic and selective models. Features such as spatially and temporally variable selection coefficients and demography are incorporated in a highly flexible manner. popRange is implemented as an R package and presented with an example simulation exploring a selected allele's trajectory in multiple subpopulations.
CONCLUSIONS: popRange allows researchers to evaluate and test complex scenarios by simulating large-scale data with complicated demographic and selective features. popRange is available for download at http://cran.r-project.org/web/packages/popRange/index.html.
PMID: 25883677 [PubMed]
An observational study of adults seeking emergency care in Cambodia.
Bull World Health Organ. 2015 Feb 1;93(2):84-92
Authors: Yan LD, Mahadevan SV, Yore M, Pirrotta EA, Woods J, Somontha K, Sovannra Y, Raman M, Cornell E, Grundmann C, Strehlow MC
OBJECTIVE: To describe the characteristics and chief complaints of adults seeking emergency care at two Cambodian provincial referral hospitals.
METHODS: Adults aged 18 years or older who presented without an appointment at two public referral hospitals were enrolled in an observational study. Clinical and demographic data were collected and factors associated with hospital admission were identified. Patients were followed up 48 hours and 14 days after presentation.
FINDINGS: In total, 1295 hospital presentations were documented. We were able to follow up 85% (1098) of patients at 48 hours and 77% (993) at 14 days. The patients' mean age was 42 years and 64% (823) were females. Most arrived by motorbike (722) or taxi or tuk-tuk (312). Most common chief complaints were abdominal pain (36%; 468), respiratory problems (15%; 196) and headache (13%; 174). Of the 1050 patients with recorded vital signs, 280 had abnormal values, excluding temperature, on arrival. Performed diagnostic tests were recorded for 539 patients: 1.2% (15) of patients had electrocardiography and 14% (175) had diagnostic imaging. Subsequently, 783 (60%) patients were admitted and 166 of these underwent surgery. Significant predictors of admission included symptom onset within 3 days before presentation, abnormal vital signs and fever. By 14-day follow-up, 3.9% (39/993) of patients had died and 19% (192/993) remained functionally impaired.
CONCLUSION: In emergency admissions in two public hospitals in Cambodia, there is high admission-to-death ratio and limited application of diagnostic techniques. We identified ways to improve procedures, including better documentation of vital signs and increased use of diagnostic techniques.
PMID: 25883401 [PubMed - in process]
Skin fibrosis. Identification and isolation of a dermal lineage with intrinsic fibrogenic potential.
Science. 2015 Apr 17;348(6232):aaa2151
Authors: Rinkevich Y, Walmsley GG, Hu MS, Maan ZN, Newman AM, Drukker M, Januszyk M, Krampitz GW, Gurtner GC, Lorenz HP, Weissman IL, Longaker MT
Dermal fibroblasts represent a heterogeneous population of cells with diverse features that remain largely undefined. We reveal the presence of at least two fibroblast lineages in murine dorsal skin. Lineage tracing and transplantation assays demonstrate that a single fibroblast lineage is responsible for the bulk of connective tissue deposition during embryonic development, cutaneous wound healing, radiation fibrosis, and cancer stroma formation. Lineage-specific cell ablation leads to diminished connective tissue deposition in wounds and reduces melanoma growth. Using flow cytometry, we identify CD26/DPP4 as a surface marker that allows isolation of this lineage. Small molecule-based inhibition of CD26/DPP4 enzymatic activity during wound healing results in diminished cutaneous scarring. Identification and isolation of these lineages hold promise for translational medicine aimed at in vivo modulation of fibrogenic behavior.
PMID: 25883361 [PubMed - in process]
Infectious disease. Combating emerging viral threats.
Science. 2015 Apr 17;348(6232):282-3
Authors: Bekerman E, Einav S
PMID: 25883340 [PubMed - in process]
Inhibition of cathepsin proteases attenuates migration and sensitizes aggressive N-Myc amplified human neuroblastoma cells to doxorubicin.
Oncotarget. 2015 Mar 14;
Authors: Gangoda L, Keerthikumar S, Fonseka P, Edgington LE, Ang CS, Ozcitti C, Bogyo M, Parker BS, Mathivanan S
Neuroblastoma arises from the sympathetic nervous system and accounts for 15% of childhood cancer mortality. Amplification of the oncogene N-Myc is reported to occur in more than 20% of patients. While N-Myc amplification status strongly correlates with higher tumour aggression and resistance to treatment, the role of N-Myc in the aggressive progression of the disease is poorly understood. N-Myc being a transcription factor can modulate the secretion of key proteins that may play a pivotal role in tumorigenesis. Characterising the soluble secreted proteins or secretome will aid in understanding their role in the tumour microenvironment, such as promoting cancer cell invasion and resistance to treatment. The aim of this study is to characterise the secretome of human malignant neuroblastoma SK-N-BE2 (N-Myc amplified, more aggressive) and SH-SY5Y (N-Myc non-amplified, less aggressive) cells. Conditioned media from SK-N-BE2 and SH-SY5Y cell lines were subjected to proteomics analysis. We report a catalogue of 894 proteins identified in the secretome isolated from the two neuroblastoma cell lines, SK-N-BE2 and SH-SY5Y. Functional enrichment analysis using FunRich software identified enhanced secretion of proteins implicated in cysteine peptidase activity in the aggressive N-Myc amplified SK-N-BE2 secretome compared to the less tumorigenic SH-SY5Y cells. Protein-protein interaction-based network analysis highlighted the enrichment of cathepsin and epithelial-to-mesenchymal transition sub-networks. For the first time, inhibition of cathepsins by inhibitors sensitized the resistant SK-N-BE2 cells to doxorubicin as well as decreased its migratory potential. The dataset of secretome proteins of N-Myc amplified (more aggressive) and non-amplified (less aggressive) neuroblastoma cells represent the first inventory of neuroblastoma secretome. The study also highlights the prominent role of cathepsins in the N-Myc amplified neuroblastoma pathogenesis. As N-Myc amplification correlates with aggressive neuroblastoma and chemotherapy-based treatment failure, co-treatment with cathepsin inhibitors might be a better avenue for disease management.
PMID: 25883214 [PubMed - as supplied by publisher]
Integrative genomic analysis reveals widespread enhancer regulation by p53 in response to DNA damage.
Nucleic Acids Res. 2015 Apr 16;
Authors: Younger ST, Kenzelmann-Broz D, Jung H, Attardi LD, Rinn JL
The tumor suppressor p53 has been studied extensively as a direct transcriptional activator of protein-coding genes. Recent studies, however, have shed light on novel regulatory functions of p53 within noncoding regions of the genome. Here, we use a systematic approach that integrates transcriptome-wide expression analysis, genome-wide p53 binding profiles and chromatin state maps to characterize the global regulatory roles of p53 in response to DNA damage. Notably, our approach identified conserved features of the p53 network in both human and mouse primary fibroblast models. In addition to known p53 targets, we identify many previously unappreciated mRNAs and long noncoding RNAs that are regulated by p53. Moreover, we find that p53 binding occurs predominantly within enhancers in both human and mouse model systems. The ability to modulate enhancer activity offers an additional layer of complexity to the p53 network and greatly expands the diversity of genomic elements directly regulated by p53.
PMID: 25883152 [PubMed - as supplied by publisher]
Anterior Septal Reconstruction for Treatment of Severe Caudal Septal Deviation: Clinical Severity and Outcomes.
Otolaryngol Head Neck Surg. 2015 Apr 16;
Authors: Surowitz J, Lee MK, Most SP
OBJECTIVE: To report the long-term efficacy of a modified extracorporeal septoplasty technique in the treatment of anterocaudal septal deviations.
STUDY DESIGN: Case series with chart review.
SETTING: Academic tertiary care medical center.
SUBJECTS AND METHODS: Data were obtained by a retrospective review of patients treated by a single surgeon (S.P.M.) from December 2010 to April 2014. A total of 77 patients (52 male, 25 female) met inclusion criteria. The Nasal Obstruction Septoplasty Effectiveness (NOSE) scale and a visual analog scale (VAS) were administered to all patients preoperatively and at each postoperative visit. Statistical analysis was performed using a matched-pair t test comparing preoperative and postoperative NOSE and VAS scores. A recently described severity scale for nasal obstruction was applied to NOSE scores to demonstrate postoperative results.
RESULTS: Average follow-up was 4.7 months. Average preoperative NOSE and VAS scores were 68.2 ± 17.4 and 7.2 ± 1.8, respectively, placing these patients in the "severe" symptoms classification. Average NOSE and VAS scores in the early postoperative period (1-3 months after surgery) were 21.1 ± 19.8 (P < .0001) and 2.1 ± 2.6 (P < .0001), respectively. Average NOSE and VAS scores in the late postoperative period (>3 months after surgery) were 15.8 ± 19.0 (P < .0001) and 1.4 ± 1.8 (P < .0001), respectively. Both early and late postoperative NOSE scores represented "mild" symptomatology.
CONCLUSIONS: Anterior septal reconstruction represents a powerful method for correction of nasal valve stenosis resulting from severe anterocaudal septal deviations.
PMID: 25883105 [PubMed - as supplied by publisher]
RNA-Puzzles Round II: assessment of RNA structure prediction programs applied to three large RNA structures.
RNA. 2015 Apr 16;
Authors: Miao Z, Adamiak RW, Blanchet MF, Boniecki M, Bujnicki JM, Chen SJ, Cheng C, Chojnowski G, Chou FC, Cordero P, Cruz JA, Ferré-D'amaré AR, Das R, Ding F, Dokholyan NV, Dunin-Horkawicz S, Kladwang W, Krokhotin A, Lach G, Magnus M, Major F, Mann TH, Masquida B, Matelska D, Meyer M, Peselis A, Popenda M, Purzycka KJ, Serganov A, Stasiewicz J, Szachniuk M, Tandon A, Tian S, Wang J, Xiao Y, Xu X, Zhang J, Zhao P, Zok T, Westhof E
This paper is a report of a second round of RNA-Puzzles, a collective and blind experiment in three-dimensional (3D) RNA structure prediction. Three puzzles, Puzzles 5, 6, and 10, represented sequences of three large RNA structures with limited or no homology with previously solved RNA molecules. A lariat-capping ribozyme, as well as riboswitches complexed to adenosylcobalamin and tRNA, were predicted by seven groups using RNAComposer, ModeRNA/SimRNA, Vfold, Rosetta, DMD, MC-Fold, 3dRNA, and AMBER refinement. Some groups derived models using data from state-of-the-art chemical-mapping methods (SHAPE, DMS, CMCT, and mutate-and-map). The comparisons between the predictions and the three subsequently released crystallographic structures, solved at diffraction resolutions of 2.5-3.2 Å, were carried out automatically using various sets of quality indicators. The comparisons clearly demonstrate the state of present-day de novo prediction abilities as well as the limitations of these state-of-the-art methods. All of the best prediction models have similar topologies to the native structures, which suggests that computational methods for RNA structure prediction can already provide useful structural information for biological problems. However, the prediction accuracy for non-Watson-Crick interactions, key to proper folding of RNAs, is low and some predicted models had high Clash Scores. These two difficulties point to some of the continuing bottlenecks in RNA structure prediction. All submitted models are available for download at http://ahsoka.u-strasbg.fr/rnapuzzles/.
PMID: 25883046 [PubMed - as supplied by publisher]
Intended and unintended effects of large-scale adverse event disclosure: a controlled before-after analysis of five large-scale notifications.
BMJ Qual Saf. 2015 May;24(5):295-302
Authors: Wagner TH, Taylor T, Cowgill E, Asch SM, Su P, Bokhour B, Durfee J, Martinello RA, Maguire E, Elwy AR
BACKGROUND AND OBJECTIVE: How patients respond to being notified of a large-scale adverse event (LSAE), such as improper sterilisation of medical equipment that exposes them to bloodborne pathogens, is not well known. The objective of this study was to determine, using administrative data, the intended and unintended consequences of patient notification following a LSAE.
METHODS: We examined five LSAEs where patients may have been inadvertently exposed to hepatitis C virus (HCV), HIV, and hepatitis B virus (HBV). A total of 9638 cases were identified at five Department of Veteran Affairs (VA) medical facilities between 2009 and 2012. We identified controls at the same facility prior to the exposure period and at neighbouring facilities (n=45 274). Difference-in-differences models were used with Veterans Health Administration (VHA) and Medicare data to examine infectious disease testing rates and subsequent utilisation patterns.
RESULTS: Receipt of a LSAE notification was associated with a 73.2, 76.8 and 77.1 adjusted percentage point increase for HCV, HIV and HBV testing, respectively (all p<0.001). Compared with white patients, African-American patients were significantly less likely to return to VHA for follow-up testing. Patients exposed to a dental LSAE reduced their use of preventive and restorative dental care over the subsequent year, but they eventually came back to VHA for dental services 18-months post exposure.
CONCLUSIONS: The majority of patients notified of a LSAE responded by getting tested for HCV, HIV and HBV, although there remains room for improvement. Potential exposure to a LSAE was associated with increased odds of subsequently using non-VA facilities, but the size and timing of the shift depended on the type of care.
PMID: 25882785 [PubMed - in process]
Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles nanoparticles.
Breast Cancer Res. 2015 Mar 31;17(1):48
Authors: Campbell D, Saenz R, Bharati IS, Seible D, Zhang L, Esener S, Messmer B, Larsson M, Messmer D
INTRODUCTION: Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as potent immune adjuvant.
METHOD: In this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2) positive breast cancer.
RESULTS: Free peptide did not significantly augment immune responses but, when delivered in poly(D,L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2 specific T cells was observed in vitro. Vaccination of HER2NEU transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91 loaded PLGA-NPs enhanced the activation of HER2 specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival.
CONCLUSION: Taken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine.
PMID: 25882711 [PubMed - as supplied by publisher]
A call to include people with mental illness and substance use disorders alongside 'regular' smokers in smoking cessation research.
Tob Control. 2015 Apr 16;
Authors: Lembke A, Humphreys K
This commentary points out that smoking is increasingly concentrated among people with psychiatric problems and other substance use disorders (eg, alcohol use disorder), and argues that for clinical, ethical and efficiency reasons, such individuals should be routinely enrolled in smoking cessation research.
PMID: 25882685 [PubMed - as supplied by publisher]
Advances in Imaging Technologies in the Evaluation of High-Grade Bladder Cancer.
Urol Clin North Am. 2015 May;42(2):147-157
Authors: Zlatev DV, Altobelli E, Liao JC
Bladder cancer ranges from a low-grade variant to high-grade disease. Assessment for treatment depends on white light cystoscopy, however because of its limitations there is a need for improved visualization of flat, multifocal, high-grade, and muscle-invasive lesions. Photodynamic diagnosis and narrow-band imaging provide additional contrast enhancement of bladder tumors and have been shown to improve detection rates. Confocal laser endomicroscopy and optical coherence tomography enable real-time, high-resolution, subsurface tissue characterization with spatial resolutions similar to histology. Molecular imaging offers the potential for the combination of optical imaging technologies with cancer-specific molecular agents to improve the specificity of disease detection.
PMID: 25882557 [PubMed - as supplied by publisher]
Multimorbidity and healthcare utilisation among high-cost patients in the US Veterans Affairs Health Care System.
BMJ Open. 2015;5(4):e007771
Authors: Zulman DM, Pal Chee C, Wagner TH, Yoon J, Cohen DM, Holmes TH, Ritchie C, Asch SM
OBJECTIVES: To investigate the relationship between multimorbidity and healthcare utilisation patterns among the highest cost patients in a large, integrated healthcare system.
DESIGN: In this retrospective cross-sectional study of all patients in the U.S. Veterans Affairs (VA) Health Care System, we aggregated costs of individuals' outpatient and inpatient care, pharmacy services and VA-sponsored contract care received in 2010. We assessed chronic condition prevalence, multimorbidity as measured by comorbidity count, and multisystem multimorbidity (number of body systems affected by chronic conditions) among the 5% highest cost patients. Using multivariate regression, we examined the association between multimorbidity and healthcare utilisation and costs, adjusting for age, sex, race/ethnicity, marital status, homelessness and health insurance status.
SETTING: USA VA Health Care System.
PARTICIPANTS: 5.2 million VA patients.
MEASURES: Annual total costs; absolute and share of costs generated through outpatient, inpatient, pharmacy and VA-sponsored contract care; number of visits to primary, specialty and mental healthcare; number of emergency department visits and hospitalisations.
RESULTS: The 5% highest cost patients (n=261 699) accounted for 47% of total VA costs. Approximately two-thirds of these patients had chronic conditions affecting ≥3 body systems. Patients with cancer and schizophrenia were less likely to have documented comorbid conditions than other high-cost patients. Multimorbidity was generally associated with greater outpatient and inpatient utilisation. However, increased multisystem multimorbidity was associated with a higher outpatient share of total costs (1.6 percentage points per affected body system, p<0.01) but a lower inpatient share of total costs (-0.6 percentage points per affected body system, p<0.01).
CONCLUSIONS: Multisystem multimorbidity is common among high-cost VA patients. While some patients might benefit from disease-specific programmes, for most patients with multimorbidity there is a need for interventions that coordinate and maximise efficiency of outpatient services across multiple conditions.
PMID: 25882486 [PubMed - in process]
Biomechanical Evaluation of Capsulotomy, Capsulectomy, and Capsular Repair on Hip Rotation.
Arthroscopy. 2015 Apr 14;
Authors: Abrams GD, Hart MA, Takami K, Bayne CO, Kelly BT, Espinoza Orías AA, Nho SJ
PURPOSE: To determine the effect of different types of capsulotomies on hip rotational biomechanical characteristics.
METHODS: Seven fresh-frozen cadaveric hip specimens were thawed and dissected, leaving the hip capsule and labrum intact. The femur was transected and potted, and each specimen was placed in a custom loading apparatus that allowed for adjustment of flexion, extension, and axial rotation of the femur. Six reflective infrared markers were attached to the specimens to track the motion of the femoral head with respect to the acetabulum in real time, and external rotation was produced by applying a torque of 10 Nm to the hip specimens. Data analysis was performed using the 3-dimensional position of the markers in space. The specimens were tested in neutral flexion and 40° of flexion in the following capsular states: intact, interportal capsulotomy, T-capsulotomy, repaired capsulotomy, and capsulectomy. Paired t tests and analysis of variance were used with an α value of .05 set as significant.
RESULTS: With the hip in neutral flexion, there was increased external rotation with a T-capsulotomy (91.1° ± 20.3°, P = .029) and capsulectomy (91.9° ± 19.6°, P = .015) compared with the intact hip (83.2° ± 20.5°). After complete repair of the T-capsulotomy (87.4° ± 20.6°), there was no significant difference in external rotation compared with the intact hip. No significant differences were seen between groups at 40° of hip flexion.
CONCLUSIONS: A T-capsulotomy showed significantly increased external rotation versus the intact and interportal capsulotomy states. The repaired T-capsulotomy restored the rotational profile back to the native state.
CLINICAL RELEVANCE: Many methods of capsular treatment during hip arthroscopy exist. Capsulotomy and capsulectomy do not restore the external rotation restraint of the hip back to its native state.
PMID: 25882176 [PubMed - as supplied by publisher]
Are adaptive randomised trials or non-randomised studies the best way to address the Ebola outbreak in west Africa?
Lancet Infect Dis. 2015 Apr 13;
Authors: Lanini S, Zumla A, Ioannidis JP, Caro AD, Krishna S, Gostin L, Girardi E, Pletschette M, Strada G, Baritussio A, Portella G, Apolone G, Cavuto S, Satolli R, Kremsner P, Vairo F, Ippolito G
The Ebola outbreak that has devastated parts of west Africa represents an unprecedented challenge for research and ethics. Estimates from the past three decades emphasise that the present effort to contain the epidemic in the three most affected countries (Guinea, Liberia, and Sierra Leone) has been insufficient, with more than 24 900 cases and about 10 300 deaths, as of March 25, 2015. Faced with such an exceptional event and the urgent response it demands, the use of randomised controlled trials (RCT) for Ebola-related research might be both unethical and infeasible and that potential interventions should be assessed in non-randomised studies on the basis of compassionate use. However, non-randomised studies might not yield valid conclusions, leading to large residual uncertainty about how to interpret the results, and can also waste scarce intervention-related resources, making them profoundly unethical. Scientifically sound and rigorous study designs, such as adaptive RCTs, could provide the best way to reduce the time needed to develop new interventions and to obtain valid results on their efficacy and safety while preserving the application of ethical precepts. We present an overview of clinical studies registered at present at the four main international trial registries and provide a simulation on how adaptive RCTs can behave in this context, when mortality varies simultaneously in either the control or the experimental group.
PMID: 25881871 [PubMed - as supplied by publisher]
Racial Disparities in Postoperative Complications After Radical Nephrectomy: A Population-based Analysis.
Urology. 2015 Apr 14;
Authors: Chung BI, Leow JJ, Gelpi-Hammerschmidt F, Wang Y, Del Giudice F, De S, Chou EP, Song KH, Almario L, Chang SL
OBJECTIVE: To perform a population-based study that evaluates contemporary racial disparities in the morbidity profile of patients undergoing radical nephrectomy in the United States.
METHODS: Using the Premier hospital database (Premier Inc, Charlotte, NC), which collects data from over 600 nonfederal hospitals throughout the United States, we identified patients undergoing a total nephrectomy as their primary procedure and also had a concurrent diagnosis of a kidney mass or cancer from 2003 to 2010. The primary outcome was 90-day major complication rates, based on the Clavien classification system. Multivariate logistic regression models were performed, adjusting for clustering by hospitals and survey weighting to ensure nationally representative estimates.
RESULTS: The study population included 25,517 patients translating into a weighted sample of 185,135 radical nephrectomies. In a multivariate model including patient, hospital, and surgical characteristics, blacks were more commonly associated with a major complication (odds ratio, 2.1; P <.0001). When we incorporated Charlson comorbidity score into the model, the racial disparity in major complications was attenuated by 36% (odds ratio, 1.7; P <.0001). Adjusting for annual surgical volume in the multivariate model did not alter results.
CONCLUSION: Our contemporary evaluation of patients undergoing radical nephrectomy in the United States demonstrates that blacks are associated with a markedly elevated rate of major complications as compared to whites. This disparity is possibly a result of unequal access to routine health care.
PMID: 25881864 [PubMed - as supplied by publisher]
Special Commentary: Supporting Innovation for Safe and Effective Minimally Invasive Glaucoma Surgery: Summary of a Joint Meeting of the American Glaucoma Society and the Food and Drug Administration, Washington, DC, February 26, 2014.
Ophthalmology. 2015 Apr 13;
Authors: Caprioli J, Kim JH, Friedman DS, Kiang T, Moster MR, Parrish RK, Rorer EM, Samuelson T, Tarver ME, Singh K, Eydelman MB
PMID: 25881513 [PubMed - as supplied by publisher]
Emergent Salvage Direct Intrahepatic Portocaval Shunt Procedure for Acute Variceal Hemorrhage.
J Vasc Interv Radiol. 2015 Apr 13;
Authors: Ward TJ, Techasith T, Louie JD, Hwang GL, Hofmann LV, Sze DY
PURPOSE: To review the safety and effectiveness of direct intrahepatic portocaval shunt (DIPS) creation with variceal embolization for acute variceal hemorrhage after a failed transjugular intrahepatic portosystemic shunt (TIPS) creation attempt or in patients with prohibitive anatomy.
MATERIALS AND METHODS: TIPS and DIPS procedures performed for variceal hemorrhage between January 2008 and July 2014 were reviewed. The default procedure was TIPS creation, with DIPS creation reserved for patients with unfavorable anatomy or who had technically unsuccessful TIPS creation. Thirteen patients underwent DIPS creation (mean age, 60 y ± 12; Child-Pugh class A/B/C, 8%/62%/30%; Model for End-stage Liver Disease score, 15 ± 5; range, 8-26) and 117 underwent TIPS creation. Four patients underwent a TIPS attempt and were converted to DIPS creation upon technical failure; nine were treated primarily with DIPS creation because of preprocedural imaging revealing unfavorable anatomy (intrahepatic portal thrombosis, n = 2; venous distortion from prior hepatic resections, n = 2; severely angulated hepatic veins, n = 5).
RESULTS: DIPS creation with variceal embolization (six gastric or esophageal; seven stomal, duodenal, or rectal) was successful in all patients; 11 also had concomitant variceal sclerotherapy. Mean DIPS procedure time was less than 2 hours. There was one major procedural complication. During a mean follow-up of 13.0 months ± 15.5, one patient developed DIPS thrombosis and recurrent hemorrhage; one patient underwent successful transplantation. Two deaths were observed within 30 days, neither associated with recurrent hemorrhage.
CONCLUSIONS: DIPS creation appears to be a safe, expedient, and effective treatment for patients with acute variceal hemorrhage who are poor anatomic candidates for TIPS creation or who have undergone unsuccessful TIPS creation attempts.
PMID: 25881512 [PubMed - as supplied by publisher]
Functional maintenance of differentiated embryoid bodies in microfluidic systems: a platform for personalized medicine.
Stem Cells Transl Med. 2015 Mar;4(3):261-8
Authors: Guven S, Lindsey JS, Poudel I, Chinthala S, Nickerson MD, Gerami-Naini B, Gurkan UA, Anchan RM, Demirci U
Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30-120 pg/ml and 150-450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine.
PMID: 25666845 [PubMed - indexed for MEDLINE]
A delicate balance: the cost effectiveness of new antiplatelet agents.
J Am Coll Cardiol. 2015 Feb 10;65(5):477-9
Authors: Kazi DS, Hlatky MA
PMID: 25660926 [PubMed - indexed for MEDLINE]
Economic analysis of ticagrelor therapy from a U.S. perspective: results from the PLATO study.
J Am Coll Cardiol. 2015 Feb 10;65(5):465-76
Authors: Cowper PA, Pan W, Anstrom KJ, Kaul P, Wallentin L, Davidson-Ray L, Nikolic E, Janzon M, Levin LÅ, Cannon CP, Harrington RA, Mark DB
BACKGROUND: Based on results of the PLATO (Platelet Inhibition and Patient Outcomes) trial comparing ticagrelor with clopidogrel therapy, the U.S. Food and Drug Administration approved ticagrelor in 2011 for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) with the proviso that it be taken with low-dose aspirin.
OBJECTIVES: This study sought to assess the cost and cost effectiveness of ticagrelor therapy relative to clopidogrel in treating ACS patients from the perspective of the U.S. health care system.
METHODS: We estimated within-trial resource use and costs using U.S. low-dose aspirin patients in PLATO (n = 547). Quality-adjusted life expectancy was estimated using the total PLATO population (n = 18,624), combined with baseline risk and long-term survival data from an external ACS patient cohort. Study drugs were valued at current costs. Cost effectiveness was assessed, as was the sensitivity of results to sampling and methodological uncertainties.
RESULTS: One year of ticagrelor therapy, relative to that of generic clopidogrel, cost $29,665/quality-adjusted life-year gained, with 99% of bootstrap estimates falling under a $100,000 willingness-to-pay threshold. Results were robust to extensive sensitivity analyses, including variations in clopidogrel cost, exclusion of costs in extended years of life, and a recalibrated estimate of survival reflecting a lower underlying mortality risk in the United States.
CONCLUSIONS: For PLATO-eligible ACS patients, a U.S. perspective comparison of the current standard of dual antiplatelet therapy of aspirin with clopidogrel versus aspirin plus ticagrelor showed that the ticagrelor regimen increased life expectancy at an incremental cost well within accepted benchmarks of good value for money. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).
PMID: 25660925 [PubMed - indexed for MEDLINE]
Enabling consistency in pluripotent stem cell-derived products for research and development and clinical applications through material standards.
Stem Cells Transl Med. 2015 Mar;4(3):217-23
Authors: French A, Bravery C, Smith J, Chandra A, Archibald P, Gold JD, Artzi N, Kim HW, Barker RW, Meissner A, Wu JC, Knowles JC, Williams D, García-Cardeña G, Sipp D, Oh S, Loring JF, Rao MS, Reeve B, Wall I, Carr AJ, Bure K, Stacey G, Karp JM, Snyder EY, Brindley DA
There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes.
PMID: 25650438 [PubMed - indexed for MEDLINE]
Reply: Studies in fat grafting: part I. Effects of injection technique on in vitro fat viability and in vivo volume retention; and studies in fat grafting: part II. Effects of injection mechanics on material properties of fat.
Plast Reconstr Surg. 2015 Feb;135(2):448e-9e
Authors: Wan DC, Gurtner GC, Longaker MT
PMID: 25626833 [PubMed - indexed for MEDLINE]
Exercise induces stromal cell-derived factor-1α-mediated release of endothelial progenitor cells with increased vasculogenic function.
Plast Reconstr Surg. 2015 Feb;135(2):340e-50e
Authors: Chang E, Paterno J, Duscher D, Maan ZN, Chen JS, Januszyk M, Rodrigues M, Rennert RC, Bishop S, Whitmore AJ, Whittam AJ, Longaker MT, Gurtner GC
BACKGROUND: Endothelial progenitor cells have been shown to traffic to and incorporate into ischemic tissues, where they participate in new blood vessel formation, a process termed vasculogenesis. Previous investigation has demonstrated that endothelial progenitor cells appear to mobilize from bone marrow to the peripheral circulation after exercise. In this study, the authors investigate potential etiologic factors driving this mobilization and investigate whether the mobilized endothelial progenitor cells are the same as those present at baseline.
METHODS: Healthy volunteers (n = 5) performed a monitored 30-minute run to maintain a heart rate greater than 140 beats/min. Venous blood samples were collected before, 10 minutes after, and 24 hours after exercise. Endothelial progenitor cells were isolated and evaluated.
RESULTS: Plasma levels of stromal cell-derived factor-1α significantly increased nearly two-fold immediately after exercise, with a nearly four-fold increase in circulating endothelial progenitor cells 24 hours later. The endothelial progenitor cells isolated following exercise demonstrated increased colony formation, proliferation, differentiation, and secretion of angiogenic cytokines. Postexercise endothelial progenitor cells also exhibited a more robust response to hypoxic stimulation.
CONCLUSIONS: Exercise appears to mobilize endothelial progenitor cells and augment their function by means of stromal cell-derived factor 1α-dependent signaling. The population of endothelial progenitor cells mobilized following exercise is primed for vasculogenesis with increased capacity for proliferation, differentiation, secretion of cytokines, and responsiveness to hypoxia. Given the evidence demonstrating positive regenerative effects of exercise, this may be one possible mechanism for its benefits.
PMID: 25626819 [PubMed - indexed for MEDLINE]
Hebbian and neuromodulatory mechanisms interact to trigger associative memory formation.
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):E5584-92
Authors: Johansen JP, Diaz-Mataix L, Hamanaka H, Ozawa T, Ycu E, Koivumaa J, Kumar A, Hou M, Deisseroth K, Boyden ES, LeDoux JE
A long-standing hypothesis termed "Hebbian plasticity" suggests that memories are formed through strengthening of synaptic connections between neurons with correlated activity. In contrast, other theories propose that coactivation of Hebbian and neuromodulatory processes produce the synaptic strengthening that underlies memory formation. Using optogenetics we directly tested whether Hebbian plasticity alone is both necessary and sufficient to produce physiological changes mediating actual memory formation in behaving animals. Our previous work with this method suggested that Hebbian mechanisms are sufficient to produce aversive associative learning under artificial conditions involving strong, iterative training. Here we systematically tested whether Hebbian mechanisms are necessary and sufficient to produce associative learning under more moderate training conditions that are similar to those that occur in daily life. We measured neural plasticity in the lateral amygdala, a brain region important for associative memory storage about danger. Our findings provide evidence that Hebbian mechanisms are necessary to produce neural plasticity in the lateral amygdala and behavioral memory formation. However, under these conditions Hebbian mechanisms alone were not sufficient to produce these physiological and behavioral effects unless neuromodulatory systems were coactivated. These results provide insight into how aversive experiences trigger memories and suggest that combined Hebbian and neuromodulatory processes interact to engage associative aversive learning.
PMID: 25489081 [PubMed - indexed for MEDLINE]
Risk factors predictive of endogenous endophthalmitis among hospitalized patients with hematogenous infections in the United States.
Am J Ophthalmol. 2015 Mar;159(3):498-504
Authors: Vaziri K, Pershing S, Albini TA, Moshfeghi DM, Moshfeghi AA
PURPOSE: To identify potential risk factors associated with endogenous endophthalmitis among hospitalized patients with hematogenous infections.
DESIGN: Retrospective cross-sectional study.
METHODS: MarketScan Commercial Claims and Encounters, and Medicare Supplemental and Coordination of Benefit inpatient databases from the years 2007-2011 were obtained. Utilizing ICD-9 codes, logistic regression was used to identify potential predictors/comorbidities for developing endophthalmitis in patients with hematogenous infections.
RESULTS: Among inpatients with hematogenous infections, the overall incidence rate of presumed endogenous endophthalmitis was 0.05%-0.4% among patients with fungemia and 0.04% among patients with bacteremia. Comorbid human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) (OR = 4.27; CI, 1.55-11.8; P = .005), tuberculosis (OR = 8.5; CI, 1.2-61.5; P = .03), endocarditis (OR = 8.3; CI, 4.9-13.9; P < .0001), bacterial meningitis (OR = 3.8; CI, 1.2-12.0; P = .023), fungal meningitis (OR = 59.1; CI, 14.1-247.8; P < .0001), internal organ abscess (OR = 2.9; CI, 1.2-6.4; P = .02), lymphoma/leukemia (OR = 2.9; CI, 1.6-5.3; P < .0001), skin abscess/cellulitis (OR = 1.75; CI, 1.1-2.8; P = .02), pyogenic arthritis (OR = 4.2; CI, 1.8-9.6; P = .001), diabetes with ophthalmic manifestations (OR = 7.0; CI, 1.7-28.3; P = .006), and urinary tract infection (OR = 0.04; CI, 0.3-0.9; P = .023) were each significantly associated with a diagnosis of endogenous endophthalmitis. Patients aged 0-17 years (OR = 2.61; CI, 1.2-5.7; P = .02), 45-54 years (OR = 3.4; CI, 2.0-5.4; P < .0001), and 55-64 years (OR = 2.9; CI, 1.8-4.8; P < .0001); those having length of stay of 3-10 days (OR = 1.9; CI, 1.1-3.3; P = .01), 11-30 days (OR = 3.1; CI, 1.8-5.5; P < .0001), and 31+ days (OR = 5.3; CI, 2.7-10.4; P < .0001); and those with intensive care unit/neonatal intensive care unit (ICU/NICU) admissions (OR = 1.5; CI, 1.4-1.6; P < .0001) were all more likely to be diagnosed with endogenous endophthalmitis.
CONCLUSIONS: Endogenous endophthalmitis is rare among hospitalized patients in the United States. Among patients with hematogenous infections, odds of endogenous endophthalmitis were higher for children and middle-aged patients, and for patients with endocarditis, bacterial meningitis, lymphoma/leukemia, HIV/AIDS, internal organ abscess, diabetes with ophthalmic manifestations, skin cellulitis/abscess, pyogenic arthritis, tuberculosis, longer hospital stays, and/or ICU/NICU admission.
PMID: 25486541 [PubMed - indexed for MEDLINE]
Anaerobic methane oxidation coupled to denitrification is the dominant methane sink in a deep lake.
Proc Natl Acad Sci U S A. 2014 Dec 23;111(51):18273-8
Authors: Deutzmann JS, Stief P, Brandes J, Schink B
Anaerobic methane oxidation coupled to denitrification, also known as "nitrate/nitrite-dependent anaerobic methane oxidation" (n-damo), was discovered in 2006. Since then, only a few studies have identified this process and the associated microorganisms in natural environments. In aquatic sediments, the close proximity of oxygen- and nitrate-consumption zones can mask n-damo as aerobic methane oxidation. We therefore investigated the vertical distribution and the abundance of denitrifying methanotrophs related to Candidatus Methylomirabilis oxyfera with cultivation-independent molecular techniques in the sediments of Lake Constance. Additionally, the vertical distribution of methane oxidation and nitrate consumption zones was inferred from high-resolution microsensor profiles in undisturbed sediment cores. M. oxyfera-like bacteria were virtually absent at shallow-water sites (littoral sediment) and were very abundant at deep-water sites (profundal sediment). In profundal sediment, the vertical distribution of M. oxyfera-like bacteria showed a distinct peak in anoxic layers that coincided with the zone of methane oxidation and nitrate consumption, a strong indication for n-damo carried out by M. oxyfera-like bacteria. Both potential n-damo rates calculated from cell densities (660-4,890 µmol CH4⋅m(-2)⋅d(-1)) and actual rates calculated from microsensor profiles (31-437 µmol CH4⋅m(-2)⋅d(-1)) were sufficiently high to prevent methane release from profundal sediment solely by this process. Additionally, when nitrate was added to sediment cores exposed to anoxic conditions, the n-damo zone reestablished well below the sediment surface, completely preventing methane release from the sediment. We conclude that the previously overlooked n-damo process can be the major methane sink in stable freshwater environments if nitrate is available in anoxic zones.
PMID: 25472842 [PubMed - indexed for MEDLINE]
Double-stranded RNA under force and torque: similarities to and striking differences from double-stranded DNA.
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15408-13
Authors: Lipfert J, Skinner GM, Keegstra JM, Hensgens T, Jager T, Dulin D, Köber M, Yu Z, Donkers SP, Chou FC, Das R, Dekker NH
RNA plays myriad roles in the transmission and regulation of genetic information that are fundamentally constrained by its mechanical properties, including the elasticity and conformational transitions of the double-stranded (dsRNA) form. Although double-stranded DNA (dsDNA) mechanics have been dissected with exquisite precision, much less is known about dsRNA. Here we present a comprehensive characterization of dsRNA under external forces and torques using magnetic tweezers. We find that dsRNA has a force-torque phase diagram similar to that of dsDNA, including plectoneme formation, melting of the double helix induced by torque, a highly overwound state termed "P-RNA," and a highly underwound, left-handed state denoted "L-RNA." Beyond these similarities, our experiments reveal two unexpected behaviors of dsRNA: Unlike dsDNA, dsRNA shortens upon overwinding, and its characteristic transition rate at the plectonemic buckling transition is two orders of magnitude slower than for dsDNA. Our results challenge current models of nucleic acid mechanics, provide a baseline for modeling RNAs in biological contexts, and pave the way for new classes of magnetic tweezers experiments to dissect the role of twist and torque for RNA-protein interactions at the single-molecule level.
PMID: 25313077 [PubMed - indexed for MEDLINE]
Beyond emotional benefits: physical activity and sedentary behaviour affect psychosocial resources through emotions.
Psychol Health. 2015;30(3):354-69
Authors: Hogan CL, Catalino LI, Mata J, Fredrickson BL
Physical activity is known to improve emotional experiences, and positive emotions have been shown to lead to important life outcomes, including the development of psychosocial resources. In contrast, time spent sedentary may negatively impact emotional experiences and, consequently, erode psychosocial resources. Two studies tested whether activity independently influenced emotions and psychosocial resources, and whether activity indirectly influenced psychosocial resources through emotional experiences. Using cross-sectional (Study 1a) and longitudinal (Study 1b) methods, we found that time spent physically active independently predicted emotions and psychosocial resources. Mediation analyses suggested that emotions may account for the relation between activity and psychosocial resources. The improved emotional experiences associated with physical activity may help individuals build psychosocial resources known to improve mental health. Study 1a provided first indicators to suggest that, in contrast, sedentary behaviour may reduce positive emotions, which could in turn lead to decrements in psychosocial resources.
PMID: 25307453 [PubMed - indexed for MEDLINE]
Functional specialization of stomatal bHLHs through modification of DNA-binding and phosphoregulation potential.
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15585-90
Authors: Davies KA, Bergmann DC
Transcription factor duplication events and subsequent specialization can drive evolution by facilitating biological innovation and developmental complexity. Identification of sequences that confer distinct biochemical function in vivo is an important step in understanding how related factors could refine specific developmental processes over time. Functional analysis of the basic helix-loop-helix (bHLH) protein SPEECHLESS, one of three closely related transcription factors required for stomatal lineage progression in Arabidopsis thaliana, allowed a dissection of motifs associated with specific developmental outputs. Phosphorylated residues, shown previously to quantitatively affect activity, also allow a qualitative shift in function between division and cell fate-promoting activities. Our data also provide surprising evidence that, despite deep sequence conservation in DNA-binding domains, the functional requirement for these domains has diverged, with the three stomatal bHLHs exhibiting absolute, partial, or no requirements for DNA-binding residues for their in vivo activities. Using these data, we build a plausible model describing how the current unique and overlapping roles of these proteins might have evolved from a single ancestral protein.
PMID: 25304637 [PubMed - indexed for MEDLINE]
Where are the women editors?
Acad Psychiatry. 2014 Aug;38(4):391-3
Authors: Roberts LW
PMID: 25001430 [PubMed - indexed for MEDLINE]
The critical need to diversify the clinical and academic workforce.
Acad Psychiatry. 2014 Aug;38(4):394-7
Authors: Roberts LW, Maldonado Y, Coverdale JH, Balon R, Louie AK, Beresin EV
PMID: 24989990 [PubMed - indexed for MEDLINE]
From school health to integrated health: expanding our children's public mental health system.
Acad Psychiatry. 2014 Aug;38(4):405-8
Authors: Adelsheim S
There is a substantial unmet need for mental health and substance abuse services in the USA. In 2009, the Institute of Medicine recommended increased early identification and intervention for young people with mental, emotional, and behavioral disorders. With the expansion of integrated models in primary care settings, we now have the chance to improve outcomes for young people with mental health conditions, just as we have by improving the early identification and treatment of other preventable and/or treatable conditions such as obesity, asthma, or HIV. This is a moment of great opportunity to fundamentally change how young people access mental health care in our country. Through strategic integration of care, we can increase access to care for those who would not seek out mental health services because of the stigma or inconvenience of reaching out to a mental health provider; we can identify those who need care earlier and reduce the impact of mental illness on individuals, family, and community through early identification and treatment; and we can purposefully embed integration into provider training programs for both primary care and mental health providers to ensure sustainability.
PMID: 24912970 [PubMed - indexed for MEDLINE]
Best practices in philanthropy in medical schools.
Acad Psychiatry. 2014 Aug;38(4):489-92
Authors: Schiele M
This paper is for academic leaders and administrators who are interested in growing their philanthropic revenue stream. Growing the philanthropic revenue stream will be especially meaningful to leaders and administrators who have seen their other revenue streams decline or stagnate in the last few years. This paper focuses on four best practices for a high-performing development program and gives examples about how to execute on these best practices.
PMID: 24800731 [PubMed - indexed for MEDLINE]
Immunoglobulin and T cell receptor gene high-throughput sequencing quantifies minimal residual disease in acute lymphoblastic leukemia and predicts post-transplantation relapse and survival.
Biol Blood Marrow Transplant. 2014 Sep;20(9):1307-13
Authors: Logan AC, Vashi N, Faham M, Carlton V, Kong K, Buño I, Zheng J, Moorhead M, Klinger M, Zhang B, Waqar A, Zehnder JL, Miklos DB
Minimal residual disease (MRD) quantification is an important predictor of outcome after treatment for acute lymphoblastic leukemia (ALL). Bone marrow ALL burden ≥ 10(-4) after induction predicts subsequent relapse. Likewise, MRD ≥ 10(-4) in bone marrow before initiation of conditioning for allogeneic (allo) hematopoietic cell transplantation (HCT) predicts transplantation failure. Current methods for MRD quantification in ALL are not sufficiently sensitive for use with peripheral blood specimens and have not been broadly implemented in the management of adults with ALL. Consensus-primed immunoglobulin (Ig), T cell receptor (TCR) amplification and high-throughput sequencing (HTS) permit use of a standardized algorithm for all patients and can detect leukemia at 10(-6) or lower. We applied the LymphoSIGHT HTS platform (Sequenta Inc., South San Francisco, CA) to quantification of MRD in 237 samples from 29 adult B cell ALL patients before and after allo-HCT. Using primers for the IGH-VDJ, IGH-DJ, IGK, TCRB, TCRD, and TCRG loci, MRD could be quantified in 93% of patients. Leukemia-associated clonotypes at these loci were identified in 52%, 28%, 10%, 35%, 28%, and 41% of patients, respectively. MRD ≥ 10(-4) before HCT conditioning predicted post-HCT relapse (hazard ratio [HR], 7.7; 95% confidence interval [CI], 2.0 to 30; P = .003). In post-HCT blood samples, MRD ≥10(-6) had 100% positive predictive value for relapse with median lead time of 89 days (HR, 14; 95% CI, 4.7 to 44, P < .0001). The use of HTS-based MRD quantification in adults with ALL offers a standardized approach with sufficient sensitivity to quantify leukemia MRD in peripheral blood. Use of this approach may identify a window for clinical intervention before overt relapse.
PMID: 24769317 [PubMed - indexed for MEDLINE]
Highly stretchable transistors using a microcracked organic semiconductor.
Adv Mater. 2014 Jul 2;26(25):4253-9
Authors: Chortos A, Lim J, To JW, Vosgueritchian M, Dusseault TJ, Kim TH, Hwang S, Bao Z
PMID: 24740928 [PubMed - indexed for MEDLINE]
Janus kinase inhibitors and allogeneic stem cell transplantation for myelofibrosis.
Biol Blood Marrow Transplant. 2014 Sep;20(9):1274-81
Authors: Gupta V, Gotlib J, Radich JP, Kröger NM, Rondelli D, Verstovsek S, Deeg HJ
Myelofibrosis (MF) is a manifestation of several disorders of hematopoiesis, collectively referred to as myeloproliferative neoplasms. Allogeneic hematopoietic stem cell transplantation (ASCT) is the only therapy with proven curative potential. However, most patients with MF are in their 6th or 7th decade of life, and only some of these patients have been considered suitable transplantation candidates. The development of reduced-intensity conditioning regimens with limited toxicity has allowed clinicians to offer ASCT to a growing number of older patients. The availability of Janus Kinase (JAK) 1/2 inhibitors allows clinicians to provide symptom relief and improved quality of life for MF patients. These drugs may also affect the decision regarding, in particular, the timing of ASCT. Future studies need to address the role of JAK1/2 inhibitors in patients who are transplantation candidates and determine their role before and, possibly, after transplantation. The identification of indications for the use of JAK1/2 inhibitors in the context of transplantation may lead to new therapeutic strategies for patients with MF.
PMID: 24680977 [PubMed - indexed for MEDLINE]
Personalized normative feedback for depression symptoms: a qualitative pilot study of female undergraduates.
Acad Psychiatry. 2014 Aug;38(4):464-9
Authors: Hom M, Heaney C, Koopman C
OBJECTIVE: This pilot study explored students' responses to feedback about their own and their peers' depression symptoms. The study also examined how experiences with the normative feedback might vary according to academic exposure to depression-related topics.
METHODS: For 9 weeks, female undergraduates (N=73) completed a weekly web-based version of the 8-item Patient Health Questionnaire, which gauges depression symptom levels. Next, they participated in semi-structured face-to-face interviews where they responded to the personalized normative feedback. The interviews were transcribed, coded, and analyzed.
RESULTS: Students responded favorably to the feedback and without notable distress. The feedback increased students' awareness of their own depression symptoms and those of their peers. Those with higher academic exposure to depression-related topics were more likely to have accurate perceptions of their peers' depression symptoms and were less likely to be surprised by information in the feedback than students with less exposure.
CONCLUSIONS: Personalized normative feedback for depression symptoms has potential as an effective tool for promoting more accurate views of personal and peer depression symptoms and reducing barriers to help-seeking. Students with less academic exposure to depression-related topics may benefit from increased knowledge of how to gauge their own depression symptoms and increased awareness of their peers' symptoms. Further research is needed to more fully evaluate the effects of this feedback and to directly assess the effects of this feedback on help-seeking behaviors.
PMID: 24664603 [PubMed - indexed for MEDLINE]
Comparing the utility of a novel neonatal resuscitation cart with a generic code cart using simulation: a randomised, controlled, crossover trial.
BMJ Qual Saf. 2013 Feb;22(2):124-9
Authors: Chitkara R, Rajani AK, Lee HC, Snyder Hansen SF, Halamek LP
OBJECTIVE: To compare a novel neonatal resuscitation cart (NRC) to a generic code cart (GCC).
STUDY DESIGN: A prospective, randomised, controlled, crossover trial was performed to compare the utility of the NRC with the GCC during simulated deliveries of extremely low birthweight infants and infants with gastroschisis. Fifteen subjects participated. Mean times and accuracy of equipment and supply retrieval were compared for each scenario using the Wilcoxon test.
RESULTS: Mean acquisition times for the NRC were always faster (by 58% to 74%) regardless of scenario (p<0.01). Accuracy of equipment selection did not differ. Ease of use was judged using a Likert scale (1=easiest to use; 5=most difficult), with mean score for NRC 1.1 and GCC 3.7 (p<0.0001). All subjects rated the NRC as easier to use.
CONCLUSIONS: The NRC was superior to the GCC in acquisition speed, supply selection and ease of use.
PMID: 23112286 [PubMed - indexed for MEDLINE]
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