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- Assembly and Architecture of the EBV B Cell Entry Triggering Complex.Sathiyamoorthy K, Jiang J, Hu YX, Rowe CL, Möhl BS, Chen J, Jiang W, Mellins ED, Longnecker R, Zhou ZH, Jardetzky TSPLoS Pathog
- Precocious puberty.Neely EK, Crossen SSCurr Opin Obstet Gynecol
- Corneal Cell Adhesion to Contact Lens Hydrogel Materials Enhanced via Tear Film Protein Deposition.Elkins CM, Qi QM, Fuller GGPLoS One
- Rapidly Self-Renewing Human Multipotent Marrow Stromal Cells (hMSC) Express Sialyl Lewis X and Actively Adhere to Arterial Endothelium in a Chick Embryo Model System.McFerrin HE, Olson SD, Gutschow MV, Semon JA, Sullivan DE, Prockop DJPLoS One
- Dietary pattern and asthma: a systematic review and meta-analysis.Lv N, Xiao L, Ma JJ Asthma Allergy
- Anti-MET immunoPET for non-small cell lung cancer using fully human antibody fragments.Li K, Tavare R, Zettlitz KA, Mumenthaler SM, Mallick P, Zhou Y, Marks JD, Wu AMMol Cancer Ther
- Organic Cation Transporter Variation and Response to Smoking Cessation Therapies.Bergen AW, Javitz HS, Krasnow R, Michel M, Nishita D, Conti DV, Edlund CK, Kwok PY, McClure JB, Kim RB, Hall S, Tyndale RF, Baker TB, Benowitz NL, Swan GENicotine Tob Res
- FACTERA: a practical method for the discovery of genomic rearrangements at breakpoint resolution.Newman AM, Bratman SV, Stehr H, Lee LJ, Liu CL, Diehn M, Alizadeh AABioinformatics
- Irreversible xenon insertion into a small-pore zeolite at moderate pressures and temperatures.Seoung D, Lee Y, Cynn H, Park C, Choi KY, Blom DA, Evans WJ, Kao CC, Vogt T, Lee YNat Chem
- Clinical and Immunologic Predictors of Death After an Acute Opportunistic Infection: Results from ACTG A5164.Grant PM, Komarow L, Sanchez A, Sattler FR, Asmuth DM, Pollard RB, Zolopa ARHIV Clin Trials
- Evaluation of a new pediatric positive airway pressure mask.Kushida CA, Halbower AC, Kryger MH, Pelayo R, Assalone V, Cardell CY, Huston S, Willes L, Wimms AJ, Mendoza JJ Clin Sleep Med
- Development and evaluation of a treatment fidelity instrument for family-based treatment of adolescent anorexia nervosa.Forsberg S, Fitzpatrick KK, Darcy A, Aspen V, Accurso EC, Bryson SW, Agras S, Arnow KD, Le Grange D, Lock JInt J Eat Disord
- Periodic Leg Movements during Sleep Are Associated with Polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD.Moore H, Winkelmann J, Lin L, Finn L, Peppard P, Mignot ESleep
- Involution of Eruptive Melanocytic Nevi on Combination BRAF and MEK Inhibitor Therapy.Chen FW, Tseng D, Reddy S, Daud AI, Swetter SMJAMA Dermatol
- ACR Committee on Pediatric Imaging Research.Daldrup-Link HE, Voss S, Donig J, ACR committeePediatr Radiol
- A Rwandan Woman.Roberts LWAcad Psychiatry
- A Review of Multidisciplinary Clinical Practice Guidelines in Suicide Prevention: Toward an Emerging Standard in Suicide Risk Assessment and Management, Training and Practice.Bernert RA, Hom MA, Roberts LWAcad Psychiatry
- Reward Processing in Healthy Offspring of Parents With Bipolar Disorder.Singh MK, Kelley RG, Howe ME, Reiss AL, Gotlib IH, Chang KDJAMA Psychiatry
- Obesity, physical activity, and their interaction in incident atrial fibrillation in postmenopausal women.Azarbal F, Stefanick ML, Salmoirago-Blotcher E, Manson JE, Albert CM, LaMonte MJ, Larson JC, Li W, Martin LW, Nassir R, Garcia L, Assimes TL, Tharp KM, Hlatky MA, Perez MVJ Am Heart Assoc
- Perovskite solar cells: Continuing to soar.McGehee MDNat Mater
- Response to letter regarding article, "Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve".Fearon WF, Shilane D, Pijls NH, Boothroyd DB, Tonino PA, Barbato E, Juni P, De Bruyne B, Hlatky MA, FAME 2 InvestigatorsCirculation
- Impact of diffusion-weighted imaging Alberta stroke program early computed tomography score on the success of endovascular reperfusion therapy.Inoue M, Olivot JM, Labreuche J, Mlynash M, Tai W, Albucher JF, Meseguer E, Amarenco P, Mazighi MStroke
- Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial.Bernard TJ, Rivkin MJ, Scholz K, deVeber G, Kirton A, Gill JC, Chan AK, Hovinga CA, Ichord RN, Grotta JC, Jordan LC, Benedict S, Friedman NR, Dowling MM, Elbers J, Torres M, Sultan S, Cummings DD, Grabowski EF, McMillan HJ, Beslow LA, Amlie-Lefond C, Thrombolysis in Pediatric Stroke StudyStroke
- Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes.Shi ZS, Liebeskind DS, Xiang B, Ge SG, Feng L, Albers GW, Budzik R, Devlin T, Gupta R, Jansen O, Jovin TG, Killer-Oberpfalzer M, Lutsep HL, Macho J, Nogueira RG, Rymer M, Smith WS, Wahlgren N, Duckwiler GR, Multi MERCI, TREVO, and TREVO 2 InvestigatorsStroke
- Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy.Rasgon NL, Kenna HA, Wroolie TE, Williams KE, DeMuth BN, Silverman DHPsychiatry Res
- New-onset pancytopenia: a diagnostic approach-reply.Weinzierl E, Arber DAHum Pathol
- Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial.Di Biase L, Burkhardt JD, Santangeli P, Mohanty P, Sanchez JE, Horton R, Gallinghouse GJ, Themistoclakis S, Rossillo A, Lakkireddy D, Reddy M, Hao S, Hongo R, Beheiry S, Zagrodzky J, Rong B, Mohanty S, Elayi CS, Forleo G, Pelargonio G, Narducci ML, Dello Russo A, Casella M, Fassini G, Tondo C, Schweikert RA, Natale ACirculation
- Revising the economic imperative for US STEM education.Donovan BM, Moreno Mateos D, Osborne JF, Bisaccio DJPLoS Biol
- Sensory cell fates: four defaults for the price of one.Wernet MF, Desplan CCurr Biol
- Immune mechanisms in medium and large-vessel vasculitis.Weyand CM, Goronzy JJNat Rev Rheumatol
- The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium.Schutz FA, Xie W, Donskov F, Sircar M, McDermott DF, Rini BI, Agarwal N, Pal SK, Srinivas S, Kollmannsberger C, North SA, Wood LA, Vaishampayan U, Tan MH, Mackenzie MJ, Lee JL, Rha SY, Yuasa T, Heng DY, Choueiri TKEur Urol
- Decellularized human tendon-bone grafts for composite flexor tendon reconstruction: a cadaveric model of initial mechanical properties.Fox PM, Farnebo S, Lindsey D, Chang J, Schmitt T, Chang JJ Hand Surg Am
- An integrated peptide-antigen microarray on plasmonic gold films for sensitive human antibody profiling.Zhang B, Jarrell JA, Price JV, Tabakman SM, Li Y, Gong M, Hong G, Feng J, Utz PJ, Dai HPLoS One
- Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG).Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, Girinsky T, Hoppe RT, Mauch P, Mikhaeel NG, Ng A, ILROGInt J Radiat Oncol Biol Phys
Assembly and Architecture of the EBV B Cell Entry Triggering Complex.
PLoS Pathog. 2014 Aug;10(8):e1004309
Authors: Sathiyamoorthy K, Jiang J, Hu YX, Rowe CL, Möhl BS, Chen J, Jiang W, Mellins ED, Longnecker R, Zhou ZH, Jardetzky TS
Epstein-Barr Virus (EBV) is an enveloped double-stranded DNA virus of the gammaherpesvirinae sub-family that predominantly infects humans through epithelial cells and B cells. Three EBV glycoproteins, gH, gL and gp42, form a complex that targets EBV infection of B cells. Human leukocyte antigen (HLA) class II molecules expressed on B cells serve as the receptor for gp42, triggering membrane fusion and virus entry. The mechanistic role of gHgL in herpesvirus entry has been largely unresolved, but it is thought to regulate the activation of the virally-encoded gB protein, which acts as the primary fusogen. Here we study the assembly and function of the reconstituted B cell entry complex comprised of gHgL, gp42 and HLA class II. The structure from negative-stain electron microscopy provides a detailed snapshot of an intermediate state in EBV entry and highlights the potential for the triggering complex to bring the two membrane bilayers into proximity. Furthermore, gHgL interacts with a previously identified, functionally important hydrophobic pocket on gp42, defining the overall architecture of the complex and playing a critical role in membrane fusion activation. We propose a macroscopic model of the initiating events in EBV B cell fusion centered on the formation of the triggering complex in the context of both viral and host membranes. This model suggests how the triggering complex may bridge the two membrane bilayers, orienting critical regions of the N- and C- terminal ends of gHgL to promote the activation of gB and efficient membrane fusion.
PMID: 25144748 [PubMed - as supplied by publisher]
Curr Opin Obstet Gynecol. 2014 Aug 20;
Authors: Neely EK, Crossen SS
PURPOSE OF REVIEW: Precocious puberty continues to elicit great interest and concern among medical practitioners, as well as the public.
RECENT FINDINGS: Studies have elucidated neural regulation of puberty by kisspeptin, neurokinin B, and other factors. Cohort studies from the North America and Europe suggest that the age of thelarche may be earlier than determined 2 decades ago, and menarche may be slightly earlier, but the causes are unclear. Long-term outcomes of gonadotropin-releasing hormone analog therapy demonstrate increases in final height in the youngest treated patients, with no apparent adverse bone or reproductive consequences.
SUMMARY: Although the appropriate threshold age of onset of central puberty remains uncertain, gonadotropin-releasing hormone analog therapy is well tolerated and effective in suppressing luteinizing hormone pulses and ovarian activity.
PMID: 25144596 [PubMed - as supplied by publisher]
Corneal Cell Adhesion to Contact Lens Hydrogel Materials Enhanced via Tear Film Protein Deposition.
PLoS One. 2014;9(8):e105512
Authors: Elkins CM, Qi QM, Fuller GG
Tear film protein deposition on contact lens hydrogels has been well characterized from the perspective of bacterial adhesion and viability. However, the effect of protein deposition on lens interactions with the corneal epithelium remains largely unexplored. The current study employs a live cell rheometer to quantify human corneal epithelial cell adhesion to soft contact lenses fouled with the tear film protein lysozyme. PureVision balafilcon A and AirOptix lotrafilcon B lenses were soaked for five days in either phosphate buffered saline (PBS), borate buffered saline (BBS), or Sensitive Eyes Plus Saline Solution (Sensitive Eyes), either pure or in the presence of lysozyme. Treated contact lenses were then contacted to a live monolayer of corneal epithelial cells for two hours, after which the contact lens was sheared laterally. The apparent cell monolayer relaxation modulus was then used to quantify the extent of cell adhesion to the contact lens surface. For both lens types, lysozyme increased corneal cell adhesion to the contact lens, with the apparent cell monolayer relaxation modulus increasing up to an order of magnitude in the presence of protein. The magnitude of this increase depended on the identity of the soaking solution: lenses soaked in borate-buffered solutions (BBS, Sensitive Eyes) exhibited a much greater increase in cell attachment upon protein addition than those soaked in PBS. Significantly, all measurements were conducted while subjecting the cells to moderate surface pressures and shear rates, similar to those experienced by corneal cells in vivo.
PMID: 25144576 [PubMed - as supplied by publisher]
Rapidly Self-Renewing Human Multipotent Marrow Stromal Cells (hMSC) Express Sialyl Lewis X and Actively Adhere to Arterial Endothelium in a Chick Embryo Model System.
PLoS One. 2014;9(8):e105411
Authors: McFerrin HE, Olson SD, Gutschow MV, Semon JA, Sullivan DE, Prockop DJ
BACKGROUND: There have been conflicting observations regarding the receptors utilized by human multipotent mesenchymal bone marrow stromal cells (hMSC) to adhere to endothelial cells (EC). To address the discrepancies, we performed experiments with cells prepared with a standardized, low-density protocol preserving a sub-population of small cells that are rapidly self-renewing.
METHODS: Sialyl Lewis X (SLeX) and α4 integrin expression were determined by flow cytometry. Fucosyltransferase expression was determined by quantitative realtime RT-PCR. Cell adhesion assays were carried out with a panel of endothelial cells from arteries, veins and the microvasculature in vitro. In vivo experiments were performed to determine single cell interactions in the chick embryo chorioallantoic membrane (CAM). The CAM is a well-characterized respiratory organ allowing for time-lapse image acquisition of large numbers of cells treated with blocking antibodies against adhesion molecules expressed on hMSC.
RESULTS: hMSC expressed α4 integrin, SLeX and fucosyltransferase 4 and adhered to human EC from arteries, veins and the microvasculature under static conditions in vitro. In vivo, hMSC rolled on and adhered to arterioles in the chick embryo CAM, whereas control melanoma cells embolized. Inhibition of α4 integrin and/or SLeX with blocking antibodies reduced rolling and adhesion in arterioles and increased embolism of hMSC.
CONCLUSIONS: The results demonstrated that rapidly self-renewing hMSC were retained in the CAM because they rolled on and adhered to respiratory arteriolar EC in an α4 integrin- and SLeX-dependent manner. It is therefore important to select cells based on their cell adhesion receptor profile as well as size depending on the intended target of the cell and the injection route.
PMID: 25144321 [PubMed - as supplied by publisher]
Dietary pattern and asthma: a systematic review and meta-analysis.
J Asthma Allergy. 2014;7:105-21
Authors: Lv N, Xiao L, Ma J
BACKGROUND: The literature on the relationship between diet and asthma has largely focused on individual nutrients, with conflicting results. People consume a combination of foods from various groups that form a dietary pattern. Studying the role of dietary patterns in asthma is an emerging area of research. The purpose of this study was to systematically review dietary patterns and asthma outcomes in adults and children, to review maternal diet and child asthma, and to conduct a meta-analysis on the association between asthma prevalence and dietary patterns in adults.
METHODS: We searched Medline, Scopus, and ISI Web of Knowledge up to January 2014. Two researchers independently reviewed studies meeting the inclusion criteria using the American Dietetic Association quality criteria. A linear mixed model was used to derive the pooled effect size (95% confidence interval) for each of three dietary pattern categories (healthy, unhealthy, and neutral).
RESULTS: Thirty-one studies were identified (16 cross-sectional, one case-control, 13 cohort, and one randomized controlled trial), including 12 in adults, 13 in children, five in pregnant woman-child pairs, and one in both children and pregnant woman-child pairs. Six of the 12 adult studies reported significant associations between dietary patterns and asthma outcomes (eg, ever asthma and forced expiratory volume in one second). Seven of ten studies examining the Mediterranean diet showed protective effects on child asthma and/or wheeze. Four of the six studies in mother-child pairs showed that maternal dietary patterns during pregnancy were not associated with child asthma or wheeze. The meta-analysis including six adult studies, the primary outcome of which was the prevalence of current or ever asthma, showed no association with healthy, unhealthy, or neutral dietary patterns.
CONCLUSION: The evidence suggests no association of dietary patterns with asthma prevalence in adults or of maternal diet with child asthma or wheeze. The Mediterranean diet in children may prevent asthma or wheeze, but randomized controlled trials are lacking.
PMID: 25143747 [PubMed]
Anti-MET immunoPET for non-small cell lung cancer using fully human antibody fragments.
Mol Cancer Ther. 2014 Aug 20;
Authors: Li K, Tavare R, Zettlitz KA, Mumenthaler SM, Mallick P, Zhou Y, Marks JD, Wu AM
MET, the receptor of hepatocyte growth factor, plays important roles in tumorigenesis and drug resistance in numerous cancers including non-small cell lung cancer. As increasing numbers of MET inhibitors are being developed for clinical applications, antibody fragment based immuno-positron emission tomography (immunoPET) has the potential to rapidly quantify in vivo MET expression levels for drug response evaluation and patient stratification for these targeted therapies. Here, fully human single-chain variable fragments (scFvs) isolated from a phage display library were re-formatted into bivalent cys-diabodies (scFv-cys dimers) with affinities to MET ranging from 0.7 nM to 5.1 nM. The candidate with the highest affinity, H2, was radiolabeled with 89Zr for immunoPET studies targeting non-small cell lung cancer xenografts: low MET expressing Hcc827 and the gefitinib-resistant Hcc827-GR6 with 4-fold MET over-expression. ImmunoPET at as early as 4 hours post injection produced high contrast images, and ex vivo biodistribution analysis at 20 hours post injection showed about 2-fold difference in tracer uptake levels between the parental and resistant tumors (p < 0.01). Further immunoPET studies using a larger fragment, the H2 minibody (scFv-CH3 dimer) produced similar results at later time points. Two of the antibody clones (H2 and H5) showed in vitro growth inhibitory effects on MET-dependent gefitinib-resistant cell lines, while no effects were observed on resistant lines lacking MET activation. In conclusion, these fully human antibody fragments inhibit MET-dependent cancer cells and enable rapid immunoPET imaging to assess MET expression levels, showing potential for both therapeutic and diagnostic applications.
PMID: 25143449 [PubMed - as supplied by publisher]
Organic Cation Transporter Variation and Response to Smoking Cessation Therapies.
Nicotine Tob Res. 2014 Aug 20;
Authors: Bergen AW, Javitz HS, Krasnow R, Michel M, Nishita D, Conti DV, Edlund CK, Kwok PY, McClure JB, Kim RB, Hall S, Tyndale RF, Baker TB, Benowitz NL, Swan GE
INTRODUCTION: We evaluated chr6q25.3 organic cation transporter gene (SLC22A1, SLC22A2, SLC22A3) variation and response to smoking cessation therapies. The corresponding proteins are low affinity transporters of choline, acetylcholine and monoamines, and of smoking cessation pharmacotherapies, expressed in multiple tissues.
METHODS: We selected seven common polymorphisms for mega-regression analysis. We assessed additive model association of polymorphisms with seven day point prevalence abstinence overall, and by assigned pharmacotherapy, at end of treatment, and at six months, in European ancestry participants of seven randomized controlled trials, adjusted for demographic, population genetic, and trial covariates.
RESULTS: Initial results were obtained in six trials and 1,839 individuals. Nominally statistically significant associations of two SLC22A2 polymorphisms were observed: with rs316019 at six months, overall [(c.808T>G; p.Ser270Ala), OR=1.306 (95%CI 1.034-1.649) P=0.025], and among those randomized to nicotine replacement therapy (NRT) [OR=1.784 (1.072-2.970) P=0.026]; and with rs316006 (c.1502-529A>T) among those randomized to varenicline [OR=1.420 (1.038-1.944) P=0.028, OR=1.362 (1.001-1.853) P=0.049] at end of treatment and six months. Individuals randomized to NRT from a seventh trial were genotyped for rs316019; rs316019 was associated with a nominally statistically significant effect on abstinence overall at six months in 2,233 individuals [OR=1.249 (1.007-1.550) P=0.043].
CONCLUSIONS: The functional OCT2 Ser270Ala polymorphism is nominally statistically significantly associated with abstinence in European-ancestry treatment-seeking smokers after adjustments for pharmacotherapy, demographics, population genetics, and without adjustment for multiple testing of seven SNPs. Replication of these preliminary findings in additional randomized controlled trials of smoking cessation therapies, and from multiple continental populations, would describe another pharmacogenetic role for SLC22A2/OCT2.
PMID: 25143296 [PubMed - as supplied by publisher]
FACTERA: a practical method for the discovery of genomic rearrangements at breakpoint resolution.
Bioinformatics. 2014 Aug 20;
Authors: Newman AM, Bratman SV, Stehr H, Lee LJ, Liu CL, Diehn M, Alizadeh AA
SUMMARY: For practical and robust de novo identification of genomic fusions and breakpoints from targeted paired-end DNA sequencing data, we developed Fusion And Chromosomal Translocation Enumeration and Recovery Algorithm (FACTERA). Our method has minimal external dependencies, works directly on a preexisting Binary Alignment/Map (BAM) file, and produces easily interpretable output. We demonstrate FACTERA's ability to rapidly identify breakpoint-resolution fusion events with high sensitivity and specificity in patients with non-small cell lung cancer (NSCLC), including novel rearrangements. We anticipate that FACTERA will be broadly applicable to the discovery and analysis of clinically relevant fusions from both targeted and genome-wide sequencing datasets. Availability and implementation: http://factera.stanford.edu.
CONTACT: firstname.lastname@example.org (A.A.A.), email@example.com (M.D.) SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
PMID: 25143292 [PubMed - as supplied by publisher]
Irreversible xenon insertion into a small-pore zeolite at moderate pressures and temperatures.
Nat Chem. 2014 Sep;6(9):835-9
Authors: Seoung D, Lee Y, Cynn H, Park C, Choi KY, Blom DA, Evans WJ, Kao CC, Vogt T, Lee Y
Pressure drastically alters the chemical and physical properties of materials and allows structural phase transitions and chemical reactions to occur that defy much of our understanding gained under ambient conditions. Particularly exciting is the high-pressure chemistry of xenon, which is known to react with hydrogen and ice at high pressures and form stable compounds. Here, we show that Ag16Al16Si24O8·16H2O (Ag-natrolite) irreversibly inserts xenon into its micropores at 1.7 GPa and 250 °C, while Ag(+) is reduced to metallic Ag and possibly oxidized to Ag(2+). In contrast to krypton, xenon is retained within the pores of this zeolite after pressure release and requires heat to desorb. This irreversible insertion and trapping of xenon in Ag-natrolite under moderate conditions sheds new light on chemical reactions that could account for the xenon deficiency relative to argon observed in terrestrial and Martian atmospheres.
PMID: 25143221 [PubMed - in process]
Clinical and Immunologic Predictors of Death After an Acute Opportunistic Infection: Results from ACTG A5164.
HIV Clin Trials. 2014 Jul-Aug;15(4):133-9
Authors: Grant PM, Komarow L, Sanchez A, Sattler FR, Asmuth DM, Pollard RB, Zolopa AR
BACKGROUND: In the pre-antiretroviral therapy (ART) era, markers of increased disease severity during an acute opportunistic infection (OI) were associated with mortality. Even with ART, mortality remains high during the first year after an OI in persons with advanced HIV infection, but it is unclear whether previous predictors of mortality remain valid in the current era.
OBJECTIVE: To determine clinical and immunological predictors of death after an OI.
METHODS: We used clinical data and stored plasma from ACTG A5164, a multicenter study evaluating the optimal timing of ART during a nontuberculous OI. We developed Cox models evaluating associations between clinical parameters and plasma marker levels at entry and time to death over the first 48 weeks after the diagnosis of OI. We developed multivariable models incorporating only clinical parameters, only plasma marker levels, or both.
RESULTS: The median CD4+ T-cell count in study participants at baseline was 29 cells/µL. Sixty-four percent of subjects had Pneumocystis jirovecii pneumonia (PCP). Twenty-three of 282 (8.2%) subjects died. In univariate analyses, entry mycobacterial infection, OI number, hospitalization, low albumin, low hemoglobin, lower CD4, and higher IL-8 and sTNFrII levels and lower IL-17 levels were associated with mortality. In the combined model using both clinical and immunologic parameters, the presence of an entry mycobacterial infection and higher sTNFrII levels were significantly associated with death.
CONCLUSIONS: In the ART era, clinical risk factors for death previously identified in the pre-ART era remain predictive. Additionally, activation of the innate immune system is associated with an increased risk of death following an acute OI.
PMID: 25143022 [PubMed - in process]
Evaluation of a new pediatric positive airway pressure mask.
J Clin Sleep Med. 2014;10(9)
Authors: Kushida CA, Halbower AC, Kryger MH, Pelayo R, Assalone V, Cardell CY, Huston S, Willes L, Wimms AJ, Mendoza J
STUDY OBJECTIVES: The choice and variety of pediatric masks for continuous positive airway pressure (CPAP) is limited in the US. Therefore, clinicians often prescribe modified adult masks. Until recently a mask for children aged < 7 years was not available. This study evaluated apnea-hypopnea index (AHI) equivalence and acceptability of a new pediatric CPAP mask for children aged 2-7 years (Pixi; ResMed Ltd, Sydney, Australia).
METHODS: Patients aged 2-7 years were enrolled and underwent in-lab baseline polysomnography (PSG) using their previous mask, then used their previous mask and the VPAP III ST-A flow generator for ≥ 10 nights at home. Thereafter, patients switched to the Pixi mask for ≥ 2 nights before returning for a PSG during PAP therapy via the Pixi mask. Patients then used the Pixi mask at home for ≥ 21 nights. Patients and their parents/guardians returned to the clinic for follow-up and provided feedback on the Pixi mask versus their previous mask.
RESULTS: AHI with the Pixi mask was 1.1 ± 1.5/h vs 2.6 ± 5.4/h with the previous mask (p = 0.3538). Parents rated the Pixi mask positively for: restfulness of the child's sleep, trouble in getting the child to sleep, and trouble in having the child stay asleep. The Pixi mask was also rated highly for leaving fewer or no marks on the upper lip and under the child's ears, and being easy to remove.
CONCLUSIONS: The Pixi mask is suitable for children aged 2-7 years and provides an alternative to other masks available for PAP therapy in this age group.
PMID: 25142768 [PubMed - in process]
Development and evaluation of a treatment fidelity instrument for family-based treatment of adolescent anorexia nervosa.
Int J Eat Disord. 2014 Aug 20;
Authors: Forsberg S, Fitzpatrick KK, Darcy A, Aspen V, Accurso EC, Bryson SW, Agras S, Arnow KD, Le Grange D, Lock J
OBJECTIVE: This study provides data on the psychometric properties of a newly developed measure of treatment fidelity in Family-Based Treatment (FBT) for adolescent anorexia nervosa (AN). The Family Therapy Fidelity and Adherence Check (FBT-FACT) was created to evaluate therapist adherence and competency on the core interventions in FBT.
METHOD: Participants were 45 adolescents and their families sampled from three randomized clinical trials evaluating treatment for AN. Trained fidelity raters evaluated 19 therapists across 90 early session recordings using the FBT-FACT. They also rated an additional 15 session 1 recordings of an alternate form of family therapy-Systemic Family Therapy for the purpose of evaluating discriminant validity of the FBT-FACT. The process of development and the psychometric properties of the FBT-FACT are presented.
RESULTS: Overall fidelity ratings for each session demonstrated moderate to strong inter-rater agreement. Internal consistency of the measure was strong for sessions 1 and 2 and poor for session 3. Principal components analysis suggests sessions 1 and 2 are distinct interventions.
DISCUSSION: The FBT-FACT demonstrates good reliability and validity as a measure of treatment fidelity in the early phase of FBT. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014).
PMID: 25142619 [PubMed - as supplied by publisher]
Periodic Leg Movements during Sleep Are Associated with Polymorphisms in BTBD9, TOX3/BC034767, MEIS1, MAP2K5/SKOR1, and PTPRD.
Authors: Moore H, Winkelmann J, Lin L, Finn L, Peppard P, Mignot E
STUDY OBJECTIVES: To examine association between periodic leg movements (PLM) and 13 single nucleotide polymorphisms (SNPs) in 6 loci known to increase risk of restless legs syndrome (RLS).
SETTING: Stanford Center for Sleep Sciences and Medicine and Clinical Research Unit of University of Wisconsin Institute for Clinical and Translational Research.
PATIENTS: Adult participants (n = 1,090, mean age = 59.7 years) from the Wisconsin Sleep Cohort (2,394 observations, 2000-2012).
DESIGN AND INTERVENTIONS: A previously validated automatic detector was used to measure PLMI. Thirteen SNPs within BTBD9, TOX3/BC034767, MEIS1 (2 unlinked loci), MAP2K5/SKOR1, and PTPRD were tested. Analyses were performed using a linear model and by PLM category using a 15 PLM/h cutoff. Statistical significance for loci was Bonferroni corrected for 6 loci (p < 8.3×10-3). RLS symptoms were categorized into four groups: likely, possible, no symptoms, and unknown based on a mailed survey response.
MEASUREMENTS AND RESULTS: Prevalence of PLMI ≥15 was 33%. Subjects with PLMs were older, more likely to be male, and had more frequent RLS symptoms, a shorter total sleep time, and higher wake after sleep onset. Strong associations were found at all loci except one. Highest associations for PLMI >15/h were obtained using a multivariate model including age, sex, sleep disturbances, and the best SNPs for each loci, yielding the following odds ratios (OR) and P values: BTBD9 rs3923809(A) OR = 1.65, P = 1.5%10-8; TOX3/BC034767 rs3104788(T) OR = 1.35, P = 9.0×10-5; MEIS1 rs12469063(G) OR = 1.38, P = 2.0×10-4; MAP2K5/SKOR1 rs6494696(G) OR = 1.24, P = 1.3×10-2; and PTPRD(A) rs1975197 OR = 1.31, P = 6.3×10-3. Linear regression models also revealed significant PLM effects for BTBD9, TOX3/BC034767, and MEIS1. Co-varying for RLS symptoms only modestly reduced the genetic associations.
CONCLUSIONS: SNPs demonstrated to increase risk of RLS are strongly linked to increased PLM as well, although some loci may have more effects on one versus the other phenotype.
PMID: 25142570 [PubMed - in process]
Involution of Eruptive Melanocytic Nevi on Combination BRAF and MEK Inhibitor Therapy.
JAMA Dermatol. 2014 Aug 20;
Authors: Chen FW, Tseng D, Reddy S, Daud AI, Swetter SM
Importance: Eruptive melanocytic nevi (EMN) are characterized by the sudden onset of numerous melanocytic nevi and have been traditionally described in the setting of immunosuppression. Selective BRAF inhibitors, such as vemurafenib cause multiple cutaneous adverse effects, including the formation of cutaneous squamous cell carcinoma, as well as EMN. We describe the first reported case, to our knowledge, of involution of BRAF inhibitor-induced EMN following the concomitant addition of a MEK inhibitor, cobimetinib.
Observations: A woman in her 20s with a history of metastatic melanoma developed EMN while receiving therapy with vemurafenib, a selective BRAF inhibitor. After disease progression, the patient was placed on a clinical trial that combined vemurafenib with a MEK inhibitor, cobimetinib. Within months, we noted clinical involution of many of her EMN. In addition, numerous preexisting nevi were noted to fade in color on the dual regimen. Over a year after initiating this combination therapy, most of the patient's EMN were no longer clinically evident.
Conclusions and Relevance: Our case report describing the involution of EMN supports data from previous clinical trials indicating that combination BRAF and MEK inhibition may reduce cutaneous proliferative effects that arise on BRAF inhibitor monotherapy. Further studies are necessary to characterize the biological mechanisms underlying this phenomenon.
PMID: 25142409 [PubMed - as supplied by publisher]
ACR Committee on Pediatric Imaging Research.
Pediatr Radiol. 2014 Sep;44(9):1193-4
Authors: Daldrup-Link HE, Voss S, Donig J, ACR committee
PMID: 25142332 [PubMed - in process]
A Rwandan Woman.
Acad Psychiatry. 2014 Aug 21;
Authors: Roberts LW
PMID: 25142248 [PubMed - as supplied by publisher]
A Review of Multidisciplinary Clinical Practice Guidelines in Suicide Prevention: Toward an Emerging Standard in Suicide Risk Assessment and Management, Training and Practice.
Acad Psychiatry. 2014 Aug 21;
Authors: Bernert RA, Hom MA, Roberts LW
OBJECTIVE: The current paper aims to: (1) examine clinical practice guidelines in suicide prevention across fields, organizations, and clinical specialties and (2) inform emerging standards in clinical practice, research, and training.
METHODS: The authors conducted a systematic literature review to identify clinical practice guidelines and resource documents in suicide prevention and risk management. The authors used PubMed, Google Scholar, and Google Search, and keywords included: clinical practice guideline, practice guideline, practice parameters, suicide, suicidality, suicidal behaviors, assessment, and management. To assess for commonalities, the authors reviewed guidelines and resource documents across 13 key content categories and assessed whether each document suggested validated assessment measures.
RESULTS: The search generated 101 source documents, which included N = 10 clinical practice guidelines and N = 12 additional resource documents (e.g., non-formalized guidelines, tool-kits). All guidelines (100 %) provided detailed recommendations for the use of evidence-based risk factors and protective factors, 80 % provided brief (but not detailed) recommendations for the assessment of suicidal intent, and 70 % recommended risk management strategies. By comparison, only 30 % discussed standardization of risk-level categorizations and other content areas considered central to best practices in suicide prevention (e.g., restricting access to means, ethical considerations, confidentiality/legal issues, training, and postvention practices). Resource documents were largely consistent with these findings.
CONCLUSIONS: Current guidelines address similar aspects of suicide risk assessment and management, but significant discrepancies exist. A lack of consensus was evident in recommendations across core competencies, which may be improved by increased standardization in practice and training. Additional resources appear useful for supplemental use.
PMID: 25142247 [PubMed - as supplied by publisher]
Reward Processing in Healthy Offspring of Parents With Bipolar Disorder.
JAMA Psychiatry. 2014 Aug 20;
Authors: Singh MK, Kelley RG, Howe ME, Reiss AL, Gotlib IH, Chang KD
Importance: Bipolar disorder (BD) is highly familial and characterized by deficits in reward processing. It is not known, however, whether these deficits precede illness onset or are a consequence of the disorder.
Objective: To determine whether anomalous neural processing of reward characterizes children at familial risk for BD in the absence of a personal history of a psychopathologic disorder.
Design, Setting, and Participants: This study compared neural activity and behaviors of children at high and low risk for mania while they anticipate and respond to reward and loss. The study was performed from September 15, 2009, through February 17, 2012, in a university functional magnetic resonance imaging facility and included 8- to 15-year-old children without disorders born to a parent with BD (n = 20 high-risk children) and demographically matched healthy comparison children (n = 25 low-risk children).
Main Outcomes and Measures: Neural activity, as measured with functional magnetic resonance imaging, during anticipation and receipt of reward and loss during a monetary incentive delay task.
Results: While anticipating losses, high-risk children had less activation in the pregenual cingulate than did their low-risk counterparts (t19 = -2.44, P = .02). When receiving rewards, high-risk children had greater activation in the left lateral orbitofrontal cortex than did low-risk children (t43 = -3.04, P = .004). High-risk children also had weaker functional connectivity between the pregenual cingulate and the right ventrolateral prefrontal cortex while anticipating rewards than did low-risk children (t19 = -4.38, P < .001) but had a stronger connectivity between these regions while anticipating losses (t24 = 2.76, P = .01). Finally, in high- but not low-risk children, novelty seeking was associated with increased striatal and amygdalar activation in the anticipation of losses, and impulsivity was associated with increased striatal and insula activation in the receipt of rewards.
Conclusions and Relevance: Aberrant prefrontal activations and connectivities during reward processing suggest mechanisms that underlie early vulnerabilities for developing dysfunctional regulation of goal pursuit and motivation in children at high risk for mania. Longitudinal studies are needed to examine whether these patterns of neural activation predict the onset of mania and other mood disorders in high-risk children.
PMID: 25142103 [PubMed - as supplied by publisher]
Obesity, physical activity, and their interaction in incident atrial fibrillation in postmenopausal women.
J Am Heart Assoc. 2014;3(4)
Authors: Azarbal F, Stefanick ML, Salmoirago-Blotcher E, Manson JE, Albert CM, LaMonte MJ, Larson JC, Li W, Martin LW, Nassir R, Garcia L, Assimes TL, Tharp KM, Hlatky MA, Perez MV
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with increased risk of stroke and death. Obesity is an independent risk factor for AF, but modifiers of this risk are not well known. We studied the roles of obesity, physical activity, and their interaction in conferring risk of incident AF.
METHODS AND RESULTS: The Women's Health Initiative (WHI) Observational Study was a prospective observational study of 93 676 postmenopausal women followed for an average of 11.5 years. Incident AF was identified using WHI-ascertained hospitalization records and diagnostic codes from Medicare claims. A multivariate Cox's hazard regression model adjusted for demographic and clinical risk factors was used to evaluate the interaction between obesity and physical activity and its association with incident AF. After exclusion of women with prevalent AF, incomplete data, or underweight body mass index (BMI), 9792 of the remaining 81 317 women developed AF. Women were, on average, 63.4 years old, 7.8% were African American, and 3.6% were Hispanic. Increased BMI (hazard ratio [HR], 1.12 per 5-kg/m(2) increase; 95% confidence interval [CI], 1.10 to 1.14) and reduced physical activity (>9 vs. 0 metabolic equivalent task hours per week; HR, 0.90; 95% CI, 0.85 to 0.96) were independently associated with higher rates of AF after multivariate adjustment. Higher levels of physical activity reduced the AF risk conferred by obesity (interaction P=0.033).
CONCLUSIONS: Greater physical activity is associated with lower rates of incident AF and modifies the association between obesity and incident AF.
PMID: 25142057 [PubMed - in process]
Perovskite solar cells: Continuing to soar.
Nat Mater. 2014 Aug 21;13(9):845-6
Authors: McGehee MD
PMID: 25141807 [PubMed - in process]
Response to letter regarding article, "Cost-effectiveness of percutaneous coronary intervention in patients with stable coronary artery disease and abnormal fractional flow reserve".
Circulation. 2014 Jun 24;129(25):e684
Authors: Fearon WF, Shilane D, Pijls NH, Boothroyd DB, Tonino PA, Barbato E, Juni P, De Bruyne B, Hlatky MA, FAME 2 Investigators
PMID: 24958760 [PubMed - indexed for MEDLINE]
Impact of diffusion-weighted imaging Alberta stroke program early computed tomography score on the success of endovascular reperfusion therapy.
Stroke. 2014 Jul;45(7):1992-8
Authors: Inoue M, Olivot JM, Labreuche J, Mlynash M, Tai W, Albucher JF, Meseguer E, Amarenco P, Mazighi M
BACKGROUND AND PURPOSE: In acute ischemic stroke patients treated by intravenous thrombolysis, a diffusion-weighted imaging (DWI) Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an independent factor of functional outcomes. Our aim was to assess the impact of pretreatment DWI-ASPECTS on outcomes after endovascular therapy, with a specific emphasis on recanalization.
METHODS: We analyzed data collected between April 2007 and March 2013 in a prospective clinical registry of acute ischemic stroke patients treated by endovascular approach. Every patient with a documented internal carotid artery or middle cerebral artery occlusion who underwent an acute DWI-MRI before treatment was eligible for this study. The primary outcome was a favorable outcome defined by modified Rankin Scale of 0 to 2 at 90 days.
RESULTS: Two hundred ten patients were included and median DWI-ASPECTS was 7 (interquartile range, 4-8). DWI-ASPECTS≥5 was the optimal threshold to predict a favorable outcome (area under the curve=0.69; sensitivity, 90%; specificity, 38%). In a multivariate analysis including confounding variables, the adjusted odds ratio for favorable outcomes associated with a DWI-ASPECTS of ≥5 was 5.06 (95% confidence interval, 1.86-13.77; P=0.002). Nonetheless, the occurrence of a complete recanalization was associated with an increased rate of favorable outcomes in patients with DWI-ASPECTS under 5 (50% versus 3%, P<0.001).
CONCLUSIONS: DWI-ASPECTS≥5 seems to be the optimal threshold to predict favorable outcomes among patients undergoing endovascular reperfusion within 6 hours. Selected patients with a DWI-ASPECTS of <5 may still benefit when a complete reperfusion is achieved.
PMID: 24923724 [PubMed - indexed for MEDLINE]
Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial.
Stroke. 2014 Jul;45(7):2018-23
Authors: Bernard TJ, Rivkin MJ, Scholz K, deVeber G, Kirton A, Gill JC, Chan AK, Hovinga CA, Ichord RN, Grotta JC, Jordan LC, Benedict S, Friedman NR, Dowling MM, Elbers J, Torres M, Sultan S, Cummings DD, Grabowski EF, McMillan HJ, Beslow LA, Amlie-Lefond C, Thrombolysis in Pediatric Stroke Study
BACKGROUND AND PURPOSE: In adult stroke, the advent of thrombolytic therapy led to the development of primary stroke centers capable to diagnose and treat patients with acute stroke rapidly. We describe the development of primary pediatric stroke centers through preparation of participating centers in the Thrombolysis in Pediatric Stroke (TIPS) trial.
METHODS: We collected data from the 17 enrolling TIPS centers regarding the process of becoming an acute pediatric stroke center with capability to diagnose, evaluate, and treat pediatric stroke rapidly, including use of thrombolytic therapy.
RESULTS: Before 2004, <25% of TIPS sites had continuous 24-hour availability of acute stroke teams, MRI capability, or stroke order sets, despite significant pediatric stroke expertise. After TIPS preparation, >80% of sites now have these systems in place, and all sites reported increased readiness to treat a child with acute stroke. Use of a 1- to 10-Likert scale on which 10 represented complete readiness, median center readiness increased from 6.2 before site preparation to 8.7 at the time of site activation (P≤0.001).
CONCLUSIONS: Before preparing for TIPS, centers interested in pediatric stroke had not developed systematic strategies to diagnose and treat acute pediatric stroke. TIPS trial preparation has resulted in establishment of pediatric acute stroke centers with clinical and system preparedness for evaluation and care of children with acute stroke, including use of a standardized protocol for evaluation and treatment of acute arterial stroke in children that includes use of intravenous tissue-type plasminogen activator.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01591096.
PMID: 24916908 [PubMed - indexed for MEDLINE]
Predictors of functional dependence despite successful revascularization in large-vessel occlusion strokes.
Stroke. 2014 Jul;45(7):1977-84
Authors: Shi ZS, Liebeskind DS, Xiang B, Ge SG, Feng L, Albers GW, Budzik R, Devlin T, Gupta R, Jansen O, Jovin TG, Killer-Oberpfalzer M, Lutsep HL, Macho J, Nogueira RG, Rymer M, Smith WS, Wahlgren N, Duckwiler GR, Multi MERCI, TREVO, and TREVO 2 Investigators
BACKGROUND AND PURPOSE: High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy.
METHODS: We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization.
RESULTS: Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence.
CONCLUSIONS: One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867.
PMID: 24876082 [PubMed - indexed for MEDLINE]
Insulin resistance and medial prefrontal gyrus metabolism in women receiving hormone therapy.
Psychiatry Res. 2014 Jul 30;223(1):28-36
Authors: Rasgon NL, Kenna HA, Wroolie TE, Williams KE, DeMuth BN, Silverman DH
Insulin resistance (IR) is a putative risk factor for cognitive decline and dementia, and has been shown to impede neuronal glucose metabolism in animal models. This post hoc study focused on metabolic changes in the medial prefrontal region, a brain region exhibiting decline years before documented cognitive changes, relative to high or low IR status in a cohort of postmenopausal women at risk for dementia who were randomized to continue or discontinue existing stable hormone therapy (HT) for 2 years. Subjects were dichotomized into high and low IR groups based on the homeostatic model assessment of insulin resistance, which was within clinically normal limits for the group as a whole at both baseline and 2-year follow-up. Results showed that high and low IR groups showed significant differences in metabolic decline of the medial prefrontal gyrus, regardless of HT randomization group. However, HT randomization was predictive of metabolic decline only in women with low HOMA (homeostatic assessment of insulin resistance). Performance in working memory was consistent with observed metabolic changes. These results suggest IR may be an independent moderator of regional metabolic changes, while protective metabolic effects of HT are most apparent in those at low-end range of IR. If replicated in future studies, these findings will help to better understand the interaction between putative risk and protective factors, and further delineate cohort postmenopausal women who may benefit from HT.
PMID: 24819305 [PubMed - indexed for MEDLINE]
New-onset pancytopenia: a diagnostic approach-reply.
Hum Pathol. 2014 Jul;45(7):1552-3
Authors: Weinzierl E, Arber DA
PMID: 24796507 [PubMed - indexed for MEDLINE]
Periprocedural stroke and bleeding complications in patients undergoing catheter ablation of atrial fibrillation with different anticoagulation management: results from the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) randomized trial.
Circulation. 2014 Jun 24;129(25):2638-44
Authors: Di Biase L, Burkhardt JD, Santangeli P, Mohanty P, Sanchez JE, Horton R, Gallinghouse GJ, Themistoclakis S, Rossillo A, Lakkireddy D, Reddy M, Hao S, Hongo R, Beheiry S, Zagrodzky J, Rong B, Mohanty S, Elayi CS, Forleo G, Pelargonio G, Narducci ML, Dello Russo A, Casella M, Fassini G, Tondo C, Schweikert RA, Natale A
BACKGROUND: Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists.
METHODS AND RESULTS: This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1-55.6; P<0.001).
CONCLUSION: This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin.
CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.
PMID: 24744272 [PubMed - indexed for MEDLINE]
Revising the economic imperative for US STEM education.
PLoS Biol. 2014 Jan;12(1):e1001760
Authors: Donovan BM, Moreno Mateos D, Osborne JF, Bisaccio DJ
Over the last decade macroeconomic studies have established a clear link between student achievement on science and math tests and per capita gross domestic product (GDP) growth, supporting the widely held belief that science, technology, engineering, and math(STEM) education are important factors in the production of economic prosperity. We critique studies that use science and math tests to predict GDP growth, arguing that estimates of the future economic value of STEM education involve substantial speculation because they ignore the impacts of economic growth on biodiversity and ecosystem functionality, which, in the long-term, limit the potential for future economic growth. Furthermore, we argue that such ecological impacts can be enabled by STEM education. Therefore, we contend that the real economic imperative for the STEM pipeline is not just raising standardized test scores, but also empowering students to assess, preserve, and restore ecosystems in order to reduce ecological degradation and increase economic welfare.
PMID: 24453938 [PubMed - indexed for MEDLINE]
Sensory cell fates: four defaults for the price of one.
Curr Biol. 2013 Dec 16;23(24):R1089-91
Authors: Wernet MF, Desplan C
The specification of different subtypes of olfactory sensilla, which harbor the olfactory receptor neurons (ORNs) in the Drosophila antennae, is poorly understood. Loss of the transcription factor Rotund (Rn) leads to a simultaneous mis-specification of several ORN classes, transforming them into different 'default' cell fates.
PMID: 24355782 [PubMed - indexed for MEDLINE]
Immune mechanisms in medium and large-vessel vasculitis.
Nat Rev Rheumatol. 2013 Dec;9(12):731-40
Authors: Weyand CM, Goronzy JJ
Vasculitis of the medium and large arteries, most often presenting as giant cell arteritis (GCA), is an infrequent, but potentially fatal, type of immune-mediated vascular disease. The site of the aberrant immune reaction, the mural layers of the artery, is strictly defined by vascular dendritic cells, endothelial cells, vascular smooth muscle cells and fibroblasts, which engage in an interaction with T cells and macrophages to, ultimately, cause luminal stenosis or aneurysmal wall damage of the vessel. A multitude of effector cytokines, all known as critical mediators in host-protective immunity, have been identified in vasculitic lesions. Two dominant cytokine clusters--the IL-6-IL-17 axis and the IL-12-IFN-γ axis--have been linked to disease activity. These two clusters seem to serve different roles in the vasculitic process. The IL-6-IL-17 cluster is highly responsive to standard corticosteroid therapy, whereas the IL-12-IFN-γ cluster is resistant to steroid-mediated immunosuppression. The information exchange between vascular and immune cells and stabilization of the vasculitic process involves members of the Notch receptor and ligand family. Focusing on elements in the tissue context of GCA, instead of broadly suppressing host immunity, might enable a more tailored therapeutic approach that avoids unwanted adverse effects of aggressive immunosuppression.
PMID: 24189842 [PubMed - indexed for MEDLINE]
The impact of low serum sodium on treatment outcome of targeted therapy in metastatic renal cell carcinoma: results from the International Metastatic Renal Cell Cancer Database Consortium.
Eur Urol. 2014 Apr;65(4):723-30
Authors: Schutz FA, Xie W, Donskov F, Sircar M, McDermott DF, Rini BI, Agarwal N, Pal SK, Srinivas S, Kollmannsberger C, North SA, Wood LA, Vaishampayan U, Tan MH, Mackenzie MJ, Lee JL, Rha SY, Yuasa T, Heng DY, Choueiri TK
BACKGROUND: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients treated with immunotherapy.
OBJECTIVE: To investigate the influence of baseline hyponatremia in mRCC patients treated with targeted therapy in the International Metastatic Renal Cell Carcinoma Database Consortium.
DESIGN, SETTING, AND PARTICIPANTS: Data on 1661 patients treated with first-line vascular endothelial growth factor (VEGF) or mammalian target of rapamycin (mTOR) targeted therapy for mRCC were available from 18 cancer centers to study the impact of hyponatremia (serum sodium level <135 mmol/l) on clinical outcomes.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary objective was overall survival (OS) and secondary end points included time to treatment failure (TTF) and the disease control rate (DCR). The chi-square test was used to compare the DCR in patients with and without hyponatremia. OS and TTF were estimated with the Kaplan-Meier method and differences between groups were examined by the log-rank test. Multivariable logistic regression (for DCR) and Cox regression (for OS and TTF) were undertaken adjusted for prognostic risk factors.
RESULTS AND LIMITATIONS: Median OS after treatment initiation was 18.5 mo (95% confidence interval [CI], 17.5-19.8 mo), with 552 (33.2%) of patients remaining alive on a median follow-up of 22.1 mo. Median baseline serum sodium was 138 mmol/l (range: 122-159 mmol/l), and hyponatremia was found in 14.6% of patients. On univariate analysis, hyponatremia was associated with shorter OS (7.0 vs 20.9 mo), shorter TTF (2.9 vs 7.4 mo), and lower DCR rate (54.9% vs 78.8%) (p<0.0001 for all comparisons). In multivariate analysis, these effects remain significant (hazard ratios: 1.51 [95% CI, 1.26-1.80] for OS, and 1.57 [95% CI, 1.34-1.83] for TTF; odds ratio: 0.50 [95% CI, 34-0.72] for DCR; adjusted p<0.001). Results were similar if sodium was analyzed as a continuous variable (adjusted p<0.0001 for OS, TTF, and DCR).
CONCLUSIONS: This is the largest multi-institutional report to show that hyponatremia is independently associated with a worse outcome in mRCC patients treated with VEGF- and mTOR-targeted agents.
PMID: 24184025 [PubMed - indexed for MEDLINE]
Decellularized human tendon-bone grafts for composite flexor tendon reconstruction: a cadaveric model of initial mechanical properties.
J Hand Surg Am. 2013 Dec;38(12):2323-8
Authors: Fox PM, Farnebo S, Lindsey D, Chang J, Schmitt T, Chang J
PURPOSE: After complex hand trauma, restoration of tendon strength is challenging. Tendon insertion tears typically heal as fibrous scars after surgical reconstruction and create a weak point at the tendon-bone interface. In addition, major tendon loss may overwhelm the amount of available autograft for reconstruction. An off-the-shelf product may help address these challenges. We hypothesized that decellularized human flexor digitorum profundus and distal phalanx tendon-bone composite grafts were a feasible option for flexor tendon reconstruction after complex hand trauma. By replacing the entire injured composite segment, the need for tendon repair within the tendon sheath, reconstruction of the tendon-bone interface, and use of limited autograft could be eliminated.
METHODS: Paired human cadaver forearms were dissected to obtain the flexor digitorum profundus tendon with an attached block of distal phalanx. Tendon-bone grafts were pair-matched and divided into 2 groups: decellularized grafts (n = 12) and untreated (control) grafts (n = 11). Grafts in the decellularized group were subjected to physiochemical decellularization. Pair-matched tendon-bone grafts (decellularized and untreated) were placed back into the flexor tendon sheath and secured distally using a tie-over button and proximally by weaving the graft into the flexor digitorum superficialis tendon in the distal forearm. The ultimate load, location of failure, and excursion were determined.
RESULTS: Decellularized tendon-bone composite grafts demonstrated no significant difference in ultimate failure load or stiffness compared with untreated grafts. Both groups eventually failed in varied locations along the repair. The most common site of failure in both groups was the tie-over button. The decellularized group failed at the tendon-bone insertion in 3 specimens (25%) compared with none in the untreated group. Both groups demonstrated an average tendon excursion of approximately 82 mm before failure.
CONCLUSIONS: Decellularization of human flexor tendon-distal phalanx tendon-bone constructs did not compromise initial strength despite chemical and mechanical decellularization in a cadaveric model. At the time of repair, decellularized flexor tendon-bone grafts can exceed the strength and excursion needed for hand therapy immediately after reconstruction.
CLINICAL RELEVANCE: These tendon-bone grafts may become an option for complex hand reconstruction at or near tendon-bone insertions and throughout the tendon sheath. Further work is required to assess the role of reseeding in an in vivo model.
PMID: 24055133 [PubMed - indexed for MEDLINE]
An integrated peptide-antigen microarray on plasmonic gold films for sensitive human antibody profiling.
PLoS One. 2013;8(7):e71043
Authors: Zhang B, Jarrell JA, Price JV, Tabakman SM, Li Y, Gong M, Hong G, Feng J, Utz PJ, Dai H
High-throughput screening for interactions of peptides with a variety of antibody targets could greatly facilitate proteomic analysis for epitope mapping, enzyme profiling, drug discovery and biomarker identification. Peptide microarrays are suited for such undertaking because of their high-throughput capability. However, existing peptide microarrays lack the sensitivity needed for detecting low abundance proteins or low affinity peptide-protein interactions. This work presents a new peptide microarray platform constructed on nanostructured plasmonic gold substrates capable of metal enhanced NIR fluorescence enhancement (NIR-FE) by hundreds of folds for screening peptide-antibody interactions with ultrahigh sensitivity. Further, an integrated histone peptide and whole antigen array is developed on the same plasmonic gold chip for profiling human antibodies in the sera of systemic lupus erythematosus (SLE) patients, revealing that collectively a panel of biomarkers against unmodified and post-translationally modified histone peptides and several whole antigens allow more accurate differentiation of SLE patients from healthy individuals than profiling biomarkers against peptides or whole antigens alone.
PMID: 23923050 [PubMed - indexed for MEDLINE]
Modern radiation therapy for Hodgkin lymphoma: field and dose guidelines from the international lymphoma radiation oncology group (ILROG).
Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):854-62
Authors: Specht L, Yahalom J, Illidge T, Berthelsen AK, Constine LS, Eich HT, Girinsky T, Hoppe RT, Mauch P, Mikhaeel NG, Ng A, ILROG
Radiation therapy (RT) is the most effective single modality for local control of Hodgkin lymphoma (HL) and an important component of therapy for many patients. These guidelines have been developed to address the use of RT in HL in the modern era of combined modality treatment. The role of reduced volumes and doses is addressed, integrating modern imaging with 3-dimensional (3D) planning and advanced techniques of treatment delivery. The previously applied extended field (EF) and original involved field (IF) techniques, which treated larger volumes based on nodal stations, have now been replaced by the use of limited volumes, based solely on detectable nodal (and extranodal extension) involvement at presentation, using contrast-enhanced computed tomography, positron emission tomography/computed tomography, magnetic resonance imaging, or a combination of these techniques. The International Commission on Radiation Units and Measurements concepts of gross tumor volume, clinical target volume, internal target volume, and planning target volume are used for defining the targeted volumes. Newer treatment techniques, including intensity modulated radiation therapy, breath-hold, image guided radiation therapy, and 4-dimensional imaging, should be implemented when their use is expected to decrease significantly the risk for normal tissue damage while still achieving the primary goal of local tumor control. The highly conformal involved node radiation therapy (INRT), recently introduced for patients for whom optimal imaging is available, is explained. A new concept, involved site radiation therapy (ISRT), is introduced as the standard conformal therapy for the scenario, commonly encountered, wherein optimal imaging is not available. There is increasing evidence that RT doses used in the past are higher than necessary for disease control in this era of combined modality therapy. The use of INRT and of lower doses in early-stage HL is supported by available data. Although the use of ISRT has not yet been validated in a formal study, it is more conservative than INRT, accounting for suboptimal information and appropriately designed for safe local disease control. The goal of modern smaller field radiation therapy is to reduce both treatment volume and treatment dose while maintaining efficacy and minimizing acute and late sequelae. This review is a consensus of the International Lymphoma Radiation Oncology Group (ILROG) Steering Committee regarding the modern approach to RT in the treatment of HL, outlining a new concept of ISRT in which reduced treatment volumes are planned for the effective control of involved sites of HL. Nodal and extranodal non-Hodgkin lymphomas (NHL) are covered separately by ILROG guidelines.
PMID: 23790512 [PubMed - indexed for MEDLINE]
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