Recent Stanford Publications in PubMed
- NF-κB Decoy Oligodeoxynucleotide Enhanced Osteogenesis in Mesenchymal Stem Cells Exposed to Polyethylene Particle.Lin TH, Sato T, Barcay KR, Waters H, Loi F, Zhang R, Pajarinen J, Egashira K, Yao Z, Goodman SBTissue Eng Part A
- Isoniazid preventive therapy in medium-incidence settings: the price is right.Stout JE, Andrews JRInt J Tuberc Lung Dis
- Septris: A Novel, Mobile, Online, Simulation Game That Improves Sepsis Recognition and Management.Evans KH, Daines W, Tsui J, Strehlow M, Maggio P, Shieh LAcad Med
- Fertility: The Role of mTOR Signaling and KIT Ligand.Hsueh AJCurr Biol
- Implications of Workforce and Financing Changes for Primary Care Practice Utilization, Revenue, and Cost: A Generalizable Mathematical Model for Practice Management.Basu S, Landon BE, Song Z, Bitton A, Phillips RSMed Care
- Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site.Fuchs G, Petrov AN, Marceau CD, Popov LM, Chen J, O'Leary SE, Wang R, Carette JE, Sarnow P, Puglisi JDProc Natl Acad Sci U S A
- Change in emotion regulation during the course of treatment predicts binge abstinence in guided self-help dialectical behavior therapy for binge eating disorder.Wallace LM, Masson PC, Safer DL, von Ranson KMJ Eat Disord
- Automatic Selection of Order Parameters in the Analysis of Large Scale Molecular Dynamics Simulations.Sultan MM, Kiss G, Shukla D, Pande VSJ Chem Theory Comput
- The relationship between male BMI and waist circumference on semen quality: data from the LIFE study.Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Louis GMHum Reprod
- Validated Contemporary Risk Model of Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions: Insights From the National Cardiovascular Data Registry Cath-PCI Registry.Tsai TT, Patel UD, Chang TI, Kennedy KF, Masoudi FA, Matheny ME, Kosiborod M, Amin AP, Weintraub WS, Curtis JP, Messenger JC, Rumsfeld JS, Spertus JAJ Am Heart Assoc
- Immunodeficiency at start of ART: the persistent problem of late presentation to care.Ford N, Mills EJ, Egger MClin Infect Dis
- Reading abilities in school-aged preterm children: a review and meta-analysis.Kovachy VN, Adams JN, Tamaresis JS, Feldman HMDev Med Child Neurol
- CORR Insights(®): A Dedicated Research Program Increases the Quantity and Quality of Orthopaedic Resident Publications.Bishop JAClin Orthop Relat Res
- Hypersomnia subtypes, sleep and relapse in bipolar disorder.Kaplan KA, McGlinchey EL, Soehner A, Gershon A, Talbot LS, Eidelman P, Gruber J, Harvey AGPsychol Med
- Handling the fragile vase of scientific practices.Ioannidis JPAddiction
- Challenges of metagenomics and single-cell genomics approaches for exploring cyanobacterial diversity.Davison M, Hall E, Zare R, Bhaya DPhotosynth Res
- Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.Sazzad HM, Rainey JJ, Kahn AL, Mach O, Liyanage JB, Alam AN, Kawser CA, Hossain A, Sutter R, Luby SPJ Infect Dis
- Inflammatory monocytes determine endothelial nitric-oxide synthase uncoupling and nitro-oxidative stress induced by angiotensin II.Kossmann S, Hu H, Steven S, Schönfelder T, Fraccarollo D, Mikhed Y, Brähler M, Knorr M, Brandt M, Karbach SH, Becker C, Oelze M, Bauersachs J, Widder J, Münzel T, Daiber A, Wenzel PJ Biol Chem
- Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset.Sato M, Sagawa Y, Hirai N, Sato S, Okuro M, Kumar S, Kanbayashi T, Shimizu T, Sakai N, Nishino SExp Neurol
- The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases.Reese ML, Shah N, Boothroyd JCJ Biol Chem
- Regulation of microRNA-mediated gene silencing by microRNA precursors.Roy-Chaudhuri B, Valdmanis PN, Zhang Y, Wang Q, Luo QJ, Kay MANat Struct Mol Biol
- Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy.Zahr NM, Alt C, Mayer D, Rohlfing T, Manning-Bog A, Luong R, Sullivan EV, Pfefferbaum AExp Neurol
- PharmGKB summary: very important pharmacogene information for SLC22A1.Goswami S, Gong L, Giacomini K, Altman RB, Klein TEPharmacogenet Genomics
- Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials.Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KWPsychosom Med
- Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial.Genovese MC, Tena CP, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon-Campos JA, Box J, Legerton CW, Nasonov E, Durez P, Delaet I, Teng J, Alten RJ Rheumatol
- Development of a disease activity and responder index for psoriatic arthritis--report of the Psoriatic Arthritis Module at OMERACT 11.Coates LC, FitzGerald O, Mease PJ, Gladman DD, Strand V, Goel N, Campbell I, Krueger G, McHugh NJ, Helliwell PSJ Rheumatol
- Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.Saketkoo LA, Mittoo S, Frankel S, LeSage D, Sarver C, Phillips K, Strand V, Matteson EL, OMERACT Connective Tissue Disease–Interstitial Lung Diseases Working Group, OMERACT Connective Tissue Disease-Interstitial Lung Diseases Working GroupJ Rheumatol
- Cutaneous innervation of the ankle: an anatomical study showing danger zones for ankle surgery.Duscher D, Wenny R, Entenfellner J, Weninger P, Hirtler LClin Anat
- Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis.Moss RBEur Respir J
NF-κB Decoy Oligodeoxynucleotide Enhanced Osteogenesis in Mesenchymal Stem Cells Exposed to Polyethylene Particle.
Tissue Eng Part A. 2014 Dec 17;
Authors: Lin TH, Sato T, Barcay KR, Waters H, Loi F, Zhang R, Pajarinen J, Egashira K, Yao Z, Goodman SB
Excessive generation of wear particles after total joint replacement may lead to local inflammation and periprosthetic osteolysis. Modulation of the key transcription factor NF-κB in immune cells could potentially mitigate the osteolytic process. We previously showed that local delivery of ultra-high molecular weight polyethylene (UHMWPE) particles recruited osteoprogenitor cells and reduced osteolysis. However, the biological effects of modulating the NF-κB signaling pathway on osteoprogenitor/mesenchymal stem cells (MSCs) remain unclear. Here we showed that decoy oligodeoxynucleotide (ODN) increased cell viability when primary murine MSCs were exposed to UHMWPE particles, but had no effects on cellular apoptosis. Decoy ODN increased TGF-β1 and osteoprotegerin in MSCs exposed to UHMWPE particles. Mechanistic studies showed that decoy ODN up-regulated osteoprotegerin expression through a TGF-β1 dependent pathway. By measuring alkaline phosphatase activity, osteocalcin levels, Runx2 and osteopontin expression, and performing a bone mineralization assay, we found that decoy ODN increased MSC osteogenic ability when the cells were exposed to UHMWPE particles. Furthermore, the cellular response to decoy ODN and UHMWPE particles with regards to cell phenotype, cell viability and osteogenic ability were confirmed using primary human MSCs. Our results suggest that modulation of wear particle induced inflammation by NF-κB decoy ODN had no adverse effects on MSCs, and may potentially further mitigate peri-prosthetic osteolysis by protecting MSC viability and osteogenic ability.
PMID: 25518013 [PubMed - as supplied by publisher]
Isoniazid preventive therapy in medium-incidence settings: the price is right.
Int J Tuberc Lung Dis. 2014 Dec;18(12):1388
Authors: Stout JE, Andrews JR
PMID: 25517800 [PubMed - as supplied by publisher]
Septris: A Novel, Mobile, Online, Simulation Game That Improves Sepsis Recognition and Management.
Acad Med. 2014 Dec 16;
Authors: Evans KH, Daines W, Tsui J, Strehlow M, Maggio P, Shieh L
PROBLEM: Annually affecting over 18 million people worldwide, sepsis is common, deadly, and costly. Despite significant effort by the Surviving Sepsis Campaign and other initiatives, sepsis remains underrecognized and undertreated.
APPROACH: Research indicates that educating providers may improve sepsis diagnosis and treatment; thus, the Stanford School of Medicine has developed a mobile-accessible, case-based, online game entitled Septris (http://med.stanford.edu/septris/). Septris, launched online worldwide in December 2011, takes an innovative approach to teaching early sepsis identification and evidence-based management. The free gaming platform leverages the massive expansion over the past decade of smartphones and the popularity of noneducational gaming.The authors sought to assess the game's dissemination and its impact on learners' sepsis-related knowledge, skills, and attitudes. In 2012, the authors trained Stanford pregraduate (clerkship) and postgraduate (resident) medical learners (n = 156) in sepsis diagnosis and evidence-based practices via 20 minutes of self-directed game play with Septris. The authors administered pre- and posttests.
OUTCOMES: By October 2014, Septris garnered over 61,000 visits worldwide. After playing Septris, both pre- and postgraduate groups improved their knowledge on written testing in recognizing and managing sepsis (P < .001). Retrospective self-reporting on their ability to identify and manage sepsis also improved (P < .001). Over 85% of learners reported that they would or would maybe recommend Septris.
NEXT STEPS: Future evaluation of Septris should assess its effectiveness among different providers, resource settings, and cultures; generate information about how different learners make clinical decisions; and evaluate the correlation of game scores with sepsis knowledge.This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License, where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
PMID: 25517703 [PubMed - as supplied by publisher]
Fertility: The Role of mTOR Signaling and KIT Ligand.
Curr Biol. 2014 Nov 3;24(21):R1040-R1042
Authors: Hsueh AJ
Activation of a limited pool of diminishing ovarian follicles determines women's reproductive lifespan. A recent rodent study describes the role of mTOR signaling and KIT ligand in granulosa cells of primordial follicles for follicle activation and for reproductive lifespan regulation.
PMID: 25517366 [PubMed - as supplied by publisher]
Implications of Workforce and Financing Changes for Primary Care Practice Utilization, Revenue, and Cost: A Generalizable Mathematical Model for Practice Management.
Med Care. 2014 Dec 16;
Authors: Basu S, Landon BE, Song Z, Bitton A, Phillips RS
BACKGROUND:: Primary care practice transformations require tools for policymakers and practice managers to understand the financial implications of workforce and reimbursement changes.
OBJECTIVE:: To create a simulation model to understand how practice utilization, revenues, and expenses may change in the context of workforce and financing changes.
RESEARCH DESIGN:: We created a simulation model estimating clinic-level utilization, revenues, and expenses using user-specified or public input data detailing practice staffing levels, salaries and overhead expenditures, patient characteristics, clinic workload, and reimbursements. We assessed whether the model could accurately estimate clinic utilization, revenues, and expenses across the nation using labor compensation, medical expenditure, and reimbursements databases, as well as cost and revenue data from independent practices of varying size. We demonstrated the model's utility in a simulation of how utilization, revenue, and expenses would change after hiring a nurse practitioner (NP) compared with hiring a part-time physician.
RESULTS:: Modeled practice utilization and revenue closely matched independent national utilization and reimbursement data, disaggregated by patient age, sex, race/ethnicity, insurance status, and ICD diagnostic group; the model was able to estimate independent revenue and cost estimates, with highest accuracy among larger practices. A demonstration analysis revealed that hiring an NP to work independently with a subset of patients diagnosed with diabetes or hypertension could increase net revenues, if NP visits involve limited MD consultation or if NP reimbursement rates increase.
CONCLUSIONS:: A model of utilization, revenue, and expenses in primary care practices may help policymakers and managers understand the implications of workforce and financing changes.
PMID: 25517074 [PubMed - as supplied by publisher]
Kinetic pathway of 40S ribosomal subunit recruitment to hepatitis C virus internal ribosome entry site.
Proc Natl Acad Sci U S A. 2014 Dec 16;
Authors: Fuchs G, Petrov AN, Marceau CD, Popov LM, Chen J, O'Leary SE, Wang R, Carette JE, Sarnow P, Puglisi JD
Translation initiation can occur by multiple pathways. To delineate these pathways by single-molecule methods, fluorescently labeled ribosomal subunits are required. Here, we labeled human 40S ribosomal subunits with a fluorescent SNAP-tag at ribosomal protein eS25 (RPS25). The resulting ribosomal subunits could be specifically labeled in living cells and in vitro. Using single-molecule Förster resonance energy transfer (FRET) between RPS25 and domain II of the hepatitis C virus (HCV) internal ribosome entry site (IRES), we measured the rates of 40S subunit arrival to the HCV IRES. Our data support a single-step model of HCV IRES recruitment to 40S subunits, irreversible on the initiation time scale. We furthermore demonstrated that after binding, the 40S:HCV IRES complex is conformationally dynamic, undergoing slow large-scale rearrangements. Addition of translation extracts suppresses these fluctuations, funneling the complex into a single conformation on the 80S assembly pathway. These findings show that 40S:HCV IRES complex formation is accompanied by dynamic conformational rearrangements that may be modulated by initiation factors.
PMID: 25516984 [PubMed - as supplied by publisher]
Change in emotion regulation during the course of treatment predicts binge abstinence in guided self-help dialectical behavior therapy for binge eating disorder.
J Eat Disord. 2014;2(1):35
Authors: Wallace LM, Masson PC, Safer DL, von Ranson KM
BACKGROUND: Dialectical behavior therapy (DBT), which appears to be an effective treatment for binge eating disorder (BED), focuses on teaching emotion regulation skills. However, the role of improved emotion regulation in predicting treatment outcome in BED is uncertain.
METHODS: This secondary analysis explored whether change in self-reported emotion regulation (as measured by the Difficulties in Emotion Regulation Scale) during treatment was associated with abstinence from binge eating at post-treatment and 4-, 5-, and 6-month follow-up in individuals who received a guided self-help adaptation of DBT for BED. Participants were 60 community-based men and women with BED who received a self-help manual and six 20-minute support phone calls.
RESULTS: Greater improvement in self-reported emotion regulation between pre- and post-treatment predicted abstinence from binge eating at post-treatment, 4-, 5-, and 6-month follow-up. However, some follow-up results were no longer significant when imputed data was excluded, suggesting that the effect of emotion regulation on binge abstinence may be strongest at 4-month follow-up but decline across a longer duration of follow-up.
CONCLUSIONS: This study provides preliminary support for the theoretical role played by improved emotion regulation in achieving binge eating abstinence. If this finding is replicated with larger samples, further research should identify specific techniques to help more individuals to effectively regulate their emotions over a longer duration.
PMID: 25516798 [PubMed]
Automatic Selection of Order Parameters in the Analysis of Large Scale Molecular Dynamics Simulations.
J Chem Theory Comput. 2014 Dec 9;10(12):5217-5223
Authors: Sultan MM, Kiss G, Shukla D, Pande VS
Given the large number of crystal structures and NMR ensembles that have been solved to date, classical molecular dynamics (MD) simulations have become powerful tools in the atomistic study of the kinetics and thermodynamics of biomolecular systems on ever increasing time scales. By virtue of the high-dimensional conformational state space that is explored, the interpretation of large-scale simulations faces difficulties not unlike those in the big data community. We address this challenge by introducing a method called clustering based feature selection (CB-FS) that employs a posterior analysis approach. It combines supervised machine learning (SML) and feature selection with Markov state models to automatically identify the relevant degrees of freedom that separate conformational states. We highlight the utility of the method in the evaluation of large-scale simulations and show that it can be used for the rapid and automated identification of relevant order parameters involved in the functional transitions of two exemplary cell-signaling proteins central to human disease states.
PMID: 25516725 [PubMed - as supplied by publisher]
The relationship between male BMI and waist circumference on semen quality: data from the LIFE study.
Hum Reprod. 2014 Dec 15;
Authors: Eisenberg ML, Kim S, Chen Z, Sundaram R, Schisterman EF, Louis GM
PMID: 25516559 [PubMed - as supplied by publisher]
Validated Contemporary Risk Model of Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions: Insights From the National Cardiovascular Data Registry Cath-PCI Registry.
J Am Heart Assoc. 2014;3(6)
Authors: Tsai TT, Patel UD, Chang TI, Kennedy KF, Masoudi FA, Matheny ME, Kosiborod M, Amin AP, Weintraub WS, Curtis JP, Messenger JC, Rumsfeld JS, Spertus JA
BACKGROUND: We developed risk models for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) after percutaneous coronary intervention (PCI) to support quality assessment and the use of preventative strategies.
METHODS AND RESULTS: AKI was defined as an absolute increase of ≥0.3 mg/dL or a relative increase of 50% in serum creatinine (AKIN Stage 1 or greater) and AKI-D was a new requirement for dialysis following PCI. Data from 947 012 consecutive PCI patients and 1253 sites participating in the NCDR Cath/PCI registry between 6/09 and 7/11 were used to develop the model, with 70% randomly assigned to a derivation cohort and 30% for validation. AKI occurred in 7.33% of the derivation and validation cohorts. Eleven variables were associated with AKI: older age, baseline renal impairment (categorized as mild, moderate, and severe), prior cerebrovascular disease, prior heart failure, prior PCI, presentation (non-ACS versus NSTEMI versus STEMI), diabetes, chronic lung disease, hypertension, cardiac arrest, anemia, heart failure on presentation, balloon pump use, and cardiogenic shock. STEMI presentation, cardiogenic shock, and severe baseline CKD were the strongest predictors for AKI. The full model showed good discrimination in the derivation and validation cohorts (c-statistic of 0.72 and 0.71, respectively) and identical calibration (slope of calibration line=1.01). The AKI-D model had even better discrimination (c-statistic=0.89) and good calibration (slope of calibration line=0.99).
CONCLUSION: The NCDR AKI prediction models can successfully risk-stratify patients undergoing PCI. The potential for this tool to aid clinicians in counseling patients regarding the risk of PCI, identify patients for preventative strategies, and support local quality improvement efforts should be prospectively tested.
PMID: 25516439 [PubMed - as supplied by publisher]
Immunodeficiency at start of ART: the persistent problem of late presentation to care.
Clin Infect Dis. 2014 Dec 16;
Authors: Ford N, Mills EJ, Egger M
PMID: 25516184 [PubMed - as supplied by publisher]
Reading abilities in school-aged preterm children: a review and meta-analysis.
Dev Med Child Neurol. 2014 Dec 17;
Authors: Kovachy VN, Adams JN, Tamaresis JS, Feldman HM
AIM: Children born preterm (at ≤32wks) are at risk of developing deficits in reading ability. This meta-analysis aims to determine whether or not school-aged preterm children perform worse than those born at term in single-word reading (decoding) and reading comprehension.
METHOD: Electronic databases were searched for studies published between 2000 and 2013, which assessed decoding or reading comprehension performance in English-speaking preterm and term-born children aged between 6 years and 13 years, and born after 1990. Standardized mean differences in decoding and reading comprehension scores were calculated.
RESULTS: Nine studies were suitable for analysis of decoding, and five for analysis of reading comprehension. Random-effects meta-analyses showed that children born preterm had significantly lower scores (reported as Cohen's d values [d] with 95% confidence intervals [CIs]) than those born at term for decoding (d=-0.42, 95% CI -0.57 to -0.27, p<0.001) and reading comprehension (d=-0.57, 95% CI -0.68 to -0.46, p<0.001). Meta-regressions showed that lower gestational age was associated with larger differences in decoding (Q=5.92, p=0.02) and reading comprehension (Q=4.69, p=0.03) between preterm and term groups. Differences between groups increased with age for reading comprehension (Q=5.10, p=0.02) and, although not significant, there was also a trend for increased group differences for decoding (Q=3.44, p=0.06).
INTERPRETATION: Preterm children perform worse than peers born at term on decoding and reading comprehension. These findings suggest that preterm children should receive more ongoing monitoring for reading difficulties throughout their education.
PMID: 25516105 [PubMed - as supplied by publisher]
CORR Insights(®): A Dedicated Research Program Increases the Quantity and Quality of Orthopaedic Resident Publications.
Clin Orthop Relat Res. 2014 Dec 17;
Authors: Bishop JA
PMID: 25516003 [PubMed - as supplied by publisher]
Hypersomnia subtypes, sleep and relapse in bipolar disorder.
Psychol Med. 2014 Dec 17;:1-13
Authors: Kaplan KA, McGlinchey EL, Soehner A, Gershon A, Talbot LS, Eidelman P, Gruber J, Harvey AG
Background. Though poorly defined, hypersomnia is associated with negative health outcomes and new-onset and recurrence of psychiatric illness. Lack of definition impedes generalizability across studies. The present research clarifies hypersomnia diagnoses in bipolar disorder by exploring possible subgroups and their relationship to prospective sleep data and relapse into mood episodes. Method. A community sample of 159 adults (aged 18-70 years) with bipolar spectrum diagnoses, euthymic at study entry, was included. Self-report inventories and clinician-administered interviews determined features of hypersomnia. Participants completed sleep diaries and wore wrist actigraphs at home to obtain prospective sleep data. Approximately 7 months later, psychiatric status was reassessed. Factor analysis and latent profile analysis explored empirical groupings within hypersomnia diagnoses. Results. Factor analyses confirmed two separate subtypes of hypersomnia ('long sleep' and 'excessive sleepiness') that were uncorrelated. Latent profile analyses suggested a four-class solution, with 'long sleep' and 'excessive sleepiness' again representing two separate classes. Prospective sleep data suggested that the sleep of 'long sleepers' is characterized by a long time in bed, not long sleep duration. Longitudinal assessment suggested that 'excessive sleepiness' at baseline predicted mania/hypomania relapse. Conclusions. This study is the largest of hypersomnia to include objective sleep measurement, and refines our understanding of classification, characterization and associated morbidity. Hypersomnia appears to be comprised of two separate subgroups: long sleep and excessive sleepiness. Long sleep is characterized primarily by long bedrest duration. Excessive sleepiness is not associated with longer sleep or bedrest, but predicts relapse to mania/hypomania. Understanding these entities has important research and treatment implications.
PMID: 25515854 [PubMed - as supplied by publisher]
Handling the fragile vase of scientific practices.
Addiction. 2015 Jan;110(1):9-10
Authors: Ioannidis JP
PMID: 25515825 [PubMed - in process]
Challenges of metagenomics and single-cell genomics approaches for exploring cyanobacterial diversity.
Photosynth Res. 2014 Dec 17;
Authors: Davison M, Hall E, Zare R, Bhaya D
Cyanobacteria have played a crucial role in the history of early earth and continue to be instrumental in shaping our planet, yet applications of cutting edge technology have not yet been widely used to explore cyanobacterial diversity. To provide adequate background, we briefly review current sequencing technologies and their innovative uses in genomics and metagenomics. Next, we focus on current cell capture technologies and the challenges of using them with cyanobacteria. We illustrate the utility in coupling breakthroughs in DNA amplification with cell capture platforms, with an example of microfluidic isolation and subsequent targeted amplicon sequencing from individual terrestrial thermophilic cyanobacteria. Single cells of thermophilic, unicellular Synechococcus sp. JA-2-3-B'a(2-13) (Syn OS-B') were sorted in a microfluidic device, lysed, and subjected to whole genome amplification by multiple displacement amplification. We amplified regions from specific CRISPR spacer arrays, which are known to be highly diverse, contain semi-palindromic repeats which form secondary structure, and can be difficult to amplify. Cell capture, lysis, and genome amplification on a microfluidic device have been optimized, setting a stage for further investigations of individual cyanobacterial cells isolated directly from natural populations.
PMID: 25515769 [PubMed - as supplied by publisher]
Screening for long-term poliovirus excretion among children with primary immunodeficiency disorders: preparation for the polio posteradication era in Bangladesh.
J Infect Dis. 2014 Nov 1;210 Suppl 1:S373-9
Authors: Sazzad HM, Rainey JJ, Kahn AL, Mach O, Liyanage JB, Alam AN, Kawser CA, Hossain A, Sutter R, Luby SP
BACKGROUND: Persons with primary immune deficiency disorders (PIDD) who receive oral poliovirus vaccine (OPV) may transmit immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) and cause paralytic polio. The objective of this study was to identify children with PIDD in Bangladesh, and estimate the proportion with chronic poliovirus excretion.
METHODS: Patients admitted at 5 teaching hospitals were screened for PIDD according to standardized clinical case definitions. PIDD was confirmed by age-specific quantitative immunoglobulin levels. Stool specimens were collected from patients with confirmed PIDD.
RESULTS: From February 2011 through January 2013, approximately 96 000 children were screened, and 53 patients were identified who met the clinical case definition for PIDD. Thirteen patients (24%) had age-specific quantitative immunoglobulins results that confirmed PIDD. Of these, 9 (69%) received OPV 3-106 months before stool specimen collection. Among 11 patients, stool specimens from 1 patient tested positive for polioviruses 34 months after OPV ingestion. However, the poliovirus isolate was not available for genetic sequencing, and a subsequent stool specimen 45 days later was negative.
CONCLUSIONS: The risk of chronic poliovirus excretion among children with PIDD in Bangladesh seems to be low. The national polio eradication program should incorporate strategies for screening for poliovirus excretion among patients with PIDD.
PMID: 25316858 [PubMed - indexed for MEDLINE]
Inflammatory monocytes determine endothelial nitric-oxide synthase uncoupling and nitro-oxidative stress induced by angiotensin II.
J Biol Chem. 2014 Oct 3;289(40):27540-50
Authors: Kossmann S, Hu H, Steven S, Schönfelder T, Fraccarollo D, Mikhed Y, Brähler M, Knorr M, Brandt M, Karbach SH, Becker C, Oelze M, Bauersachs J, Widder J, Münzel T, Daiber A, Wenzel P
Endothelial nitric-oxide synthase (eNOS) uncoupling and increased inducible NOS (iNOS) activity amplify vascular oxidative stress. The role of inflammatory myelomonocytic cells as mediators of these processes and their impact on tetrahydrobiopterin availability and function have not yet been defined. Angiotensin II (ATII, 1 mg/kg/day for 7 days) increased Ly6C(high) and CD11b(+)/iNOS(high) leukocytes and up-regulated levels of eNOS glutathionylation in aortas of C57BL/6 mice. Vascular iNOS-dependent NO formation was increased, whereas eNOS-dependent NO formation was decreased in aortas of ATII-infused mice as assessed by electron paramagnetic resonance (EPR) spectroscopy. Diphtheria toxin-mediated ablation of lysozyme M-positive (LysM(+)) monocytes in ATII-infused LysM(iDTR) transgenic mice prevented eNOS glutathionylation and eNOS-derived N(ω)-nitro-L-arginine methyl ester-sensitive superoxide formation in the endothelial layer. ATII increased vascular guanosine triphosphate cyclohydrolase I expression and biopterin synthesis in parallel, which was reduced in monocyte-depleted LysM(iDTR) mice. Vascular tetrahydrobiopterin was increased by ATII infusion but was even higher in monocyte-depleted ATII-infused mice, which was paralleled by a strong up-regulation of dihydrofolate reductase expression. EPR spectroscopy revealed that both vascular iNOS- and eNOS-dependent NO formation were normalized in ATII-infused mice following monocyte depletion. Additionally, deletion as well as pharmacologic inhibition of iNOS prevented ATII-induced endothelial dysfunction. In summary, ATII induces an inflammatory cell-dependent increase of iNOS, guanosine triphosphate cyclohydrolase I, tetrahydrobiopterin, NO formation, and nitro-oxidative stress as well as eNOS uncoupling in the vessel wall, which can be prevented by ablation of LysM(+) monocytes.
PMID: 25143378 [PubMed - indexed for MEDLINE]
Noninvasive detection of sleep/wake changes and cataplexy-like behaviors in orexin/ataxin-3 transgenic narcoleptic mice across the disease onset.
Exp Neurol. 2014 Nov;261:744-51
Authors: Sato M, Sagawa Y, Hirai N, Sato S, Okuro M, Kumar S, Kanbayashi T, Shimizu T, Sakai N, Nishino S
Sleep and behavioral monitoring of young mice is necessary for understating the progress of symptoms in congenital and acquired diseases associated with sleep and movement disorders. In the current study, we have developed a non-invasive sleep monitoring system that identifies wake and sleep patterns of newborn mice using a simple piezoelectric transducer (PZT). Using this system, we have succeeded in detecting age-dependent occurrences and changes in sleep fragmentation of orexin/ataxin-3 narcoleptic mice (a narcoleptic mouse model with postnatal hypocretin/orexin cell death) across the disease onset. We also detected REM sleep/cataplexy patterns (i.e., immobility with clear heartbeat [IMHB] signals due to the flaccid posture) by the PZT system, and found that sudden onset of REM sleep-like episodes specifically occur in narcoleptic, but not in wild type mice, suggesting that these episodes are likely cataplexy. In contrast, gradual onset of IMHB likely reflects occurrence of REM sleep. In summary, we have shown that the PZT system is useful as a non-invasive sleep and behavior monitoring system to analyze the developmental aspects of sleep and movement disorders in mice models.
PMID: 25118620 [PubMed - indexed for MEDLINE]
The Toxoplasma pseudokinase ROP5 is an allosteric inhibitor of the immunity-related GTPases.
J Biol Chem. 2014 Oct 3;289(40):27849-58
Authors: Reese ML, Shah N, Boothroyd JC
The Red Queen hypothesis proposes that there is an evolutionary arms race between host and pathogen. One possible example of such a phenomenon could be the recently discovered interaction between host defense proteins known as immunity-related GTPases (IRGs) and a family of rhoptry pseudokinases (ROP5) expressed by the protozoan parasite, Toxoplasma gondii. Mouse IRGs are encoded by an extensive and rapidly evolving family of over 20 genes. Similarly, the ROP5 family is highly polymorphic and consists of 4-10 genes, depending on the strain of Toxoplasma. IRGs are known to be avidly bound and functionally inactivated by ROP5 proteins, but the molecular basis of this interaction/inactivation has not previously been known. Here we show that ROP5 uses a highly polymorphic surface to bind adjacent to the nucleotide-binding domain of an IRG and that this produces a profound allosteric change in the IRG structure. This has two dramatic effects: 1) it prevents oligomerization of the IRG, and 2) it alters the orientation of two threonine residues that are targeted by the Toxoplasma Ser/Thr kinases, ROP17 and ROP18. ROP5s are highly specific in the IRGs that they will bind, and the fact that it is the most highly polymorphic surface of ROP5 that binds the IRG strongly supports the notion that these two protein families are co-evolving in a way predicted by the Red Queen hypothesis.
PMID: 25118287 [PubMed - indexed for MEDLINE]
Regulation of microRNA-mediated gene silencing by microRNA precursors.
Nat Struct Mol Biol. 2014 Sep;21(9):825-32
Authors: Roy-Chaudhuri B, Valdmanis PN, Zhang Y, Wang Q, Luo QJ, Kay MA
Processing of microRNAs (miRNAs) from their precursors to their biologically active mature forms is regulated during development and cancer. We show that mouse pri- or pre-miR-151 can bind to and compete with mature miR-151-5p and miR-151-3p for binding sites contained within the complementary regions of the E2f6 mRNA 3' untranslated region (UTR). E2f6 mRNA levels were directly regulated by pri- or pre-miR-151. Conversely, miR-151-mediated repression of ARHGDIA mRNA was dependent on the level of mature miR-151 because only the mature miRNA binds the 3' UTR. Thus, processing of miR-151 can have different effects on separate mRNA targets within a cell. A bioinformatics pipeline revealed additional candidate regions where precursor miRNAs can compete with their mature miRNA counterparts. We validated this experimentally for miR-124 and the SNAI2 3' UTR. Hence, miRNA precursors can serve as post-transcriptional regulators of miRNA activity and are not mere biogenesis intermediates.
PMID: 25086740 [PubMed - indexed for MEDLINE]
Associations between in vivo neuroimaging and postmortem brain cytokine markers in a rodent model of Wernicke's encephalopathy.
Exp Neurol. 2014 Nov;261:109-19
Authors: Zahr NM, Alt C, Mayer D, Rohlfing T, Manning-Bog A, Luong R, Sullivan EV, Pfefferbaum A
Thiamine (vitamin B1) deficiency, associated with a variety of conditions, including chronic alcoholism and bariatric surgery for morbid obesity, can result in the neurological disorder Wernicke's encephalopathy (WE). Recent work building upon early observations in animal models of thiamine deficiency has demonstrated an inflammatory component to the neuropathology observed in thiamine deficiency. The present, multilevel study including in vivo magnetic resonance imaging (MRI) and spectroscopy (MRS) and postmortem quantification of chemokine and cytokine proteins sought to determine whether a combination of these in vivo neuroimaging tools could be used to characterize an in vivo MR signature for neuroinflammation. Thiamine deficiency for 12days was used to model neuroinflammation; glucose loading in thiamine deficiency was used to accelerate neurodegeneration. Among 38 animals with regional brain tissue assayed postmortem for cytokine/chemokine protein levels, three groups of rats (controls+glucose, n=6; pyrithiamine+saline, n=5; pyrithiamine+glucose, n=13) underwent MRI/MRS at baseline (time 1), after 12days of treatment (time 2), and 3h after challenge (glucose or saline, time 3). In the thalamus of glucose-challenged, thiamine deficient animals, correlations between in vivo measures of pathology (lower levels of N-acetyle aspartate and higher levels of lactate) and postmortem levels of monocyte chemotactic protein-1 (MCP-1, also known as chemokine ligand 2, CCL2) support a role for this chemokine in thiamine deficiency-related neurodegeneration, but do not provide a unique in vivo signature for neuroinflammation.
PMID: 24973622 [PubMed - indexed for MEDLINE]
PharmGKB summary: very important pharmacogene information for SLC22A1.
Pharmacogenet Genomics. 2014 Jun;24(6):324-8
Authors: Goswami S, Gong L, Giacomini K, Altman RB, Klein TE
PMID: 24681965 [PubMed - indexed for MEDLINE]
Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials.
Psychosom Med. 2014 Apr;76(3):190-6
Authors: Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KW
OBJECTIVE: The aim of this study was to review the effects of vitamin D supplementation on depressive symptoms in randomized controlled trials. Although low vitamin D levels have been observationally associated with depressive symptoms, the effect of vitamin D supplementation as an antidepressant remains uncertain.
METHODS: MEDLINE, CINAHL, AMED, PsycINFO, Scopus, The Cochrane Library, and references of included reports (through May 2013) were searched. Two independent reviewers identified and extracted data from randomized trials that compared the effect of vitamin D supplementation on depressive symptoms to a control condition. Two additional reviewers assessed study quality using The Cochrane Risk of Bias Tool. Seven trials (3191 participants) were included.
RESULTS: Vitamin D supplementation had no overall effect on depressive symptoms (standardized mean difference [SMD], 0.14; 95% confidence interval [CI], -0.33 to 0.05, p = .16), although considerable heterogeneity was observed. Subgroup analysis showed that vitamin D supplementation for participants with clinically significant depressive symptoms or depressive disorder had a moderate, statistically significant effect (2 studies: SMD, -0.60; 95% CI, -1.19 to -0.01; p = .046), but a small, nonsignificant effect for those without clinically significant depression (5 studies: SMD, -0.04; 95% CI, -0.20 to 0.12; p = .61). Most trials had unclear or high risk of bias. Studies varied in the amount, frequency, duration, and mode of delivery of vitamin D supplementation.
CONCLUSIONS: Vitamin D supplementation may be effective for reducing depressive symptoms in patients with clinically significant depression; however, further high-quality research is needed.
PMID: 24632894 [PubMed - indexed for MEDLINE]
Subcutaneous abatacept for the treatment of rheumatoid arthritis: longterm data from the ACQUIRE trial.
J Rheumatol. 2014 Apr;41(4):629-39
Authors: Genovese MC, Tena CP, Covarrubias A, Leon G, Mysler E, Keiserman M, Valente R, Nash P, Simon-Campos JA, Box J, Legerton CW, Nasonov E, Durez P, Delaet I, Teng J, Alten R
OBJECTIVE: Assess longterm tolerability, safety, and efficacy of subcutaneous (SC) abatacept (ABA) in methotrexate-refractory patients with rheumatoid arthritis (RA).
METHODS: The phase III, multinational Abatacept Comparison of Sub[QU]cutaneous Versus Intravenous in Inadequate Responders to MethotrexatE (ACQUIRE) trial comprised a 6-month, randomized, double-blind (DB) period, in which patients received intravenous (IV) or SC ABA, plus MTX, followed by an open-label, longterm extension (LTE), in which patients received SC ABA, 125 mg/week. Safety and efficacy from the LTE (∼3.5 yrs of exposure) are reported.
RESULTS: Patients who completed the DB period (1372/1385, 99.1%) entered the LTE; 1134 patients (82.7%) kept taking the treatment at time of reporting. Mean (SD) was 31.9 months (6.8); median (range) exposure was 33.0 (8-44) months. Patients entering the LTE had longstanding, moderate-to-severe disease [mean 7.6 (7.9) yrs and DAS28 (C-reactive protein) 6.2 (0.9)]. Incidence rates (events/100 patient-yrs) were reported for serious adverse events (8.76, 95% CI 7.71, 9.95), infections (44.80, 95% CI 41.76, 48.01), serious infections (1.72, 95% CI 1.30, 2.27), malignancies (1.19, 95% CI 0.86, 1.66), and autoimmune events (1.31, 95% CI 0.95, 1.79). Twenty-seven patients (2%) experienced injection-site reactions; all except 1 were mild. American College of Rheumatology 20, 50, and 70 responses achieved during the DB period were maintained through the LTE, and on Day 981 were 80.2% (95% CI 77.2, 83.2), 63.5% (95% CI 58.2, 68.9), and 39.5% (95% CI 34.0, 44.9) for patients who kept taking SC ABA, and 80.0% (95% CI 77.0, 83.0), 63.2% (95% CI 57.8, 68.7), and 39.2% (95% CI 33.7, 44.7) for those who switched from IV to SC ABA.
CONCLUSION: These findings support SC ABA as a well-tolerated and efficacious longterm treatment for patients with RA and inadequate response to MTX (ClinicalTrials.gov identifier NCT00559585).
PMID: 24584926 [PubMed - indexed for MEDLINE]
Development of a disease activity and responder index for psoriatic arthritis--report of the Psoriatic Arthritis Module at OMERACT 11.
J Rheumatol. 2014 Apr;41(4):782-91
Authors: Coates LC, FitzGerald O, Mease PJ, Gladman DD, Strand V, Goel N, Campbell I, Krueger G, McHugh NJ, Helliwell PS
This module reflected work within the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) to develop and validate composite disease activity measures in psoriatic arthritis (PsA). At the Outcome Measures in Rheumatology (OMERACT) 8 Meeting, a core set of domains to be assessed in randomized controlled trials (RCT) and longitudinal observational studies of PsA was agreed upon. At OMERACT 10, 5 proposed composite responder definitions for PsA were reviewed and discussed, including new data from the GRACE (GRAppa Composite Exercise) study. At OMERACT 11, ongoing retrospective analyses of RCT data using the 3 proposed measures (Composite Psoriatic Disease Activity Index, Psoriatic Arthritis Disease Activity Score, and Arithmetic Mean of the Desirability Function) were discussed in detail. There was agreement that developing composite outcome measures for use in RCT and longitudinal observational studies in PsA was important. Concerns were expressed regarding development of a single measure that encompassed diverse domains, such as joint counts, quality of life (QOL), and disability measures. It was emphasized that the use of any composite measure should include the ability to differentiate between activity in individual domains, such as enthesitis or psoriasis, such that the effect of each could be assessed independently. It was also agreed that patients would be systematically involved in further development and refinement of composite measures. Future plans include qualitative work with patients to explore their experience of disease activity and statistical modeling to explore how each of the proposed measures will perform in different disease subgroups.
PMID: 24488420 [PubMed - indexed for MEDLINE]
Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.
J Rheumatol. 2014 Apr;41(4):792-8
Authors: Saketkoo LA, Mittoo S, Frankel S, LeSage D, Sarver C, Phillips K, Strand V, Matteson EL, OMERACT Connective Tissue Disease–Interstitial Lung Diseases Working Group, OMERACT Connective Tissue Disease-Interstitial Lung Diseases Working Group
Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.
PMID: 24488412 [PubMed - indexed for MEDLINE]
Cutaneous innervation of the ankle: an anatomical study showing danger zones for ankle surgery.
Clin Anat. 2014 May;27(4):653-8
Authors: Duscher D, Wenny R, Entenfellner J, Weninger P, Hirtler L
Three nerves innervate the skin in the foot and ankle region: the saphenous, sural, and superficial peroneal nerves. Because they are close to the medial and lateral malleoli, these nerves are at significant risk during orthopedic interventions. The aims of this study were to investigate the distal courses of the three cutaneous nerves of the ankle and to determine their exact relationships with easily identifiable bony landmarks. Ten freshly frozen and 40 embalmed lower extremities of adults were dissected. The positions of the superficial peroneal, sural, and saphenous nerves were determined using reference lines based on easily palpable osseous landmarks. The frequencies and distributions of all three nerves and their branches were converted into absolute numbers. A danger zone for each nerve was established on the basis of the distribution of crossings between the nerves and the different reference lines. Determination of the exact orientation of the nerves around the ankle should help minimize the nerve injury rate during surgical approaches in this area. Using this easily translatable new grid system, the course and danger zones of each cutaneous nerve around the ankle can be estimated clinically.
PMID: 24343871 [PubMed - indexed for MEDLINE]
Treatment options in severe fungal asthma and allergic bronchopulmonary aspergillosis.
Eur Respir J. 2014 May;43(5):1487-500
Authors: Moss RB
Severe asthma with fungal sensitisation and allergic bronchopulmonary aspergillosis encompass two closely related subgroups of patients with severe allergic asthma. Pulmonary disease is due to pronounced host inflammatory responses to noninvasive subclinical endobronchial infection with filamentous fungi, usually Aspergillus fumigatus. These patients usually do not achieve satisfactory disease control with conventional treatment of severe asthma, i.e. high-dose inhaled corticosteroids and long-acting bronchodilators. Although prolonged systemic corticosteroids are effective, they carry a substantial toxicity profile. Supplementary or alternative therapies have primarily focused on use of antifungal agents including oral triazoles and inhaled amphotericin B. Immunomodulation with omalizumab, a humanised anti-IgE monoclonal antibody, or "pulse" monthly high-dose intravenous corticosteroid, has also been employed. This article considers the experience with these approaches, with emphasis on recent clinical trials.
PMID: 24311776 [PubMed - indexed for MEDLINE]
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