Recent Stanford Publications in PubMed
- Mitochondrial Mutations in Subjects with Psychiatric Disorders.Sequeira A, Rollins B, Magnan C, van Oven M, Baldi P, Myers RM, Barchas JD, Schatzberg AF, Watson SJ, Akil H, Bunney WE, Vawter MPPLoS One
- Cancer of unknown primary is associated with diabetes.Hemminki K, Försti A, Sundquist K, Li XEur J Cancer Prev
- Detecting gene-environment interactions in human birth defects: Study designs and statistical methods.Tai CG, Graff RE, Liu J, Passarelli MN, Mefford JA, Shaw GM, Hoffmann TJ, Witte JSBirth Defects Res A Clin Mol Teratol
- Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder.Kremer S, Renard F, Achard S, Lana-Peixoto MA, Palace J, Asgari N, Klawiter EC, Tenembaum SN, Banwell B, Greenberg BM, Bennett JL, Levy M, Villoslada P, Saiz A, Fujihara K, Chan KH, Schippling S, Paul F, Kim HJ, de Seze J, Wuerfel JT, and the Guthy-Jackson Charitable Foundation (GJCF) Neuromyelitis Optica (NMO) International Clinical Consortium and Biorepository, Cabre P, Marignier R, Tedder T, van Pelt D, Broadley S, Chitnis T, Wingerchuk D, Pandit L, Leite MI, Apiwattanakul M, Kleiter I, Prayoonwiwat N, Han M, Hellwig K, van Herle K, John G, Hooper DC, Nakashima I, Sato D, Yeaman MR, Waubant E, Zamvil S, Stüve O, Aktas O, Smith TJ, Jacob A, O'Connor KJAMA Neurol
- Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.Tyndale RF, Zhu AZ, George TP, Cinciripini P, Hawk LW, Schnoll RA, Swan GE, Benowitz NL, Heitjan DF, Lerman C, PGRN-PNAT Research GroupPLoS One
- Chronic Intermittent Hypoxia Is Independently Associated with Reduced Postoperative Opioid Consumption in Bariatric Patients Suffering from Sleep-Disordered Breathing.Turan A, You J, Egan C, Fu A, Khanna A, Eshraghi Y, Ghosh R, Bose S, Qavi S, Arora L, Sessler DI, Doufas AGPLoS One
- The Posterior Medial Cortex in Urologic Chronic Pelvic Pain Syndrome: Detachment from Default Mode Network. A Resting-State Study from the MAPP Research Network.Martucci KT, Shirer WR, Bagarinao E, Johnson KA, Farmer MA, Labus JS, Apkarian AV, Deutsch G, Harris RE, Mayer EA, Clauw DJ, Greicius MD, Mackey SCPain
- Development of an Accelerometer-Linked Online Intervention System to Promote Physical Activity in Adolescents.Guthrie N, Bradlyn A, Thompson SK, Yen S, Haritatos J, Dillon F, Cole SWPLoS One
- FRAP, FLIM, and FRET: Detection and analysis of cellular dynamics on a molecular scale using fluorescence microscopy.De Los Santos C, Chang CW, Mycek MA, Cardullo RAMol Reprod Dev
- An overhang-based DNA block shuffling method for creating a customized random library.Fujishima K, Venter C, Wang K, Ferreira R, Rothschild LJSci Rep
- Teaching and assessing non-technical skills.DeTata CClin Teach
- A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies.Gubens MA, Burns M, Perkins SM, Pedro-Salcedo MS, Althouse SK, Loehrer PJ, Wakelee HALung Cancer
- Conventional versus virtual radiographs of the injured pelvis and acetabulum.Bishop JA, Rao AJ, Pouliot MA, Beaulieu C, Bellino MSkeletal Radiol
- Characterization of novel transcripts in pseudorabies virus.Tombácz D, Csabai Z, Oláh P, Havelda Z, Sharon D, Snyder M, Boldogkői ZViruses
- 50 Years Ago in TheJournal ofPediatrics: Cerebrospinal Fluid Protein Values of Premature Infants.Wallenstein MB, Wusthoff CJJ Pediatr
- 50 Years Ago in TheJournal ofPediatrics: Treatment of Hydrocephalus with Acetazolamide: Results in 15 Cases.Fisher PGJ Pediatr
- Endoscopic Plantar Fasciotomy Improves Early Postoperative Results: A Retrospective Comparison of Outcomes After Endoscopic Versus Open Plantar Fasciotomy.Chou AC, Ng SY, Koo KOJ Foot Ankle Surg
- Indicators of microbial-rich environments and the development of papillary thyroid cancer in the California Teachers Study.Clarke CA, Reynolds P, Oakley-Girvan I, Lee E, Lu Y, Yang J, Moy LM, Bernstein L, Horn-Ross PLCancer Epidemiol
- Unexpected edge conduction in mercury telluride quantum wells under broken time-reversal symmetry.Ma EY, Calvo MR, Wang J, Lian B, Mühlbauer M, Brüne C, Cui YT, Lai K, Kundhikanjana W, Yang Y, Baenninger M, König M, Ames C, Buhmann H, Leubner P, Molenkamp LW, Zhang SC, Goldhaber-Gordon D, Kelly MA, Shen ZXNat Commun
- Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.Cornel JH, Lopes RD, James S, Stevens SR, Neely ML, Liaw D, Miller J, Mohan P, Amerena J, Raev D, Huo Y, Urina-Triana M, Gallegos Cazorla A, Vinereanu D, Fridrich V, Harrington RA, Wallentin L, Alexander JH, APPRAISE-2 Study GroupAm Heart J
- Cardiovascular Safety Outcome Trials: A meeting report from the Cardiac Safety Research Consortium.Sager PT, Seltzer J, Turner JR, Anderson JL, Hiatt WR, Kowey P, Prochaska JJ, Stockbridge N, White WBAm Heart J
- Real life trumps laboratory in matters of public health.Zeitzer JMProc Natl Acad Sci U S A
- Pregnancy-related mortality in California: causes, characteristics, and improvement opportunities.Main EK, McCain CL, Morton CH, Holtby S, Lawton ESObstet Gynecol
- Peripheral blood-derived mesenchymal stem cells: candidate cells responsible for healing critical-sized calvarial bone defects.Li S, Huang KJ, Wu JC, Hu MS, Sanyal M, Hu M, Longaker MT, Lorenz HPStem Cells Transl Med
- Echocardiographic and electrocardiographic characteristics of male and female squirrel monkeys (Saimiri spp.).Huss MK, Ikeno F, Buckmaster CL, Albertelli MAJ Am Assoc Lab Anim Sci
- A modified retromaxillary approach to the infratemporal fossa: three case studies.Woodford R, Chaudhary N, Wolf A, Lownie S, Armstrong JEJ Oral Maxillofac Surg
- Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma.Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, Liu L, Kim YHBlood
- On the stability of parainfluenza virus 5 F proteins.Poor TA, Song AS, Welch BD, Kors CA, Jardetzky TS, Lamb RAJ Virol
- Prolactin: a versatile regulator of inflammation and autoimmune pathology.Costanza M, Binart N, Steinman L, Pedotti RAutoimmun Rev
- Distinct patterns of B-cell activation and priming by natural influenza virus infection versus inactivated influenza vaccination.He XS, Holmes TH, Sanyal M, Albrecht RA, García-Sastre A, Dekker CL, Davis MM, Greenberg HBJ Infect Dis
- Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.Cordero-Schmidt G, Wallenstein MB, Ozen M, Shah NA, Jackson E, Hovsepian DM, Palma JPJ Perinatol
- Increased coupling of intrinsic networks in remitted depressed youth predicts rumination and cognitive control.Jacobs RH, Jenkins LM, Gabriel LB, Barba A, Ryan KA, Weisenbach SL, Verges A, Baker AM, Peters AT, Crane NA, Gotlib IH, Zubieta JK, Phan KL, Langenecker SA, Welsh RCPLoS One
- Simulated cytoskeletal collapse via tau degradation.Sendek A, Fuller HR, Hayre NR, Singh RR, Cox DLPLoS One
- Fluorescent imaging of cancerous tissues for targeted surgery.Bu L, Shen B, Cheng ZAdv Drug Deliv Rev
- Structural remodeling of coronary resistance arteries: effects of age and exercise training.Hanna MA, Taylor CR, Chen B, La HS, Maraj JJ, Kilar CR, Behnke BJ, Delp MD, Muller-Delp JMJ Appl Physiol (1985)
- Social regulation of cortisol receptor gene expression.Korzan WJ, Grone BP, Fernald RDJ Exp Biol
- Tetralogy of Fallot: aorto-pulmonary collaterals and pulmonary arteries have distinctly different transcriptomes.Ma X, Barboza LA, Siyahian A, Reinhartz O, Maeda K, Reddy VM, Hanley FL, Riemer RKPediatr Res
- Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape.Camp JG, Frank CL, Lickwar CR, Guturu H, Rube T, Wenger AM, Chen J, Bejerano G, Crawford GE, Rawls JFGenome Res
- The first metabolic and bariatric surgery accreditation and quality improvement program quality initiative: decreasing readmissions through opportunities provided.Morton JSurg Obes Relat Dis
- Reentry device aided endovascular aneurysm repair in patients with abdominal aortic aneurysm and unilateral iliac artery occlusion.Varu VN, Lee GK, Chang S, Lee JTAnn Vasc Surg
- Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes.Ferreira Tojais N, Peghaire C, Franzl N, Larrieu-Lahargue F, Jaspard B, Reynaud A, Moreau C, Couffinhal T, Duplàa C, Dufourcq PCardiovasc Res
- Communication about social status.Fernald RDCurr Opin Neurobiol
- House calls by community health workers and public health nurses to improve adherence to isoniazid monotherapy for latent tuberculosis infection: a retrospective study.Chang AH, Polesky A, Bhatia GBMC Public Health
Mitochondrial Mutations in Subjects with Psychiatric Disorders.
PLoS One. 2015;10(5):e0127280
Authors: Sequeira A, Rollins B, Magnan C, van Oven M, Baldi P, Myers RM, Barchas JD, Schatzberg AF, Watson SJ, Akil H, Bunney WE, Vawter MP
A considerable body of evidence supports the role of mitochondrial dysfunction in psychiatric disorders and mitochondrial DNA (mtDNA) mutations are known to alter brain energy metabolism, neurotransmission, and cause neurodegenerative disorders. Genetic studies focusing on common nuclear genome variants associated with these disorders have produced genome wide significant results but those studies have not directly studied mtDNA variants. The purpose of this study is to investigate, using next generation sequencing, the involvement of mtDNA variation in bipolar disorder, schizophrenia, major depressive disorder, and methamphetamine use. MtDNA extracted from multiple brain regions and blood were sequenced (121 mtDNA samples with an average of 8,800x coverage) and compared to an electronic database containing 26,850 mtDNA genomes. We confirmed novel and rare variants, and confirmed next generation sequencing error hotspots by traditional sequencing and genotyping methods. We observed a significant increase of non-synonymous mutations found in individuals with schizophrenia. Novel and rare non-synonymous mutations were found in psychiatric cases in mtDNA genes: ND6, ATP6, CYTB, and ND2. We also observed mtDNA heteroplasmy in brain at a locus previously associated with schizophrenia (T16519C). Large differences in heteroplasmy levels across brain regions within subjects suggest that somatic mutations accumulate differentially in brain regions. Finally, multiplasmy, a heteroplasmic measure of repeat length, was observed in brain from selective cases at a higher frequency than controls. These results offer support for increased rates of mtDNA substitutions in schizophrenia shown in our prior results. The variable levels of heteroplasmic/multiplasmic somatic mutations that occur in brain may be indicators of genetic instability in mtDNA.
PMID: 26011537 [PubMed - as supplied by publisher]
Cancer of unknown primary is associated with diabetes.
Eur J Cancer Prev. 2015 May 18;
Authors: Hemminki K, Försti A, Sundquist K, Li X
The incidences of both type 1 diabetes (T1D) and T2D are increasing worldwide. T2D is associated with many cancers. However, no data are available on cancer of unknown primary (CUP), a relatively common, fatal cancer for which tobacco smoking is the only known risk factor. At diagnosis, CUP metastases are found in various organs, which has implications for prognosis. We carried out a nationwide study on the association of CUP with T1D and T2D. 32 600 T1D patients and 178 000 T2D patients were identified from the national healthcare registers and these were linked to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for CUP from 1997 through 2010 using anyone without diabetes as a reference. The SIR of CUP in 421 diabetic patients was 1.71, highest for CUP with liver (2.17) and respiratory system (1.95) metastases. The SIR was 2.91 for T1D, but with a small number of patients, 1.38 for T2D with insulin treatment, and 1.78 for the main group of T2D. CUP with liver and respiratory system metastases increased for each diabetic type; however, for T2D, CUP with gastrointestinal and bone metastases also increased. The results provide the first demonstration that CUP is one of the cancers associated with diabetes, with definite evidence on T2D. CUP has a poor prognosis, which may be even worse when diabetes is the underlying comorbidity. A mechanistic question for future work is to determine whether diabetes promotes primaries that escape detection or their metastatic spread.
PMID: 26011105 [PubMed - as supplied by publisher]
Detecting gene-environment interactions in human birth defects: Study designs and statistical methods.
Birth Defects Res A Clin Mol Teratol. 2015 May 23;
Authors: Tai CG, Graff RE, Liu J, Passarelli MN, Mefford JA, Shaw GM, Hoffmann TJ, Witte JS
BACKGROUND: The National Birth Defects Prevention Study (NBDPS) contains a wealth of information on affected and unaffected family triads, and thus provides numerous opportunities to study gene-environment interactions (G×E) in the etiology of birth defect outcomes. Depending on the research objective, several analytic options exist to estimate G×E effects that use varying combinations of individuals drawn from available triads.
METHODS: In this study, we discuss important considerations in the collection of genetic data and environmental exposures.
RESULTS: We will also present several population- and family-based approaches that can be applied to data from the NBDPS including case-control, case-only, family-based trio, and maternal versus fetal effects. For each, we describe the data requirements, applicable statistical methods, advantages, and disadvantages.
CONCLUSION: A range of approaches can be used to evaluate potentially important G×E effects in the NBDPS. Investigators should be aware of the limitations inherent to each approach when choosing a study design and interpreting results. Birth Defects Research (Part A), 2015. © 2015 Wiley Periodicals, Inc.
PMID: 26010994 [PubMed - as supplied by publisher]
Use of Advanced Magnetic Resonance Imaging Techniques in Neuromyelitis Optica Spectrum Disorder.
JAMA Neurol. 2015 May 26;
Authors: Kremer S, Renard F, Achard S, Lana-Peixoto MA, Palace J, Asgari N, Klawiter EC, Tenembaum SN, Banwell B, Greenberg BM, Bennett JL, Levy M, Villoslada P, Saiz A, Fujihara K, Chan KH, Schippling S, Paul F, Kim HJ, de Seze J, Wuerfel JT, and the Guthy-Jackson Charitable Foundation (GJCF) Neuromyelitis Optica (NMO) International Clinical Consortium and Biorepository, Cabre P, Marignier R, Tedder T, van Pelt D, Broadley S, Chitnis T, Wingerchuk D, Pandit L, Leite MI, Apiwattanakul M, Kleiter I, Prayoonwiwat N, Han M, Hellwig K, van Herle K, John G, Hooper DC, Nakashima I, Sato D, Yeaman MR, Waubant E, Zamvil S, Stüve O, Aktas O, Smith TJ, Jacob A, O'Connor K
Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than gray matter degradation. These findings could be confirmed by ultrahigh-field MRI. The use of nonconventional MRI techniques may further our understanding of the pathogenic processes in NMO spectrum disorders and may help us identify the distinct radiographic features corresponding to specific phenotypic manifestations of this disease.
PMID: 26010909 [PubMed - as supplied by publisher]
Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.
PLoS One. 2015;10(5):e0128109
Authors: Tyndale RF, Zhu AZ, George TP, Cinciripini P, Hawk LW, Schnoll RA, Swan GE, Benowitz NL, Heitjan DF, Lerman C, PGRN-PNAT Research Group
CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies) in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23), OR = 1.01 (P = 0.99), and OR = 1.30 (P = 0.36) respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90), OR = 0.84 (P = 0.58), and OR = 0.74 (P = 0.29) respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95), OR = 0.75 (P = 0.35), and OR = 1.20 (P = 0.51) respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765), nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05). We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical trial; however, as expected, significant associations with baseline tobacco consumption were replicated. Our data suggest that CHRNA5-A3-B4 gene variants do not exhibit a robust association with smoking cessation and are unlikely to be useful for clinically optimizing smoking cessation pharmacotherapy for Caucasian smokers.
PMID: 26010901 [PubMed - as supplied by publisher]
Chronic Intermittent Hypoxia Is Independently Associated with Reduced Postoperative Opioid Consumption in Bariatric Patients Suffering from Sleep-Disordered Breathing.
PLoS One. 2015;10(5):e0127809
Authors: Turan A, You J, Egan C, Fu A, Khanna A, Eshraghi Y, Ghosh R, Bose S, Qavi S, Arora L, Sessler DI, Doufas AG
BACKGROUND: Evidence suggests that recurrent nocturnal hypoxemia may affect pain response and/or the sensitivity to opioid analgesia. We tested the hypothesis that nocturnal hypoxemia, quantified by sleep time spent at an arterial saturation (SaO2) < 90% and minimum nocturnal SaO2 on polysomnography, are associated with decreased pain and reduced opioid consumption during the initial 72 postoperative hours in patients having laparoscopic bariatric surgery.
METHODS: With Institutional Review Board approval, we examined the records of all patients who underwent laparoscopic bariatric surgery between 2004 and 2010 and had an available nocturnal polysomnography study. We assessed the relationships between the time-weighted average of pain score and total opioid consumption during the initial 72 postoperative hours, and: (a) the percentage of total sleep time spent at SaO2 < 90%, (b) the minimum nocturnal SaO2, and (c) the number of apnea/hypopnea episodes per hour of sleep. We used multivariable regression models to adjust for both clinical and sleep-related confounders.
RESULTS: Two hundred eighteen patients were included in the analysis. Percentage of total sleep time spent at SaO2 < 90% was inversely associated with total postoperative opioid consumption; a 5-%- absolute increase in the former would relatively decrease median opioid consumption by 16% (98.75% CI: 2% to 28%, P = 0.006). However, the percentage of total sleep time spent at SaO2 < 90% was not associated with pain. The minimum nocturnal SaO2 was associated neither with total postoperative opioid consumption nor with pain. In addition, neither pain nor total opioid consumption was significantly associated with the number of apnea/hypopnea episodes per hour of sleep.
CONCLUSIONS: Preoperative nocturnal intermittent hypoxia may enhance sensitivity to opioids.
PMID: 26010491 [PubMed - as supplied by publisher]
The Posterior Medial Cortex in Urologic Chronic Pelvic Pain Syndrome: Detachment from Default Mode Network. A Resting-State Study from the MAPP Research Network.
Pain. 2015 May 20;
Authors: Martucci KT, Shirer WR, Bagarinao E, Johnson KA, Farmer MA, Labus JS, Apkarian AV, Deutsch G, Harris RE, Mayer EA, Clauw DJ, Greicius MD, Mackey SC
Altered resting-state brain activity, as a measure of functional connectivity, is commonly observed in chronic pain. Identifying a reliable signature pattern of altered resting-state activity for chronic pain could provide strong mechanistic insights and serve as a highly beneficial neuroimaging-based diagnostic tool. We collected and analyzed resting-state fMRI data from female patients with urologic chronic pelvic pain syndrome (UCPPS, N = 45) and matched healthy participants (N = 45) as part of a NIDDK funded multicenter project (www.mappnetwork.org). Using dual regression and seed-based analyses, we observed significantly decreased functional connectivity of the default mode network (DMN) to two regions in the posterior medial cortex (PMC): the posterior cingulate cortex (PCC) and left precuneus (TFCE, FWE corrected p<0.05). Further investigation revealed that patients demonstrated increased functional connectivity between the PCC and several brain regions implicated in pain, sensory, motor, and emotion regulation processes (e.g., insular cortex, dorsolateral prefrontal cortex, thalamus, globus pallidus, putamen, amygdala, hippocampus). The left precuneus demonstrated decreased functional connectivity to several regions of pain processing, reward, and higher executive functioning within the prefrontal (orbitofrontal, anterior cingulate, ventromedial prefrontal) and parietal cortices (angular gyrus, superior and inferior parietal lobules). The altered PMC connectivity was associated with several phenotype measures, including pain and urologic symptom intensity, depression, anxiety, quality of relationships and self-esteem levels in patients. Collectively, these findings indicate that in UCPPS patients, regions of the PMC are detached from the DMN, while neurological processes of self-referential thought and introspection may be joined to pain and emotion regulatory processes.
PMID: 26010458 [PubMed - as supplied by publisher]
Development of an Accelerometer-Linked Online Intervention System to Promote Physical Activity in Adolescents.
PLoS One. 2015;10(5):e0128639
Authors: Guthrie N, Bradlyn A, Thompson SK, Yen S, Haritatos J, Dillon F, Cole SW
Most adolescents do not achieve the recommended levels of moderate-to-vigorous physical activity (MVPA), placing them at increased risk for a diverse array of chronic diseases in adulthood. There is a great need for scalable and effective interventions that can increase MVPA in adolescents. Here we report the results of a measurement validation study and a preliminary proof-of-concept experiment testing the impact of Zamzee, an accelerometer-linked online intervention system that combines proximal performance feedback and incentive motivation features to promote MVPA. In a calibration study that parametrically varied levels of physical activity in 31 12-14 year-old children, the Zamzee activity meter was shown to provide a valid measure of MVPA (sensitivity in detecting MVPA = 85.9%, specificity = 97.5%, and r = .94 correspondence with the benchmark RT3 accelerometer system; all p < .0001). In a subsequent randomized controlled multi-site experiment involving 182 middle school-aged children assessed for MVPA over 6 wks, intent-to-treat analyses found that those who received access to the Zamzee intervention had average MVPA levels 54% greater than those of a passive control group (p < 0.0001) and 68% greater than those of an active control group that received access to a commercially available active videogame (p < .0001). Zamzee's effects on MVPA did not diminish significantly over the course of the 6-wk study period, and were statistically significant in both females and males, and in normal- vs. high-BMI subgroups. These results provide promising initial indications that combining the Zamzee activity meter with online proximal performance feedback and incentive motivation features can positively impact MVPA levels in adolescents.
PMID: 26010359 [PubMed - as supplied by publisher]
FRAP, FLIM, and FRET: Detection and analysis of cellular dynamics on a molecular scale using fluorescence microscopy.
Mol Reprod Dev. 2015 May 25;
Authors: De Los Santos C, Chang CW, Mycek MA, Cardullo RA
The combination of fluorescent-probe technology plus modern optical microscopes allows investigators to monitor dynamic events in living cells with exquisite temporal and spatial resolution. Fluorescence recovery after photobleaching (FRAP), for example, has long been used to monitor molecular dynamics both within cells and on cellular surfaces. Although bound by the diffraction limit imposed on all optical microscopes, the combination of digital cameras and the application of fluorescence intensity information on large-pixel arrays have allowed such dynamic information to be monitored and quantified. Fluorescence lifetime imaging microscopy (FLIM), on the other hand, utilizes the information from an ensemble of fluorophores to probe changes in the local environment. Using either fluorescence-intensity or lifetime approaches, fluorescence resonance energy transfer (FRET) microscopy provides information about molecular interactions, with Ångstrom resolution. In this review, we summarize the theoretical framework underlying these methods and illustrate their utility in addressing important problems in reproductive and developmental systems. Mol. Reprod. Dev. © 2015 Wiley Periodicals, Inc.
PMID: 26010322 [PubMed - as supplied by publisher]
An overhang-based DNA block shuffling method for creating a customized random library.
Sci Rep. 2015;5:9740
Authors: Fujishima K, Venter C, Wang K, Ferreira R, Rothschild LJ
We present an overhang-based DNA block shuffling method to create a customized random DNA library with flexible sequence design and length. Our method enables the efficient and seamless assembly of short DNA blocks with dinucleotide overhangs through a simple ligation process. Next generation sequencing analysis of the assembled DNA library revealed that ligation was accurate, directional and unbiased. This straightforward DNA assembly method should fulfill the versatile needs of both in vivo and in vitro functional screening of random peptides and RNA created with a desired amino acid and nucleotide composition, as well as making highly repetitive gene constructs that are difficult to synthesize de novo.
PMID: 26010273 [PubMed - as supplied by publisher]
Teaching and assessing non-technical skills.
Clin Teach. 2015 Jun;12(3):219
Authors: DeTata C
PMID: 26009963 [PubMed - as supplied by publisher]
A phase II study of saracatinib (AZD0530), a Src inhibitor, administered orally daily to patients with advanced thymic malignancies.
Lung Cancer. 2015 Apr 25;
Authors: Gubens MA, Burns M, Perkins SM, Pedro-Salcedo MS, Althouse SK, Loehrer PJ, Wakelee HA
OBJECTIVES: Thymic malignancies are rare, and options are limited for metastatic disease. Src plays a role in normal thymic epithelial maturation, and its inhibition with the oral compound saracatinib was postulated to be effective in controlling thymic malignancy.
MATERIALS AND METHODS: Patients with unresectable thymic malignancy were treated with saracatinib 175mg by mouth daily in 28 days cycles with radiographic evaluation at cycle 2 day 1 for safety, then cycle 3 day 1 and every 8 weeks thereafter. Response was evaluated by RECIST 1.0. A two-stage optimal design was used, powered to detect a true response rate of 20%.
RESULTS: 21 patients were enrolled at two institutions, 12 of them with thymoma, 9 with thymic carcinoma. Thymoma patients received a median of 4.5 cycles and thymic carcinoma patients a median of 1 cycle. There were no responses, so accrual was halted after the first stage per protocol. 9 patients had stable disease beyond the first assessment. Median time to progression was 5.7 months for thymoma patients and 3.6 months for thymic carcinoma patients. Saracatinib was well tolerated.
CONCLUSION: Src inhibition by saracatinib did not produce any radiographic responses, though some patients did experience stable disease. Though negative, this study shows the feasibility of completing a trial in this rare disease, and of accruing reasonably significant numbers of thymic carcinoma patients. More clinical trials are required for this population (NCT00718809).
PMID: 26009269 [PubMed - as supplied by publisher]
Conventional versus virtual radiographs of the injured pelvis and acetabulum.
Skeletal Radiol. 2015 May 26;
Authors: Bishop JA, Rao AJ, Pouliot MA, Beaulieu C, Bellino M
BACKGROUND: Evaluation of the fractured pelvis or acetabulum requires both standard radiographic evaluation as well as computed tomography (CT) imaging. The standard anterior-posterior (AP), Judet, and inlet and outlet views can now be simulated using data acquired during CT, decreasing patient discomfort, radiation exposure, and cost to the healthcare system. The purpose of this study is to compare the image quality of conventional radiographic views of the traumatized pelvis to virtual radiographs created from pelvic CT scans.
METHODS: Five patients with acetabular fractures and ten patients with pelvic ring injuries were identified using the orthopedic trauma database at our institution. These fractures were evaluated with both conventional radiographs as well as virtual radiographs generated from a CT scan. A web-based survey was created to query overall image quality and visibility of relevant anatomic structures. This survey was then administered to members of the Orthopaedic Trauma Association (OTA).
RESULTS: Ninety-seven surgeons completed the acetabular fracture survey and 87 completed the pelvic fracture survey. Overall image quality was judged to be statistically superior for the virtual as compared to conventional images for acetabular fractures (3.15 vs. 2.98, p = 0.02), as well as pelvic ring injuries (2.21 vs. 1.45, p = 0.0001). Visibility ratings for each anatomic landmark were statistically superior with virtual images as well.
DISCUSSION: Virtual radiographs of pelvic and acetabular fractures offer superior image quality, improved comfort, decreased radiation exposure, and a more cost-effective alternative to conventional radiographs.
PMID: 26009268 [PubMed - as supplied by publisher]
Characterization of novel transcripts in pseudorabies virus.
Authors: Tombácz D, Csabai Z, Oláh P, Havelda Z, Sharon D, Snyder M, Boldogkői Z
In this study we identified two 3'-coterminal RNA molecules in the pseudorabies virus. The highly abundant short transcript (CTO-S) proved to be encoded between the ul21 and ul22 genes in close vicinity of the replication origin (OriL) of the virus. The less abundant long RNA molecule (CTO-L) is a transcriptional readthrough product of the ul21 gene and overlaps OriL. These polyadenylated RNAs were characterized by ascertaining their nucleotide sequences with the Illumina HiScanSQ and Pacific Biosciences Real-Time (PacBio RSII) sequencing platforms and by analyzing their transcription kinetics through use of multi-time-point Real-Time RT-PCR and the PacBio RSII system. It emerged that transcription of the CTOs is fully dependent on the viral transactivator protein IE180 and CTO-S is not a microRNA precursor. We propose an interaction between the transcription and replication machineries at this genomic location, which might play an important role in the regulation of DNA synthesis.
PMID: 26008709 [PubMed - in process]
50 Years Ago in TheJournal ofPediatrics: Cerebrospinal Fluid Protein Values of Premature Infants.
J Pediatr. 2015 Jun;166(6):1396
Authors: Wallenstein MB, Wusthoff CJ
PMID: 26008171 [PubMed - in process]
50 Years Ago in TheJournal ofPediatrics: Treatment of Hydrocephalus with Acetazolamide: Results in 15 Cases.
J Pediatr. 2015 Jun;166(6):1369
Authors: Fisher PG
PMID: 26008170 [PubMed - in process]
Endoscopic Plantar Fasciotomy Improves Early Postoperative Results: A Retrospective Comparison of Outcomes After Endoscopic Versus Open Plantar Fasciotomy.
J Foot Ankle Surg. 2015 May 22;
Authors: Chou AC, Ng SY, Koo KO
Plantar fasciotomy is offered to patients with recalcitrant plantar fasciitis. Few studies have characterized the functional outcomes over time for the endoscopic approach compared with the open approach. We hypothesized that patients undergoing endoscopic surgery will have better postoperative functional outcomes early in the postoperative period but equivalent long-term outcomes compared with patients undergoing open surgery. We analyzed the prospectively collected data of all patients undergoing plantar fasciotomy at our institution from December 2007 to August 2014. A total of 42 feet of 38 patients were included in the analysis. The clinical data were collected preoperatively and at 3 and 6 months and 1 year. The functional outcomes analyzed included the American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, the Medical Outcomes Study, Short-Form, 36-item Health Survey, and patient satisfaction and expectations. Patients undergoing endoscopic surgery had significantly greater American Orthopaedic Foot and Ankle Society Ankle-Hindfoot and SF-36 Health Survey scores and lower pain scores at the 3-month period. They were also significantly more likely to be satisfied with and have had their expectations met by surgery. Compared with the open approach, the patients who had undergone endoscopic plantar fasciotomy experienced significantly greater improvements in the subjective and objective functional outcomes, with less pain and greater satisfaction, and had had their expectations met earlier in the recovery period, with equivalent long-term outcomes, compared with the patients who had undergone open plantar fasciotomy.
PMID: 26007627 [PubMed - as supplied by publisher]
Indicators of microbial-rich environments and the development of papillary thyroid cancer in the California Teachers Study.
Cancer Epidemiol. 2015 May 22;
Authors: Clarke CA, Reynolds P, Oakley-Girvan I, Lee E, Lu Y, Yang J, Moy LM, Bernstein L, Horn-Ross PL
BACKGROUND: Little epidemiologic research has focused on the role of immune function in papillary thyroid cancer risk despite scattered observations suggesting it may be important (e.g., hygiene hypothesis). Here we investigate papillary thyroid cancer risk associated with self-reported living environments across the lifespan reflecting immunologically relevant exposures to microbial-rich environments.
METHODS: Among 61,803 eligible participants in the California Teachers Study cohort, 100 were diagnosed with invasive papillary thyroid cancer between 2005 and 2012. Multivariate Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI).
RESULTS: Living in a rural area during early childhood was associated with significantly reduced risk of developing papillary thyroid cancer as an adult (HR=0.51, 95% CI: 0.28-0.94). Specifically, reduced risks were observed for living within a half mile of hoofed animals (HR=0.47, 95% CI: 0.26-0.84), as was having an indoor dog or cat (HR=0.51, 95% CI: 0.32-0.80). Neither sharing a bedroom or living in a rented home as a child nor attending daycare or kindergarten was associated with reduced risk.
CONCLUSIONS: Early childhood exposures to hoofed animals or indoor furry pets were associated with reduced risk of subsequently developing papillary thyroid cancer.
IMPACT: Our findings point to immunologically relevant, early-life exposures to microbial-rich environments as potentially important in reducing thyroid cancer risk, consistent with the hygiene hypothesis and suggesting that certain, possibly animal-derived, microbial exposures may be important to immune calibration or priming.
PMID: 26007306 [PubMed - as supplied by publisher]
Unexpected edge conduction in mercury telluride quantum wells under broken time-reversal symmetry.
Nat Commun. 2015;6:7252
Authors: Ma EY, Calvo MR, Wang J, Lian B, Mühlbauer M, Brüne C, Cui YT, Lai K, Kundhikanjana W, Yang Y, Baenninger M, König M, Ames C, Buhmann H, Leubner P, Molenkamp LW, Zhang SC, Goldhaber-Gordon D, Kelly MA, Shen ZX
The realization of quantum spin Hall effect in HgTe quantum wells is considered a milestone in the discovery of topological insulators. Quantum spin Hall states are predicted to allow current flow at the edges of an insulating bulk, as demonstrated in various experiments. A key prediction yet to be experimentally verified is the breakdown of the edge conduction under broken time-reversal symmetry. Here we first establish a systematic framework for the magnetic field dependence of electrostatically gated quantum spin Hall devices. We then study edge conduction of an inverted quantum well device under broken time-reversal symmetry using microwave impedance microscopy, and compare our findings to a non-inverted device. At zero magnetic field, only the inverted device shows clear edge conduction in its local conductivity profile, consistent with theory. Surprisingly, the edge conduction persists up to 9 T with little change. This indicates physics beyond simple quantum spin Hall model, including material-specific properties and possibly many-body effects.
PMID: 26006728 [PubMed - in process]
Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial.
Am Heart J. 2015 Apr;169(4):531-8
Authors: Cornel JH, Lopes RD, James S, Stevens SR, Neely ML, Liaw D, Miller J, Mohan P, Amerena J, Raev D, Huo Y, Urina-Triana M, Gallegos Cazorla A, Vinereanu D, Fridrich V, Harrington RA, Wallentin L, Alexander JH, APPRAISE-2 Study Group
BACKGROUND: Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations.
METHODS: High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding.
RESULTS: Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF.
CONCLUSIONS: In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.
PMID: 25819860 [PubMed - indexed for MEDLINE]
Cardiovascular Safety Outcome Trials: A meeting report from the Cardiac Safety Research Consortium.
Am Heart J. 2015 Apr;169(4):486-95
Authors: Sager PT, Seltzer J, Turner JR, Anderson JL, Hiatt WR, Kowey P, Prochaska JJ, Stockbridge N, White WB
This White Paper provides a summary of presentations and discussions at a Cardiovascular Safety Outcome Trials Think Tank cosponsored by the Cardiac Safety Research Consortium, the US Food and Drug Administration, and the American College of Cardiology, held at American College of Cardiology's Heart House, Washington, DC, on February 19, 2014. Studies to assess cardiovascular (CV) risk of a new drug are sometimes requested by regulators to resolve ambiguous safety signals seen during its development or among other members of its class. Think Tank participants thought that important considerations in undertaking such studies were as follows: (1) plausibility-how likely it is that a possible signal indicating risk is real, based on strength of evidence, and/or whether a plausible mechanism of action for potential CV harm has been identified; (2) relevance-what relative and absolute CV risk would need to be excluded to determine that the drug had an acceptable benefit-to-risk balance for its use in the intended patient population; and (3) how plausibility and relevance influence the timing and approach to further safety assessment.
PMID: 25819855 [PubMed - indexed for MEDLINE]
Real life trumps laboratory in matters of public health.
Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):E1513
Authors: Zeitzer JM
PMID: 25762078 [PubMed - indexed for MEDLINE]
Pregnancy-related mortality in California: causes, characteristics, and improvement opportunities.
Obstet Gynecol. 2015 Apr;125(4):938-47
Authors: Main EK, McCain CL, Morton CH, Holtby S, Lawton ES
OBJECTIVE: To compare specific maternal and clinical characteristics and contributing factors among the five leading causes of pregnancy-related mortality to develop focused clinical and public health prevention programs.
METHODS: California pregnancy-related deaths from 2002-2005 were identified with enhanced surveillance using linked birth and death certificates. A multidisciplinary committee reviewed medical records, autopsy reports, and coroner reports to determine cause of death, clinical and demographic characteristics, chance to alter outcome, contributing factors (at health care provider, facility, and patient levels), and quality improvement opportunities. The five leading causes of death were compared with each other and with the overall California birth population.
RESULTS: Among the 207 pregnancy-related deaths, the five leading causes were cardiovascular disease, preeclampsia or eclampsia, hemorrhage, venous thromboembolism, and amniotic fluid embolism. Among the leading causes of death, we identified differing patterns for race, maternal age, body mass index, timing of death, and method of delivery. Overall, there was a good-to-strong chance to alter the outcome in 41% of deaths, with the highest rates of preventability among hemorrhage (70%) and preeclampsia (60%) deaths. Health care provider, facility, and patient contributing factors also varied by cause of death.
CONCLUSION: Pregnancy-related mortality should not be considered a single clinical entity. Reducing mortality requires in-depth examination of individual causes of death. The five leading causes exhibit different characteristics, degrees of preventability, and contributing factors, with the greatest improvement opportunities identified for hemorrhage and preeclampsia. These findings provide additional support for hospital, state, and national maternal safety programs.
PMID: 25751214 [PubMed - indexed for MEDLINE]
Peripheral blood-derived mesenchymal stem cells: candidate cells responsible for healing critical-sized calvarial bone defects.
Stem Cells Transl Med. 2015 Apr;4(4):359-68
Authors: Li S, Huang KJ, Wu JC, Hu MS, Sanyal M, Hu M, Longaker MT, Lorenz HP
Postnatal tissue-specific stem/progenitor cells hold great promise to enhance repair of damaged tissues. Many of these cells are retrieved from bone marrow or adipose tissue via invasive procedures. Peripheral blood is an ideal alternative source for the stem/progenitor cells because of its ease of retrieval. We present a coculture system that routinely produces a group of cells from adult peripheral blood. Treatment with these cells enhanced healing of critical-size bone defects in the mouse calvarium, a proof of principle that peripheral blood-derived cells can be used to heal bone defects. From these cells, we isolated a subset of CD45(-) cells with a fibroblastic morphology. The CD45(-) cells were responsible for most of the differentiation-induced calcification activity and were most likely responsible for the enhanced healing process. These CD45(-) fibroblastic cells are plastic-adherent and exhibit a surface marker profile negative for CD34, CD19, CD11b, lineage, and c-kit and positive for stem cell antigen 1, CD73, CD44, CD90.1, CD29, CD105, CD106, and CD140α. Furthermore, these cells exhibited osteogenesis, chondrogenesis, and adipogenesis capabilities. The CD45(-) fibroblastic cells are the first peripheral blood-derived cells that fulfill the criteria of mesenchymal stem cells as defined by the International Society for Cellular Therapy. We have named these cells "blood-derived mesenchymal stem cells."
PMID: 25742693 [PubMed - indexed for MEDLINE]
Echocardiographic and electrocardiographic characteristics of male and female squirrel monkeys (Saimiri spp.).
J Am Assoc Lab Anim Sci. 2015 Jan;54(1):25-8
Authors: Huss MK, Ikeno F, Buckmaster CL, Albertelli MA
Cardiomyopathy is a leading cause of mortality in aging squirrel monkeys (Saimiri spp.). However, data regarding echocardiographic measures obtained from clinically healthy nonsedated squirrel monkeys have not been published, and few electrocardiographic data are available. Here we obtained echocardiographs without sedation and electrocardiographs with minimal sedation from 63 clinically healthy squirrel monkeys that ranged from 3 to 20 y in age. 2D and M-mode echocardiography were performed on nonsedated monkeys to determine the left ventricular internal diameters at systole and diastole and the ejection fraction. Electrocardiography was performed under sedation with ketamine (15 mg/kg). Parameters evaluated included heart rate; P-wave duration; lengths of the PR, QRS, and QT intervals; R-wave amplitude, and P-wave amplitude. Initial physical examination, electrocardiography, and echocardiography indicated normal cardiac function for all monkeys. The objectives of this study were to provide reference values for nonsedated echocardiography and ketamine-sedated electrocardiography of clinically normal squirrel monkeys and to determine correlates of age and sex in these values.
PMID: 25651087 [PubMed - indexed for MEDLINE]
A modified retromaxillary approach to the infratemporal fossa: three case studies.
J Oral Maxillofac Surg. 2015 Apr;73(4):769-80
Authors: Woodford R, Chaudhary N, Wolf A, Lownie S, Armstrong JE
The infratemporal fossa (ITF) is an anatomically complex region with multiple neural and vascular structures entering and exiting through foramina in the skull base. The main obstacles to approaching the ITF are the zygomatic arch, the parotid gland, the facial nerve, and the ascending ramus AND condylar head of the mandible. Different surgical approaches to the ITF exist and the best approach should provide optimal visibility, minimal impairment of temporomandibular joint function, and preservation of motor and sensory nerve integrity. This report describes a modified Obwegeser retromaxillary approach to access lesions within the ITF. A multidisciplinary team was involved, which included an oral and maxillofacial surgery team, a neurosurgery team, and an otolaryngology team. Three patients with large skull base lesions, including an aneurysmal bone cyst, a giant cell tumor of the bone, and an invasive melanoma, underwent resection using this approach and were followed postoperatively. Excellent exposure of the floor of the middle cranial fossa and ITF was achieved with this approach. Functional status remained unchanged with respect to mastication, speech, swallowing, and cosmesis. Given the severity of the patients' conditions and extent of involvement of the skull base, outcomes were favorable, with minimal morbidity. This experience suggests that this approach provides safe access to an anatomically complex region and lessens challenges associated with more conventional approaches.
PMID: 25631866 [PubMed - indexed for MEDLINE]
Phase 1/2 study of mogamulizumab, a defucosylated anti-CCR4 antibody, in previously treated patients with cutaneous T-cell lymphoma.
Blood. 2015 Mar 19;125(12):1883-9
Authors: Duvic M, Pinter-Brown LC, Foss FM, Sokol L, Jorgensen JL, Challagundla P, Dwyer KM, Zhang X, Kurman MR, Ballerini R, Liu L, Kim YH
This phase 1/2 study evaluated the efficacy of mogamulizumab, a defucosylated, humanized, anti-CC chemokine receptor 4 monoclonal antibody, in 41 pretreated patients with cutaneous T-cell lymphoma. No dose-limiting toxicity was observed and the maximum tolerated dose was not reached in phase 1 after IV infusion of mogamulizumab (0.1, 0.3, and 1.0 mg/kg) once weekly for 4 weeks followed by a 2-week observation. In phase 2, patients were dosed with 1.0 mg/kg mogamulizumab according to the same schedule for the first course followed by infusion every 2 weeks during subsequent courses until disease progression. The most frequent treatment-emergent adverse events were nausea (31.0%), chills (23.8%), headache (21.4%), and infusion-related reaction (21.4%); the majority of events were grade 1/2. There were no significant hematologic effects. Among 38 evaluable patients, the overall response rate was 36.8%: 47.1% in Sézary syndrome (n = 17) and 28.6% in mycosis fungoides (n = 21). Eighteen of 19 (94.7%) patients with ≥B1 blood involvement had a response in blood, including 11 complete responses. Given the safety and efficacy of mogamulizumab, phase 3 investigation of mogamulizumab is warranted in cutaneous T-cell lymphoma patients. This trial was registered at www.clinicaltrials.gov as #NCT00888927.
PMID: 25605368 [PubMed - indexed for MEDLINE]
On the stability of parainfluenza virus 5 F proteins.
J Virol. 2015 Mar;89(6):3438-41
Authors: Poor TA, Song AS, Welch BD, Kors CA, Jardetzky TS, Lamb RA
The crystal structure of the F protein (prefusion form) of the paramyxovirus parainfluenza virus 5 (PIV5) WR isolate was determined. We investigated the basis by which point mutations affect fusion in PIV5 isolates W3A and WR, which differ by two residues in the F ectodomain. The P22 stabilizing site acts through a local conformational change and a hydrophobic pocket interaction, whereas the S443 destabilizing site appears sensitive to both conformational effects and amino acid charge/polarity changes.
PMID: 25589638 [PubMed - indexed for MEDLINE]
Prolactin: a versatile regulator of inflammation and autoimmune pathology.
Autoimmun Rev. 2015 Mar;14(3):223-30
Authors: Costanza M, Binart N, Steinman L, Pedotti R
Prolactin (PRL) has long been proposed as an immune-stimulating and detrimental factor in autoimmune disorders. However, recent findings have challenged this common view, showing that PRL does not play a crucial role in the development of experimental autoimmune encephalomyelitis, animal model for multiple sclerosis (MS), and even protects against adjuvant-induced model of rheumatoid arthritis (RA). In this review we provide a critical overview of data supporting a role for PRL in the regulation of immune responses. In addition, we focus on studies exploring the involvement of PRL in autoimmune diseases, such as systemic lupus erythematosus, MS and RA, in light of the recently-outlined regenerative properties of this hormone.
PMID: 25462579 [PubMed - indexed for MEDLINE]
Distinct patterns of B-cell activation and priming by natural influenza virus infection versus inactivated influenza vaccination.
J Infect Dis. 2015 Apr 1;211(7):1051-9
Authors: He XS, Holmes TH, Sanyal M, Albrecht RA, García-Sastre A, Dekker CL, Davis MM, Greenberg HB
BACKGROUND: The human B-cell response to natural influenza virus infection has not been extensively investigated at the polyclonal level.
METHODS: The overall B-cell response of patients acutely infected with the 2009 pandemic influenza A(H1N1)pdm09 virus (A[H1N1]pdm09) was analyzed by determining the reactivity of plasmablast-derived polyclonal antibodies (PPAbs) to influenza proteins. Recipients of inactivated influenza vaccine containing the same A(H1N1)pdm09 strain were studied for comparison.
RESULTS: During acute infection, robust plasmablast responses to the infecting virus were detected, characterized by a greater PPAb reactivity to the conserved influenza virus nuclear protein and to heterovariant and heterosubtypic hemagglutinins, in comparison to responses to the inactivated A(H1N1)pdm09 vaccine. In A(H1N1)pdm09 vaccinees, the presence of baseline serum neutralizing antibodies against A(H1N1)pdm09, suggesting previous exposure to natural A(H1N1)pdm09 infection, did not affect the plasmablast response to vaccination, whereas repeated immunization with inactivated A(H1N1)pdm09 vaccine resulted in significantly reduced vaccine-specific and cross-reactive PPAb responses.
CONCLUSIONS: Natural A(H1N1)pdm09 infection and inactivated A(H1N1)pdm09 vaccination result in very distinct patterns of B-cell activation and priming. These differences are likely to be associated with differences in protective immunity, especially cross-protection against heterovariant and heterosubtypic influenza virus strains.
PMID: 25336731 [PubMed - indexed for MEDLINE]
Pulmonary hypertensive crisis following ethanol sclerotherapy for a complex vascular malformation.
J Perinatol. 2014 Sep;34(9):713-5
Authors: Cordero-Schmidt G, Wallenstein MB, Ozen M, Shah NA, Jackson E, Hovsepian DM, Palma JP
Anhydrous ethanol is a commonly used sclerotic agent for treating vascular malformations. We describe the case of a full-term 15-day-old female with a complex venolymphatic malformation involving the face and orbit. During treatment of the lesion with ethanol sclerotherapy, she suffered acute pulmonary hypertensive crisis. We discuss the pathophysiology of pulmonary hypertension related to ethanol sclerotherapy, and propose that hemolysis plays a significant role. Recommendations for evaluation, monitoring and management of this complication are also discussed.
PMID: 25179381 [PubMed - indexed for MEDLINE]
Increased coupling of intrinsic networks in remitted depressed youth predicts rumination and cognitive control.
PLoS One. 2014;9(8):e104366
Authors: Jacobs RH, Jenkins LM, Gabriel LB, Barba A, Ryan KA, Weisenbach SL, Verges A, Baker AM, Peters AT, Crane NA, Gotlib IH, Zubieta JK, Phan KL, Langenecker SA, Welsh RC
OBJECTIVE: Functional connectivity MRI (fcMRI) studies of individuals currently diagnosed with major depressive disorder (MDD) document hyperconnectivities within the default mode network (DMN) and between the DMN and salience networks (SN) with regions of the cognitive control network (CCN). Studies of individuals in the remitted state are needed to address whether effects derive from trait, and not state or chronic burden features of MDD.
METHOD: fcMRI data from two 3.0 Tesla GE scanners were collected from 30 unmedicated (47% medication naïve) youth (aged 18-23, modal depressive episodes = 1, mean age of onset = 16.2, SD = 2.6) with remitted MDD (rMDD; modal years well = 4) and compared with data from 23 healthy controls (HCs) using four bilateral seeds in the DMN and SN (posterior cingulate cortex (PCC), subgenual anterior cingulate (sgACC), and amygdala), followed by voxel-based comparisons of the whole brain.
RESULTS: Compared to HCs, rMDD youth exhibited hyperconnectivities from both PCC and sgACC seeds with lateral, parietal, and frontal regions of the CCN, extending to the dorsal medial wall. A factor analysis reduced extracted data and a PCC factor was inversely correlated with rumination among rMDD youth. Two factors from the sgACC hyperconnectivity clusters were related to performance in cognitive control on a Go/NoGo task, one positively and one inversely.
CONCLUSIONS: Findings document hyperconnectivities of the DMN and SN with the CCN (BA 8/10), which were related to rumination and sustained attention. Given these cognitive markers are known predictors of response and relapse, hyperconnectivities may increase relapse risk or represent compensatory mechanisms.
PMID: 25162661 [PubMed - indexed for MEDLINE]
Simulated cytoskeletal collapse via tau degradation.
PLoS One. 2014;9(8):e104965
Authors: Sendek A, Fuller HR, Hayre NR, Singh RR, Cox DL
We present a coarse-grained two dimensional mechanical model for the microtubule-tau bundles in neuronal axons in which we remove taus, as can happen in various neurodegenerative conditions such as Alzheimers disease, tauopathies, and chronic traumatic encephalopathy. Our simplified model includes (i) taus modeled as entropic springs between microtubules, (ii) removal of taus from the bundles due to phosphorylation, and (iii) a possible depletion force between microtubules due to these dissociated phosphorylated taus. We equilibrate upon tau removal using steepest descent relaxation. In the absence of the depletion force, the transverse rigidity to radial compression of the bundles falls to zero at about 60% tau occupancy, in agreement with standard percolation theory results. However, with the attractive depletion force, spring removal leads to a first order collapse of the bundles over a wide range of tau occupancies for physiologically realizable conditions. While our simplest calculations assume a constant concentration of microtubule intercalants to mediate the depletion force, including a dependence that is linear in the detached taus yields the same collapse. Applying percolation theory to removal of taus at microtubule tips, which are likely to be the protective sites against dynamic instability, we argue that the microtubule instability can only obtain at low tau occupancy, from 0.06-0.30 depending upon the tau coordination at the microtubule tips. Hence, the collapse we discover is likely to be more robust over a wide range of tau occupancies than the dynamic instability. We suggest in vitro tests of our predicted collapse.
PMID: 25162587 [PubMed - indexed for MEDLINE]
Fluorescent imaging of cancerous tissues for targeted surgery.
Adv Drug Deliv Rev. 2014 Sep 30;76:21-38
Authors: Bu L, Shen B, Cheng Z
To maximize tumor excision and minimize collateral damage are the primary goals of cancer surgery. Emerging molecular imaging techniques have made "image-guided surgery" developed into "molecular imaging-guided surgery", which is termed as "targeted surgery" in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling "targeted surgery" to be a component of "targeted therapy". Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields.
PMID: 25064553 [PubMed - indexed for MEDLINE]
Structural remodeling of coronary resistance arteries: effects of age and exercise training.
J Appl Physiol (1985). 2014 Sep 15;117(6):616-23
Authors: Hanna MA, Taylor CR, Chen B, La HS, Maraj JJ, Kilar CR, Behnke BJ, Delp MD, Muller-Delp JM
Age is known to induce remodeling and stiffening of large-conduit arteries; however, little is known of the effects of age on remodeling and mechanical properties of coronary resistance arteries. We employed a rat model of aging to investigate whether 1) age increases wall thickness and stiffness of coronary resistance arteries, and 2) exercise training reverses putative age-induced increases in wall thickness and stiffness of coronary resistance arteries. Young (4 mo) and old (21 mo) Fischer 344 rats remained sedentary or underwent 10 wk of treadmill exercise training. Coronary resistance arteries were isolated for determination of wall-to-lumen ratio, effective elastic modulus, and active and passive responses to changes in intraluminal pressure. Elastin and collagen content of the vascular wall were assessed histologically. Wall-to-lumen ratio increased with age, but this increase was reversed by exercise training. In contrast, age reduced stiffness, and exercise training increased stiffness in coronary resistance arteries from old rats. Myogenic responsiveness was reduced with age and restored by exercise training. Collagen-to-elastin ratio (C/E) of the wall did not change with age and was reduced with exercise training in arteries from old rats. Thus age induces hypertrophic remodeling of the vessel wall and reduces the stiffness and myogenic function of coronary resistance arteries. Exercise training reduces wall-to-lumen ratio, increases wall stiffness, and restores myogenic function in aged coronary resistance arteries. The restorative effect of exercise training on myogenic function of coronary resistance arteries may be due to both changes in vascular smooth muscle phenotype and expression of extracellular matrix proteins.
PMID: 25059239 [PubMed - indexed for MEDLINE]
Social regulation of cortisol receptor gene expression.
J Exp Biol. 2014 Sep 15;217(Pt 18):3221-8
Authors: Korzan WJ, Grone BP, Fernald RD
In many social species, individuals influence the reproductive capacity of conspecifics. In a well-studied African cichlid fish species, Astatotilapia burtoni, males are either dominant (D) and reproductively competent or non-dominant (ND) and reproductively suppressed as evidenced by reduced gonadotropin releasing hormone (GnRH1) release, regressed gonads, lower levels of androgens and elevated levels of cortisol. Here, we asked whether androgen and cortisol levels might regulate this reproductive suppression. Astatotilapia burtoni has four glucocorticoid receptors (GR1a, GR1b, GR2 and MR), encoded by three genes, and two androgen receptors (ARα and ARβ), encoded by two genes. We previously showed that ARα and ARβ are expressed in GnRH1 neurons in the preoptic area (POA), which regulates reproduction, and that the mRNA levels of these receptors are regulated by social status. Here, we show that GR1, GR2 and MR mRNAs are also expressed in GnRH1 neurons in the POA, revealing potential mechanisms for both androgens and cortisol to influence reproductive capacity. We measured AR, MR and GR mRNA expression levels in a microdissected region of the POA containing GnRH1 neurons, comparing D and ND males. Using quantitative PCR (qPCR), we found D males had higher mRNA levels of ARα, MR, total GR1a and GR2 in the POA compared with ND males. In contrast, ND males had significantly higher levels of GR1b mRNA, a receptor subtype with a reduced transcriptional response to cortisol. Through this novel regulation of receptor type, neurons in the POA of an ND male will be less affected by the higher levels of cortisol typical of low status, suggesting GR receptor type change as a potential adaptive mechanism to mediate high cortisol levels during social suppression.
PMID: 25013108 [PubMed - indexed for MEDLINE]
Tetralogy of Fallot: aorto-pulmonary collaterals and pulmonary arteries have distinctly different transcriptomes.
Pediatr Res. 2014 Oct;76(4):341-6
Authors: Ma X, Barboza LA, Siyahian A, Reinhartz O, Maeda K, Reddy VM, Hanley FL, Riemer RK
BACKGROUND: Tetralogy of Fallot patients with pulmonary atresia (TOF/PA) present a pulmonary blood supply directly from aortic collateral arteries. Major aorto-pulmonary collateral arteries (MAPCAs) present substantial clinical and surgical management challenges. Surgical operations to reestablish and promote further development of a pulmonary arterial connection preferentially utilize MAPCAs for reconstruction of central pulmonary arteries. However, the propensity of some MAPCAs to develop stenosis rather than growth may impair the response to reconstructions.
METHODS: Probe sets prepared from MAPCAs, PA, and aorta mRNA were used to interrogate human genome microarrays. We compared expression differences between pairs of the three vessels to determine whether MAPCAs display distinct expression patterns.
RESULTS: Functional clustering analysis identified differences in gene expression, which were further analyzed by gene ontology classification. A subset of highly regulated genes was validated using quantitative PCR. Expression differences among vessel types were observed for multiple gene classes. Of note, we observed that MAPCAs differentially express several genes at much higher levels than either PA or aorta.
CONCLUSION: MAPCAs differ from PA or aorta by significantly altered levels in gene expression, suggesting a transcriptional basis for their physiology that will guide a further understanding of the pathobiology of MAPCAs and TOF.
PMID: 25000348 [PubMed - indexed for MEDLINE]
Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape.
Genome Res. 2014 Sep;24(9):1504-16
Authors: Camp JG, Frank CL, Lickwar CR, Guturu H, Rube T, Wenger AM, Chen J, Bejerano G, Crawford GE, Rawls JF
Microbiota regulate intestinal physiology by modifying host gene expression along the length of the intestine, but the underlying regulatory mechanisms remain unresolved. Transcriptional specificity occurs through interactions between transcription factors (TFs) and cis-regulatory regions (CRRs) characterized by nucleosome-depleted accessible chromatin. We profiled transcriptome and accessible chromatin landscapes in intestinal epithelial cells (IECs) from mice reared in the presence or absence of microbiota. We show that regional differences in gene transcription along the intestinal tract were accompanied by major alterations in chromatin accessibility. Surprisingly, we discovered that microbiota modify host gene transcription in IECs without significantly impacting the accessible chromatin landscape. Instead, microbiota regulation of host gene transcription might be achieved by differential expression of specific TFs and enrichment of their binding sites in nucleosome-depleted CRRs near target genes. Our results suggest that the chromatin landscape in IECs is preprogrammed by the host in a region-specific manner to permit responses to microbiota through binding of open CRRs by specific TFs.
PMID: 24963153 [PubMed - indexed for MEDLINE]
The first metabolic and bariatric surgery accreditation and quality improvement program quality initiative: decreasing readmissions through opportunities provided.
Surg Obes Relat Dis. 2014 May-Jun;10(3):377-8
Authors: Morton J
PMID: 24951058 [PubMed - indexed for MEDLINE]
Reentry device aided endovascular aneurysm repair in patients with abdominal aortic aneurysm and unilateral iliac artery occlusion.
Ann Vasc Surg. 2014 Oct;28(7):1800.e1-7
Authors: Varu VN, Lee GK, Chang S, Lee JT
BACKGROUND: We report 2 cases of patients undergoing endovascular aneurysm repair (EVAR) using reentry devices to recanalize unilateral iliac artery occlusions and complete a bifurcated endovascular repair.
METHODS: Patient 1 is a 70-year-old male with an enlarging 6.5-cm abdominal aortic aneurysm (AAA) and disabling left leg claudication with L external iliac occlusion with patent common and internal iliac arteries. Patient 2 is a 67-year-old male with an asymptomatic 4.0-cm AAA and L iliac chronic total occlusion (CTO) and disabling claudication. Both patients were poor operative candidates for open repair.
RESULTS: Both patients underwent elective percutaneous EVAR along with left iliac artery revascularization. Initial angiography in both cases showed a blind ending of the left common iliac artery. Retrograde subintimal dissection through the occluded iliac segment was attempted but in both cases the wire was unable to traverse back into the true aortic lumen. Using either the Outback LTD or Pioneer reentry catheter, direct visualization of the true aortic lumen was obtained to re-enter the true lumen. The subintimal iliac tract was then predilated to facilitate routine EVAR in both cases. Both patients were discharged the following day and 1-year and 6-month follow-up imaging revealed aneurysm exclusion, no endoleak, and patent bilateral common iliac arteries with resolution of claudication symptoms and normal ankle-brachial indexes. The previously patent internal iliac artery was preserved.
CONCLUSIONS: While not always technically possible, reentry device aided EVAR is safe, feasible, and durable in the mid-term and avoids the morbidity and mortality related to aortouniiliac/femoral-femoral bypass and open repair. This technique should be considered in patients with iliac artery CTO and concurrent AAA to allow total endovascular repair.
PMID: 24911810 [PubMed - indexed for MEDLINE]
Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes.
Cardiovasc Res. 2014 Jul 15;103(2):291-303
Authors: Ferreira Tojais N, Peghaire C, Franzl N, Larrieu-Lahargue F, Jaspard B, Reynaud A, Moreau C, Couffinhal T, Duplàa C, Dufourcq P
AIMS: Vascular permeability is essential for the health of normal tissues and is an important characteristic of many disease states. The role of the Wnt/frizzled pathway in vascular biology has recently been reported. The objectives of this study are to analyse the role of Frizzled7 (Fzd7) receptor in the control of vascular integrity.
METHODS AND RESULTS: Fzd7 is expressed in endothelial cells and accumulates at the points of cell-cell contact in association with VE-cadherin and β-catenin, two major adherens junction molecules. To selectively delete fzd7 in the vasculature, we developed gene targeting approaches using CreLox strategy in mice. Genetic fzd7 inhibition in the endothelium increases vascular permeability in basal and factor-induced conditions. On the cellular level, fzd7 knockdown or depletion leads to an increase in paracellular permeability with a loss of adherens junction organization. These impairments are associated with a decrease in both VE-Cadherin and β-catenin expression, a decrease in their association and an increase of tyrosine phosphorylation of VE-cadherin/β-catenin. Fzd7 transduces a Wnt/β-catenin signalling cascade that is required to regulate β-catenin and canonical target gene expression. Finally, LiCl, a GSK3 inhibitor, and β-catenin overexpression rescued endothelial integrity and adherens junction organization, induced by fzd7 deletion.
CONCLUSION: These findings establish that Fzd7 is a new partner of adherens junctional complex and represents a novel molecular switch for the control of vascular permeability via activation of the Wnt-canonical pathway.
PMID: 24866384 [PubMed - indexed for MEDLINE]
Communication about social status.
Curr Opin Neurobiol. 2014 Oct;28:1-4
Authors: Fernald RD
Dominance hierarchies are ubiquitous in social species and serve to organize social systems. Social and sexual status is communicated directly among animals via sensory systems evolved in the particular species. Such signals may be chemical, visual, auditory, postural or a combination of signals. In most species, status is initially established through physical conflict between individuals that leads to ritualized conflict or threats, reducing possibly dangerous results of fighting. Many of the status signals contain other information, as in some bird species that communicate both the size of their group and their individual rank vocally. Recent studies have shown that scent signaling among hyenas of east Africa is unique, being produced by fermentative, odor producing bacteria residing in the scent glands.
PMID: 24793315 [PubMed - indexed for MEDLINE]
House calls by community health workers and public health nurses to improve adherence to isoniazid monotherapy for latent tuberculosis infection: a retrospective study.
BMC Public Health. 2013;13:894
Authors: Chang AH, Polesky A, Bhatia G
BACKGROUND: Patient adherence to isoniazid (INH) monotherapy for latent tuberculosis infection (LTBI) has been suboptimal despite its proven efficacy. Various strategies have been studied to improve adherence, but all have been based at a clinic or treatment program. At the Santa Clara Valley Tuberculosis Clinic, it was our practice to refer a subset of high-risk LTBI patients to the Public Health Department for monthly follow-up at home instead of at the clinic. Our goal was to assess whether house calls by community health workers and public health nurses affected INH adherence or frequency of adverse effects.
METHODS: We retrospectively studied 3918 LTBI patients who received INH. At the discretion of the treating physician, 986 (25.2%) received house calls instead of clinic follow-up. Home-based follow-up included language translation, medication delivery, assessment of compliance with pill counts, monitoring for adverse effects, and active tracking of noncompliant patients. We assessed differences in patient characteristics, treatment completion, and reasons for treatment discontinuation between patients followed at home versus in the clinic. Multivariate analyses to address possible referral bias or confounding were performed using logistic regression.
RESULTS: More patients followed with house calls completed INH treatment (90% home versus 73.2% clinic). This was the case across all subgroups of patients, including those with historically the lowest adherence: patients from correctional and rehabilitation facilities (77.8% home versus 46.9% clinic), postpartum women (86.4% home versus 55.6% clinic), and patients aged between 18 and 35 years (87% home versus 63.1% clinic). After adjusting for age, place of birth, referral category (TB contacts/skin test converters, correctional/rehabilitation patients, postpartum women, tuberculin positive patients from other screening), and prescribed INH regimen duration (9 versus 6 months), home-based follow-up of LTBI patients was a significant predictor of treatment completion (AOR 2.94, 95% CI: 2.33, 3.71). Patients followed at home were 21% more likely to complete therapy (ARR 1.21, p<0.001). Risk of adverse effects was similar between the two types of follow-up.
CONCLUSION: Home-based follow-up of LTBI patients taking isoniazid was associated with improved treatment completion and no increase in adverse effects regardless of patient characteristics or prescribed duration of INH therapy.
PMID: 24073620 [PubMed - indexed for MEDLINE]
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