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- The Microtubule Plus-End Tracking Proteins SPR1 and EB1b Interact to Maintain Polar Cell Elongation and Directional Organ Growth in Arabidopsis.Galva C, Kirik V, Lindeboom JJ, Kaloriti D, Rancour DM, Hussey PJ, Bednarek SY, Ehrhardt DW, Sedbrook JCPlant Cell
- Social disparities in heart disease risk and survivor bias among autoworkers: an examination based on survival models and g-estimation.Costello S, Picciotto S, Rehkopf DH, Eisen EAOccup Environ Med
- Feather development genes and associated regulatory innovation predate the origin of Dinosauria.Lowe CB, Clarke JA, Baker AJ, Haussler D, Edwards SVMol Biol Evol
- Toward structural femtosecond chemical dynamics: imaging chemistry in space and time.Minitti MP, Budarz JM, Kirrander A, Robinson J, Lane TJ, Ratner D, Saita K, Northey T, Stankus B, Cofer-Shabica V, Hastings J, Weber PMFaraday Discuss
- Contribution of shared environmental factors to familial aggregation of common cancers: an adoption study in Sweden.Sundquist K, Sundquist J, Ji JEur J Cancer Prev
- Ultrasound-Guided Musculoskeletal Interventions in American Football: 18 Years of Experience.Dave RB, Stevens KJ, Shivaram GM, McAdams TR, Dillingham MF, Beaulieu CFAJR Am J Roentgenol
- Posttraumatic Stress Disorder and Risk of Spontaneous Preterm Birth.Shaw JG, Asch SM, Kimerling R, Frayne SM, Shaw KA, Phibbs CSObstet Gynecol
- Pregnancy Outcomes in the Super Obese, Stratified by Weight Gain Above and Below Institute of Medicine Guidelines.Swank ML, Marshall NE, Caughey AB, Main EK, Gilbert WM, Melsop KA, Chung JHObstet Gynecol
- Grafting the Alar Rim: Application as Anatomical Graft.Gruber RP, Fox P, Peled A, Belek KAPlast Reconstr Surg
- The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis.Westhorpe FG, Straight AFCold Spring Harb Perspect Biol
- The IPD and IMGT/HLA database: allele variant databases.Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SGNucleic Acids Res
- Advances in skin grafting and treatment of cutaneous wounds.Sun BK, Siprashvili Z, Khavari PAScience
- Digoxin and Risk of Death in Adults with Atrial Fibrillation: The ATRIA-CVRN Study.Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, Borowsky LH, Harrison TN, Singer DE, Go ASCirc Arrhythm Electrophysiol
- Optical Coherence Tomography Study of Retinal Changes in Normal Aging and after Ischemia.Shariati MA, Ho JK, Liao YJInvest Ophthalmol Vis Sci
- DNA Copy Number Variants of Known Glaucoma Genes in Relation to Primary Open-Angle Glaucoma.Liu Y, Garrett ME, Yaspan BL, Cooke Bailey JN, Loomis SJ, Brilliant M, Budenz DL, Christen WG, Fingert J, Gaasterland D, Gaasterland T, Kang JH, Lee RK, Lichter PR, Moroi SE, Realini T, Richards J, Schuman JS, Scott WK, Singh K, Sit AJ, Vollrath D, Weinreb RN, Wollstein G, Zack DJ, Zhang K, Pericak-Vance M, Haines JL, Pasquale LR, Wiggs JL, Allingham RR, Ashley-Koch A, Hauser MAInvest Ophthalmol Vis Sci
- HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya.Kantor R, DeLong A, Balamane M, Schreier L, Lloyd RM, Injera W, Kamle L, Mambo F, Muyonga S, Katzenstein D, Hogan J, Buziba N, Diero LJ Int AIDS Soc
- Elective ceasarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial.Cho Y, Carvalho B, Butwick A, Blumenfeld Y, Riley EBJOG
- Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells.Duscher D, Rennert RC, Januszyk M, Anghel E, Maan ZN, Whittam AJ, Perez MG, Kosaraju R, Hu MS, Walmsley GG, Atashroo D, Khong S, Butte AJ, Gurtner GCSci Rep
- Contouring variations and the role of atlas in non-small cell lung cancer radiation therapy: Analysis of a multi-institutional preclinical trial planning study.Cui Y, Chen W, Kong FM, Olsen LA, Beatty RE, Maxim PG, Ritter T, Sohn JW, Higgins J, Galvin JM, Xiao YPract Radiat Oncol
- Comparison of the transcriptional landscapes between human and mouse tissues.Lin S, Lin Y, Nery JR, Urich MA, Breschi A, Davis CA, Dobin A, Zaleski C, Beer MA, Chapman WC, Gingeras TR, Ecker JR, Snyder MPProc Natl Acad Sci U S A
- Screw Size and Insertion Technique Compared With Removal Rates for Calcaneal Displacement Osteotomies.Lucas DE, Simpson GA, Berlet GC, Philbin TM, Smith JLFoot Ankle Int
- Childhood Trauma Exposure Disrupts the Automatic Regulation of Emotional Processing.Marusak HA, Martin KR, Etkin A, Thomason MENeuropsychopharmacology
- Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations.Ohgami RS, Ma L, Merker JD, Gotlib JR, Schrijver I, Zehnder JL, Arber DAMod Pathol
The Microtubule Plus-End Tracking Proteins SPR1 and EB1b Interact to Maintain Polar Cell Elongation and Directional Organ Growth in Arabidopsis.
Plant Cell. 2014 Nov 18;
Authors: Galva C, Kirik V, Lindeboom JJ, Kaloriti D, Rancour DM, Hussey PJ, Bednarek SY, Ehrhardt DW, Sedbrook JC
The microtubule plus-end tracking proteins (+TIPs) END BINDING1b (EB1b) and SPIRAL1 (SPR1) are required for normal cell expansion and organ growth. EB proteins are viewed as central regulators of +TIPs and cell polarity in animals; SPR1 homologs are specific to plants. To explore if EB1b and SPR1 fundamentally function together, we combined genetic, biochemical, and cell imaging approaches in Arabidopsis thaliana. We found that eb1b-2 spr1-6 double mutant roots exhibit substantially more severe polar expansion defects than either single mutant, undergoing right-looping growth and severe axial twisting instead of waving on tilted hard-agar surfaces. Protein interaction assays revealed that EB1b and SPR1 bind each other and tubulin heterodimers, which is suggestive of a microtubule loading mechanism. EB1b and SPR1 show antagonistic association with microtubules in vitro. Surprisingly, our combined analyses revealed that SPR1 can load onto microtubules and function independently of EB1 proteins, setting SPR1 apart from most studied +TIPs in animals and fungi. Moreover, we found that the severity of defects in microtubule dynamics in spr1 eb1b mutant hypocotyl cells correlated well with the severity of growth defects. These data indicate that SPR1 and EB1b have complex interactions as they load onto microtubule plus ends and direct polar cell expansion and organ growth in response to directional cues.
PMID: 25415978 [PubMed - as supplied by publisher]
Social disparities in heart disease risk and survivor bias among autoworkers: an examination based on survival models and g-estimation.
Occup Environ Med. 2014 Nov 21;
Authors: Costello S, Picciotto S, Rehkopf DH, Eisen EA
OBJECTIVES: To examine gender and racial disparities in ischaemic heart disease (IHD) mortality related to metalworking fluid exposures and in the healthy worker survivor effect.
METHODS: A cohort of white and black men and women autoworkers in the USA was followed from 1941 to 1995 with quantitative exposure to respirable particulate matter from water-based metalworking fluids. Separate analyses used proportional hazards models and g-estimation.
RESULTS: The HR for IHD among black men was 3.29 (95% CI 1.49 to 7.31) in the highest category of cumulative synthetic fluid exposure. The HR for IHD among white women exposed to soluble fluid reached 2.44 (95% CI 0.96 to 6.22). However, no increased risk was observed among white men until we corrected for the healthy worker survivor effect. Results from g-estimation indicate that if white male cases exposed to soluble or synthetic fluid had been unexposed to that fluid type, then 1.59 and 1.20 years of life would have been saved on average, respectively.
CONCLUSIONS: We leveraged the strengths of two different analytic approaches to examine the IHD risks of metalworking fluids. All workers may have the same aetiological risk; however, black and female workers may experience more IHD from water-based metalworking fluid exposure because of a steeper exposure-response or weaker healthy worker survivor effect.
PMID: 25415971 [PubMed - as supplied by publisher]
Feather development genes and associated regulatory innovation predate the origin of Dinosauria.
Mol Biol Evol. 2014 Nov 18;
Authors: Lowe CB, Clarke JA, Baker AJ, Haussler D, Edwards SV
The evolution of avian feathers have recently been illuminated by fossils and the identification of genes involved in feather patterning and morphogenesis. However, molecular studies have focused mainly on protein-coding genes. Using comparative genomics and more than 600,000 conserved regulatory elements, we show that patterns of genome evolution in the vicinity of feather genes are consistent with a major role for regulatory innovation in the evolution of feathers. Rates of innovation at feather regulatory elements exhibit an extended period of innovation with peaks in the ancestors of amniotes and archosaurs. We estimate that 86% of such regulatory elements were present prior to the origin of Dinosauria. On the branch leading to modern birds, we detect a strong signal of regulatory innovation near IGFBP2 and IGFBP5, which have roles in body size reduction, and may represent a genomic signature for the miniaturization of dinosaurian body size preceding the origin of flight.
PMID: 25415961 [PubMed - as supplied by publisher]
Toward structural femtosecond chemical dynamics: imaging chemistry in space and time.
Faraday Discuss. 2014 Dec 19;171:81-91
Authors: Minitti MP, Budarz JM, Kirrander A, Robinson J, Lane TJ, Ratner D, Saita K, Northey T, Stankus B, Cofer-Shabica V, Hastings J, Weber PM
We aim to observe a chemical reaction in real time using gas-phase X-ray diffraction. In our initial experiment at the Linac Coherent Light Source (LCLS), we investigated the model system 1,3-cyclohexadiene (CHD) at very low vapor pressures. This reaction serves as a benchmark for numerous transformations in organic synthesis and natural product biology. Excitation of CHD by an ultraviolet optical pulse initiates an electrocyclic reaction that transforms the closed ring system into the open-chain structure of 1,3,5-hexatriene. We describe technical points of the experimental method and present first results. We also outline an approach to analyze the data involving nonlinear least-square optimization routines that match the experimental observations with predicted diffraction patterns calculated from trajectories for nonadiabatic vibronic wave packets.
PMID: 25415842 [PubMed - as supplied by publisher]
Contribution of shared environmental factors to familial aggregation of common cancers: an adoption study in Sweden.
Eur J Cancer Prev. 2014 Nov 20;
Authors: Sundquist K, Sundquist J, Ji J
Cancer runs in families, suggesting a heritable component, but the contribution of environmental factors cannot be neglected. Studies on spousal risk can partly disentangle the environmental contribution but miss shared environmental factors during childhood and adolescence. Here, we examined the familial aggregation of common cancers among 80 281 Swedish-born adoptees, identified from the national Swedish Multigeneration Register, and linked them to the Swedish Cancer Registry. Standardized incidence ratios (SIRs) were calculated for common cancers (colorectal, lung, breast, prostate, and skin cancers) in the adoptees whose adoptive parents were diagnosed with concordant cancers, compared with the general population. SIRs in adoptees with an affected adoptive parent ranged from 1.00 (breast cancer) to 1.28 (skin cancer), whereas the SIRs in nonadoptees with an affected parent ranged from 1.63 (colorectal cancer) to 2.12 (skin cancer). Environmental factors account for around 0-28% of the familial aggregation. Cancer sites with high environmental contributions were observed for skin and colorectal cancers, which are known to have strong environmental causes.
PMID: 25415834 [PubMed - as supplied by publisher]
Ultrasound-Guided Musculoskeletal Interventions in American Football: 18 Years of Experience.
AJR Am J Roentgenol. 2014 Dec;203(6):W674-W683
Authors: Dave RB, Stevens KJ, Shivaram GM, McAdams TR, Dillingham MF, Beaulieu CF
OBJECTIVE. Myotendinous strains, contusions, and hematomas are common injuries in American football. Along with ligament sprains and inflammatory disorders, musculoskeletal injuries often result in lost participation time. This article summarizes 18 years of experience with 128 ultrasound-guided drainages and injections in 69 football players with 88 injuries. CONCLUSION. When performed by an operator with sufficient expertise in diagnostic and procedural skills, ultrasound-guided musculoskeletal interventions are minimally invasive, are safe, and can play an integral role in injury management.
PMID: 25415734 [PubMed - as supplied by publisher]
Posttraumatic Stress Disorder and Risk of Spontaneous Preterm Birth.
Obstet Gynecol. 2014 Dec;124(6):1111-1119
Authors: Shaw JG, Asch SM, Kimerling R, Frayne SM, Shaw KA, Phibbs CS
OBJECTIVE:: To evaluate the association between antenatal posttraumatic stress disorder (PTSD) and spontaneous preterm delivery.
METHODS:: We identified antenatal PTSD status and spontaneous preterm delivery in a retrospective cohort of 16,334 deliveries covered by the Veterans Health Administration from 2000 to 2012. We divided mothers with PTSD into those with diagnoses present the year before delivery (active PTSD) and those only with earlier diagnoses (historical PTSD). We identified spontaneous preterm birth and potential confounders including age, race, military deployment, twins, hypertension, substance use, depression, and results of military sexual trauma screening and then performed multivariate regression to estimate adjusted odds ratio (OR) of spontaneous preterm delivery as a function of PTSD status.
RESULTS:: Of 16,334 births, 3,049 (19%) were to mothers with PTSD diagnoses, of whom 1,921 (12%) had active PTSD. Spontaneous preterm delivery was higher in those with active PTSD (9.2%, n=176) than those with historical (8.0%, n=90) or no PTSD (7.4%, n=982) before adjustment (P=.02). The association between PTSD and preterm birth persisted, when adjusting for covariates, only in those with active PTSD (adjusted OR 1.35, 95% confidence interval [CI] 1.14-1.61). Analyses adjusting for comorbid psychiatric and medical diagnoses revealed the association with active PTSD to be robust.
CONCLUSION:: In this cohort, containing an unprecedented number of PTSD-affected pregnancies, mothers with active PTSD were significantly more likely to suffer spontaneous preterm birth with an attributable two excess preterm births per 100 deliveries (95% CI 1-4). Posttraumatic stress disorder's health effects may extend, through birth outcomes, into the next generation. LEVEL OF EVIDENCE:: II.
PMID: 25415162 [PubMed - as supplied by publisher]
Pregnancy Outcomes in the Super Obese, Stratified by Weight Gain Above and Below Institute of Medicine Guidelines.
Obstet Gynecol. 2014 Dec;124(6):1105-1110
Authors: Swank ML, Marshall NE, Caughey AB, Main EK, Gilbert WM, Melsop KA, Chung JH
OBJECTIVE:: To examine the association of antenatal weight gain above and below the 2009 Institute of Medicine (IOM) guidelines in the super-obese population (body mass index [BMI] of 50 or higher) on the maternal and neonatal morbidities of gestational hypertension or preeclampsia (pregnancy-induced hypertension), gestational diabetes mellitus, cesarean delivery, birth weight more than 4,000 g and more than 4,500 g, low birth weight, and preterm birth.
METHODS:: The effect of gestational weight gain was assessed in this retrospective cohort study using California birth certificate and patient discharge diagnosis data. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) as a function of antenatal weight gain. Weight gain within 2009 IOM guidelines (11-20 pounds) served as the reference group.
RESULTS:: The study population consisted of 1,034 women. Women gaining below, within, and above IOM guidelines accounted for 38.3, 23.5, and 38.2%, respectively. Weight gain below IOM guidelines was not associated with a statistically increased odds of preterm birth (OR 1.82, 95% CI 0.60-5.59) or low birth weight (OR 1.20, 95% CI 0.57-2.49); however, birth weight more than 4,000 g was significantly reduced (OR 0.50, 95% CI 0.32-0.77). Excessive weight gain statistically increased the odds of pregnancy-induced hypertension (OR 1.96, 95% CI 1.26-3.03) and cesarean delivery (OR 1.40, 95% CI 1.00-1.97) while not appearing to protect against the delivery of low-birth-weight neonates (OR 0.84, 95% CI 0.40-1.78).
CONCLUSION:: Weight gain below the current guidelines in the super-obese cohort is not associated with an increase in maternal or neonatal risk while decreasing the odds of delivering a macrosomic neonate. Women with BMIs of 50 or higher may warrant separate gestational weight gain recommendations. LEVEL OF EVIDENCE:: II.
PMID: 25415161 [PubMed - as supplied by publisher]
Grafting the Alar Rim: Application as Anatomical Graft.
Plast Reconstr Surg. 2014 Dec;134(6):880e-887e
Authors: Gruber RP, Fox P, Peled A, Belek KA
BACKGROUND:: Alar rim contour and alar rim grafts have become essential components of rhinoplasty. Ideally, grafts of the nose should be anatomical in shape. So doing might make grafts of the alar rim more robust. The authors considered doing that by applying the graft as a continuous extension of the lateral crus.
METHODS:: Twelve patients (two men and 10 women) constituted the study group (seven primary and five secondary cases). Of those, there were five concave rims, two concave rims with rim retraction, two boxy tips, and three cephalically oriented lateral crura. Surgical technique included the following: (1) an open approach was used; (2) a marginal incision that ignored the caudal margin of the lateral crus (the incision went straight posteriorly to a point 5 to 6 mm from the rim margin) was used; (3) a triangular graft was made to cover the exposed vestibular skin; (4) it was secured end to end to the caudal border of the lateral crus; and (5) the poster end was allowed to sit in a small subcutaneous pocket.
RESULTS:: Follow-up was 11 to 19 months. All 12 patients exhibited good rims as judged by a blinded panel. Rim retraction was not fully corrected in one patient, but no further treatment was required. One patient did require a secondary small rim graft for residual rim concavity.
CONCLUSIONS:: The concept of grafting the alar rim is strongly supported by the authors' results. The modifications the authors applied by designing the graft to be anatomical in shape has been a technical help.
CLINICAL QUESTION/LEVEL OF EVIDENCE:: Therapeutic, IV.
PMID: 25415110 [PubMed - as supplied by publisher]
The Centromere: Epigenetic Control of Chromosome Segregation during Mitosis.
Cold Spring Harb Perspect Biol. 2014 Nov 20;
Authors: Westhorpe FG, Straight AF
A fundamental challenge for the survival of all organisms is maintaining the integrity of the genome in all cells. Cells must therefore segregate their replicated genome equally during each cell division. Eukaryotic organisms package their genome into a number of physically distinct chromosomes, which replicate during S phase and condense during prophase of mitosis to form paired sister chromatids. During mitosis, cells form a physical connection between each sister chromatid and microtubules of the mitotic spindle, which segregate one copy of each chromatid to each new daughter cell. The centromere is the DNA locus on each chromosome that creates the site of this connection. In this review, we present a brief history of centromere research and discuss our current knowledge of centromere establishment, maintenance, composition, structure, and function in mitosis.
PMID: 25414369 [PubMed - as supplied by publisher]
The IPD and IMGT/HLA database: allele variant databases.
Nucleic Acids Res. 2014 Nov 20;
Authors: Robinson J, Halliwell JA, Hayhurst JD, Flicek P, Parham P, Marsh SG
The Immuno Polymorphism Database (IPD) was developed to provide a centralized system for the study of polymorphism in genes of the immune system. Through the IPD project we have established a central platform for the curation and publication of locus-specific databases involved either directly or related to the function of the Major Histocompatibility Complex in a number of different species. We have collaborated with specialist groups or nomenclature committees that curate the individual sections before they are submitted to IPD for online publication. IPD consists of five core databases, with the IMGT/HLA Database as the primary database. Through the work of the various nomenclature committees, the HLA Informatics Group and in collaboration with the European Bioinformatics Institute we are able to provide public access to this data through the website http://www.ebi.ac.uk/ipd/. The IPD project continues to develop with new tools being added to address scientific developments, such as Next Generation Sequencing, and to address user feedback and requests. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the immunogenetics community, and the wider research and clinical communities.
PMID: 25414341 [PubMed - as supplied by publisher]
Advances in skin grafting and treatment of cutaneous wounds.
Science. 2014 Nov 21;346(6212):941-5
Authors: Sun BK, Siprashvili Z, Khavari PA
The ability of the skin to repair itself after injury is vital to human survival and is disrupted in a spectrum of disorders. The process of cutaneous wound healing is complex, requiring a coordinated response by immune cells, hematopoietic cells, and resident cells of the skin. We review the classic paradigms of wound healing and evaluate how recent discoveries have enriched our understanding of this process. We evaluate current and experimental approaches to treating cutaneous wounds, with an emphasis on cell-based therapies and skin transplantation.
PMID: 25414301 [PubMed - in process]
Digoxin and Risk of Death in Adults with Atrial Fibrillation: The ATRIA-CVRN Study.
Circ Arrhythm Electrophysiol. 2014 Nov 20;
Authors: Freeman JV, Reynolds K, Fang M, Udaltsova N, Steimle A, Pomernacki NK, Borowsky LH, Harrison TN, Singer DE, Go AS
BACKGROUND: -Digoxin remains commonly used for rate control in atrial fibrillation, but very limited data exist supporting this practice and some studies have shown an association with adverse outcomes. We examined the independent association between digoxin and risks of death and hospitalization in adults with incident atrial fibrillation and no heart failure.
METHODS AND RESULTS: -We performed a retrospective cohort study of 14,787 age, gender and high-dimensional propensity score-matched adults with incident atrial fibrillation and no prior heart failure or digoxin use in the AnTicoagulation and Risk factors In Atrial fibrillation-Cardiovascular Research Network (ATRIA-CVRN) Study within Kaiser Permanente Northern and Southern California. We examined the independent association between newly initiated digoxin and the risks of death and hospitalization using extended Cox regression. During a median 1.17 (interquartile range 0.49-1.97) years of follow-up among matched patients with atrial fibrillation, incident digoxin use was associated with higher rates of death (8.3 vs. 4.9 per 100 person-years, P<0.001) and hospitalization (60.1 vs. 37.2 per 100 person-years, P<0.001). Incident digoxin use was independently associated with a 71% higher risk of death (hazard ratio [HR] 1.71, 95%CI:1.52-1.93) and a 63% higher risk of hospitalization (HR 1.63, 95%CI:1.56-1.71). Results were consistent in subgroups of age and gender and when using "intent-to-treat" or "on-treatment" analytic approaches.
CONCLUSIONS: -In adults with atrial fibrillation, digoxin use was independently associated with higher risks of death and hospitalization. Given other available rate control options, digoxin should be used with caution in the management of atrial fibrillation.
PMID: 25414270 [PubMed - as supplied by publisher]
Optical Coherence Tomography Study of Retinal Changes in Normal Aging and after Ischemia.
Invest Ophthalmol Vis Sci. 2014 Nov 20;
Authors: Shariati MA, Ho JK, Liao YJ
Purpose. Age-related thinning of the retinal ganglion cell axons in the nerve fiber layer has been measured in humans using optical coherence tomography (OCT). In this study, we used OCT to measure inner retinal changes in 3-months-, one-year, and two-year-old mice and after experimental anterior ischemic optic neuropathy (AION). Methods. We used OCT to quantify retinal thickness in over 200 eyes at different ages before and after photochemical thrombosis model of AION. The scans were manually or automatically segmented. Results. In normal aging, there was 1.3 µm thinning of the ganglion cell complex (GCC) between 3-months and 1-year (P < 0.0001) and no further thinning at 2-years. In studying age-related inner retinal changes, measurement of the GCC (circular scan) was superior to the total retinal thickness (posterior pole scan) despite the need for manual segmentation because it was not contaminated by outer retinal changes. Three-weeks after AION, there was 8.9 µm thinning of the GCC (circular scan; P < 0.0001) and 50 µm thinning of the optic disc (posterior pole scan; P < 0.0001), and 17 µm thinning of the retinae (posterior pole scan; P < 0.0001) in the 3 months-old group. Changes in the older eyes were similar to that of the 3-month-old group. Conclusions. OCT imaging of a large number eyes showed that, like humans, mice exhibited small, age-related inner retinal thinning. GCC was superior to quantify age-related changes after AION, and both circular and posterior pole scans were useful to track short-term changes after AION.
PMID: 25414186 [PubMed - as supplied by publisher]
DNA Copy Number Variants of Known Glaucoma Genes in Relation to Primary Open-Angle Glaucoma.
Invest Ophthalmol Vis Sci. 2014 Nov 20;
Authors: Liu Y, Garrett ME, Yaspan BL, Cooke Bailey JN, Loomis SJ, Brilliant M, Budenz DL, Christen WG, Fingert J, Gaasterland D, Gaasterland T, Kang JH, Lee RK, Lichter PR, Moroi SE, Realini T, Richards J, Schuman JS, Scott WK, Singh K, Sit AJ, Vollrath D, Weinreb RN, Wollstein G, Zack DJ, Zhang K, Pericak-Vance M, Haines JL, Pasquale LR, Wiggs JL, Allingham RR, Ashley-Koch A, Hauser MA
Purpose: To examine the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG). Methods: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non-blood derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥ 5kb in size and interrogated by ≥ 5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC. Results: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried aTBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls. Conclusions: CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.
PMID: 25414181 [PubMed - as supplied by publisher]
HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya.
J Int AIDS Soc. 2014;17(1):19262
Authors: Kantor R, DeLong A, Balamane M, Schreier L, Lloyd RM, Injera W, Kamle L, Mambo F, Muyonga S, Katzenstein D, Hogan J, Buziba N, Diero L
INTRODUCTION: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information.
METHODS: We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS-USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveSTTM-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance.
RESULTS: Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS.
CONCLUSIONS: In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.
PMID: 25413893 [PubMed - in process]
Elective ceasarean section at 38 weeks versus 39 weeks: neonatal and maternal outcomes in a randomised controlled trial.
BJOG. 2014 Dec;121(13):1748
Authors: Cho Y, Carvalho B, Butwick A, Blumenfeld Y, Riley E
PMID: 25413764 [PubMed - in process]
Aging disrupts cell subpopulation dynamics and diminishes the function of mesenchymal stem cells.
Sci Rep. 2014;4:7144
Authors: Duscher D, Rennert RC, Januszyk M, Anghel E, Maan ZN, Whittam AJ, Perez MG, Kosaraju R, Hu MS, Walmsley GG, Atashroo D, Khong S, Butte AJ, Gurtner GC
Advanced age is associated with an increased risk of vascular morbidity, attributable in part to impairments in new blood vessel formation. Mesenchymal stem cells (MSCs) have previously been shown to play an important role in neovascularization and deficiencies in these cells have been described in aged patients. Here we utilize single cell transcriptional analysis to determine the effect of aging on MSC population dynamics. We identify an age-related depletion of a subpopulation of MSCs characterized by a pro-vascular transcriptional profile. Supporting this finding, we demonstrate that aged MSCs are also significantly compromised in their ability to support vascular network formation in vitro and in vivo. Finally, aged MSCs are unable to rescue age-associated impairments in cutaneous wound healing. Taken together, these data suggest that age-related changes in MSC population dynamics result in impaired therapeutic potential of aged progenitor cells. These findings have critical implications for therapeutic cell source decisions (autologous versus allogeneic) and indicate the necessity of strategies to improve functionality of aged MSCs.
PMID: 25413454 [PubMed - in process]
Contouring variations and the role of atlas in non-small cell lung cancer radiation therapy: Analysis of a multi-institutional preclinical trial planning study.
Pract Radiat Oncol. 2014 Oct 30;
Authors: Cui Y, Chen W, Kong FM, Olsen LA, Beatty RE, Maxim PG, Ritter T, Sohn JW, Higgins J, Galvin JM, Xiao Y
PURPOSE: To quantify variations in target and normal structure contouring and evaluate dosimetric impact of these variations in non-small cell lung cancer (NSCLC) cases. To study whether providing an atlas can reduce potential variation.
METHODS AND MATERIALS: Three NSCLC cases were distributed sequentially to multiple institutions for contouring and radiation therapy planning. No segmentation atlas was provided for the first 2 cases (Case 1 and Case 2). Contours were collected from submitted plans and consensus contour sets were generated. The volume variation among institution contours and the deviation of them from consensus contours were analyzed. The dose-volume histograms for individual institution plans were recalculated using consensus contours to quantify the dosimetric changes. An atlas containing targets and critical structures was constructed and was made available when the third case (Case 3) was distributed for planning. The contouring variability in the submitted plans of Case 3 was compared with that in first 2 cases.
RESULTS: Planning target volume (PTV) showed large variation among institutions. The PTV coverage in institutions' plans decreased dramatically when reevaluated using the consensus PTV contour. The PTV contouring consistency did not show improvement with atlas use in Case 3. For normal structures, lung contours presented very good agreement, while the brachial plexus showed the largest variation. The consistency of esophagus and heart contouring improved significantly (t test; P < .05) in Case 3. Major factors contributing to the contouring variation were identified through a survey questionnaire.
CONCLUSIONS: The amount of contouring variations in NSCLC cases was presented. Its impact on dosimetric parameters can be significant. The segmentation atlas improved the contour agreement for esophagus and heart, but not for the PTV in this study. Quality assurance of contouring is essential for a successful multi-institutional clinical trial.
PMID: 25413413 [PubMed - as supplied by publisher]
Comparison of the transcriptional landscapes between human and mouse tissues.
Proc Natl Acad Sci U S A. 2014 Nov 20;
Authors: Lin S, Lin Y, Nery JR, Urich MA, Breschi A, Davis CA, Dobin A, Zaleski C, Beer MA, Chapman WC, Gingeras TR, Ecker JR, Snyder MP
Although the similarities between humans and mice are typically highlighted, morphologically and genetically, there are many differences. To better understand these two species on a molecular level, we performed a comparison of the expression profiles of 15 tissues by deep RNA sequencing and examined the similarities and differences in the transcriptome for both protein-coding and -noncoding transcripts. Although commonalities are evident in the expression of tissue-specific genes between the two species, the expression for many sets of genes was found to be more similar in different tissues within the same species than between species. These findings were further corroborated by associated epigenetic histone mark analyses. We also find that many noncoding transcripts are expressed at a low level and are not detectable at appreciable levels across individuals. Moreover, the majority lack obvious sequence homologs between species, even when we restrict our attention to those which are most highly reproducible across biological replicates. Overall, our results indicate that there is considerable RNA expression diversity between humans and mice, well beyond what was described previously, likely reflecting the fundamental physiological differences between these two organisms.
PMID: 25413365 [PubMed - as supplied by publisher]
Screw Size and Insertion Technique Compared With Removal Rates for Calcaneal Displacement Osteotomies.
Foot Ankle Int. 2014 Nov 20;
Authors: Lucas DE, Simpson GA, Berlet GC, Philbin TM, Smith JL
BACKGROUND: The calcaneal displacement osteotomy is frequently used by foot and ankle surgeons to correct hindfoot angular deformity. Headed compression screws are often used for this purpose, but a common complication is postoperative plantar heel pain from prominent hardware. We evaluated hardware removal rates after calcaneal displacement osteotomies and analyzed technical factors including screw size, position, and angle. We hypothesized that larger screws placed more plantarly would have been removed more frequently. We also believed that although 2 smaller screws cost more initially, when removal rates and cost are accounted for, savings would be demonstrated with this technique.
METHODS: We retrospectively collected data on type of fixation, cost of fixation, and frequency of removal. After exclusions we had 30 patients in our screw removal cohort and 119 in our screws retained cohort. A basic cost analysis and statistical analysis was performed.
RESULTS: The small screw group had a hardware removal rate of 9% (4/43) compared to 25% (26/104) of the larger screw group (P = .032). While the cost of 2 smaller screws is more than that of 1 larger screw, when the cost of removal and the rates of doing so are considered, the smaller screws resulted in substantial cost savings.
CONCLUSION: Technical considerations for the medial displacement calcaneal osteotomy, including the use of multiple smaller screws, provided for a lower rate of hardware removal and likely decreased long-term costs.
LEVEL OF EVIDENCE: Level III, comparative series.
PMID: 25413309 [PubMed - as supplied by publisher]
Childhood Trauma Exposure Disrupts the Automatic Regulation of Emotional Processing.
Neuropsychopharmacology. 2014 Nov 21;
Authors: Marusak HA, Martin KR, Etkin A, Thomason ME
Early life trauma is one of the strongest risk factors for later emotional psychopathology. While research in adults highlights that childhood trauma predicts deficits in emotion regulation that persist decades later, it is unknown if neural and behavioral changes that may precipitate illness are evident during formative, developmental years. The present study examined whether automatic regulation of emotional conflict is perturbed in a high-risk urban sample of trauma-exposed children and adolescents. 14 trauma-exposed and 16 age-, sex-, and IQ-matched comparison youth underwent functional MRI while performing an emotional conflict task that involved categorizing facial affect while ignoring an overlying emotion word. Engagement of the conflict regulation system was evaluated at neural and behavioral levels. Results showed that trauma-exposed youth failed to dampen dorsolateral prefrontal cortex activity and engage amygdala-pregenual cingulate inhibitory circuitry during the regulation of emotional conflict, and were less able to regulate emotional conflict. In addition, trauma-exposed youth showed greater conflict-related amygdala reactivity, which was associated with diminished levels of trait reward sensitivity. These data point to a trauma-related deficit in automatic regulation of emotional processing, and increase in sensitivity to emotional conflict in neural systems implicated in threat detection. Aberrant amygdala response to emotional conflict was related to diminished reward sensitivity, which is emerging as a critical stress-susceptibility trait that may contribute to the emergence of mental illness during adolescence. These results suggest that deficits in conflict regulation for emotional material may underlie heightened risk for psychopathology in individuals that endure early life trauma.Neuropsychopharmacology accepted article preview online, 21 November 2014. doi:10.1038/npp.2014.311.
PMID: 25413183 [PubMed - as supplied by publisher]
Next-generation sequencing of acute myeloid leukemia identifies the significance of TP53, U2AF1, ASXL1, and TET2 mutations.
Mod Pathol. 2014 Nov 21;
Authors: Ohgami RS, Ma L, Merker JD, Gotlib JR, Schrijver I, Zehnder JL, Arber DA
We assessed the frequency and clinicopathologic significance of 19 genes currently identified as significantly mutated in myeloid neoplasms, RUNX1, ASXL1, TET2, CEBPA, IDH1, IDH2, DNMT3A, FLT3, NPM1, TP53, NRAS, EZH2, CBL, U2AF1, SF3B1, SRSF2, JAK2, CSF3R, and SETBP1, across 93 cases of acute myeloid leukemia (AML) using capture target enrichment and next-generation sequencing. Of these cases, 79% showed at least one nonsynonymous mutation, and cases of AML with recurrent genetic abnormalities showed a lower frequency of mutations versus AML with myelodysplasia-related changes (P<0.001). Mutational analysis further demonstrated that TP53 mutations are associated with complex karyotype AML, whereas ASXL1 and U2AF1 mutations are associated with AML with myelodysplasia-related changes. Furthermore, U2AF1 mutations were specifically associated with trilineage morphologic dysplasia. Univariate analysis demonstrated that U2AF1 and TP53 mutations are associated with absence of clinical remission, poor overall survival (OS), and poor disease-free survival (DFS; P<0.0001), whereas TET2 and ASXL1 mutations are associated with poor OS (P<0.03). In multivariate analysis, U2AF1 and TP53 mutations retained independent prognostic significance in OS and DFS, respectively. Our results demonstrate unique relationships between mutations in AML, clinicopathologic prognosis, subtype categorization, and morphologic dysplasia.Modern Pathology advance online publication, 21 November 2014; doi:10.1038/modpathol.2014.160.
PMID: 25412851 [PubMed - as supplied by publisher]
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