Recent Stanford Publications in PubMed
- Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.Wang N, Rajasekaran N, Hou T, Macaubas C, Mellins EDPLoS One
- Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap.Nurnberg ST, Cheng K, Raiesdana A, Kundu R, Miller CL, Kim JB, Arora K, Carcamo-Oribe I, Xiong Y, Tellakula N, Nanda V, Murthy N, Boisvert WA, Hedin U, Perisic L, Aldi S, Maegdefessel L, Pjanic M, Owens GK, Tallquist MD, Quertermous TPLoS Genet
- Chemical Plausibility of Cu(III) with Biological Ligation in pMMO.Citek C, Gary JB, Wasinger EC, Stack TDJ Am Chem Soc
- Signature Patterns of MHC Diversity in Three Gombe Communities of Wild Chimpanzees Reflect Fitness in Reproduction and Immune Defense against SIVcpz.Wroblewski EE, Norman PJ, Guethlein LA, Rudicell RS, Ramirez MA, Li Y, Hahn BH, Pusey AE, Parham PPLoS Biol
- Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models.Karr JR, Williams AH, Zucker JD, Raue A, Steiert B, Timmer J, Kreutz C, DREAM8 Parameter Estimation Challenge Consortium, Wilkinson S, Allgood BA, Bot BM, Hoff BR, Kellen MR, Covert MW, Stolovitzky GA, Meyer PPLoS Comput Biol
- Predicting Cortical Dark/Bright Asymmetries from Natural Image Statistics and Early Visual Transforms.Cooper EA, Norcia AMPLoS Comput Biol
- Mycobacterium bovis Enterocolitis in An Immunocompromised Host.Winger BA, Foy E, Sud SR, MacKenzie JD, Pua HH, Lau AH, Heyman MB, Laszik Z, Tureen JJ Pediatr Gastroenterol Nutr
- Three-dimensional Dynamic Contrast-enhanced US Imaging for Early Antiangiogenic Treatment Assessment in a Mouse Colon Cancer Model.Wang H, Hristov D, Qin J, Tian L, Willmann JKRadiology
- High-Throughput Screening of Surface Marker Expression on Undifferentiated and Differentiated Human Adipose-Derived Stromal Cells.Walmsley GG, Atashroo DA, Maan ZN, Hu MS, Zielins ER, Tsai JM, Duscher D, Paik K, Tevlin R, Marecic O, Wan DC, Gurtner GC, Longaker MTTissue Eng Part A
- Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci.Sazonova O, Zhao Y, Nürnberg S, Miller C, Pjanic M, Castano VG, Kim JB, Salfati EL, Kundaje AB, Bejerano G, Assimes T, Yang X, Quertermous TPLoS Genet
- Reporting of IMMPACT-recommended core outcome domains among trials assessing opioids for chronic non-cancer pain.Mulla SM, Maqbool A, Sivananthan L, Lopes LC, Schandelmaier S, Kamaleldin M, Hsu S, Riva JJ, Vandvik PO, Tsoi L, Lam T, Ebrahim S, Johnston BC, Olivieri L, Montoya L, Kunz R, Scheidecker A, Buckley DN, Sessler DI, Guyatt GH, Busse JWPain
- GFVO: the Genomic Feature and Variation Ontology.Baran J, Durgahee BS, Eilbeck K, Antezana E, Hoehndorf R, Dumontier MPeerJ
- Reinforcement learning in multidimensional environments relies on attention mechanisms.Niv Y, Daniel R, Geana A, Gershman SJ, Leong YC, Radulescu A, Wilson RCJ Neurosci
- Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates.Courbet A, Endy D, Renard E, Molina F, Bonnet JSci Transl Med
- Insulin B chain 9-23 gene transfer to hepatocytes protects from type 1 diabetes by inducing Ag-specific FoxP3+ Tregs.Akbarpour M, Goudy KS, Cantore A, Russo F, Sanvito F, Naldini L, Annoni A, Roncarolo MGSci Transl Med
- Pictionary-based fMRI paradigm to study the neural correlates of spontaneous improvisation and figural creativity.Saggar M, Quintin EM, Kienitz E, Bott NT, Sun Z, Hong WC, Chien YH, Liu N, Dougherty RF, Royalty A, Hawthorne G, Reiss ALSci Rep
- Frozen blastocyst embryo transfer using a supplemented natural cycle protocol has a similar live birth rate compared to a programmed cycle protocol.Lathi RB, Chi YY, Liu J, Saravanabavanandhan B, Hegde A, Baker VLJ Assist Reprod Genet
- Treatment Outcomes With First-line Therapies With Entecavir and Tenofovir in Treatment-Naive Chronic Hepatitis B Patients in a Routine Clinical Practice.Ha NB, Trinh HN, Rosenblatt L, Nghiem D, Nguyen MHJ Clin Gastroenterol
- Development and Validation of an Assessment of Regional Anesthesia Ultrasound Interpretation Skills.Woodworth GE, Carney PA, Cohen JM, Kopp SL, Vokach-Brodsky LE, Horn JL, Missair A, Banks SE, Dieckmann NF, Maniker RBReg Anesth Pain Med
- Tendon regeneration with a novel tendon hydrogel: in vitro effects of platelet-rich plasma on rat adipose-derived stem cells.Crowe CS, Chiou G, McGoldrick R, Hui K, Pham H, Chang JPlast Reconstr Surg
- Electroacupuncture remediates glial dysfunction and ameliorates neurodegeneration in the astrocytic α-synuclein mutant mouse model.Deng J, Lv E, Yang J, Gong X, Zhang W, Liang X, Wang J, Jia J, Wang XJ Neuroinflammation
- Exercise Is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats.Mika A, Van Treuren W, González A, Herrera JJ, Knight R, Fleshner MPLoS One
- The Effect of Processing Additives on Energetic Disorder in Highly Efficient Organic Photovoltaics: A Case Study on PBDTTT-C-T:PC71 BM.Gao F, Himmelberger S, Andersson M, Hanifi D, Xia Y, Zhang S, Wang J, Hou J, Salleo A, Inganäs OAdv Mater
- Neuroscience: Internal compass puts flies in their place.Clandinin TR, Giocomo LMNature
- Neuroinflammation in Alzheimer's disease.Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MPLancet Neurol
- In reply.Girsen AI, Osmundson SS, Garabedian MJ, Naqvi M, Lyell DJObstet Gynecol
- An anti-H5N1 influenza virus FcDART antibody is a highly efficacious therapeutic agent and prophylactic against H5N1 influenza virus infection.Zanin M, Keck ZY, Rainey GJ, Lam CY, Boon AC, Rubrum A, Darnell D, Wong SS, Griffin Y, Xia J, Webster RG, Webby R, Johnson S, Foung SJ Virol
- Gendered innovations in orthopaedic science: civil liberties, Darwin, and the evolution of science.Ladd ALClin Orthop Relat Res
- AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.Neveu G, Ziv-Av A, Barouch-Bentov R, Berkerman E, Mulholland J, Einav SJ Virol
- The endoplasmic reticulum membrane J protein C18 executes a distinct role in promoting simian virus 40 membrane penetration.Bagchi P, Walczak CP, Tsai BJ Virol
- Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression.Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NLBlood
- How I use fibrinogen replacement therapy in acquired bleeding.Levy JH, Goodnough LTBlood
- Total knee arthroplasty in patients with ipsilateral fused hip: a technical note.Goodman SB, Huddleston JI, Hur D, Song SJClin Orthop Surg
- The burden of selected congenital anomalies amenable to surgery in low and middle-income regions: cleft lip and palate, congenital heart anomalies and neural tube defects.Higashi H, Barendregt JJ, Kassebaum NJ, Weiser TG, Bickler SW, Vos TArch Dis Child
- Inferior vena cava filters and postoperative outcomes in patients undergoing bariatric surgery: a meta-analysis.Kaw R, Pasupuleti V, Wayne Overby D, Deshpande A, Coleman CI, Ioannidis JP, Hernandez AV, Cardiovascular Meta-analysis Research GroupSurg Obes Relat Dis
- Adaptive human CDKAL1 variants underlie hormonal response variations at the enteroinsular axis.Chang CL, Cai JJ, Huang SY, Cheng PJ, Chueh HY, Hsu SYPLoS One
- Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the U.S. multi-society task force on colorectal cancer.Johnson DA, Barkun AN, Cohen LB, Dominitz JA, Kaltenbach T, Martel M, Robertson DJ, Boland CR, Giardello FM, Lieberman DA, Levin TR, Rex DKGastrointest Endosc
- Coming of age of genetic investigations in late-life mental health.O'Hara R, Hallmayer JAm J Geriatr Psychiatry
- Seasonal patterns in human A (H5N1) virus infection: analysis of global cases.Mathur MB, Patel RB, Gould M, Uyeki TM, Bhattacharya J, Xiao Y, Gillaspie Y, Chae C, Khazeni NPLoS One
- On-line visualization of ischemic burden during repetitive ischemia/reperfusion.Pavo N, Emmert MY, Giricz Z, Varga ZV, Ankersmit HJ, Maurer G, Hoerstrup SP, Ferdinandy P, Wu JC, Gyöngyösi MJACC Cardiovasc Imaging
- RNAi pathway genes are resistant to small RNA mediated gene silencing in the protozoan parasite Entamoeba histolytica.Pompey JM, Morf L, Singh UPLoS One
- Socioeconomic status and age at menarche: an examination of multiple indicators in an ethnically diverse cohort.Deardorff J, Abrams B, Ekwaru JP, Rehkopf DHAnn Epidemiol
- Coping with college and inflammatory bowel disease: implications for clinical guidance and support.Schwenk HT, Lightdale JR, Arnold JH, Goldmann DA, Weitzman ERInflamm Bowel Dis
- Affordable Care Act and bariatric surgery.Morton JSurg Obes Relat Dis
- What variables are associated with successful weight loss outcomes for bariatric surgery after 1 year?Robinson AH, Adler S, Stevens HB, Darcy AM, Morton JM, Safer DLSurg Obes Relat Dis
- A randomized comparison of long-axis and short-axis imaging for in-plane ultrasound-guided popliteal-sciatic perineural catheter insertion.Kim TE, Howard SK, Funck N, Harrison TK, Walters TL, Wagner MJ, Ganaway T, Mullens J, Lehnert B, Mariano ERJ Anesth
- Role of grandparenting in postmenopausal women's cognitive health: results from the Women's Healthy Aging Project.Burn KF, Henderson VW, Ames D, Dennerstein L, Szoeke CMenopause
- Multiple ethnic origins of mitochondrial DNA lineages for the population of Mauritius.Fregel R, Seetah K, Betancor E, Suárez NM, Čaval D, Caval S, Janoo A, Pestano JPLoS One
Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.
PLoS One. 2015;10(5):e0128494
Authors: Wang N, Rajasekaran N, Hou T, Macaubas C, Mellins ED
Type I diabetes (T1D), mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC) transplantation. Older non-obese diabetic (NOD) mice recipients (3m, at disease-onset stage) receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage). FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg) and lower proportion of proliferating T conventional cells (Tcon) in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN), blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.
PMID: 26020954 [PubMed - as supplied by publisher]
Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap.
PLoS Genet. 2015 May;11(5):e1005155
Authors: Nurnberg ST, Cheng K, Raiesdana A, Kundu R, Miller CL, Kim JB, Arora K, Carcamo-Oribe I, Xiong Y, Tellakula N, Nanda V, Murthy N, Boisvert WA, Hedin U, Perisic L, Aldi S, Maegdefessel L, Pjanic M, Owens GK, Tallquist MD, Quertermous T
Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including "vascular disease," "disorder of artery," and "occlusion of artery," as well as disease-related cellular functions including "cellular movement" and "cellular growth and proliferation." In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.
PMID: 26020946 [PubMed - as supplied by publisher]
Chemical Plausibility of Cu(III) with Biological Ligation in pMMO.
J Am Chem Soc. 2015 May 28;
Authors: Citek C, Gary JB, Wasinger EC, Stack TD
The mechanisms of dioxygen activation and methane C-H oxidation in particulate methane monooxygenase (pMMO) are currently unknown. Recent studies support a binuclear copper site as the catalytic center. We report the low-temperature assembly of a high-valent dicopper(III) bis(μ-oxide) complex bearing marked structural fidelity to the proposed active site of pMMO. This unprecedented dioxygen-bonded Cu(III) species with exclusive biological ligation directly informs on the chemical plausibility and thermodynamic stability of the bis(μ-oxide) structure in such dicopper sites and foretells unusual optical signatures of an oxygenation product in pMMO. Though the ultimate pMMO active oxidant is still debated, C-H oxidation of exogenous substrates is observed with the reported Cu(III) complexes. The assembly of a high valent species both narrows the search for relevant pMMO intermediates and provides evidence to substantiate the role of Cu(III) in biological redox processes.
PMID: 26020834 [PubMed - as supplied by publisher]
Signature Patterns of MHC Diversity in Three Gombe Communities of Wild Chimpanzees Reflect Fitness in Reproduction and Immune Defense against SIVcpz.
PLoS Biol. 2015 May;13(5):e1002144
Authors: Wroblewski EE, Norman PJ, Guethlein LA, Rudicell RS, Ramirez MA, Li Y, Hahn BH, Pusey AE, Parham P
Major histocompatibility complex (MHC) class I molecules determine immune responses to viral infections. These polymorphic cell-surface glycoproteins bind peptide antigens, forming ligands for cytotoxic T and natural killer cell receptors. Under pressure from rapidly evolving viruses, hominoid MHC class I molecules also evolve rapidly, becoming diverse and species-specific. Little is known of the impact of infectious disease epidemics on MHC class I variant distributions in human populations, a context in which the chimpanzee is the superior animal model. Population dynamics of the chimpanzees inhabiting Gombe National Park, Tanzania have been studied for over 50 years. This population is infected with SIVcpz, the precursor of human HIV-1. Because HLA-B is the most polymorphic human MHC class I molecule and correlates strongly with HIV-1 progression, we determined sequences for its ortholog, Patr-B, in 125 Gombe chimpanzees. Eleven Patr-B variants were defined, as were their frequencies in Gombe's three communities, changes in frequency with time, and effect of SIVcpz infection. The growing populations of the northern and central communities, where SIVcpz is less prevalent, have stable distributions comprising a majority of low-frequency Patr-B variants and a few high-frequency variants. Driving the latter to high frequency has been the fecundity of immigrants to the northern community, whereas in the central community, it has been the fecundity of socially dominant individuals. In the declining population of the southern community, where greater SIVcpz prevalence is associated with mortality and emigration, Patr-B variant distributions have been changing. Enriched in this community are Patr-B variants that engage with natural killer cell receptors. Elevated among SIVcpz-infected chimpanzees, the Patr-B*06:03 variant has striking structural and functional similarities to HLA-B*57, the human allotype most strongly associated with delayed HIV-1 progression. Like HLA-B*57, Patr-B*06:03 correlates with reduced viral load, as assessed by detection of SIVcpz RNA in feces.
PMID: 26020813 [PubMed - as supplied by publisher]
Summary of the DREAM8 Parameter Estimation Challenge: Toward Parameter Identification for Whole-Cell Models.
PLoS Comput Biol. 2015 May;11(5):e1004096
Authors: Karr JR, Williams AH, Zucker JD, Raue A, Steiert B, Timmer J, Kreutz C, DREAM8 Parameter Estimation Challenge Consortium, Wilkinson S, Allgood BA, Bot BM, Hoff BR, Kellen MR, Covert MW, Stolovitzky GA, Meyer P
Whole-cell models that explicitly represent all cellular components at the molecular level have the potential to predict phenotype from genotype. However, even for simple bacteria, whole-cell models will contain thousands of parameters, many of which are poorly characterized or unknown. New algorithms are needed to estimate these parameters and enable researchers to build increasingly comprehensive models. We organized the Dialogue for Reverse Engineering Assessments and Methods (DREAM) 8 Whole-Cell Parameter Estimation Challenge to develop new parameter estimation algorithms for whole-cell models. We asked participants to identify a subset of parameters of a whole-cell model given the model's structure and in silico "experimental" data. Here we describe the challenge, the best performing methods, and new insights into the identifiability of whole-cell models. We also describe several valuable lessons we learned toward improving future challenges. Going forward, we believe that collaborative efforts supported by inexpensive cloud computing have the potential to solve whole-cell model parameter estimation.
PMID: 26020786 [PubMed - as supplied by publisher]
Predicting Cortical Dark/Bright Asymmetries from Natural Image Statistics and Early Visual Transforms.
PLoS Comput Biol. 2015 May;11(5):e1004268
Authors: Cooper EA, Norcia AM
The nervous system has evolved in an environment with structure and predictability. One of the ubiquitous principles of sensory systems is the creation of circuits that capitalize on this predictability. Previous work has identified predictable non-uniformities in the distributions of basic visual features in natural images that are relevant to the encoding tasks of the visual system. Here, we report that the well-established statistical distributions of visual features -- such as visual contrast, spatial scale, and depth -- differ between bright and dark image components. Following this analysis, we go on to trace how these differences in natural images translate into different patterns of cortical input that arise from the separate bright (ON) and dark (OFF) pathways originating in the retina. We use models of these early visual pathways to transform natural images into statistical patterns of cortical input. The models include the receptive fields and non-linear response properties of the magnocellular (M) and parvocellular (P) pathways, with their ON and OFF pathway divisions. The results indicate that there are regularities in visual cortical input beyond those that have previously been appreciated from the direct analysis of natural images. In particular, several dark/bright asymmetries provide a potential account for recently discovered asymmetries in how the brain processes visual features, such as violations of classic energy-type models. On the basis of our analysis, we expect that the dark/bright dichotomy in natural images plays a key role in the generation of both cortical and perceptual asymmetries.
PMID: 26020624 [PubMed - as supplied by publisher]
Mycobacterium bovis Enterocolitis in An Immunocompromised Host.
J Pediatr Gastroenterol Nutr. 2014 Aug 13;
Authors: Winger BA, Foy E, Sud SR, MacKenzie JD, Pua HH, Lau AH, Heyman MB, Laszik Z, Tureen J
PMID: 26020480 [PubMed - as supplied by publisher]
Three-dimensional Dynamic Contrast-enhanced US Imaging for Early Antiangiogenic Treatment Assessment in a Mouse Colon Cancer Model.
Radiology. 2015 May 22;:142824
Authors: Wang H, Hristov D, Qin J, Tian L, Willmann JK
Purpose To evaluate feasibility and reproducibility of three-dimensional (3D) dynamic contrast material-enhanced (DCE) ultrasonographic (US) imaging by using a clinical matrix array transducer to assess early antiangiogenic treatment effects in human colon cancer xenografts in mice. Materials and Methods Animal studies were approved by the Institutional Administrative Panel on Laboratory Animal Care at Stanford University. Three-dimensional DCE US imaging with two techniques (bolus and destruction-replenishment) was performed in human colon cancer xenografts (n = 38) by using a clinical US system and transducer. Twenty-one mice were imaged twice to assess reproducibility. Seventeen mice were scanned before and 24 hours after either antiangiogenic (n = 9) or saline-only (n = 8) treatment. Data sets of 3D DCE US examinations were retrospectively segmented into consecutive 1-mm imaging planes to simulate two-dimensional (2D) DCE US imaging. Six perfusion parameters (peak enhancement [PE], area under the time-intensity curve [AUC], time to peak [TTP], relative blood volume [rBV], relative blood flow [rBF], and blood flow velocity) were measured on both 3D and 2D data sets. Percent area of blood vessels was quantified ex vivo with immunofluorescence. Statistical analyses were performed with the Wilcoxon rank test by calculating intraclass correlation coefficients and by using Pearson correlation analysis. Results Reproducibility of both 3D DCE US imaging techniques was good to excellent (intraclass correlation coefficient, 0.73-0.86). PE, AUC, rBV, and rBF significantly decreased (P ≤ .04) in antiangiogenic versus saline-treated tumors. rBV (r = 0.74; P = .06) and rBF (r = 0.85; P = .02) correlated with ex vivo percent area of blood vessels, although the statistical significance of rBV was not reached, likely because of small sample size. Overall, 2D DCE-US overestimated and underestimated treatment effects from up to 125-fold to170-fold compared with 3D DCE US imaging. If the central tumor plane was assessed, treatment response was underestimated up to threefold or overestimated up to 57-fold on 2D versus 3D DCE US images. Conclusion Three-dimensional DCE US imaging with a clinical matrix array transducer is feasible and reproducible to assess tumor perfusion in human colon cancer xenografts in mice and allows for assessment of early treatment response after antiangiogenic therapy. (©) RSNA, 2015.
PMID: 26020439 [PubMed - as supplied by publisher]
High-Throughput Screening of Surface Marker Expression on Undifferentiated and Differentiated Human Adipose-Derived Stromal Cells.
Tissue Eng Part A. 2015 May 28;
Authors: Walmsley GG, Atashroo DA, Maan ZN, Hu MS, Zielins ER, Tsai JM, Duscher D, Paik K, Tevlin R, Marecic O, Wan DC, Gurtner GC, Longaker MT
Adipose tissue contains an abundant source of multipotent mesenchymal cells termed "adipose-derived stromal cells" (ASCs) which hold potential for regenerative medicine. However, the heterogeneity inherent to ASCs harvested using standard methodologies remains largely undefined, particularly in regards to differences across donors. Identifying the subpopulations of ASCs predisposed towards differentiation along distinct lineages holds value for improving graft survival, predictability, and efficiency. Human (h)ASCs from three different donors were independently isolated by density-based centrifugation from adipose tissue and maintained in culture or differentiated along either adipogenic or osteogenic lineages using differentiation media. Undifferentiated and differentiated hASCs were then analyzed for the presence of 242 human surface markers by flow cytometry analysis. By comprehensively characterizing the surface marker profile of undifferentiated hASCs using flow cytometry, we gained novel insight into the heterogeneity underlying protein expression on the surface of cultured undifferentiated hASCs across different donors. Comparing the surface marker profile of undifferentiated hASCs to hASCs that have undergone osteogenic or adipogenic differentiation allowed for the identification of surface markers upregulated and downregulated by osteogenic or adipogenic differentiation. Osteogenic differentiation induced upregulation of CD164 and downregulation of CD49a, CD49b, CD49c, CD49d, CD55, CD58, CD105, and CD166 while adipogenic differentiation induced upregulation of CD36, CD40, CD146, CD164, and CD271 and downregulation of CD49b, CD49c, CD49d, CD71, CD105, and CD166. These results lend support to the notion that hASCs isolated using standard methodologies represent a heterogeneous population and serve as a foundation for future studies seeking to maximize their regenerative potential through FACS-based selection prior to therapy.
PMID: 26020286 [PubMed - as supplied by publisher]
Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci.
PLoS Genet. 2015 May;11(5):e1005202
Authors: Sazonova O, Zhao Y, Nürnberg S, Miller C, Pjanic M, Castano VG, Kim JB, Salfati EL, Kundaje AB, Bejerano G, Assimes T, Yang X, Quertermous T
To functionally link coronary artery disease (CAD) causal genes identified by genome wide association studies (GWAS), and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq) with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC). Analysis of identified TCF21 target genes for enrichment of molecular and cellular annotation terms identified processes relevant to CAD pathophysiology, including "growth factor binding," "matrix interaction," and "smooth muscle contraction." We characterized the canonical binding sequence for TCF21 as CAGCTG, identified AP-1 binding sites in TCF21 peaks, and by conducting ChIP-Seq for JUN and JUND in HCASMC confirmed that there is significant overlap between TCF21 and AP-1 binding loci in this cell type. Expression quantitative trait variation mapped to target genes of TCF21 was significantly enriched among variants with low P-values in the GWAS analyses, suggesting a possible functional interaction between TCF21 binding and causal variants in other CAD disease loci. Separate enrichment analyses found over-representation of TCF21 target genes among CAD associated genes, and linkage disequilibrium between TCF21 peak variation and that found in GWAS loci, consistent with the hypothesis that TCF21 may affect disease risk through interaction with other disease associated loci. Interestingly, enrichment for TCF21 target genes was also found among other genome wide association phenotypes, including height and inflammatory bowel disease, suggesting a functional profile important for basic cellular processes in non-vascular tissues. Thus, data and analyses presented here suggest that study of GWAS transcription factors may be a highly useful approach to identifying disease gene interactions and thus pathways that may be relevant to complex disease etiology.
PMID: 26020271 [PubMed - as supplied by publisher]
Reporting of IMMPACT-recommended core outcome domains among trials assessing opioids for chronic non-cancer pain.
Pain. 2015 May 26;
Authors: Mulla SM, Maqbool A, Sivananthan L, Lopes LC, Schandelmaier S, Kamaleldin M, Hsu S, Riva JJ, Vandvik PO, Tsoi L, Lam T, Ebrahim S, Johnston BC, Olivieri L, Montoya L, Kunz R, Scheidecker A, Buckley DN, Sessler DI, Guyatt GH, Busse JW
The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) has recommended that trialists evaluating treatments for chronic pain should consider reporting nine patient-important outcome domains. We examined the extent to which clinical trials evaluating the effect of opioids for chronic non-cancer pain (CNCP) report outcome domains recommended by IMMPACT. We systematically searched electronic databases for English-language studies that randomized patients with CNCP to receive an opioid or a non-opioid control. In duplicate and independently, reviewers established the eligibility of each identified study, and recorded all reported outcome domains from eligible trials. We conducted a priori regression analyses to explore factors that may be associated with IMMPACT recommended outcome domains. Among 156 eligible trials, reporting of IMMPACT recommended outcome domains was highly variable, ranging from 99% for pain to 7% for interpersonal functioning. Recently published trials were more likely to report the effect of treatment on physical functioning, emotional functioning, role functioning, sleep and fatigue, and participant disposition. Trials for which the corresponding author was from North America were more likely to report treatment effects on physical functioning, and participant ratings of improvement and satisfaction with treatment. Trials published in higher impact journals were more likely to report treatment effects on emotional function, but less likely to report participant ratings of improvement and satisfaction with treatment. Most IMMPACT domains showed an increased rate of reporting over time, although many patient-important outcome domains remained unreported by over half of all trials evaluating the effects of opioids for CNCP.
PMID: 26020224 [PubMed - as supplied by publisher]
GFVO: the Genomic Feature and Variation Ontology.
Authors: Baran J, Durgahee BS, Eilbeck K, Antezana E, Hoehndorf R, Dumontier M
Falling costs in genomic laboratory experiments have led to a steady increase of genomic feature and variation data. Multiple genomic data formats exist for sharing these data, and whilst they are similar, they are addressing slightly different data viewpoints and are consequently not fully compatible with each other. The fragmentation of data format specifications makes it hard to integrate and interpret data for further analysis with information from multiple data providers. As a solution, a new ontology is presented here for annotating and representing genomic feature and variation dataset contents. The Genomic Feature and Variation Ontology (GFVO) specifically addresses genomic data as it is regularly shared using the GFF3 (incl. FASTA), GTF, GVF and VCF file formats. GFVO simplifies data integration and enables linking of genomic annotations across datasets through common semantics of genomic types and relations. Availability and implementation. The latest stable release of the ontology is available via its base URI; previous and development versions are available at the ontology's GitHub repository: https://github.com/BioInterchange/Ontologies; versions of the ontology are indexed through BioPortal (without external class-/property-equivalences due to BioPortal release 4.10 limitations); examples and reference documentation is provided on a separate web-page: http://www.biointerchange.org/ontologies.html. GFVO version 1.0.2 is licensed under the CC0 1.0 Universal license (https://creativecommons.org/publicdomain/zero/1.0) and therefore de facto within the public domain; the ontology can be appropriated without attribution for commercial and non-commercial use.
PMID: 26019997 [PubMed]
Reinforcement learning in multidimensional environments relies on attention mechanisms.
J Neurosci. 2015 May 27;35(21):8145-57
Authors: Niv Y, Daniel R, Geana A, Gershman SJ, Leong YC, Radulescu A, Wilson RC
In recent years, ideas from the computational field of reinforcement learning have revolutionized the study of learning in the brain, famously providing new, precise theories of how dopamine affects learning in the basal ganglia. However, reinforcement learning algorithms are notorious for not scaling well to multidimensional environments, as is required for real-world learning. We hypothesized that the brain naturally reduces the dimensionality of real-world problems to only those dimensions that are relevant to predicting reward, and conducted an experiment to assess by what algorithms and with what neural mechanisms this "representation learning" process is realized in humans. Our results suggest that a bilateral attentional control network comprising the intraparietal sulcus, precuneus, and dorsolateral prefrontal cortex is involved in selecting what dimensions are relevant to the task at hand, effectively updating the task representation through trial and error. In this way, cortical attention mechanisms interact with learning in the basal ganglia to solve the "curse of dimensionality" in reinforcement learning.
PMID: 26019331 [PubMed - in process]
Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates.
Sci Transl Med. 2015 May 27;7(289):289ra83
Authors: Courbet A, Endy D, Renard E, Molina F, Bonnet J
Whole-cell biosensors have several advantages for the detection of biological substances and have proven to be useful analytical tools. However, several hurdles have limited whole-cell biosensor application in the clinic, primarily their unreliable operation in complex media and low signal-to-noise ratio. We report that bacterial biosensors with genetically encoded digital amplifying genetic switches can detect clinically relevant biomarkers in human urine and serum. These bactosensors perform signal digitization and amplification, multiplexed signal processing with the use of Boolean logic gates, and data storage. In addition, we provide a framework with which to quantify whole-cell biosensor robustness in clinical samples together with a method for easily reprogramming the sensor module for distinct medical detection agendas. Last, we demonstrate that bactosensors can be used to detect pathological glycosuria in urine from diabetic patients. These next-generation whole-cell biosensors with improved computing and amplification capacity could meet clinical requirements and should enable new approaches for medical diagnosis.
PMID: 26019219 [PubMed - in process]
Insulin B chain 9-23 gene transfer to hepatocytes protects from type 1 diabetes by inducing Ag-specific FoxP3+ Tregs.
Sci Transl Med. 2015 May 27;7(289):289ra81
Authors: Akbarpour M, Goudy KS, Cantore A, Russo F, Sanvito F, Naldini L, Annoni A, Roncarolo MG
Antigen (Ag)-specific tolerance in type 1 diabetes (T1D) in human has not been achieved yet. Targeting lentiviral vector (LV)-mediated gene expression to hepatocytes induces active tolerance toward the encoded Ag. The insulin B chain 9-23 (InsB9-23) is an immunodominant T cell epitope in nonobese diabetic (NOD) mice. To determine whether auto-Ag gene transfer to hepatocytes induces tolerance and control of T1D, NOD mice were treated with integrase-competent LVs (ICLVs) that selectively target the expression of InsB9-23 to hepatocytes. ICLV treatment induced InsB9-23-specific effector T cells but also FoxP3(+) regulatory T cells (Tregs), which halted islet immune cell infiltration, and protected from T1D. Moreover, ICLV treatment combined with a single suboptimal dose of anti-CD3 monoclonal antibody (mAb) is effective in T1D reversal. Splenocytes from LV.InsB9-23-treated mice, but not from LV.OVA (ovalbumin)-treated control mice, stopped diabetes development, demonstrating that protection is Ag-specific. Depletion of CD4(+)CD25(+)FoxP3(+) T cells led to diabetes progression, indicating that Ag-specific FoxP3(+) Tregs mediate protection. Integrase-defective LVs (IDLVs).InsB9-23, which alleviate the concerns for insertional mutagenesis and support transient transgene expression in hepatocytes, were also efficient in protecting from T1D. These data demonstrate that hepatocyte-targeted auto-Ag gene expression prevents and resolves T1D and that stable integration of the transgene is not required for this protection. Gene transfer to hepatocytes can be used to induce Ag-specific tolerance in autoimmune diseases.
PMID: 26019217 [PubMed - in process]
Pictionary-based fMRI paradigm to study the neural correlates of spontaneous improvisation and figural creativity.
Sci Rep. 2015;5:10894
Authors: Saggar M, Quintin EM, Kienitz E, Bott NT, Sun Z, Hong WC, Chien YH, Liu N, Dougherty RF, Royalty A, Hawthorne G, Reiss AL
A novel game-like and creativity-conducive fMRI paradigm is developed to assess the neural correlates of spontaneous improvisation and figural creativity in healthy adults. Participants were engaged in the word-guessing game of Pictionary(TM), using an MR-safe drawing tablet and no explicit instructions to be "creative". Using the primary contrast of drawing a given word versus drawing a control word (zigzag), we observed increased engagement of cerebellum, thalamus, left parietal cortex, right superior frontal, left prefrontal and paracingulate/cingulate regions, such that activation in the cingulate and left prefrontal cortices negatively influenced task performance. Further, using parametric fMRI analysis, increasing subjective difficulty ratings for drawing the word engaged higher activations in the left pre-frontal cortices, whereas higher expert-rated creative content in the drawings was associated with increased engagement of bilateral cerebellum. Altogether, our data suggest that cerebral-cerebellar interaction underlying implicit processing of mental representations has a facilitative effect on spontaneous improvisation and figural creativity.
PMID: 26018874 [PubMed - as supplied by publisher]
Frozen blastocyst embryo transfer using a supplemented natural cycle protocol has a similar live birth rate compared to a programmed cycle protocol.
J Assist Reprod Genet. 2015 May 28;
Authors: Lathi RB, Chi YY, Liu J, Saravanabavanandhan B, Hegde A, Baker VL
PURPOSE: The purpose of this study is to compare outcomes for a supplemented natural cycle with a programmed cycle protocol for frozen blastocyst transfer.
METHODS: A retrospective analysis was performed of frozen autologous blastocyst transfers, at a single academic fertility center (519 supplemented natural cycles and 106 programmed cycles). Implantation, clinical pregnancy, miscarriage, and live birth and birth weight were compared using Pearson's Chi-squared test, T-test, or Fisher's exact test.
RESULTS: There was no significant difference between natural and programmed frozen embryo transfers with respect to implantation (21.9 vs. 18.1 %), clinical pregnancy (35.5 vs. 29.2 %), and live birth rates (27.7 vs. 23.6 %). Mean birth weights were also similar between natural and programmed cycles for singletons (3354 vs. 3340 g) and twins (2422 vs. 2294 g) CONCLUSION: Frozen blastocyst embryo transfers using supplemented natural or programmed protocols experience similar success rates. Patient preference should be considered in choosing a protocol.
PMID: 26018319 [PubMed - as supplied by publisher]
Treatment Outcomes With First-line Therapies With Entecavir and Tenofovir in Treatment-Naive Chronic Hepatitis B Patients in a Routine Clinical Practice.
J Clin Gastroenterol. 2015 May 19;
Authors: Ha NB, Trinh HN, Rosenblatt L, Nghiem D, Nguyen MH
BACKGROUND: Given their high efficacy, entecavir (ETV) and tenofovir (TDF), are the recommended first-line therapies for chronic hepatitis B, but it is not clear whether the efficacy reported from pivotal trials is similar to the outcomes seen in routine practice.
GOALS: Our goal was to examine the treatment outcomes of antiviral therapy in such setting.
PATIENTS AND METHODS: We conducted a retrospective study of 557 consecutive treatment-naive patients who started either ETV (n=443) or TDF (n=114) at 3 US liver clinics between January 2005 and 2012. Primary study endpoint was complete viral suppression (CVS) rate (hepatitis B virus DNA<40 IU/mL).
RESULTS: The majority of patients in both ETV and TDF groups were Asians, hepatitis B e antigen (HBeAg) negative, male, and with similar pretreatment alanine aminotransferase and hepatitis B virus DNA levels. Similar proportions of patients in the ETV and TDF groups achieved CVS at 24 months: 87.7% versus 87.0%, respectively. Cumulative rates of virological breakthrough in the ETV and TDF groups were 1.0% versus 4.8% (P=0.26) and 3.7% versus 9.8% (P=0.04) at month 12 and 24, respectively; and all were associated with medication nonadherence. Cumulative rate of medication nonadherence was lower in the ETV than TDF group: 4.6% versus 7.8% at month 12 and 8.9% versus 16.9% at month 24, respectively.
CONCLUSIONS: Patients treated with either ETV or TDF achieve a similar rate of CVS at 24 months. The primary contributor to suboptimal response was medication nonadherence. Attention to medication adherence is needed in a routine clinical setting.
PMID: 26018133 [PubMed - as supplied by publisher]
Development and Validation of an Assessment of Regional Anesthesia Ultrasound Interpretation Skills.
Reg Anesth Pain Med. 2015 May 26;
Authors: Woodworth GE, Carney PA, Cohen JM, Kopp SL, Vokach-Brodsky LE, Horn JL, Missair A, Banks SE, Dieckmann NF, Maniker RB
BACKGROUND: Interpretation of ultrasound images and knowledge of anatomy are essential skills for ultrasound-guided peripheral nerve blocks. Competency-based educational models promoted by the Accreditation Council for Graduate Medical Education require the development of assessment tools for the achievement of different competency milestones to demonstrate the longitudinal development of skills that occur during training.
METHODS: A rigorous study guided by psychometric principles was undertaken to identify and validate the domains and items in an assessment of ultrasound interpretation skills for regional anesthesia. A survey of residents, academic faculty, and community anesthesiologists, as well as video recordings of experts teaching ultrasound-guided peripheral nerve blocks, was used to develop short video clips with accompanying multiple choice-style questions. Four rounds of pilot testing produced a 50-question assessment that was subsequently administered online to residents, fellows, and faculty from multiple institutions.
RESULTS: Test results from 90 participants were analyzed with Item Response Theory model fitting indicating that a 47-item subset of the test fits the model well (P = 0.11). There was a significant linear relation between expected and predicted item difficulty (P < 0.001). Overall test scores increased linearly with higher levels of formal anesthesia training, regional anesthesia training, number of ultrasound-guided blocks performed per year, and a self-rating of regional anesthesia skill (all P < 0.001).
CONCLUSIONS: This study provides evidence for the reliability, content validity, and construct validity of a 47-item multiple choice-style online test of ultrasound interpretation skills for regional anesthesia, which can be used as an assessment of competency milestone achievement in anesthesiology training.
PMID: 26017720 [PubMed - as supplied by publisher]
Tendon regeneration with a novel tendon hydrogel: in vitro effects of platelet-rich plasma on rat adipose-derived stem cells.
Plast Reconstr Surg. 2015 Jun;135(6):981e-9e
Authors: Crowe CS, Chiou G, McGoldrick R, Hui K, Pham H, Chang J
BACKGROUND: Tendon hydrogel is a promising new injectable substance that has been shown to improve repair strength after tendon injury. This study assesses the capacity of platelet-rich plasma to stimulate proliferation and migration of rat adipose-derived stem cells in tendon hydrogel in vitro.
METHODS: To assess proliferation, adipose-derived stem cells were exposed to plasma, plasma supplemented with growth factors, or platelet-rich plasma in culture medium and tendon hydrogel. To assess migration, adipose-derived stem cells were plated onto tendon hydrogel -coated wells and covered with medium containing plasma, plasma supplemented with growth factors, platelet-rich plasma, or bovine serum albumin. Migration from cell-seeded to cell-free zones was assessed at 12-hour intervals.
RESULTS: Platelet-rich plasma augmented proliferation to a greater extent compared with plasma and plasma supplemented with growth factors (10%: optical density, 1.18 versus 0.75 versus 0.98, respectively). Platelet-rich plasma was superior to plasma in tendon hydrogel (10%: optical density, 1.19 versus 0.85) but did not augment proliferation to the extent that plasma supplemented with growth factors did (10%: optical density, 1.19 versus 1.56). Platelet-rich plasma enhanced the migration of adipose-derived stem cells compared with serum-free medium (bovine serum albumin) (36 hours: platelet-rich plasma, 1.88; plasma, 1.51; plasma plus growth factor, 1.80; bovine serum albumin, 1.43).
CONCLUSIONS: Tendon healing is mediated by migration of cells to the injured area and cellular proliferation at that site. Tendon hydrogel supplemented with platelet-rich plasma stimulates these processes. Future studies will evaluate this combination's ability to stimulate healing in chronic tendon injuries in vivo.
PMID: 26017614 [PubMed - in process]
Electroacupuncture remediates glial dysfunction and ameliorates neurodegeneration in the astrocytic α-synuclein mutant mouse model.
J Neuroinflammation. 2015 May 28;12(1):103
Authors: Deng J, Lv E, Yang J, Gong X, Zhang W, Liang X, Wang J, Jia J, Wang X
BACKGROUND: The acupuncture or electroacupuncture (EA) shows the therapeutic effect on various neurodegenerative diseases. This effect was thought to be partially achieved by its ability to alleviate existing neuroinflammation and glial dysfunction. In this study, we systematically investigated the effect of EA on abnormal neurochemical changes and motor symptoms in a mouse neurodegenerative disease model.
METHODS: The transgenic mouse which expresses a mutant α-synuclein (α-syn) protein, A53T α-syn, in brain astrocytic cells was used. These mice exhibit extensive neuroinflammatory and motor phenotypes of neurodegenerative disorders. In this study, the effects of EA on these phenotypic changes were examined in these mice.
RESULTS: EA improved the movement detected in multiple motor tests in A53T mutant mice. At the cellular level, EA significantly reduced the activation of microglia and prevented the loss of dopaminergic neurons in the midbrain and motor neurons in the spinal cord. At the molecular level, EA suppressed the abnormal elevation of proinflammatory factors (tumor necrosis factor-α and interleukin-1β) in the striatum and midbrain of A53T mice. In contrast, EA increased striatal and midbrain expression of a transcription factor, nuclear factor E2-related factor 2, and its downstream antioxidants (heme oxygenase-1 and glutamate-cysteine ligase modifier subunits).
CONCLUSIONS: These results suggest that EA possesses the ability to ameliorate mutant α-syn-induced motor abnormalities. This ability may be due to that EA enhances both anti-inflammatory and antioxidant activities and suppresses aberrant glial activation in the diseased sites of brains.
PMID: 26016857 [PubMed - as supplied by publisher]
Exercise Is More Effective at Altering Gut Microbial Composition and Producing Stable Changes in Lean Mass in Juvenile versus Adult Male F344 Rats.
PLoS One. 2015;10(5):e0125889
Authors: Mika A, Van Treuren W, González A, Herrera JJ, Knight R, Fleshner M
The mammalian intestine harbors a complex microbial ecosystem that influences many aspects of host physiology. Exposure to specific microbes early in development affects host metabolism, immune function, and behavior across the lifespan. Just as the physiology of the developing organism undergoes a period of plasticity, the developing microbial ecosystem is characterized by instability and may also be more sensitive to change. Early life thus presents a window of opportunity for manipulations that produce adaptive changes in microbial composition. Recent insights have revealed that increasing physical activity can increase the abundance of beneficial microbial species. We therefore investigated whether six weeks of wheel running initiated in the juvenile period (postnatal day 24) would produce more robust and stable changes in microbial communities versus exercise initiated in adulthood (postnatal day 70) in male F344 rats. 16S rRNA gene sequencing was used to characterize the microbial composition of juvenile versus adult runners and their sedentary counterparts across multiple time points during exercise and following exercise cessation. Alpha diversity measures revealed that the microbial communities of young runners were less even and diverse, a community structure that reflects volatility and malleability. Juvenile onset exercise altered several phyla and, notably, increased Bacteroidetes and decreased Firmicutes, a configuration associated with leanness. At the genus level of taxonomy, exercise altered more genera in juveniles than in the adults and produced patterns associated with adaptive metabolic consequences. Given the potential of these changes to contribute to a lean phenotype, we examined body composition in juvenile versus adult runners. Interestingly, exercise produced persistent increases in lean body mass in juvenile but not adult runners. Taken together, these results indicate that the impact of exercise on gut microbiota composition as well as body composition may depend on the developmental stage during which exercise is initiated.
PMID: 26016739 [PubMed - as supplied by publisher]
The Effect of Processing Additives on Energetic Disorder in Highly Efficient Organic Photovoltaics: A Case Study on PBDTTT-C-T:PC71 BM.
Adv Mater. 2015 May 27;
Authors: Gao F, Himmelberger S, Andersson M, Hanifi D, Xia Y, Zhang S, Wang J, Hou J, Salleo A, Inganäs O
Energetic disorder, an important parameter affecting the performance of organic photovoltaics, is significantly decreased upon the addition of processing additives in a highly efficient benzodithiophene-based copolymer blend (PBDTTT-C-T:PC71 BM). Wide-angle and small-angle X-ray scattering measurements suggest that the origin of this reduced energetic disorder is due to increased aggregation and a larger average fullerene domain size together with purer phases.
PMID: 26016473 [PubMed - as supplied by publisher]
Neuroscience: Internal compass puts flies in their place.
Nature. 2015 May 14;521(7551):165-6
Authors: Clandinin TR, Giocomo LM
PMID: 25971505 [PubMed - indexed for MEDLINE]
Neuroinflammation in Alzheimer's disease.
Lancet Neurol. 2015 Apr;14(4):388-405
Authors: Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP
Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease.
PMID: 25792098 [PubMed - indexed for MEDLINE]
Obstet Gynecol. 2015 Mar;125(3):740
Authors: Girsen AI, Osmundson SS, Garabedian MJ, Naqvi M, Lyell DJ
PMID: 25730244 [PubMed - indexed for MEDLINE]
An anti-H5N1 influenza virus FcDART antibody is a highly efficacious therapeutic agent and prophylactic against H5N1 influenza virus infection.
J Virol. 2015 Apr;89(8):4549-61
Authors: Zanin M, Keck ZY, Rainey GJ, Lam CY, Boon AC, Rubrum A, Darnell D, Wong SS, Griffin Y, Xia J, Webster RG, Webby R, Johnson S, Foung S
UNLABELLED: Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and continue to be a pandemic threat. While vaccines are available, other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. To produce a therapeutic agent that is highly efficacious at low doses and is broadly specific against antigenically drifted H5N1 influenza viruses, we developed two neutralizing monoclonal antibodies and combined them into a single bispecific Fc fusion protein (the Fc dual-affinity retargeting [FcDART] molecule). In mice, a single therapeutic or prophylactic dose of either monoclonal antibody at 2.5 mg/kg of body weight provided 100% protection against challenge with A/Vietnam/1203/04 (H5N1) or the antigenically drifted strain A/Whooper swan/Mongolia/244/05 (H5N1). In ferrets, a single 1-mg/kg prophylactic dose provided 100% protection against A/Vietnam/1203/04 challenge. FcDART was also effective, as a single 2.5-mg/kg therapeutic or prophylactic dose in mice provided 100% protection against A/Vietnam/1203/04 challenge. Antibodies bound to conformational epitopes in antigenic sites on the globular head of the hemagglutinin protein, on the basis of analysis of mutants with antibody escape mutations. While it was possible to generate escape mutants in vitro, they were neutralized by the antibodies in vivo, as mice infected with escape mutants were 100% protected after only a single therapeutic dose of the antibody used to generate the escape mutant in vitro. In summary, we have combined the antigen specificities of two highly efficacious anti-H5N1 influenza virus antibodies into a bispecific FcDART molecule, which represents a strategy to produce broadly neutralizing antibodies that are effective against antigenically diverse influenza viruses.
IMPORTANCE: Highly pathogenic H5N1 avian influenza viruses are associated with severe disease in humans and are a pandemic threat. A vaccine is available, but other approaches are required for patients that typically respond poorly to vaccination, such as the elderly and the immunocompromised. The variability of the virus means that such an approach must be broad spectrum. To achieve this, we developed two antibodies that neutralize H5N1 influenza viruses. In mice, these antibodies provided complete protection against a spectrum of H5N1 influenza viruses at a single low dose. We then combined the two antibodies into a single molecule, FcDART, which combined the broad-spectrum activity and protective efficacy of both antibodies. This treatment provides a novel and effective therapeutic agent or prophylactic with activity against highly pathogenic H5N1 avian influenza viruses.
PMID: 25673719 [PubMed - indexed for MEDLINE]
Gendered innovations in orthopaedic science: civil liberties, Darwin, and the evolution of science.
Clin Orthop Relat Res. 2015 May;473(5):1560-5
Authors: Ladd AL
PMID: 25666144 [PubMed - indexed for MEDLINE]
AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.
J Virol. 2015 Apr;89(8):4387-404
Authors: Neveu G, Ziv-Av A, Barouch-Bentov R, Berkerman E, Mulholland J, Einav S
UNLABELLED: Hepatitis C virus (HCV) enters its target cell via clathrin-mediated endocytosis. AP-2-associated protein kinase 1 (AAK1) and cyclin G-associated kinase (GAK) are host kinases that regulate clathrin adaptor protein (AP)-mediated trafficking in the endocytic and secretory pathways. We previously reported that AAK1 and GAK regulate HCV assembly by stimulating binding of the μ subunit of AP-2, AP2M1, to HCV core protein. We also discovered that AAK1 and GAK inhibitors, including the approved anticancer drugs sunitinib and erlotinib, could block HCV assembly. Here, we hypothesized that AAK1 and GAK regulate HCV entry independently of their effect on HCV assembly. Indeed, silencing AAK1 and GAK expression inhibited entry of pseudoparticles and cell culture grown-HCV and internalization of Dil-labeled HCV particles with no effect on HCV attachment or RNA replication. AAK1 or GAK depletion impaired epidermal growth factor (EGF)-mediated enhanced HCV entry and endocytosis of EGF receptor (EGFR), an HCV entry cofactor and erlotinib's cancer target. Moreover, either RNA interference-mediated depletion of AP2M1 or NUMB, each a substrate of AAK1 and/or GAK, or overexpression of either an AP2M1 or NUMB phosphorylation site mutant inhibited HCV entry. Last, in addition to affecting assembly, sunitinib and erlotinib inhibited HCV entry at a postbinding step, their combination was synergistic, and their antiviral effect was reversed by either AAK1 or GAK overexpression. Together, these results validate AAK1 and GAK as critical regulators of HCV entry that function in part by activating EGFR, AP2M1, and NUMB and as the molecular targets underlying the antiviral effect of sunitinib and erlotinib (in addition to EGFR), respectively.
IMPORTANCE: Understanding the host pathways hijacked by HCV is critical for developing host-centered anti-HCV approaches. Entry represents a potential target for antiviral strategies; however, no FDA-approved HCV entry inhibitors are currently available. We reported that two host kinases, AAK1 and GAK, regulate HCV assembly. Here, we provide evidence that AAK1 and GAK regulate HCV entry independently of their role in HCV assembly and define the mechanisms underlying AAK1- and GAK-mediated HCV entry. By regulating temporally distinct steps in the HCV life cycle, AAK1 and GAK represent "master regulators" of HCV infection and potential targets for antiviral strategies. Indeed, approved anticancer drugs that potently inhibit AAK1 or GAK inhibit HCV entry in addition to assembly. These results contribute to an understanding of the mechanisms of HCV entry and reveal attractive host targets for antiviral strategies as well as approved candidate inhibitors of these targets, with potential implications for other viruses that hijack clathrin-mediated pathways.
PMID: 25653444 [PubMed - indexed for MEDLINE]
The endoplasmic reticulum membrane J protein C18 executes a distinct role in promoting simian virus 40 membrane penetration.
J Virol. 2015 Apr;89(8):4058-68
Authors: Bagchi P, Walczak CP, Tsai B
UNLABELLED: The nonenveloped simian virus 40 (SV40) hijacks the three endoplasmic reticulum (ER) membrane-bound J proteins B12, B14, and C18 to escape from the ER into the cytosol en route to successful infection. How C18 controls SV40 ER-to-cytosol membrane penetration is the least understood of these processes. We previously found that SV40 triggers B12 and B14 to reorganize into discrete puncta in the ER membrane called foci, structures postulated to represent the cytosol entry site (C. P. Walczak, M. S. Ravindran, T. Inoue, and B. Tsai, PLoS Pathog 10: e1004007, 2014). We now find that SV40 also recruits C18 to the virus-induced B12/B14 foci. Importantly, the C18 foci harbor membrane penetration-competent SV40, further implicating this structure as the membrane penetration site. Consistent with this, a mutant SV40 that cannot penetrate the ER membrane and promote infection fails to induce C18 foci. C18 also regulates the recruitment of B12/B14 into the foci. In contrast to B14, C18's cytosolic Hsc70-binding J domain, but not the lumenal domain, is essential for its targeting to the foci; this J domain likewise is necessary to support SV40 infection. Knockdown-rescue experiments reveal that C18 executes a role that is not redundant with those of B12/B14 during SV40 infection. Collectively, our data illuminate C18's contribution to SV40 ER membrane penetration, strengthening the idea that SV40-triggered foci are critical for cytosol entry.
IMPORTANCE: Polyomaviruses (PyVs) cause devastating human diseases, particularly in immunocompromised patients. As this virus family continues to be a significant human pathogen, clarifying the molecular basis of their cellular entry pathway remains a high priority. To infect cells, PyV traffics from the cell surface to the ER, where it penetrates the ER membrane to reach the cytosol. In the cytosol, the virus moves to the nucleus to cause infection. ER-to-cytosol membrane penetration is a critical yet mysterious infection step. In this study, we clarify the role of an ER membrane protein called C18 in mobilizing the simian PyV SV40, a PyV archetype, from the ER into the cytosol. Our findings also support the hypothesis that SV40 induces the formation of punctate structures in the ER membrane, called foci, that serve as the portal for cytosol entry of the virus.
PMID: 25631089 [PubMed - indexed for MEDLINE]
Brentuximab vedotin demonstrates objective responses in a phase 2 study of relapsed/refractory DLBCL with variable CD30 expression.
Blood. 2015 Feb 26;125(9):1394-402
Authors: Jacobsen ED, Sharman JP, Oki Y, Advani RH, Winter JN, Bello CM, Spitzer G, Palanca-Wessels MC, Kennedy DA, Levine P, Yang J, Bartlett NL
Several non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), variably express CD30. This phase 2, open-label study evaluated the efficacy of brentuximab vedotin, an anti-CD30 antibody-drug conjugate, in relapsed/refractory CD30(+) NHL. This planned subset analysis of B-cell NHLs includes 49 patients with DLBCL and 19 with other B-cell NHLs. Objective response rate was 44% for DLBCL, including 8 (17%) complete remissions (CRs) with a median duration of 16.6 months thus far (range, 2.7 to 22.7+ months). There was no statistical correlation between response and level of CD30 expression; however, all responding patients had quantifiable CD30 by computer-assisted assessment of immunohistochemistry. DLBCL patients were generally refractory to first-line (76%) and most recent therapies (82%), and 44% of these refractory patients responded (15% CRs). Patients with other B-cell lymphomas also responded: 1 CR, 2 partial responses (PRs) of 6 with gray zone, 1 CR of 6 with primary mediastinal B-cell, and 1 CR of 3 with posttransplant lymphoproliferative disorder. Adverse events were consistent with known toxicities. The combination of brentuximab vedotin with rituximab was generally well tolerated and had activity similar to brentuximab vedotin alone. Overall, significant activity with brentuximab vedotin was observed in relapsed/refractory DLBCL, and responses occurred across a range of CD30 expression. This study was registered at www.clinicaltrials.gov as #NCT01421667.
PMID: 25573987 [PubMed - indexed for MEDLINE]
How I use fibrinogen replacement therapy in acquired bleeding.
Blood. 2015 Feb 26;125(9):1387-93
Authors: Levy JH, Goodnough LT
Fibrinogen is a critical protein for hemostasis and clot formation. However, transfusion guidelines have variable recommendations for maintaining fibrinogen levels in bleeding patients. An increasing number of studies support the practice of fibrinogen replacement therapy for acquired coagulopathies, and additional studies are underway. Fibrinogen therapy can be administered with cryoprecipitate or fibrinogen concentrates, and clinical practice varies according to their availability and licensing status. Fibrinogen concentrate therapy has been studied in animal models and clinical trials and supports the critical role of fibrinogen repletion in bleeding patients. Point-of-care testing will have an important role in guiding fibrinogen replacement for hemostatic therapy in clinical settings such as cardiovascular surgery, postpartum hemorrhage, and trauma. Fibrinogen therapy is an important component of a multimodal strategy for the treatment of coagulopathic bleeding.
PMID: 25519751 [PubMed - indexed for MEDLINE]
Total knee arthroplasty in patients with ipsilateral fused hip: a technical note.
Clin Orthop Surg. 2014 Dec;6(4):476-9
Authors: Goodman SB, Huddleston JI, Hur D, Song SJ
We report the surgical technique used to perform posterior-stabilized total knee arthroplasty (TKA) in two patients with a well positioned and functional hip arthrodesis. Intraoperatively, the operating table was placed in an increased Trendelenburg position. Episodically, we flexed the foot of the table by 90° to allow maximal knee flexion to facilitate exposure and bone cuts. We opted to resect the patella and tibia first to enable exposure, given the stiffness of the arthritic knee. One patient's medical condition prohibited complex conversion total hip arthroplasty (THA) prior to the TKA. The other patient's scarred soft tissues around the hip, due to chronic infection and multiple operations, made THA risky. The final outcome provided satisfactory results at a minimum of 2 years postoperatively. TKA can be successfully performed with adjustments of table position and modification of the sequence of surgical steps in patients with ipsilateral hip fusion.
PMID: 25436074 [PubMed - indexed for MEDLINE]
The burden of selected congenital anomalies amenable to surgery in low and middle-income regions: cleft lip and palate, congenital heart anomalies and neural tube defects.
Arch Dis Child. 2015 Mar;100(3):233-8
Authors: Higashi H, Barendregt JJ, Kassebaum NJ, Weiser TG, Bickler SW, Vos T
OBJECTIVE: To quantify the burden of selected congenital anomalies in low and middle-income countries (LMICs) that could be reduced should surgical programmes cover the entire population with access to quality care.
DESIGN: Burden of disease and epidemiological modelling.
SETTING: LMICs from all global regions.
POPULATION: All prevalent cases of selected congenital anomalies at birth in 2010.
MAIN OUTCOME MEASURES: Disability-adjusted life years (DALYs).
INTERVENTIONS AND METHODS: Surgical programmes for three congenital conditions were analysed: clefts (lip and palate); congenital heart anomalies; and neural tube defects. Data from the Global Burden of Disease 2010 Study were used to estimate the combination of fatal burden that could be addressed by surgical care and the additional long-term non-fatal burden associated with increased survival.
RESULTS: Of the estimated 21.6 million DALYs caused by these three conditions in LMICs, 12.4 million DALYs (57%) are potentially addressable by surgical care among the population born with such conditions. Neural tube defects have the largest potential with 76% of burden amenable by surgery, followed by clefts (59%) and congenital heart anomalies (49%). Sub-Saharan Africa and South Asia have the greatest proportion of surgically addressable burden for clefts (68%), North Africa and Middle East for congenital heart anomalies (73%), and South Asia for neural tube defects (81%).
CONCLUSIONS: There is an important and neglected role surgical programmes can play in reducing the burden of congenital anomalies in LMICs.
PMID: 25260520 [PubMed - indexed for MEDLINE]
Inferior vena cava filters and postoperative outcomes in patients undergoing bariatric surgery: a meta-analysis.
Surg Obes Relat Dis. 2014 Jul-Aug;10(4):725-33
Authors: Kaw R, Pasupuleti V, Wayne Overby D, Deshpande A, Coleman CI, Ioannidis JP, Hernandez AV, Cardiovascular Meta-analysis Research Group
PMID: 25224168 [PubMed - indexed for MEDLINE]
Adaptive human CDKAL1 variants underlie hormonal response variations at the enteroinsular axis.
PLoS One. 2014;9(9):e105410
Authors: Chang CL, Cai JJ, Huang SY, Cheng PJ, Chueh HY, Hsu SY
Recent analyses have identified positively selected loci that explain differences in immune responses, body forms, and adaptations to extreme climates, but variants that describe adaptations in energy-balance regulation remain underexplored. To identify variants that confer adaptations in energy-balance regulation, we explored the evolutionary history and functional associations of candidate variants in 207 genes. We screened single nucleotide polymorphisms in genes that had been associated with energy-balance regulation for unusual genetic patterns in human populations, followed by studying associations among selected variants and serum levels of GIP, insulin, and C-peptide in pregnant women after an oral glucose tolerance test. Our analysis indicated that 5' variants in CDKAL1, CYB5R4, GAD2, and PPARG are marked with statistically significant signals of gene-environment interactions. Importantly, studies of serum hormone levels showed that variants in CDKAL1 are associated with glucose-induced GIP and insulin responses (p<0.05). On the other hand, a GAD2 variant exhibited a significant association with glucose-induced C-peptide response. In addition, simulation analysis indicated that a type 2 diabetes risk variant in CDKAL1 (rs7754840) was selected in East Asians ∼6,900 years ago. Taken together, these data indicated that variants in CDKAL1 and GAD2 were targets of prior environmental selection. Because the selection of the CDKAL1 variant overlapped with the selection of a cluster of GIP variants in the same population ∼11,800 to 2,000 years ago, we speculate that these regulatory genes at the human enteroinsular axis could be highly responsive to environmental selection in recent human history.
PMID: 25222615 [PubMed - indexed for MEDLINE]
Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the U.S. multi-society task force on colorectal cancer.
Gastrointest Endosc. 2014 Oct;80(4):543-62
Authors: Johnson DA, Barkun AN, Cohen LB, Dominitz JA, Kaltenbach T, Martel M, Robertson DJ, Boland CR, Giardello FM, Lieberman DA, Levin TR, Rex DK
PMID: 25220509 [PubMed - indexed for MEDLINE]
Coming of age of genetic investigations in late-life mental health.
Am J Geriatr Psychiatry. 2014 Oct;22(10):953-6
Authors: O'Hara R, Hallmayer J
PMID: 25217024 [PubMed - indexed for MEDLINE]
Seasonal patterns in human A (H5N1) virus infection: analysis of global cases.
PLoS One. 2014;9(9):e106171
Authors: Mathur MB, Patel RB, Gould M, Uyeki TM, Bhattacharya J, Xiao Y, Gillaspie Y, Chae C, Khazeni N
BACKGROUND: Human cases of highly pathogenic avian influenza (HPAI) A (H5N1) have high mortality. Despite abundant data on seasonal patterns in influenza epidemics, it is unknown whether similar patterns exist for human HPAI H5N1 cases worldwide. Such knowledge could help decrease avian-to-human transmission through increased prevention and control activities during peak periods.
METHODS: We performed a systematic search of published human HPAI H5N1 cases to date, collecting month, year, country, season, hemisphere, and climate data. We used negative binomial regression to predict changes in case incidence as a function of season. To investigate hemisphere as a potential moderator, we used AIC and the likelihood-ratio test to compare the season-only model to nested models including a main effect or interaction with hemisphere. Finally, we visually assessed replication of seasonal patterns across climate groups based on the Köppen-Geiger climate classification.
FINDINGS: We identified 617 human cases (611 with complete seasonal data) occurring in 15 countries in Southeast Asia, Africa, and the Middle East. Case occurrence was much higher in winter (n = 285, p = 0.03) than summer (n = 64), and the winter peak occurred across diverse climate groups. There was no significant interaction between hemisphere and season.
INTERPRETATION: Across diverse climates, HPAI H5N1 virus infection in humans increases significantly in winter. This is consistent with increased poultry outbreaks and HPAI H5N1 virus transmission during cold and dry conditions. Prioritizing prevention and control activities among poultry and focusing public health messaging to reduce poultry exposures during winter months may help to reduce zoonotic transmission of HPAI H5N1 virus in resource-limited settings.
PMID: 25215608 [PubMed - indexed for MEDLINE]
On-line visualization of ischemic burden during repetitive ischemia/reperfusion.
JACC Cardiovasc Imaging. 2014 Sep;7(9):956-8
Authors: Pavo N, Emmert MY, Giricz Z, Varga ZV, Ankersmit HJ, Maurer G, Hoerstrup SP, Ferdinandy P, Wu JC, Gyöngyösi M
PMID: 25212802 [PubMed - indexed for MEDLINE]
RNAi pathway genes are resistant to small RNA mediated gene silencing in the protozoan parasite Entamoeba histolytica.
PLoS One. 2014;9(9):e106477
Authors: Pompey JM, Morf L, Singh U
The RNA interference pathway in the protist Entamoeba histolytica plays important roles in permanent gene silencing as well as in the regulation of virulence determinants. Recently, a novel RNA interference (RNAi)-based silencing technique was developed in this parasite that uses a gene endogenously silenced by small RNAs as a "trigger" to induce silencing of other genes that are fused to it. Fusion to a trigger gene induces the production of gene-specific antisense small RNAs, resulting in robust and permanent silencing of the cognate gene. This approach has silenced multiple genes including those involved in virulence and transcriptional regulation. We now demonstrate that all tested genes of the amebic RNAi pathway are unable to be silenced using the trigger approach, including Argonaute genes (Ago2-1, Ago2-2, and Ago2-3), RNaseIII, and RNA-dependent RNA polymerase (RdRP). In all situations (except for RdRP), fusion to a trigger successfully induces production of gene-specific antisense small RNAs to the cognate gene. These small RNAs are capable of silencing a target gene in trans, indicating that they are functional; despite this, however, they cannot silence the RNAi pathway genes. Interestingly, when a trigger is fused to RdRP, small RNA induction to RdRP does not occur, a unique phenotype hinting that either RdRP is highly resistant to being a target of small RNAs or that small RNA generation may be controlled by RdRP. The inability of the small RNA pathway to silence RNAi genes in E. histolytica, despite the generation of functional small RNAs to these loci suggest that epigenetic factors may protect certain genomic loci and thus determine susceptibility to small RNA mediated silencing.
PMID: 25198343 [PubMed - indexed for MEDLINE]
Socioeconomic status and age at menarche: an examination of multiple indicators in an ethnically diverse cohort.
Ann Epidemiol. 2014 Oct;24(10):727-33
Authors: Deardorff J, Abrams B, Ekwaru JP, Rehkopf DH
PURPOSE: Ethnic disparities exist in US girls' ages at menarche. Overweight and low socioeconomic status (SES) may contribute to these disparities but past research has been equivocal. We sought to determine which SES indicators were associated uniquely with menarche, for which ethnic groups, and whether associations operated through overweight.
METHODS: Using National Longitudinal Study of Youth data, we examined associations between SES indicators and age at menarche. Participants were 4851 girls and their mothers. We used survival analyses to examine whether SES, at various time points, was associated with menarche, whether body mass index mediated associations, and whether race/ethnicity modified associations.
RESULTS: Black and Hispanic girls experienced menarche earlier than whites. After adjusting for SES, there was a 50% reduction in the effect estimate for "being Hispanic" and 40% reduction for "being black" versus "being white" on menarche. SES indicators were associated uniquely with earlier menarche, including mother's unmarried status and lower family income. Associations varied by race/ethnicity. Body mass index did not mediate associations.
CONCLUSIONS: Racial differences in menarche may in large part be due to SES differences. Future experimental or quasiexperimental studies should examine whether intervening on SES factors could have benefits for delaying menarche among blacks and Hispanics.
PMID: 25108688 [PubMed - indexed for MEDLINE]
Coping with college and inflammatory bowel disease: implications for clinical guidance and support.
Inflamm Bowel Dis. 2014 Sep;20(9):1618-27
Authors: Schwenk HT, Lightdale JR, Arnold JH, Goldmann DA, Weitzman ER
BACKGROUND: Studies have shown that young adults with chronic diseases, including inflammatory bowel disease (IBD), experience greater difficulty during the transition to college, reaching lower levels of educational attainment and reporting greater levels of perceived stress than their otherwise-healthy peers. We performed a qualitative study to better understand how underlying illness shapes the college experience for patients with IBD and how the college experience, in turn, impacts disease management.
METHODS: Fifteen college students with IBD were recruited from the Boston Children's Hospital Center for IBD. We conducted an approximately 1 hour semistructured qualitative interview with each participant, and the interviews were thematically analyzed after an iterative and inductive process.
RESULTS: Four primary themes were identified: (1) The transition experience of college students with IBD is shaped by their health status, perceived readiness, and preparedness, (2) Elements of the college environment pose specific challenges to young adults with IBD that require adaptive strategies, (3) College students with IBD integrate their underlying illness with their individual and social identity, and (4) College students navigate health management by conceptualizing themselves, their families, and providers as serving particular roles.
CONCLUSIONS: For young adults with IBD, college is a proving ground for demonstrating self-care and disease management practices. Future initiatives aimed at this population should recognize the evolving roles of patients, parents, and providers in disease management. Increased attention should also be paid to the promotion of patient's self-management and the unique challenges of the structural and psychosocial college environment.
PMID: 25105948 [PubMed - indexed for MEDLINE]
Affordable Care Act and bariatric surgery.
Surg Obes Relat Dis. 2014 Jul-Aug;10(4):571-2
Authors: Morton J
PMID: 24958645 [PubMed - indexed for MEDLINE]
What variables are associated with successful weight loss outcomes for bariatric surgery after 1 year?
Surg Obes Relat Dis. 2014 Jul-Aug;10(4):697-704
Authors: Robinson AH, Adler S, Stevens HB, Darcy AM, Morton JM, Safer DL
BACKGROUND: Prior evidence indicates that predictors of weight loss outcomes after gastric bypass surgery fall within 5 domains: 1) presurgical factors, 2) postsurgical psychosocial variables (e.g., support group attendance), 3) postsurgical eating patterns, 4) postsurgical physical activity, and 5) follow-up at postsurgical clinic. However, little data exist on which specific behavioral predictors are most associated with successful outcomes (e.g.,≥ 50% excess weight loss) when considering the 5 domains simultaneously. The objective of this study was to specify the behavioral variables, and their respective cutoff points, most associated with successful weight loss outcomes.
METHODS: Signal detection analysis evaluated associations between 84 pre- and postsurgical behavioral variables (within the 5 domains) and successful weight loss at ≥ 1 year in 274 postgastric bypass surgery patients.
RESULTS: Successful weight loss was highest (92.6%) among those reporting dietary adherence of>3 on a 9-point scale (median = 5) who grazed no more than once-per-day. Among participants reporting dietary adherence<3 and grazing daily or less, success rates more than doubled when highest lifetime body mass index was<53.7 kg/m(2). Success rates also doubled for participants with dietary adherence = 3 if attending support groups. No variables from the physical activity or postsurgical follow-up domains were significant, nor were years since surgery. The overall model's sensitivity = .62, specificity = .92.
CONCLUSIONS: To our knowledge, this is the first study to simultaneously consider the relative contribution of behavioral variables within 5 domains and offer clinicians an assessment algorithm identifying cut-off points for behaviors most associated with successful postsurgical weight loss. Such data may inform prospective study designs and postsurgical interventions.
PMID: 24913590 [PubMed - indexed for MEDLINE]
A randomized comparison of long-axis and short-axis imaging for in-plane ultrasound-guided popliteal-sciatic perineural catheter insertion.
J Anesth. 2014 Dec;28(6):854-60
Authors: Kim TE, Howard SK, Funck N, Harrison TK, Walters TL, Wagner MJ, Ganaway T, Mullens J, Lehnert B, Mariano ER
PURPOSE: Ultrasound-guided long-axis in-plane sciatic perineural catheter insertion has been described but not validated. For the popliteal-sciatic nerve, we hypothesized that a long-axis in-plane technique, placing the catheter parallel and posterior to the nerve, results in faster onset of sensory anesthesia compared to a short-axis in-plane technique.
METHODS: Preoperatively, patients receiving a popliteal-sciatic perineural catheter were randomly assigned to either the long-axis or short-axis technique. Mepivacaine 2% was administered via the catheter following insertion. The primary outcome was time to achieve complete sensory anesthesia. Secondary outcomes included procedural time, onset time of motor block, and pain on postoperative day 1.
RESULTS: Fifty patients were enrolled. In the long-axis group (n = 25), all patients except 1 (4%) had successful catheter placement per protocol. Two patients (8%) in the long-axis group and 1 patient (4%) in the short-axis group (n = 25) did not achieve sensory anesthesia by 30 min and were withdrawn. Seventeen of 24 (71%) and 17 of 22 (77%) patients in the short-axis and long-axis groups, respectively, achieved the primary outcome of complete sensory anesthesia (p = 0.589). The short-axis group (n = 17) required a median (10th-90th ‰) of 18.0 (8.4-30.0) min compared to 18.0 (11.4-27.6) min for the long-axis group (n = 17, p = 0.208) to achieve complete sensory anesthesia. Procedural time was 6.5 (4.0-12.0) min for the short-axis and 9.5 (7.0-12.7) min for the long-axis (p < 0.001) group. There were no statistically significant differences in other secondary outcomes.
CONCLUSION: Long-axis in-plane popliteal-sciatic perineural catheter insertion requires more time to perform compared to a short-axis in-plane technique without demonstrating any advantages.
PMID: 24789659 [PubMed - indexed for MEDLINE]
Role of grandparenting in postmenopausal women's cognitive health: results from the Women's Healthy Aging Project.
Menopause. 2014 Oct;21(10):1069-74
Authors: Burn KF, Henderson VW, Ames D, Dennerstein L, Szoeke C
OBJECTIVE: Preserving aging cognition improves quality of life and delays dementia onset. Previous studies have shown that social engagement can maintain cognition; however, none has examined the effects of grandparenting, an important role among postmenopausal women. This study aims to examine the role of grandparenting in cognition among postmenopausal women.
METHODS: Participants were 186 Australian women from the longitudinal prospective Women's Healthy Aging Project. Cognition was assessed using the Symbol-Digit Modalities Test (SDMT), California Verbal Learning Test, and Tower of London.
RESULTS: Amount of time spent minding grandchildren predicted differences in SDMT performance (P < 0.01). The highest cognitive scores for most tests were seen in participants who minded grandchildren for 1 day/week. Minding grandchildren for 1 day/week was also a significant positive predictor of California Verbal Learning Test immediate recall performance (P < 0.05). However, minding grandchildren for 5 days or more per week predicted lower SDMT performance (P < 0.05).
CONCLUSIONS: The data suggest that the highest cognitive performance is demonstrated by postmenopausal women who spend 1 day/week minding grandchildren; however, minding grandchildren for 5 days or more per week predicts lower working memory performance and processing speed. These results indicate that highly frequent grandparenting predicts lower cognitive performance.
PMID: 24714623 [PubMed - indexed for MEDLINE]
Multiple ethnic origins of mitochondrial DNA lineages for the population of Mauritius.
PLoS One. 2014;9(3):e93294
Authors: Fregel R, Seetah K, Betancor E, Suárez NM, Čaval D, Caval S, Janoo A, Pestano J
This article reports on the first genetic assessment of the contemporary Mauritian population. Small island nodes such as Mauritius played a critical role in historic globalization processes and revealing high-resolution details of labour sourcing is crucial in order to better understand early-modern diaspora events. Mauritius is a particularly interesting case given detailed historic accounts attesting to European (Dutch, French and British), African and Asian points of origin. Ninety-seven samples were analysed for mitochondrial DNA to begin unravelling the complex dynamics of the island's modern population. In corroboration with general demographic information, the majority of maternal lineages were derived from South Asia (58.76%), with Malagasy (16.60%), East/Southeast Asian (11.34%) and Sub-Saharan African (10.21%) also making significant contributions. This study pinpoints specific regional origins for the South Asian genetic contribution, showing a greater influence on the contemporary population from northern and southeast India. Moreover, the analysis of lineages related to the slave trade demonstrated that Madagascar and East Asia were the main centres of origin, with less influence from West Africa.
PMID: 24676463 [PubMed - indexed for MEDLINE]
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