Levels of Intestinal Inflammation and Fibrosis in Resection Specimens after Preoperative Anti-Tumor Necrosis Factor Alpha Treatment in Patients with Crohn's Disease:A Comparative Pilot Study

Background. Strictures are a common complication in Crohn’s disease (CD), found in more than 50% of patients. They are characterized by the excessive deposition of extracellular proteins in the tissue as a result of the chronic inflammatory process. The effect of anti-tumor necrosis factor alpha (TNF-α) therapy on the development of fibrosis is not yet fully understood. Aim. To investigate whether the degree of intestinal inflammation and fibrosis is correlated with preoperative anti-TNF-α therapy in patients with CD who are undergoing bowel resection. Methods. This unblinded, prospective, single tertiary center, pilot cohort study included all adult patients with CD who underwent elective, laparoscopic, or open intestinal resection. Preoperative investigations included measurement of blood TNF-α concentration, specific antidrug antibodies, and the concentration of selected inflammatory cytokines. Three pathologists independently examined the specimens and assessed the degree of inflammation and fibrosis. Results. Histopathological specimens from 10 patients with CD who underwent ileocecal or ileocolic resections were retrieved. Four of those patients were on anti-TNF-α treatment prior to surgery. The last dose of the anti-TNF-α agent was administered 1–9 weeks prior to bowel resection. Patients on anti-TNF-α treatment had a higher fibrosis score than controls (p=0.01). Anti-TNF-α treatment was not associated with an increase in CD68- or CD163-positive macrophages. There was no significant relationship between the time from the final preoperative anti-TNF-α dose to surgery and the fibrosis score. No significant association was found between the concentration of major inflammatory cytokines, including TNF-α, and the fibrosis score or degree of inflammation. Conclusions. Patients who underwent preoperative anti-TNF-α treatment had a higher fibrosis score than controls

Aging in Dense Colloids as Diffusion in the Logarithm of Time

The far-from-equilibrium dynamics of glassy systems share important phenomenological traits. A transition is generally observed from a time-homogeneous dynamical regime to an aging regime where physical changes occur intermittently and, on average, at a decreasing rate. It has been suggested that a global change of the independent time variable to its logarithm may render the aging dynamics homogeneous: for colloids, this entails diffusion but on a logarithmic time scale. Our novel analysis of experimental colloid data confirms that the mean square displacement grows linearly in time at low densities and shows that it grows linearly in the logarithm of time at high densities. Correspondingly, pairs of particles initially in close contact survive as pairs with a probability which decays exponentially in either time or its logarithm. The form of the Probability Density Function of the displacements shows that long-ranged spatial correlations are very long-lived in dense colloids. A phenomenological stochastic model is then introduced which relies on the growth and collapse of strongly correlated clusters ("dynamic heterogeneity"), and which reproduces the full spectrum of observed colloidal behaviors depending on the form assumed for the probability that a cluster collapses during a Monte Carlo update. In the limit where large clusters dominate, the collapse rate is ~1/t, implying a homogeneous, log-Poissonian process that qualitatively reproduces the experimental results for dense colloids. Finally an analytical toy-model is discussed to elucidate the strong dependence of the simulation results on the integrability (or lack thereof) of the cluster collapse probability function.Comment: 6 pages, extensively revised, final version; for related work, see http://www.physics.emory.edu/faculty/boettcher/ or http://www.fysik.sdu.dk/staff/staff-vip/pas-personal.htm

Coronary artery disease-associated genetic variants and biomarkers of inflammation

Introduction: Genetic constitution and inflammation both contribute to development of coronary artery disease (CAD). Several CAD-associated single-nucleotide polymorphisms (SNPs) have recently been identified, but their functions are largely unknown. We investigated the associations between CAD-associated SNPs and five CAD-related inflammatory biomarkers. Methods: We genotyped 45 CAD-associated SNPs in 701 stable CAD patients in whom levels of high-sensitivity C-reactive protein (hsRCP), interleukin-6, calprotectin, fibrinogen and complement component 3 levels had previously been measured. A genetic risk score was calculated to assess the combined risk associated with all the genetic variants. A multiple linear regression model was used to assess associations between the genetic risk score, single SNPs, and the five inflammatory biomarkers. Results: The minor allele (G) (CAD risk allele) of rs2075650 (TOMM40/APOE) was associated with lower levels of high-sensitivity C-reactive protein (effect per risk allele: -0.37 mg/l [95%CI -0.56 to -0.18 mg/l]). The inflammatory markers tested showed no association with the remaining 44 SNPs or with the genetic risk score. Conclusions: In stable CAD patients, the risk allele of a common CAD-associated marker at the TOMM40/APOE locus was associated with lower hsCRP levels. No other genetic variants or the combined effect of all variants were associated with the five inflammatory biomarkers

DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1

DNA single-strand breaks (SSBs) are the commonest DNA lesions arising spontaneously in cells, and if not repaired may block transcription or may be converted into potentially lethal/clastogenic DNA double-strand breaks (DSBs). Recently, evidence has emerged that defects in the rapid repair of SSBs preferentially impact the nervous system. In particular, spinocerebellar ataxia with axonal neuropathy (SCAN1) is a human disease that is associated with mutation of TDP1 (tyrosyl DNA phosphodiesterase 1) protein and with a defect in repairing certain types of SSBs. Although SCAN1 is a rare neurodegenerative disorder, understanding the molecular basis of this disease will lead to better understanding of neurodegenerative processes. Here we review recent progress in our understanding of TDP1, single-strand break repair (SSBR), and neurodegenerative disease

Growth Hormone Induces Transforming Growth Factor‐Beta‐Induced Protein in Podocytes: Implications for Podocyte Depletion and Proteinuria

The glomerular podocytes form a major size selective barrier for the filtration of serum proteins and reduced podocyte number is a critical event in the pathogenesis of proteinuria during diabetic nephropathy (DN). An elevated level of growth hormone (GH) is implicated as a causative factor in the development of nephropathy in patients with type 1 diabetes mellitus. We have previously shown that podocytes express GH receptor and are a target for GH action. To elucidate the molecular basis for the effects of GH on podocyte depletion, we conducted PCR‐array analyses for extracellular matrix and adhesion molecules in podocytes. Our studies reveal that GH increases expression of a gene that encodes transforming growth factor‐beta‐induced protein (TGFBIp) expression. Similarly, microarray data retrieved from the Nephromine database revealed elevation of TGFBIp in patients with DN. Treatment with GH results in increased secretion of extracellular TGFBIp by podocytes. Both GH and TGFBIp induced apoptosis and epithelial mesenchymal transition (EMT) of podocytes. Exposure of podocytes to GH and TGFBIp resulted in increased migration of cells and altered podocyte permeability to albumin across podocyte monolayer. Administration of GH to rats induced EMT and apoptosis in the glomerular fraction of the kidney. Therefore, we conclude that the GH‐dependent increase in TGFBIp in the podocyte is one of the mechanisms responsible for podocyte depletion in DN. J. Cell. Biochem. 116: 1947–1956, 2015. © 2015 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/112213/1/jcb25150.pd

Head and neck squamous cell carcinoma of unknown primary: Neck dissection and radiotherapy or definitive radiotherapy

Background Management of head and neck carcinoma from unknown primary (HNCUP) remains controversial, with neck dissection and radiotherapy (RT) or definitive RT both commonly used. The purpose of this study was to characterize HNCUP and retrospectively compare outcomes for patients treated with neck dissection + RT versus definitive RT. Methods From 1994 to 2009, 41 patients with HNCUP underwent either neck dissection + RT ( n  = 22) or definitive RT ± concurrent chemotherapy ( n  = 19) at our institution. Treatment outcomes were compared using Kaplan–Meier methods and log‐rank test. Results There were no differences between patients treated with neck dissection + RT and definitive RT in overall survival (OS), progression‐free survival (PFS), locoregional relapse‐free survival (LRFS), freedom from locoregional failure (FFLRG), or freedom from distant failure (FFDF). Among 17 patients who underwent neck dissection + RT for whom human papillomavirus (HPV) status could be determined, HPV(+) patients trended toward improved OS ( p  = .06) and PFS ( p  = .15). Conclusion Neck dissection and postoperative RT resulted in similar outcomes as definitive RT. The prognostic implications of HPV(+) nodes in HNCUP are similar to those in oropharyngeal primary cancers. © 2013 Wiley Periodicals, Inc. Head Neck 36: 1589–1595, 2014Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109313/1/hed23479.pd

Categorizing facial creases: A review

Ensuring uniformity in the nomenclature standardization of facial creases is important to enable the scholarly community to follow and debate the advancements in research. This review highlights the prevailing disparity in the nomenclature that refers to the same facial crease by researchers and laypeople, and suggests uniform names for the facial creases based on available literature. The previous and current trends in facial crease classification are also discussed. The nomenclature of the facial creases considered for this review include the following: the nasolabial fold, corner of the mouth lines, upper and lower lip creases around the mouth region, the mandibular folds, the bifid nose, the transverse nasal line, the vertical glabellar line, chin crease, the mental crease, four type of creases around the eyes, forehead creases, and periauricular creases. A figure illustrating the above facial creases is included as reference. It is hoped that the proposed standardization of nomenclature would ensure a more scientific referencing of facial creases enabling more effective scientific interaction among the scholarly community as well as the laypeople interested in the research and application of facial creases

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO