bluuebunny/crossref_metadata_2025 huggingface dataset:
Prospective Evaluation of a Clinical Pathway for Suspected Appendicitis
Authors: Saucier Ashley , Huang Eunice Y. , Emeremni Chetachi A. , Pershad Jay
Published: December 2013

OBJECTIVE:

To evaluate the diagnostic accuracy of a clinical pathway for suspected appendicitis combining the Samuel’s pediatric appendicitis score (PAS) and selective use of ultrasonography (US) as the primary imaging modality.

METHODS:

Prospective, observational cohort study conducted at an urban, academic pediatric emergency department. After initial evaluation, patients were determined to be at low (PAS 1–3), intermediate (PAS 4–7), or high (PAS 8–10) risk for appendicitis. Low-risk patients were discharged with telephone follow-up. High-risk patients received immediate surgical consultation. Patients at intermediate risk for appendicitis underwent US.

RESULTS:

Of the 196 patients enrolled, 65 (33.2%) had appendicitis. An initial PAS of 1–3 was noted in 44 (22.4%), 4–7 in 119 (60.7%), and 8–10 in 33 (16.9%) patients. Ultrasonography was performed in 128 (65.3%) patients, and 48 (37.5%) were positive. An abdominal computed tomography scan was requested by the surgical consultants in 13 (6.6%) patients. The negative appendectomy rate was 3 of 68 (4.4%). Follow-up was established on 190 of 196 (96.9%) patients. Overall diagnostic accuracy of the pathway was 94% (95% confidence interval [CI] 91%–97%) with a sensitivity of 92.3% (95% CI 83.0%–97.5%), specificity of 94.7% (95% CI 89.3%–97.8%), likelihood ratio (+) 17.3 (95% CI 8.4–35.6) and likelihood ratio (−) 0.08 (95% CI 0.04–0.19).

CONCLUSIONS:

Our protocol demonstrates high sensitivity and specificity for diagnosis of appendicitis in children. Institutions should consider investing in resources that increase the availability of expertise in pediatric US. Standardization of care may decrease radiation exposure associated with use of computed tomography scans.
Acute Lower Respiratory Infection Among Bacille Calmette-Guérin (BCG)–Vaccinated Children
Authors: Hollm-Delgado Maria-Graciela , Stuart Elizabeth A. , Black Robert E.
Published: December 2013

OBJECTIVE:

To determine whether Bacille Calmette-Guerin (BCG) vaccination is linked to the risk of acute lower respiratory infection (ALRI) among children <5 years of age.

METHODS:

Data from Macro International Demographic and Health Surveys and United Nations Children’s Fund Multiple Indicator Cluster Surveys were used to identify a primary cohort of 58 021 children in 19 countries (2005–2010) and a secondary cohort of 93 301 children in 18 countries (2000–2007). Information was collected by trained interviewers during home visits using standardized questionnaires, review of vaccination health cards, and measurement of health indicators.

RESULTS:

BCG vaccination was associated with a 17% to 37% risk reduction for suspected ALRI in both cohorts. The only vaccine or vitamin supplement to modify the effect of BCG was diphtheria-tetanus-pertussis (DTP; P < .001). The order in which the vaccines were first received was central to this phenomena (BCG before DTP, adjusted/propensity score–weighted relative risk [apRR]: 0.79, 95% confidence interval [CI]: 0.70–0.89; BCG with DTP, apRR: 0.82, 95% CI: 0.71–0.94; and BCG after DTP, apRR: 1.00, 95% CI: 0.87–1.13) but not number of DTP doses received. Other modifiers included vaccine strain used in immunization programs, chlorinating drinking water, using wood-burning fuel cook stoves, and owning livestock.

CONCLUSIONS:

Children vaccinated with BCG had a significantly lower risk of suspected ALRI. Clarification is needed as to whether this is due to reductions in the underlying risk of tuberculosis or ALRI per se.
Recognition and Management of Iatrogenically Induced Opioid Dependence and Withdrawal in Children
Authors: Galinkin Jeffrey , Koh Jeffrey Lee ,   COMMITTEE ON DRUGS,   SECTION ON ANESTHESIOLOGY AND PAIN MEDICINE, Frattarelli Daniel A. C. , Green Thomas P. , Johnson Timothy D. , Neville Kathleen A. , Paul Ian M. , Van Den Anker John N. , Bannister Carolyn Fleming , Tobias Joseph , Anderson Corrie T. M. , Goldschneider Kenneth R. , Polaner David Mark
Published: December 2013

This Clinical Report was reaffirmed July 2023.

Opioids are often prescribed to children for pain relief related to procedures, acute injuries, and chronic conditions. Round-the-clock dosing of opioids can produce opioid dependence within 5 days. According to a 2001 Consensus Paper from the American Academy of Pain Medicine, American Pain Society, and American Society of Addiction Medicine, dependence is defined as “a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist.” Although the experience of many children undergoing iatrogenically induced withdrawal may be mild or goes unreported, there is currently no guidance for recognition or management of withdrawal for this population. Guidance on this subject is available only for adults and primarily for adults with substance use disorders. The guideline will summarize existing literature and provide readers with information currently not available in any single source specific for this vulnerable pediatric population.
Surfactant Replacement Therapy for Preterm and Term Neonates With Respiratory Distress
Authors: Polin Richard A. , Carlo Waldemar A. ,   COMMITTEE ON FETUS AND NEWBORN, Papile Lu-Ann , Polin Richard A. , Carlo Waldemar , Tan Rosemarie , Kumar Praveen , Benitz William , Eichenwald Eric , Cummings James , Baley Jill
Published: December 2013

Respiratory failure secondary to surfactant deficiency is a major cause of morbidity and mortality in preterm infants. Surfactant therapy substantially reduces mortality and respiratory morbidity for this population. Secondary surfactant deficiency also contributes to acute respiratory morbidity in late-preterm and term neonates with meconium aspiration syndrome, pneumonia/sepsis, and perhaps pulmonary hemorrhage; surfactant replacement may be beneficial for these infants. This statement summarizes the evidence regarding indications, administration, formulations, and outcomes for surfactant-replacement therapy. The clinical strategy of intubation, surfactant administration, and extubation to continuous positive airway pressure and the effect of continuous positive airway pressure on outcomes and surfactant use in preterm infants are also reviewed.
Use of Inhaled Nitric Oxide in Preterm Infants
Authors: Kumar Praveen ,   COMMITTEE ON FETUS AND NEWBORN, Papile Lu-Ann , Polin Richard A. , Carlo Waldemar A. , Tan Rosemarie , Benitz William , Eichenwald Eric , Cummings James , Baley Jill
Published: December 2013

Nitric oxide, an important signaling molecule with multiple regulatory effects throughout the body, is an important tool for the treatment of full-term and late-preterm infants with persistent pulmonary hypertension of the newborn and hypoxemic respiratory failure. Several randomized controlled trials have evaluated its role in the management of preterm infants ≤34 weeks’ gestational age with varying results. The purpose of this clinical report is to summarize the existing evidence for the use of inhaled nitric oxide in preterm infants and provide guidance regarding its use in this population.
Significance of microRNA expression in body fluids in the diagnosis of gastrointestinal tumors
Authors: Igaz Iván , Topa Lajos
Published: December 2013

MicroRNAs are small, non-coding, single strained RNAs that regulate gene expression at the posttranscriptional level. They are involved in all major aspects of cellular functions, such as cell cycle, differentiation, migration, apoptosis etc. The role of microRNAs as potential biomarkers of several malignant diseases is being intensively investigated, since they can be found in the body fluids, too, besides their usual intracellular localisation. MicroRNAs have been detected in blood, saliva, stool, breast milk, urine, bile etc. In this review the authors discuss recent findings in the field of microRNAs in stool, bile and saliva, underlying their potential significance in the diagnosis of gastrointestinal tumors. Orv. Hetil., 2014, 155(1), 11–15.
The role of fetuin-A in cardiovascular diseases
Authors: Vörös Krisztián , Cseh Károly , Kalabay László
Published: December 2013

Fetuin-A (also known as α2-Heremans–Schmid glycoprotein) is a multifunctional molecule secreted by the liver. It is a negative acute phase reactant with a debated role in subclinical inflammation. Fetuin-A is an inhibitor of the insulin receptor and its serum level correlates with insulin resistance. The protein has been implicated in adipocyte dysfunction and it is associated with obesity and non-alcoholic fatty liver disease. Although all these properties seem to promote atherosclerosis, the role of fetuin-A in cardiovascular diseases is more complex. As a natural inhibitor of tissue and vascular calcification, fetuin-A also acts as a protective factor in atherosclerosis. The potential role and prognostic value of fetuin-A in arterial calcification and cardiovascular diseases is discussed in this review, along with explanations for seemingly contradicting results in the literature and possible directions for future research. Orv. Hetil., 2014, 155(1), 16–23.
Paths on the doubly covered region of a covering of the plane by unit discs
Authors: Roldán-Pensado Edgardo
Published: December 2013

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Comment on the paper of J. Mills: “certain congruences on orthodox semigroups”
Authors: Gigoń Roman
Published: December 2013

In the paper we give some remarks on the article of Janet Mills. In particular, the proof of Lemma 1.2 (in her work) is incorrect, and so the proof of Theorem 3.5 is not valid, too. Using different methods we show the mentioned theorem. Moreover, we find a new equivalent condition to the statements in Theorem 3.5. In particular, an explicit definition of a new class of orthodox semigroups is introduced.
Characterizations of selfadjoint operators
Authors: Sebestyén Zoltán , Tarcsay Zsigmond
Published: December 2013

The purpose of this paper is to revise von Neumann’s characterizations of selfadjoint operators among symmetric ones. In fact, we do not assume that the underlying Hilbert space is complex, nor that the corresponding operator is densely defined, moreover, that it is closed. Following Arens, we employ algebraic arguments instead of the geometric approach of von Neumann using the Cayley transform.
On app skew generalized power series rings
Authors: Majidinya A. , Moussavi A.
Published: December 2013

By [12], a ring R is left APP if R has the property that “the left annihilator of a principal ideal is pure as a left ideal”. Equivalently, R is a left APP-ring if R modulo the left annihilator of any principal left ideal is flat. Let R be a ring, (S, ≦) a strictly totally ordered commutative monoid and ω: S → End(R) a monoid homomorphism. Following [16], we show that, when R is a (S, ω)-weakly rigid and (S, ω)-Armendariz ring, then the skew generalized power series ring R[[S≦, ω]] is right APP if and only if rR(A) is S-indexed left s-unital for every S-indexed generated right ideal A of R. We also show that when R is a (S, ω)-strongly Armendariz ring and ω(S) ⫅ Aut(R), then the ring R[[S≦, ω]] is left APP if and only if ℓR(∑a∈A ∑s∈SRωs(a)) is S-indexed right s-unital, for any S-indexed subset A of R. In particular, when R is Armendariz relative to S, then R[[S≦]] is right APP if and only if rR(A) is S-indexed left s-unital, for any S-indexed generated right ideal A of R.
Shortest path avoiding balls
Authors: Tóth Gábor
Published: December 2013

It is shown that in a packing of open circular discs with radii not exceeding 1, any two points lying outside the circles at distance d from one another can be connected by a path traveling outside the circles and having length at most \documentclass{aastex}
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A magnetic flux leakage analysis model based on finite element neural network
Authors: Yuan Xichao , Wang Changlong , Ji Fengzhu , Zuo Xianzhang
Published: December 2013

The major drawback of the finite element method (FEM), which is commonly used in magnetic leakage field testing, is the high cost of calculation. In this paper, a finite element neural network (FENN), which embeds a finite element model in a neural network structure, is adopted that
enables a faster and more accurate solution for the forward model compared with FEM. The second-order Newton method is introduced as a learning algorithm. The FENN model for magnetic flux leakage (MFL) testing is established and comparisons between the gradient decent algorithm and the second-order
Newton method, under the circumstances of various defects, are presented. The vector plot of magnetic field intensity and the vertical components of magnetic flux density are analysed. The relevant results indicate that the second-order Newton method-based FENN can resolve the MFL forward
model in parallel, which has the advantages of rapidness and stability, and it is a valid and feasible calculation method.
Experimental and finite element analysis study of 3D magnetic field sensing for pulsed magnetic flux leakage defect characterisation
Authors: Tang Ying , Pan MengChun , Luo FeiLu , Tan XiangLin
Published: December 2013

Magnetic flux leakage (MFL) testing is commonly used as an inspection technique in ferromagnetic metal material. In this paper, measurement of the three-dimensional (3D) pulsed magnetic leakage flux field (PMFL) is proposed to overcome the shortcomings of traditional MFL measurement,
which only uses the x-axis component of the magnetic field. The finite element method (FEM) has been used to simulate and analyse the characteristics of a surface axial and circumferential defect magnetic field in three independent x-, y- and z-axes. The experimental and FEM results show that
data from x-, y- and z-axis components can give comprehensive positional information about defects, particularly their shape and orientation, especially when the defect is parallel to the applied field. The experimental results show good correlation with the simulation. The work concludes
that 3D pulsed magnetic leakage field sensing could be used to improve the defect characterisation capabilities, and FEM can help to improve the design of the PMFL systems.
Towards a business enterprise strategy to support the integration of proactive aerospace maintenance technologies
Authors: Phillips P , Diston D , Starr A
Published: December 2013

Within the aerospace industry there is a desired paradigm shift to move aircraft maintenance towards offering maintenance programmes with predictive, rather than purely preventative, capabilities, which would utilise health monitoring technologies. This maintenance revolution will not
just incorporate new technologies into key aircraft systems such as engines, wing/fuselage structures and landing gear, but would result in aircraft maintenance packages tailored towards individual customer requirements. The difficulties with incorporating health monitoring into systems do
not just extend to the technical, but also require clear identification of a clear commercial business need. It is identified that the development of aerospace health monitoring systems offers a variety of often overlooked commercial challenges, which are required to be addressed to enable
integration into often well-defined business practices. This paper provides a digest of recent research into the commercial challenges associated with the integration of health monitoring products into electromechanical actuation systems for aircraft landing gear. Discussions on current aircraft
maintenance practice and how a move towards a predictive philosophy built upon health monitoring systems is likely to affect future maintenance operations are used to develop the business case for health monitoring within this application. Three proposed pricing strategies, which are aimed
at formulating part of a business strategy, are reviewed, highlighting the need to carefully consider the impact of the new technology on business strategies before adopting them. These considerations of how a landing gear manufacturer would incorporate health monitoring systems integrated
into their products are a fundamental part of health monitoring systems' integration and development.
Bees collect polyurethane and polyethylene plastics as novel nest materials
Authors: MacIvor J. Scott , Moore Andrew E.
Published: December 2013

Plastic waste pervades the global landscape. Although adverse impacts on both species and ecosystems have been documented, there are few observations of behavioral flexibility and adaptation in species, especially insects, to increasingly plastic‐rich environments. Here, two species of megachilid bee are described independently using different types of polyurethane and polyethylene plastics in place of natural materials to construct and close brood cells in nests containing successfully emerging brood. The plastics collected by each bee species resembled the natural materials usually sought; Megachile rotundata, which uses cut plant leaves, was found constructing brood cells out of cut pieces of polyethylene‐based plastic bags, and Megachile campanulae, which uses plant and tree resins, had brood cells constructed out of a polyurethane‐based exterior building sealant. Although perhaps incidentally collected, the novel use of plastics in the nests of bees could reflect ecologically adaptive traits necessary for survival in an increasingly human‐dominated environment.
Internal Auditors' Experiences and Opinions Regarding Green IT: Assessing the Gap in Normative and Positive Perspectives
Authors: Gray Glen L. , No Won Gyun , Miller David W.
Published: December 2013

Organizations' sustainability and environmental compliance activities are escalating. Information technology (IT) is an essential environmental compliance component under the rubric of green IT, which can include the designing, manufacturing, implementing, and disposing of IT components and the supporting electrical and cooling infrastructure. Green IT has numerous compliance, governance, and control issues, and management needs assurance that green IT metrics reported to management, regulators, and other stakeholders are accurate, complete, and timely. Boards, executives, the Institute of Internal Auditors (IIA), and the Committee of Sponsoring Organizations of the Treadway Commission (COSO) view internal auditors as control experts. This paper summarizes a survey of internal auditors as to what internal auditors should be doing in this domain and what they are actually doing. The results indicate that even though internal auditors believe that they should be more involved in green IT activities, their current involvement is limited to the traditional role as assurance provider, not as facilitators or consultants. The results also suggest that internal auditors' current involvement in green IT activities varies depending on the types of environmental sustainability strategies practiced by their organizations, whereas their perceived roles in green IT activities did not.

Data Availability: Data used in this study are available from the authors on request.
Ranking Faculties, Ph.D. Programs, Individual Scholars, and Influential Articles in Accounting Information Systems Based on Citations to Publications in the Journal of Information Systems
Authors: Guffey Daryl M. , Harp Nancy L.
Published: December 2013

This paper ranks systems faculties, accounting doctoral programs, individual accounting systems researchers, and the most influential accounting systems articles based on Google Scholar citations to publications in the Journal of Information Systems (JIS). All articles published in JIS for its first 25 years of existence are included and four citation metrics are used. Information is presented over three time periods (1986–1993, 1994–2001, and 2002–2010) to provide additional insights on changes over time. The study also analyzes the content and research methods of “most cited” articles and describes trends in the types of systems research that have had the greatest impact. Findings suggest that JIS's impact has consistently improved over time. The H-index for JIS also suggests that the journal compares favorably among its peers. A correlation analysis between the four citation metrics and the number of articles published in JIS provides evidence that counting articles published is a reasonable proxy for the influence or significance of authors. Potential doctoral students with an interest in accounting information systems, new Ph.D.s with an interest in accounting information systems, current accounting information systems faculty, department chairs, deans, and other administrators will find these results informative.
HSP72 Is a Mitochondrial Stress Sensor Critical for Parkin Action, Oxidative Metabolism, and Insulin Sensitivity in Skeletal Muscle
Authors: Drew Brian G. , Ribas Vicente , Le Jamie A. , Henstridge Darren C. , Phun Jennifer , Zhou Zhenqi , Soleymani Teo , Daraei Pedram , Sitz Daniel , Vergnes Laurent , Wanagat Jonathan , Reue Karen , Febbraio Mark A. , Hevener Andrea L.
Published: December 2013

Increased heat shock protein (HSP) 72 expression in skeletal muscle prevents obesity and glucose intolerance in mice, although the underlying mechanisms of this observation are largely unresolved. Herein we show that HSP72 is a critical regulator of stress-induced mitochondrial triage signaling since Parkin, an E3 ubiquitin ligase known to regulate mitophagy, was unable to ubiquitinate and control its own protein expression or that of its central target mitofusin (Mfn) in the absence of HSP72. In wild-type cells, we show that HSP72 rapidly translocates to depolarized mitochondria prior to Parkin recruitment and immunoprecipitates with both Parkin and Mfn2 only after specific mitochondrial insult. In HSP72 knockout mice, impaired Parkin action was associated with retention of enlarged, dysmorphic mitochondria and paralleled by reduced muscle respiratory capacity, lipid accumulation, and muscle insulin resistance. Reduced oxygen consumption and impaired insulin action were recapitulated in Parkin-null myotubes, confirming a role for the HSP72-Parkin axis in the regulation of muscle insulin sensitivity. These data suggest that strategies to maintain HSP72 may provide therapeutic benefit to enhance mitochondrial quality and insulin action to ameliorate complications associated with metabolic diseases, including type 2 diabetes.
Additive Effects of MicroRNAs and Transcription Factors on CCL2 Production in Human White Adipose Tissue
Authors: Kulyté Agné , Belarbi Yasmina , Lorente-Cebrián Silvia , Bambace Clara , Arner Erik , Daub Carsten O. , Hedén Per , Rydén Mikael , Mejhert Niklas , Arner Peter
Published: December 2013

Adipose tissue inflammation is present in insulin-resistant conditions. We recently proposed a network of microRNAs (miRNAs) and transcription factors (TFs) regulating the production of the proinflammatory chemokine (C-C motif) ligand-2 (CCL2) in adipose tissue. We presently extended and further validated this network and investigated if the circuits controlling CCL2 can interact in human adipocytes and macrophages. The updated subnetwork predicted that miR-126/-193b/-92a control CCL2 production by several TFs, including v-ets erythroblastosis virus E26 oncogene homolog 1 (avian) (ETS1), MYC-associated factor X (MAX), and specificity protein 12 (SP1). This was confirmed in human adipocytes by the observation that gene silencing of ETS1, MAX, or SP1 attenuated CCL2 production. Combined gene silencing of ETS1 and MAX resulted in an additive reduction in CCL2 production. Moreover, overexpression of miR-126/-193b/-92a in different pairwise combinations reduced CCL2 secretion more efficiently than either miRNA alone. However, although effects on CCL2 secretion by co-overexpression of miR-92a/-193b and miR-92a/-126 were additive in adipocytes, the combination of miR-126/-193b was primarily additive in macrophages. Signals for miR-92a and -193b converged on the nuclear factor-κB pathway. In conclusion, TF and miRNA-mediated regulation of CCL2 production is additive and partly relayed by cell-specific networks in human adipose tissue that may be important for the development of insulin resistance/type 2 diabetes.
Deoxysphingolipids, Novel Biomarkers for Type 2 Diabetes, Are Cytotoxic for Insulin-Producing Cells
Authors: Zuellig Richard A. , Hornemann Thorsten , Othman Alaa , Hehl Adrian B. , Bode Heiko , Güntert Tanja , Ogunshola Omolara O. , Saponara Enrica , Grabliauskaite Kamile , Jang Jae-Hwi , Ungethuem Udo , Wei Yu , von Eckardstein Arnold , Graf Rolf , Sonda Sabrina
Published: December 2013

Irreversible failure of pancreatic β-cells is the main culprit in the pathophysiology of diabetes, a disease that is now a global epidemic. Recently, elevated plasma levels of deoxysphingolipids, including 1-deoxysphinganine, have been identified as a novel biomarker for the disease. In this study, we analyzed whether deoxysphingolipids directly compromise the functionality of insulin-producing Ins-1 cells and primary islets. Treatment with 1-deoxysphinganine induced dose-dependent cytotoxicity with senescent, necrotic, and apoptotic characteristics and compromised glucose-stimulated insulin secretion. In addition, 1-deoxysphinganine altered cytoskeleton dynamics, resulting in intracellular accumulation of filamentous actin and activation of the Rho family GTPase Rac1. Moreover, 1-deoxysphinganine selectively upregulated ceramide synthase 5 expression and was converted to 1-deoxy-dihydroceramides without altering normal ceramide levels. Inhibition of intracellular 1-deoxysphinganine trafficking and ceramide synthesis improved the viability of the cells, indicating that the intracellular metabolites of 1-deoxysphinganine contribute to its cytotoxicity. Analyses of signaling pathways identified Jun N-terminal kinase and p38 mitogen-activated protein kinase as antagonistic effectors of cellular senescence. The results revealed that 1-deoxysphinganine is a cytotoxic lipid for insulin-producing cells, suggesting that the increased levels of this sphingolipid observed in diabetic patients may contribute to the reduced functionality of pancreatic β-cells. Thus, targeting deoxysphingolipid synthesis may complement the currently available therapies for diabetes.
Regulation of Hypothalamic Neuronal Sensing and Food Intake by Ketone Bodies and Fatty Acids
Authors: Le Foll Christelle , Dunn-Meynell Ambrose A. , Miziorko Henri M. , Levin Barry E.
Published: December 2013

Metabolic sensing neurons in the ventromedial hypothalamus (VMH) alter their activity when ambient levels of metabolic substrates, such as glucose and fatty acids (FA), change. To assess the relationship between a high-fat diet (HFD; 60%) intake on feeding and serum and VMH FA levels, rats were trained to eat a low-fat diet (LFD; 13.5%) or an HFD in 3 h/day and were monitored with VMH FA microdialysis. Despite having higher serum levels, HFD rats had lower VMH FA levels but ate less from 3 to 6 h of refeeding than did LFD rats. However, VMH β-hydroxybutyrate (β-OHB) and VMH-to-serum β-OHB ratio levels were higher in HFD rats during the first 1 h of refeeding, suggesting that VMH astrocyte ketone production mediated their reduced intake. In fact, using calcium imaging in dissociated VMH neurons showed that ketone bodies overrode normal FA sensing, primarily by exciting neurons that were activated or inhibited by oleic acid. Importantly, bilateral inhibition of VMH ketone production with a 3-hydroxy-3-methylglutaryl-CoA synthase inhibitor reversed the 3- to 6-h HFD-induced inhibition of intake but had no effect in LFD-fed rats. These data suggest that a restricted HFD intake regimen inhibits caloric intake as a consequence of FA-induced VMH ketone body production by astrocytes.
Otopetrin 1 Protects Mice From Obesity-Associated Metabolic Dysfunction Through Attenuating Adipose Tissue Inflammation
Authors: Wang Guo-Xiao , Cho Kae Won , Uhm Maeran , Hu Chun-Rui , Li Siming , Cozacov Zoharit , Xu Acer E. , Cheng Ji-Xin , Saltiel Alan R. , Lumeng Carey N. , Lin Jiandie D.
Published: December 2013

Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism, in part, through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated. Here we identified otopetrin 1 (Otop1) as a component of a counterinflammatory pathway that is induced in WAT during obesity. Otop1 expression is markedly increased in obese mouse WAT and is stimulated by tumor necrosis factor-α in cultured adipocytes. Otop1 mutant mice respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation. Otop1 attenuates interferon-γ (IFN-γ) signaling in adipocytes through selective downregulation of the transcription factor STAT1. Using a tagged vector, we found that Otop1 physically interacts with endogenous STAT1. Thus, Otop1 defines a unique target of cytokine signaling that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity.
Hepcidin Is Directly Regulated by Insulin and Plays an Important Role in Iron Overload in Streptozotocin-Induced Diabetic Rats
Authors: Wang Heyang , Li Hongxia , Jiang Xin , Shi Wencai , Shen Zhilei , Li Min
Published: December 2013

Iron overload is frequently observed in type 2 diabetes mellitus (DM2), but the underlying mechanisms remain unclear. We hypothesize that hepcidin may be directly regulated by insulin and play an important role in iron overload in DM2. We therefore examined the hepatic iron content, serum iron parameters, intestinal iron absorption, and liver hepcidin expression in rats treated with streptozotocin (STZ), which was given alone or after insulin resistance induced by a high-fat diet. The direct effect of insulin on hepcidin and its molecular mechanisms were furthermore determined in vitro in HepG2 cells. STZ administration caused a significant reduction in liver hepcidin level and a marked increase in intestinal iron absorption and serum and hepatic iron content. Insulin obviously upregulated hepcidin expression in HepG2 cells and enhanced signal transducer and activator of transcription 3 protein synthesis and DNA binding activity. The effect of insulin on hepcidin disappeared when the signal transducer and activator of transcription 3 pathway was blocked and could be partially inhibited by U0126. In conclusion, the current study suggests that hepcidin can be directly regulated by insulin, and the suppressed liver hepcidin synthesis may be an important reason for the iron overload in DM2.
GLP-1/Glucagon Coagonism Restores Leptin Responsiveness in Obese Mice Chronically Maintained on an Obesogenic Diet
Authors: Clemmensen Christoffer , Chabenne Joseph , Finan Brian , Sullivan Lorraine , Fischer Katrin , Küchler Daniela , Sehrer Laura , Ograjsek Teja , Hofmann Susanna M. , Schriever Sonja C. , Pfluger Paul T. , Pinkstaff Jason , Tschöp Matthias H. , DiMarchi Richard , Müller Timo D.
Published: December 2013

We recently reported restoration of leptin responsiveness in diet-induced obese (DIO) mice using a pharmacologically optimized, polyethylene-glycolated (PEG)-leptin analog in combination with exendin-4 or FGF21. However, the return of leptin action required discontinuation of high-fat diet (HFD) exposure. Here we assess whether a single peptide possessing balanced coagonism at the glucagon-like peptide 1 (GLP-1) and glucagon receptors can restore leptin responsiveness in DIO mice maintained on a HFD. DIO mice were treated with PEG-GLP-1/glucagon (30 nmol/kg every fourth day) to induce an ∼15% body weight loss, upon which they were randomized to continue PEG-GLP-1/glucagon therapy or reassigned to receive supplemental daily PEG-leptin (185 nmol/kg/day). The addition of PEG-leptin to PEG-GLP-1/glucagon resulted in an ∼18% greater weight loss as compared with PEG-GLP-1/glucagon alone and was accompanied by further decreases in food intake and improved glucose and lipid metabolism. The beneficial effect of PEG-leptin supplementation occurred after an initial body weight loss similar to what we previously reported following reduced dietary fat along with PEG-leptin and exendin-4 or FGF21 cotreatment. In summary, we report that GLP-1/glucagon coagonism restores leptin responsiveness in mice maintained on a HFD, thus emphasizing the translational value of this polypharmacotherapy for the treatment of obesity and diabetes.
Association of Matrix Metalloproteinase 8 Genetic Polymorphisms with Bronchial Asthma in a Japanese Population
Authors: Shimoda Terufumi , Obase Yasushi , Kishikawa Reiko , Iwanaga Tomoaki
Published: December 2013

Asthma has a strong genetic component. The final disease phenotype results from complex interactions between environment and multiple genes of small-to-modest effects. We investigated whether the polymorphism in genes encoding inflammatory mediators and cytokines is important for solving the onset and progression of asthma. We investigated whether 31 single nucleotide polymorphisms (SNPs) in genes encoding cytokines or monokines (interleukin [IL]-5R, matrix metalloproteinase [MMP] 8, beta2 adrenergic receptor, cytotoxic T-lymphocyte-associated antigen 4, IL-3, C-reactive protein, cytochrome P450 (CYP) 2C9, CYP3A4, a disintegrin and metalloproteinase [ADAM] 33, cysteinyl leukotriene receptor [CysLTR] 1, CysLTR2, eosinophilic cationic protein, glucocorticoid receptor, and leukotriene A 4 hydrolase) are related to asthma development in 206 Japanese bronchial asthma patients and 127 healthy controls. Using multifactor dimensionality reduction (MDR), we identified rs17099451 in MMP8, using a single locus model, with a mean cross-validation of 87.0%. Using a two-locus model, combinations of MMP8 and rs44707 in ADAM33, and MMP8 and rs40401 in IL-3, were identified, with mean cross-validation consistencies reaching 45.0%. Of the SNPs selected by the MDR method, rs17099451 in MMP8 and rs40401 in IL-3 were regarded as the most significant results in a 2 × 2 dominant model analysis. The finding that an MMP8 allele was most strongly related to asthma development indicates that metalloproteinase function is crucial to the airflow limitation process involved in this disease.
Intracranial Mucocele Formation in the Context of Longstanding Chronic Rhinosinusitis: A Clinicopathologic Series and Literature Review
Authors: Lee Jivianne T. , Brunworth Joseph , Garg Rohit , Shibuya Terry , Keschner David B. , Vanefsky Marc , Lin Tina , Choi Soohoo , Stea Richard , Thompson Lester D. R.
Published: December 2013

Chronic rhinosinusitis (CRS) can lead to serious long-term adverse sequelae, particularly if left untreated. The aim of this study was to describe a series of intracranial mucoceles (ICMs) that arose in the context of longstanding CRS combined with a review of the pertinent literature. A retrospective chart review was performed on all patients who developed ICMs in association with CRS between 2003 and 2012. The clinical presentation, radiographic features, surgical approach, intraoperative findings, and patient outcome were examined in the context of a literature review. Sixty-five cases of mucoceles were identified in patients with a history of CRS, of which seven (10.8%) were intracranial. Five patients were men and two were women with a mean age of 42.1 years. Headache, facial pressure, retro-orbital pain, and visual disturbances were the most common presenting symptoms. Five of the seven had previously undergone sinonasal surgery. Imaging studies showed ICMs involving the anterior cranial fossa, two of which were bilateral. Latency between onset of CRS and ICM detection ranged from 3 to 19 years (mean, 9.4 years). All patients underwent endoscopic transnasal drainage with three also requiring a concurrent, open neurosurgical procedure to access the intracranial component. There were no postoperative complications, and no recurrences were observed after a mean follow-up of 2.7 years. ICMs presenting as delayed complications of CRS are uncommon and constitute a surgical challenge. Open, external skull base approaches used in conjunction with transnasal endoscopic drainage procedures may be necessary to achieve successful management of this rare condition.
Piezoelectric Sensing: Evaluation for Clinical Investigation of Deviated Nasal Septum
Authors: Manjunatha Roopa G. , Rajanna Konandur , Mahapatra Roy D. , Dorasala Srinivas
Published: December 2013

Noninvasive objective evaluation of nasal airflow is one of the important clinical aspects. The developed polyvinylidene fluoride (PVDF) sensor enables measurement of airflow through each side of the nose using its piezoelectric property. This study was designed to evaluate the diagnostic capability of the PVDF sensor in assessing the deviated nasal septum (DNS). PVDF nasal sensor uses its piezoelectric property to measure the peak-to-peak amplitude (Vp-p) of nasal airflow in both of the nostrils: right nostril (RN) and left nostril (LN), separately and simultaneously. We have compared the results of PVDF nasal sensor, visual analog scale (VAS), and clinician scale for 34 DNS patients and 28 healthy controls. Additionally, the results were further analyzed by receiver operating characteristic curve and correlation between PVDF nasal sensor and VAS in detecting DNS. We found a significant difference in the peak-to-peak amplitude values of the test group and the control group. The correlation between the PVDF nasal sensor measurements and VAS (RN and LN combined) for test group was statistically significant (–0.807; p < 0.001). Sensitivity and specificity of the PVDF nasal sensor measurements in the detection of DNS (RN and LN combined) was 85.3 and 74.4%, respectively, with optimum cutoff value <0.34 Vp-p. The developed PVDF nasal sensor is noninvasive and requires less patient efforts. The sensitivity and specificity of the PVDF nasal sensor are reliable. According to our findings, we propose that the said PVDF nasal sensor can be used as a new diagnostic tool to evaluate the DNS in routine clinical practice.
The Anatomical and Functional Relationship between Allergic Conjunctivitis and Allergic Rhinitis
Authors: Hom Milton M. , Bielory Leonard
Published: December 2013

There are numerous anatomic connections between the allergic conjunctivitis and allergic rhinitis. The most obvious reason is the physical connection via the nasolacrimal apparatus. However, a closer look at innervation, circulatory, lymphatic, and neurogenic systems reveals much more than a physical connection. The eye is richly innervated by parasympathetic nerves that enter the eyes after traveling in conjunction with the parasympathetic input to the nasal cavity. Parasympathetic innervation governing the tear film and nasal secretion can intersect at the pterygopalatine ganglion. Neurogenic inflammation affects both the eye and the nose as evidenced by the presence of the same neurogenic factors. Venous flow is in the SOV area connecting the eye and the nose, once thought to be without valves. In the past, this thinking is the basis for concern about the danger triangle of the face. Recent literature has shown otherwise. Although valves are present, there are still pathways where bidirectional flow exists and a venous connection is made. The most likely area for venous communication is the pterygoid plexus and cavernous sinus. The venous flow and connections also offers a pathway for allergic shiners. Understanding the mutual connections between the nasal mucosa and the ocular surface can also affect treatment strategies.
Use of the Hadad-Bassagasteguy Flap for Repair of Recurrent Cerebrospinal Fluid Leak after Prior Transsphenoidal Surgery
Authors: Brunworth Joseph , Lin Tina , Keschner David B. , Garg Rohit , Lee Jivianne T.
Published: December 2013

The Hadad-Bassagasteguy vascularized nasoseptal pedicled flap (HBF) is an effective technique for reconstruction of skull base defects with low incidence of postoperative cerebrospinal fluid (CSF) leak. Advanced planning is required as posterior septectomy during transsphenoidal surgery can preclude its use due to destruction of the vascular pedicle. We present four cases in which the HBF was successfully used to repair recurrent CSF leaks despite prior posterior septectomy and transsphenoidal surgery. A retrospective chart review was performed on all patients who developed recurrent CSF leak after transsphenoidal surgery over a 7-year period (2006–2013). Data were collected regarding demographics, clinical presentation, intraoperative findings, and surgical outcomes. Four patients who developed recurrent CSF drainage after transsphenoidal surgery were managed with HBF reconstruction during the study period. Two were men and two were women with a mean age of 37 years (range, 24–48 years). All had previously undergone resection of a pituitary macroadenoma via a transsphenoidal approach, with intraoperative CSF leaks repaired using multilayered free grafts. Recurrent CSF rhinorrhea arose 0.37–12 months (mean, 2.98 months) after the initial pituitary surgery. Active CSF drainage could be visualized intraoperatively with posterior septal perforations present. The HBF was successfully used in all cases, with no evidence of recurrent CSF leak after a mean follow-up of 2.35 years. The HBF may be salvaged for repair of recurrent CSF leaks even in the context of prior posterior septectomy and transsphenoidal surgery. However, longer follow-up is necessary to determine the long-term efficacy of this procedure in such revision cases.
High-Speed Rail Network Design and Station Location
Authors: Lovett Alexander , Munden Greg , Saat M. Rapik , Barkan Christopher P. L.
Published: December 2013

To improve the personal mobility, safety, and environmental impact of passenger travel and to strengthen regional and national economies, planners, governments, and transportation companies throughout the world have been building high-speed rail (HSR) systems for more than half a century. Although many early systems were principally government projects, public–private partnerships are increasingly being used to design, build, operate, and maintain these HSR networks. However, engaging the private sector requires a clear understanding of the potential profit-ability of such a system. A key question affecting this understanding is the configuration of the line in terms of its length, number and location of stations, and ultimate alignment. A computer model was developed; it used station, route, and system data to determine the most profitable routes based on the proposed stations. In addition, a sensitivity analysis was conducted to determine which variables had the greatest impact on the costs and returns of an HSR route. The sensitivity analysis led to the division of the design variables into three categories based on their impact on profitability. Variables that were found to have a major influence were project concession period, ridership, fare, annual fare increase, train set availability, cost of building on a viaduct, and land value increase. Categorizing the design variables allows the model to be used more efficiently in a multiphase approach that reduces the time and resources required to assess potential HSR lines.
Economic Impacts of Amtrak Intercity Passenger Rail Service in Michigan
Authors: Sperry Benjamin R. , Taylor John C. , Roach James L.
Published: December 2013

Amtrak operates three trains on routes in Michigan: the Wolverine, the Blue Water, and the Pere Marquette. Using the methodology established in the 2009 Michigan Passenger Rail Station Community Benefits Study, this study considered the economic impacts of Michigan Amtrak service in the 22 communities served by these routes. Results from the 2009 study were updated to reflect current ridership and ticket revenue data, as well as findings from passenger surveys conducted in spring 2011. Considering individual traveler savings, passenger spending at local businesses, and Amtrak-related expenditures, Amtrak service generated an estimated economic impact to the state of Michigan in excess of $45.8 million in 2011. The average economic impact (excluding Amtrak expenditures) was $37.87 per passenger. Every $1.00 invested by the state of Michigan for operations of the Blue Water and Pere Marquette routes returned $1.84 in economic impact to local communities and travelers along these routes. The findings of this analysis contribute to a small but growing body of literature that quantifies the economic impacts of existing Amtrak passenger rail service and have several applications for passenger rail planning, policy development, and outreach activities.
Development of Multicriteria Decision Method for Evaluating High-Speed Rail Corridor
Authors: Sperry Benjamin R. , Mueller Jon , Hunter-Zaworski Katharine
Published: December 2013

Projects for high-speed intercity passenger rail are complex and require many years of planning and environmental activities before construction can begin. Given the complexity of planning and environmental reviews associated with planning a high-speed intercity passenger rail corridor, a systematic approach for high-level screening of various alternative routings for proposed high-speed rail corridors is desirable. In this context, a multicriteria decision-making framework was proposed to assist planners of high-speed rail with the preliminary screening and ranking of potential high-speed rail corridors. The proposed framework was applied to the question of ranking 13 alternative routings for connecting the South Central and Gulf Coast federally designated highspeed rail corridors located in Texas. Attributes that were incorporated into the decision framework include population, travel demand, capital costs, land use and environmental impacts, and engineering suitability. Although the developed framework cannot be used to replace the environmental review process and formal alternatives analysis completely, it can be used by planners as a tool for preliminary screening or ranking of proposed high-speed rail corridors for detailed analysis.