bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of First-Line Tuberculosis Drugs in Tanzanian Patients
Authors: Tostmann Alma , Mtabho Charles M. , Semvua Hadija H. , van den Boogaard Jossy , Kibiki Gibson S. , Boeree Martin J. , Aarnoutse Rob E.
Published: April 2013

East Africa has a high tuberculosis (TB) incidence and mortality, yet there are very limited data on exposure to TB drugs in patients from this region. We therefore determined the pharmacokinetic characteristics of first-line TB drugs in Tanzanian patients using intensive pharmacokinetic sampling. In 20 adult TB patients, plasma concentrations were determined just before and at 1, 2, 3, 4, 6, 8, 10, and 24 h after observed drug intake with food to estimate the areas under the curve from 0 to 24 h (AUC0–24) and peak plasma concentrations (Cmax) of isoniazid, rifampin, pyrazinamide, and ethambutol. Acetylator status for isoniazid was assessed phenotypically using the isoniazid elimination half-life and the acetylisoniazid/isoniazid metabolic ratio at 3 h postdose. The geometric mean AUC0–24s were as follows: isoniazid, 11.0 h · mg/liter; rifampin, 39.9 h · mg/liter; pyrazinamide, 344 h · mg/liter; and ethambutol, 20.2 h · mg/liter. TheCmaxwas below the reference range for isoniazid in 10/19 patients and for rifampin in 7/20 patients. In none of the patients were theCmaxs for pyrazinamide and ethambutol below the reference range. Elimination half-life and metabolic ratio of isoniazid gave discordant phenotyping results in only 2/19 patients. A substantial proportion of patients had an isoniazid and/or rifampinCmaxbelow the reference range. Intake of TB drugs with food may partly explain these low drug levels, but such a drug intake reflects common practice. The finding of low TB drug concentrations is concerning because low concentrations have been associated with worse treatment outcome in several other studies.
Rho Kinase Regulates Induction of T-Cell Immune Dysfunction in Abdominal Sepsis
Authors: Hasan Z. , Palani K. , Zhang S. , Lepsenyi M. , Hwaiz R. , Rahman M. , Syk I. , Jeppsson B. , Thorlacius Henrik
Published: April 2013

T-cell dysfunction increases susceptibility to infections in patients with sepsis. In the present study, we hypothesized that Rho kinase signaling might regulate induction of T-cell dysfunction in abdominal sepsis. Male C57BL/6 mice were treated with the specific Rho kinase inhibitor Y-27632 (5 mg/kg of body weight) prior to cecal ligation and puncture (CLP). Spleen CD4 T-cell apoptosis, proliferation, and percentage of regulatory T cells (CD4
+
CD25
+
Foxp3
+
) were determined by flow cytometry. Formation of gamma interferon (IFN-γ) and interleukin 4 (IL-4) in the spleen and plasma levels of HMBG1, IL-17, and IL-6 were quantified by use of enzyme-linked immunosorbent assay (ELISA). It was found that CLP evoked apoptosis and decreased proliferation in splenic CD4 T cells. Inhibition of Rho kinase activity decreased apoptosis and enhanced proliferation of CD4 T cells in septic animals. In addition, CLP-evoked induction of regulatory T cells in the spleen was abolished by Rho kinase inhibition. CLP reduced the levels of IFN-γ and IL-4 in the spleen. Pretreatment with Y-27632 inhibited the sepsis-induced decrease in IFN-γ but not IL-4 formation in the spleen. CLP increased plasma levels of high-mobility group box 1 (HMGB1) by 20-fold and IL-6 by 19-fold. Inhibition of Rho kinase decreased this CLP-evoked increase of HMGB1, IL-6, and IL-17 levels in the plasma by more than 60%, suggesting that Rho kinase regulates systemic inflammation in sepsis. Moreover, we observed that pretreatment with Y-27632 abolished CLP-induced bacteremia. Together, our novel findings indicate that Rho kinase is a powerful regulator of T-cell immune dysfunction in abdominal sepsis. Thus, targeting Rho kinase signaling might be a useful strategy to improve T-cell immunity in patients with abdominal sepsis.
The Stimulated Innate Resistance Event in Bordetella pertussis Infection Is Dependent on Reactive Oxygen Species Production
Authors: Zurita E. , Moreno G. , Errea A. , Ormazabal M. , Rumbo M. , Hozbor D.
Published: April 2013

The exacerbated induction of innate immune responses in airways can abrogate diverse lung infections by a phenomenon known as stimulated innate resistance (StIR). We recently demonstrated that the enhancement of innate response activation can efficiently impairBordetella pertussiscolonization in a Toll-like receptor 4 (TLR4)-dependent manner. The aim of this work was to further characterize the effect of lipopolysaccharide (LPS) on StIR and to identify the mechanisms that mediate this process. Our results showed that bacterial infection was completely abrogated in treated mice when the LPS ofB. pertussis(1 μg) was added before (48 h or 24 h), after (24 h), or simultaneously with theB. pertussischallenge (107CFU). Moreover, we detected that LPS completely cleared bacterial infection as soon as 2 h posttreatment. This timing suggests that the observed StIR phenomenon should be mediated by fast-acting antimicrobial mechanisms. Although neutrophil recruitment was already evident at this time point, depletion assays using an anti-GR1 antibody showed thatB. pertussisclearance was achieved even in the absence of neutrophils. To evaluate the possible role of free radicals in StIR, we performed animal assays using the antioxidantN-acetyl cysteine (NAC), which is known to inactivate oxidant species. NAC administration blocked theB. pertussisclearance induced by LPS. Nitrite concentrations were also increased in the LPS-treated mice; however, the inhibition of nitric oxide synthetases did not suppress the LPS-induced bacterial clearance. Taken together, our results show that reactive oxygen species (ROS) play an essential role in the TLR4-dependent innate clearance ofB. pertussis.
Pasteurella multocida Toxin as a Transporter of Non-Cell-Permeating Proteins
Authors: Bergmann Stefan , Jehle Doris , Schwan Carsten , Orth Joachim H. C. , Aktories Klaus
Published: April 2013

The protein toxin
Pasteurella multocida
toxin (PMT) is the causative agent of atrophic rhinitis in pigs, leading to atrophy of the nasal turbinate bones by affecting osteoblasts and osteoclasts. The mechanism of PMT-induced intoxication is a deamidation of α-subunits of heterotrimeric G proteins, including Gα
q
, Gα
13
, and Gα
i
, thereby causing persistent activation of the G proteins. Here we utilized PMT as a transporter of the non-cell-permeating A domain of diphtheria toxin (DTa). Fusion proteins of PMT and DTa ADP-ribosylated elongation factor 2, the natural target of diphtheria toxin, leading to cell toxicity. PMT-DTa effects were competed by PMT, indicating binding to the same cell surface receptor. Fluorescently labeled PMT-DTa and PMT colocalized with specific markers of early and late endosomes. Bafilomycin A, which inhibits vacuolar H
+
-ATPase, blocked PMT-DTa-induced intoxication of HEK-293 cells. By constructing various PMT-DTa chimeras, we identified a minimal region of PMT necessary for uptake of DTa. The data suggest that PMT is able to transport cargo proteins into eukaryotic cells by utilizing the PMT-specific uptake route.
A cholestatic diagnostic dilemma
Authors: Kalinke Lukas , Rashid Mohammed
Published: April 2013

A 28-year-old man with hereditary spherocytosis presented with abdominal pain and jaundice. He had severe, mainly conjugated (642 μmol/l), hyperbilirubinaemia (1033 μmol/l), with elevated liver enzymes: alkaline phosphatase (ALP) (163 IU/l), γ-glutamyltransferase (gGT) (277 IU/l) and aspartate transaminase (AST) (358 IU/l). Abdominal ultrasound and magnetic resonance cholangiopancreatography (MRCP) showed gallstones in the gallbladder but an absence of biliary duct dilation. Liver biopsy was consistent with cholestasis but showed no large duct obstruction. The cause of the cholestasis was unclear, was it a primary intrahepatic pathology or secondary to a posthepatic cause?

He presented with similar symptoms days later with gallstones in the bile duct (choledocholithiasis) and underwent endoscopic retrograde cholangiopancreatography (ERCP) and cholecystectomy. This report guides one through the assessment of jaundice and serves as an example whereby the diagnosis of a common cause of illness is blurred by an atypical clinical presentation and relevant comorbidities. A diagnosis of benign recurrent intrahepatic cholestasis (BRIC) is also considered.
Reflections on mental capacity assessments in general hospitals
Authors: Linn Khin , Sayer Chris , O'Connor G , Magee T
Published: April 2013

Research suggests that a significant proportion of inpatients in general medical wards may lack capacity to make treatment decisions, a situation that often goes unrecognised by clinicians. We would like to briefly discuss two cases from a non-psychiatric setting, where a mental disorder served to inhibit the individual's ability to weigh-up associated risks when deciding to refuse potentially life-sustaining healthcare interventions. In both cases the history of mental disorder was well established yet, for markedly different reasons, the respective presentation was such that the influence of the disorder on decision-making was not evident to the treating teams.
Inhaled hypertonic saline+hyaluronic acid in cystic fibrosis with asthma-like symptoms: a new therapeutic chance
Authors: Cresta Federico , Naselli Aldo , Favilli Federica , Casciaro Rosaria
Published: April 2013

The aim of the paper is to report the case of a boy affected by cystic fibrosis, with non-ABPA-related recurrent wheezing and frequent pulmonary exacerbation during childhood, who had been  inhaling 7% NaCl+0.1% hyaluronic acid (HA) as a maintenance therapy. We reviewed patient database and, analysing a 7-year follow-up, considered pulmonary exacerbation, antibiotic and steroid courses, pulmonary function (forced expiratory volume in one second; FEV1) and microbiological data. After starting 7% NaCl+0.1% HA treatment, we observed a dramatic decrease of oral antibiotic need (0.55 courses/month during the pretreatment period against 0.10 courses/month in the treatment period), associated with a good initial recovery and a stability of FEV1. In our opinion this case could suggest an extended indication for inhaled 7% NaCl+0.1% HA use in CF, not only in patients who did not tolerate hypertonic saline, but also in patients with coexistent asthma-like symptoms.
Emphysematous cystitis: a tympanic bladder
Authors: Dixon Luke , Winkler Mathias
Published: April 2013

An 86-year-old woman with type 2 diabetes was admitted with increasing lethargy and hyperglycaemia. On examination she was noted to have a tender and tympanic bladder. CT revealed a distended bladder with gas locules in the bladder wall. She was diagnosed with hyperglycaemic hyperosmolar non-ketosis precipitated by emphysematous cystitis. After systemic antibiotics and bladder drainage via a urethral catheter, her symptoms readily improved. Radiographic appearances of the bladder were normal one week after instigating treatment. Emphysematous cystitis is characterized by gas within the bladder wall. Although rare it is increasingly more recognized with the advent of modern imaging. The mainstay of treatment is antibiotics and bladder drainage. Rarely surgical debridement and even cystectomy is required.
Primary intraocular central nervous system lymphoma masquerading as diffuse retinal vasculitis
Authors: Katoch Deeksha , Bansal Reema , Nijhawan Raje , Gupta Amod
Published: April 2013

A 49-year-old woman had blurred vision and floaters of 4 days duration in the right eye. Ocular examination revealed granulomatous panuveitis, vitritis and diffuse retinal vasculitis. Following a strongly positive tuberculin skin test, she received antitubercular therapy with oral steroids and immunosuppressants. A year later, despite therapy, vitritis and vasculitis persisted. Additionally, yellowish white lesions appeared beneath the retinal pigment epithelium. Fluorescein angiography revealed a leopard skin appearance. Following a negative vitreous biopsy, she was subjected to a chorioretinal biopsy which revealed non-Hodgkin's lymphoma. MRI was normal. The ocular lesions resolved following intravitreal methotrexate injections. MRI of the brain was repeated every 3 months to rule out central nervous system (CNS) involvement. About 2.5 years after initial presentation, she complained of ataxia, hypersomnia and speech difficulty. MRI of the brain now showed lesions in the thalamocapsular region and the corpus callosum splenium suggestive of CNS lymphoma. She underwent a whole brain radiation with symptomatic improvement followed by chemotherapy.
‘Eye is a window to the pulse’: bilateral ocular ischaemic syndrome as a presenting manifestation of Takayasu arteritis
Authors: Shailaja S , Vivek G , Shetty Ranjan , Kamath Yogish
Published: April 2013

A 22-year-old lady presented with gradually progressive visual loss and chronic pain in both the eyes of 3 months duration. The clinical examination and fundus fluorescein angiography were suggestive of bilateral ocular ischaemic syndrome. Her upper limb pulses were feeble and blood pressure was not recordable in the same. Carotid Doppler revealed a bilateral carotid artery occlusion. Systemic markers for inflammation were elevated. Diagnosis of Takayasu arteritis was made on the basis of clinical and laboratory findings.

Takayasu arteritis should be considered in the differential diagnosis of ocular ischaemic syndrome, particularly in young Asian women.
Calcified embolism: a rare cause of cerebral infarction
Authors: Chandran Vijay , Pai Aparna , Rao Suryanarayana
Published: April 2013

Calcified cerebral emboli (CCE) are a rare cause of stroke and these emboli can be identified on a CT scan of the brain performed for the initial evaluation of stroke. In this report we present a patient who developed a CCE following cardiac catheterisation that lodged in the left middle cerebral artery with resultant right hemiparesis and aphasia. The calcified embolus was seen on CT but could not be identified on MRI. Predisposing factors for CCE include angiography and valve or vessel wall calcification. The natural history and response to standard therapy in patients with CCE as compared with stroke of other aetiologies have not been studied until now. Increased awareness and ability to identify calcified emboli will help us to have an improved understanding of strokes resulting from CCE.
Physiologic responses to a thermogenic nutritional supplement at rest, during low-intensity exercise, and during recovery from exercise in college-aged women
Authors: Bergstrom Haley C. , Housh Terry J. , Traylor Daniel A. , Lewis Robert W. , Jenkins Nathaniel D.M. , Cochrane Kristen C. , Schmidt Richard J. , Johnson Glen O. , Housh Dona J.
Published: April 2013

This study examined acute physiologic responses to a thermogenic nutritional supplement at rest, during exercise, and during recovery from exercise in women. Twelve women (mean ± SD age, 22.9 ± 3.1 years) were recruited for this randomized, double-blinded, placebo-controlled, crossover study. Each testing session consisted of 4 phases: 30 min of presupplementation resting, followed by the ingestion of the placebo or thermogenic nutritional supplement; 50 min of postsupplementation resting; 60 min of walking (at 3.2–4.8 km·h−1); and 50 min of postexercise resting. Energy expenditure (EE), oxygen consumption, respiratory exchange ratio (RER), oxygen (O2) pulse, and heart rate (HR) values were recorded during all 4 phases. Systolic (SBP) and diastolic (DBP) blood pressure were recorded during the rest, postsupplementation, and postexercise recovery phases; ratings of perceived exertion (RPE) were recorded only during exercise. There were no significant differences for EE, oxygen consumption, O2 pulse, HR, SBP, or DBP between the supplement and placebo during the presupplementation resting or postsupplementation phases. The RER, however, was higher with the supplement at 30 min postsupplementation. During exercise, EE and O2 pulse were 3%–6% greater with the supplement than placebo; there were no significant differences in RPE. Postexercise, EE, oxygen consumption, and DBP were 3%–7% greater with the supplement than placebo. These findings suggest that a thermogenic nutritional supplement, when combined with exercise, increases metabolic rate but has no effect on the perception of effort and results in only minimal changes in cardiovascular function.
Comparison of snag densities among regeneration treatments in mixed pine–hardwood forests
Authors: Perry Roger W. , Thill Ronald E.
Published: April 2013

Standing dead trees (snags) are an important component of forest ecosystems, providing foraging, nesting, and roosting substrate for a variety of vertebrates. We examined the effects of four forest regeneration treatments on residual snag density and compared those with densities found in unharvested, naturally regenerated forests (controls) during the second, fourth, and sixth year after timber harvest in mixed pine–hardwood forests of Arkansas and Oklahoma. Regeneration treatments were clearcut with snag creation, shelterwood, single-tree selection, and group selection. Density of large snags (≥25.0 cm DBH) differed only during the sixth year after harvest, with shelterwoods having a lower density of large snags (1.0 snags/ha) than the control or group selection stands (4.0 and 4.2 snags/ha, respectively). Density of small snags (10.0–24.9 cm DBH) mirrored residual basal area, with controls and group-selection stands having the greatest snag densities. Creation of snags in clearcuts by injection with herbicides caused initial snag density in these areas to be greater than other treatments, but density in clearcuts declined sharply by 6 years after harvest. In the absence of snag creation, treatments such as shelterwoods that remove most trees may have snag densities below that required to address some management objectives without additional snag creation.
MIXED CONFORMING ELEMENTS FOR THE LARGE-BODY LIMIT IN MICROMAGNETICS
Authors: AURADA MARKUS , MELENK JENS M. , PRAETORIUS DIRK
Published: April 2013

We introduce a stabilized conforming mixed finite element method for a macroscopic model in micromagnetics. We show well-posedness of the discrete problem for higher order elements in two and three dimensions, develop a full a priori analysis for lowest order elements, and discuss the extension of the method to higher order elements. We introduce a residual-based a posteriori error estimator and present an adaptive strategy. Numerical examples illustrate the performance of the method.
NEUTRON STARS WITH KAON CONDENSATION IN RELATIVISTIC EFFECTIVE MODEL
Authors: WU CHEN , QIAN WEI-LIANG , MA YU-GANG , YANG JI-FENG
Published: April 2013

Relativistic mean-field theory with parameter sets FSUGold and IU-FSU is extended to study the properties of neutron star matter in β equilibrium by including Kaon condensation. The mixed phase of normal baryons and Kaon condensation cannot exist in neutron star matter for the FSUGold model and the IU-FSU model. In addition, it is found that when the optical potential of the K- in normal nuclear matter UK ≳ -100 MeV , the Kaon condensation phase is absent in the inner cores of the neutron stars.
COLLATERALIZED CVA VALUATION WITH RATING TRIGGERS AND CREDIT MIGRATIONS
Authors: BIELECKI TOMASZ R. , CIALENCO IGOR , IYIGUNLER ISMAIL
Published: April 2013

In this paper we discuss the issue of computation of the bilateral credit valuation adjustment (CVA) under rating triggers, and in presence of ratings-linked margin agreements. Specifically, we consider collateralized OTC contracts, that are subject to rating triggers, between two parties — an investor and a counterparty. Moreover, we model the margin process as a functional of the credit ratings of the counterparty and the investor. We employ a Markovian approach for modeling of the rating transitions of the two parties to the contract. In this framework, we derive the representation for bilateral CVA. We also introduce a new component in the decomposition of the counterparty risky price: namely the rating valuation adjustment (RVA) that accounts for the rating triggers. We give two examples of dynamic collateralization schemes where the margin thresholds are linked to the credit ratings of the parties. Our results are illustrated via computation of various counterparty risk adjustments for a CDS contract and for an IRS contract.
AN APPROXIMATION TO THE ENTROPY FOR QUANTUM DECAYING STATES
Authors: CIVITARESE OSVALDO , GADELLA MANUEL
Published: April 2013

The concept of entropy was initially defined for systems with thermodynamical equilibrium. We try to extend this notion for quantum non-relativistic decaying states. We use a technique based on path integration on coherent states in order to obtain an approximation to the entropy of a decaying state.
INVESTIGATION OF INFLUENCE OF SURFACE NANOPARTICLE ON EMISSION PROPERTIES OF SCANDIA-DOPED DISPENSER CATHODES
Authors: ZHANG XIZHU , WANG JINSHU , WANG YIMAN , LIU WEI , ZHOU MEILING , GAO ZHIYUAN
Published: April 2013

The microstructure of a fully activated scandia doped dispenser (SDD) cathode has been studied by scanning electron microscope (SEM). The observation results display that nanoparticles appear at the growth steps and the surface of tungsten grains of the fully activated SDD cathode. To study the influence of the nanoparticles on the emission, the local electric field strengths around the nanoparticles have been calculated by Maxwell 2D code and Comsol. The calculation results show that the local electric field strengths are enhanced by 1.1 to 3.8 times to average value based on different model conditions. The highest field strength is about 1.54 × 105 V/cm at an average field strength of 40 KV/cm, which is related to a space-charge limited (SCL) current density of 100 A/cm2 in the experimental configuration. This implies the field strength is not high enough to cause field emission.
'Small data' enabled prediction of Obama's win, say economists
Authors: Hyman Paul
Published: April 2013

"Big data" from crowdsourcing resulted in more complex predictions.
Fair use in Europe
Authors: Hugenholtz P. Bernt
Published: April 2013

Examining the mismatch between copyright law and technology-influenced evolving social norms in the European Union.
Max Newman
Authors: Anderson David
Published: April 2013

Reflections on a significant, yet often overlooked, computing pioneer.
Modulating Autophagy Improves Cardiac Function in a Rat Model of Early-Stage Dilated Cardiomyopathy
Authors: Xie Kun , Jin Bo , Li Yong , Luo Xinping , Zhu Jun , Ma Duan , Shi Haiming
Published: April 2013

Objectives: Previous studies reported that autophagy is activated in human dilated cardiomyopathy (DCM). It is still unknown whether modulating autophagy can improve cardiac function of the failing heart. Methods: We immunized rats with porcine cardiac myosin to set up a model of DCM. Rapamycin, a kind of mTOR inhibitor upregulating autophagy, was given to rats weeks after the immunization at low (1 mg/kg · day i.p.), intermediate (2 mg/kg · day i.p.) and high dose (4 mg/kg · day i.p.) for 2 weeks. Results: Compared to the control group (ejection fraction, EF = 81.3 ± 3.8%), the average EF decreased in both the DCM group (EF = 56.1 ± 3.3%) and the high-dose rapamycin group (EF = 55.9 ± 3.6%), but recovered in the low-/intermediate-dose rapamycin groups (EF = 64.9 ± 4.6/69.4 ± 4.4%). Phosphorylation of p70s6k and 4E-BP1 decreased and the expression of LC3BI/II increased in all rapamycin groups. Autophagic vacuoles were easily found in these groups. However, body weight was significantly reduced in the rapamycin groups. Furthermore, mortality was increased in the high-dose rapamycin group. Conclusions: Rapamycin could improve cardiac function of early-stage DCM, but the effect of rapamycin turned out to be biphasic and the effective range appeared narrow.
Nonfocal Symptoms are More Frequent in Patients with Vertebral Artery than Carotid Artery Stenosis
Authors: Compter Annette , Kappelle L. Jaap , Algra Ale , van der Worp H. Bart
Published: April 2013

Introduction: In patients with a transient ischemic attack (TIA) or ischemic stroke, the combination of focal and nonfocal symptoms has been associated with a higher risk of cardiovascular events. We hypothesized that nonfocal symptoms are more frequent in patients with symptomatic stenosis of a vertebral artery (VA) than of a carotid artery (CA). Therefore, we assessed the prevalence of nonfocal symptoms in patients with a recent TIA or nondisabling ischemic stroke and studied their relation with symptomatic CA or VA stenosis. Methods: We administered a standardized questionnaire on the occurrence of focal and nonfocal symptoms during the qualifying TIA or nondisabling ischemic stroke and in the preceding 6 months. We included 50 consecutive patients with a recently symptomatic CA stenosis ≥50%, 50 consecutive patients with a recently symptomatic VA stenosis ≥50%, 25 consecutive patients with an anterior circulation event without an ipsilateral CA stenosis ≥50%, and 25 consecutive patients with a posterior circulation event without a relevant VA stenosis ≥50%. Relative risks for the presence of nonfocal symptoms in relation to the presence of a symptomatic stenosis were calculated with univariate and multivariate Poisson regression. Adjustments were made for age, sex, stroke as the qualifying event, and cardiovascular risk factors. A subgroup analysis was performed for patients in whom the vascular territory of the event was confirmed on imaging. Results: During the qualifying ischemic event, focal symptoms were accompanied by nonfocal symptoms in 80 (53%) patients. Nonfocal symptoms occurred more frequently in patients with a VA stenosis (72%) than in patients with a CA stenosis [26%; adjusted relative risk (aRR), 2.9; 95% confidence interval (CI), 1.8-4.6]. A higher prevalence of nonfocal symptoms was found in patients with posterior circulation TIAs and strokes (73%) than in patients with anterior circulation TIAs and strokes (33%; aRR, 2.2; 95% CI, 1.6-3.1). During the preceding 6 months, 45% of patients with and 20% of patients without a symptomatic stenosis had had nonfocal symptoms (aRR, 2.4; 95% CI, 1.3-4.3). Subgroup analysis for the 89 (59%) patients with ischemia visible on imaging gave essentially the same results. Conclusions: More than half of the TIAs or nondisabling ischemic strokes were associated with nonfocal neurological symptoms. Nonfocal symptoms occurred more frequently in patients with a symptomatic VA stenosis than CA stenosis.
Aging Does Not Affect Radial Viscoelastic Behavior of the Left Ventricle
Authors: Mangual Jan O. , Föll Daniela , Jung Bernd , Pedrizzetti Gianni , Kheradvar Arash
Published: April 2013

Objectives: This study investigates the effect of aging on the radial viscoelastic behavior of the left ventricle (LV) based on a previously validated model that uses myocardial tissue phase mapping (TPM) of cine phase-contrast MRI. Methods: Previous studies suggest that aging remarkably influences regional myocardial motion, mostly myocardial velocities in both radial and long-axis directions. However, the effect of aging on cardiac viscoelasticity, which exhibits time-dependent strain, has not been elucidated yet. In this study, myocardial velocity and displacement mapping of the LV was performed using TPM in 39 healthy subjects divided into three age groups. The viscoelasticity parameters were obtained for each segment of the LV and compared among the studied groups. Results: The analyses showed that myocardial elasticity ranged from approximately 20 to -20 dyne/cm2 during a cardiac cycle, and the myocardial viscous-damping component ranged from -1 to 1 dyne × s/cm2. Overall, no statistically significant difference was observed in the viscoelasticity components among the subjects in the different age groups (p > 0.05). Conclusion: Myocardial viscoelastic behavior of the LV in radial direction was found to be considerably similar in pattern and magnitude among the studied subjects of different age groups with no statistically significant difference, despite the fact that the regional myocardial velocities change due to aging.
Pattern and Timing of the Coronary Sinus Activation to Guide Rapid Diagnosis of Atrial Tachycardia After Atrial Fibrillation Ablation
Authors: Pascale Patrizio , Shah Ashok J. , Roten Laurent , Scherr Daniel , Komatsu Yuki , Jadidi Amir S. , Ramoul Khaled , Daly Matthew , Denis Arnaud , Wilton Stephen B. , Derval Nicolas , Sacher Frédéric , Hocini Mélèze , Haïssaguerre Michel , Jaïs Pierre
Published: April 2013

Background—

Atrial tachycardias (AT) during or after ablation of atrial fibrillation frequently pose a diagnostic challenge. We hypothesized that both the patterns and the timing of coronary sinus (CS) activation could facilitate AT mapping.

Methods and Results—

A total of 140 consecutive postpersistent atrial fibrillation ablation patients with sustained AT were investigated by conventional mapping. CS activation pattern was defined as chevron or reverse chevron when the activations recorded on both the proximal and the distal CS dipoles were latest or earliest, respectively. The local activation of mid-CS was timed with reference to P
peak
–P
peak
(P–P) interval in lead V1. A ratio, mid-CS activation time to AT cycle length, was computed. Of 223 diagnosed ATs, 124 were macroreentrant (56%) and 99 were centrifugal (44%). When CS activation was chevron/reverse chevron (n=44; 20%), macroreentries were mostly roof dependent. With reference to P–P interval, mid-CS activation timing showed specific consistency for peritricuspid and perimitral AT. Proximal to distal CS activation pattern and mid-CS activation at 50% to 70% of the P–P interval (n=30; 13%) diagnosed peritricuspid AT with 81% sensitivity and 89% specificity. Distal to proximal CS activation and mid-CS activation at 10% to 40% of the P–P interval (n=44; 20%) diagnosed perimitral AT with 88% sensitivity and 75% specificity.

Conclusions—

The analysis of the patterns and timing of CS activation provides a rapid stratification of most likely macroreentrant ATs and points toward the likely origin of centrifugal ATs. It can be included in a stepwise diagnostic approach to rapidly select the most critical mapping maneuvers.
Prolyl Hydroxylase Domain Protein 2 Plays a Critical Role in Diet-Induced Obesity and Glucose Intolerance
Authors: Matsuura Hirohide , Ichiki Toshihiro , Inoue Eriko , Nomura Masatoshi , Miyazaki Ryohei , Hashimoto Toru , Ikeda Jiro , Takayanagi Ryoichi , Fong Guo-Hua , Sunagawa Kenji
Published: April 2013

Background—

Recent studies suggest that the oxygen-sensing pathway consisting of transcription factor hypoxia-inducible factor and prolyl hydroxylase domain proteins (PHDs) plays a critical role in glucose metabolism. However, the role of adipocyte PHD in the development of obesity has not been clarified. We examined whether deletion of
PHD2
, the main oxygen sensor, in adipocytes affects diet-induced obesity and associated metabolic abnormalities.

Methods and Results—

To delete
PHD2
in adipocyte,
PHD2
-floxed mice were crossed with aP2-Cre transgenic mice (
Phd2

f/f

/aP2-Cre)
.
Phd2

f/f

/aP2-Cre
mice were resistant to high-fat diet–induced obesity (36.7±1.7 versus 44.3±2.0 g in control;
P
<0.01) and showed better glucose tolerance and homeostasis model assessment–insulin resistance index than control mice (3.6±1.0 versus 11.1±2.1;
P
<0.01). The weight of white adipose tissue was lighter (epididymal fat, 758±35 versus 1208±507 mg in control;
P
<0.01) with a reduction in adipocyte size. Macrophage infiltration into white adipose tissue was also alleviated in
Phd2

f/f

/aP2-Cre
mice. Target genes of hypoxia-inducible factor, including glycolytic enzymes and adiponectin, were upregulated in adipocytes of
Phd2

f/f

/aP2-Cre
mice. Lipid content was decreased and uncoupling protein-1 expression was increased in brown adipose tissue of
Phd2

f/f

/aP2-Cre
mice. Knockdown of PHD2 in 3T3L1 adipocytes induced a decrease in the glucose level and an increase in the lactate level in the supernatant with upregulation of glycolytic enzymes and reduced lipid accumulation.

Conclusions—

PHD2 in adipose tissue plays a critical role in the development of diet-induced obesity and glucose intolerance. PHD2 might be a novel target molecule for the treatment of obesity and associated metabolic abnormalities.
Prevalence and Risk Factors for Hypertension in Hemophilia
Authors: von Drygalski Annette , Kolaitis Nicholas A. , Bettencourt Ricki , Bergstrom Jaclyn , Kruse-Jarres R. , Quon Doris V. , Wassel Christina , Li Ming C. , Waalen Jill , Elias Darlene J. , Mosnier Laurent O. , Allison Matthew
Published: April 2013

Hypertension (HTN) is a major risk factor for intracranial hemorrhage. We, therefore, investigated the prevalence, treatment, and control of HTN in adult patients with hemophilia (PWH). PWH≥18 years (n=458) from 3 geographically different cohorts in the United States were evaluated retrospectively for HTN and risk factors. Results were compared with the nationally representative sample provided by the contemporary National Health and Nutrition Examination Survey (NHANES). PWH had a significantly higher prevalence of HTN compared with NHANES. Overall, the prevalence of HTN was 49.1% in PWH compared with 31.7% in NHANES. At ages 18 to 44, 45 to 64, 65 to 74, and ≥75 years, the prevalence of HTN for PWH was 31.8%, 72.6%, 89.7%, and 100.0% compared with 12.5%, 41.2%, 64.1%, and 71.7% in NHANES, respectively. Of treated hypertensive PWH, only 27.1% were controlled, compared with 47.7% in NHANES (all
P
<0.05). Age, body mass index, diabetes mellitus, and renal function were independently associated with HTN. Among patients with moderate or severe hemophilia there was a trend (≈1.5-fold) for higher odds of having HTN compared with patients with mild hemophilia. On the basis of these results, new care models for adult PWH and further studies for the causes of HTN in hemophilia are recommended.
Video‐Assisted Harvesting of Anterolateral Thigh Free Flap: Technique Validation and Initial Results
Authors: Moreno Mauricio Alejandro
Published: April 2013

Objective

To provide a description of a minimally invasive, video‐assisted technique (VAT) to identify the cutaneous perforators of the anterolateral thigh (ALT). The objective of the study was to compare this technique with standard open exploration of the thigh and to describe the learning curve for the procedure.

Study Design

Case series with chart review.

Setting

Academic tertiary institution.

Subjects and Methods

Twenty‐six cases operated between December 2009 and June 2012. In all of these cases, an open thigh exploration, considered the gold standard, was performed immediately after the VAT. Data retrieved included surgical findings, demographics, and outcomes.

Results

There were 17 men and 9 women with a mean age of 60 years. The average flap size was 91 cm2 (range, 39‐264 cm2), and a chimeric double skin paddle flap was harvested in 6 cases. Forty‐nine of 53 total perforators were successfully identified endoscopically. Findings on endoscopic and open exploration were highly correlated (r = 0.92, P =. 000). The overall sensitivity for the technique was 92.4% (confidence interval, 80.9‐97.5) but reached 100% for perforators located at the midpoint of the anterior‐superior iliac spine–patella line. All flaps survived, and there were no technique‐related complications. The learning curve plateaued after 15 cases, with a mean endoscopic operative time of 18.2 minutes for the last 10 procedures.

Conclusion

This VAT is a safe and reliable method to identify cutaneous perforators of the lateral thigh. The procedure is straightforward and has a moderate learning curve. This approach has a role in minimizing donor site morbidity and assisting in flap design.
Preliminary Results of Diode Laser Surgery for Early Glottic Cancer
Authors: Tunçel Ümit , Cömert Ela
Published: April 2013

Objective

To analyze the complications and preliminary oncologic results of microscopic diode laser surgery.

Study Design

Prospective research.

Setting

Ankara Oncology Education and Research Hospital.

Subjects and Methods

This prospective study was conducted on a series of 64 patients with glottic carcinoma (Tis, T1, T2) treated with microscopic endolaryngeal diode laser surgery.

Results

Four patients had local recurrence (6.2%). Local control and larynx preservation rates were 93.8% and 100%, respectively, for all groups of patients. Two‐year disease‐free survival after primary surgery was 100% for the Tis group, 96.4% for the T1 group, and 89.7% for the T2 group. When considering anterior commissure involvement, 2‐year disease‐free survival after primary surgery was 100% for the AC0 group, 85.7% for the AC1 group, and 85.7% for the AC2 group.

Conclusion

Our study of microscopic diode laser resection of Tis, T1, and T2 glottic tumors showed similar oncologic results to previous reports about CO2 laser surgery. In anterior commissure tumors, both techniques had high complication and recurrence rates.
Monitoring adhesive integrity of disk-shaped transducer by electromechanical impedance
Authors: Dugnani Roberto
Published: April 2013

Structural health monitoring refers to the interdisciplinary engineering field whose objective is to monitor and evaluate the integrity of mechanical structures. Often times, structural health monitoring diagnostics utilize piezoelectric (lead zirconate titanate) transducers bonded to the surface of the structure monitored. Nonetheless, unexpected variations in the mechanical properties of the adhesive film could affect the dynamic behavior of the system and potentially mischaracterize the fitness for service of a structure. In this article, we presented an analytical model to describe the dynamic coupling between the structure and the lead zirconate titanate transducer that includes the adhesive layer. An electromechanical impedance–based method capable of assessing the integrity of the adhesive bondline was developed based on the proposed analytical model. Our study found that the phase angle of the transducer’s electrical admittance was correlated to the mechanical impedance of the adhesive film following a power law behavior. Validation of the proposed model was carried out both by testing transducers bonded to aluminum plates and through a numerical parametric study. In the future, the method proposed could be used to detect preexisting defects in the adhesive bondline, to estimate the adhesive’s thickness at manufacturing, and to monitor the degradation of the adhesive material during the life of the system.
Risk factors for pulmonary tuberculosis in patients with chronic obstructive airway disease in Taiwan: a nationwide cohort study
Authors: Lee Chih-Hsin , Lee Ming-Chia , Shu Chin-Chung , Lim Chor-Shen , Wang Jann-Yuan , Lee Li-Na , Chao Kun-Mao
Published: April 2013

Background

An association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use. Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear.

Methods

We selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB.

Results

Among 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected. Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205–2.762]) were independent risk factors for TB. Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists. Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB. The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios.

Conclusion

Keeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications. Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice.
MicroRNA profile of paclitaxel-resistant serous ovarian carcinoma based on formalin-fixed paraffin-embedded samples
Authors: Li Xiao , Lu Yaer , Chen Yaxia , Lu Weiguo , Xie Xing
Published: April 2013

Background

To assess the feasibility of validating microRNA (miRNA) profile related to paclitaxel-sensitivity in formalin-fixed paraffin-embedded (FFPE) samples of serous ovarian carcinoma (OC) patients.

Methods

Deregulated miRNAs identified by miRNA microarray were further detected in 45 FFPE OC samples using Realtime PCR. Correlations between paired FFPE and frozen tumor samples were analyzed. Survival times were compared between 6 high and low miRNAs groups. Western blot and luciferase reporter assay were used for validating the target of miRNA.

Results

Sixteen up-regulated miRNAs and twenty-three down-regulated miRNAs were revealed in pacilitaxel-resistant ST30 cells. The up-regulated miRNAs (miR-320a, 22 and 129-5p) and down-regulated miRNAs (miR-9, 155 and 640) were confirmed in paclitaxel-resistant FFPE tumor samples, compared with paclitaxel-sensitive samples. Higher miR-9 and miR-640 showed better survival time in OC patients. Expressions of miR-9, 155 and 22 in FFPE samples were closely mimicked by those in frozen tissues. RAB34 was validated as a direct target of miR-9.

Conclusions

We validated miRNA profile in pacilitaxel-resistant OC using FFPE samples, which might enable treatment stratification and help us to predict outcomes in OC patients. FFPE samples are feasible materials for miRNA research.
Limited sequence polymorphisms of four transmission-blocking vaccine candidate antigens in Plasmodium vivax Korean isolates
Authors: Kang Jung-Mi , Ju Hye-Lim , Moon Sung-Ung , Cho Pyo-Yun , Bahk Young-Yil , Sohn Woon-Mok , Park Yun-Kyu , Cha Seok Ho , Kim Tong-Soo , Na Byoung-Kuk
Published: April 2013

Background

Transmission-blocking vaccines (TBVs), which target the sexual stages of malaria parasites to interfere with and/or inhibit the parasite’s development within mosquitoes, have been regarded as promising targets for disrupting the malaria transmission cycle. In this study, genetic diversity of four TBV candidate antigens, Pvs25, Pvs28, Pvs48/45, and PvWARP, among Plasmodium vivax Korean isolates was analysed.

Methods

A total of 86 P. vivax- infected blood samples collected from patients in Korea were used for analyses. Each of the full-length genes encoding four TBV candidate antigens, Pvs25, Pvs28, Pvs48/45, and PvWARP, were amplified by PCR, cloned into T&A vector, and then sequenced. Polymorphic characteristics of the genes were analysed using the DNASTAR, MEGA4, and DnaSP programs.

Results

Polymorphism analyses of the 86 Korean P. vivax isolates revealed two distinct haplotypes in Pvs25 and Pvs48/45, and three different haplotypes in PvWARP. In contrast, Pvs28 showed only a single haplotype. Most of the nucleotide substitutions and amino acid changes identified in all four TBV candidate antigens were commonly found in P. vivax isolates from other geographic areas. The overall nucleotide diversities of the TBV candidates were much lower than those of blood stage antigens.

Conclusions

Limited sequence polymorphisms of TBV candidate antigens were identified in the Korean P. vivax population. These results provide baseline information for developing an effective TBV based on these antigens, and offer great promise for applications of a TBV against P. vivax infection in regions where the parasite is most prevalent.
Association of air pollution and use of glyceryl trinitrate against angina pectoris: a population-based case-crossover study
Authors: Finnbjornsdottir Ragnhildur Gudrun , Zoëga Helga , Olafsson Orn , Thorsteinsson Throstur , Rafnsson Vilhjalmur
Published: April 2013

Background

Ambient air pollution has been associated with increased cardiovascular morbidity and mortality. In Reykjavik, Iceland, air pollutant concentrations exceed official health limits several times every year. The aim was to study the association of concentrations of NO2, O3, PM10, and H2S in the Reykjavik capital area with the dispensing of anti-angina pectoris medication, glyceryl trinitrate to the inhabitants.

Methods

Data on daily dispensing of glyceryl trinitrate, were retrieved from the Icelandic Medicines Registry. Data on hourly concentrations of NO2, O3, PM10, and H2S were obtained from the Environment Agency of Iceland. A case-crossover design was used, based on the dispensing of glyceryl trinitrate to 5,246 individuals (≥18 years) between 2005 and 2009.

Results

For every 10 μg/m3 increase of NO2 and O3 3-day mean concentrations, the odds ratio (OR) for daily dispensing of glyceryl trinitrates was 1.136 (95% confidence intervals (CI) 1.069-1.207) and 1.094 (95% CI 1.029-1.163) at lag 0, and OR was 1.096 (95% CI 1.029-1.168) and 1.094 (95% CI 1.028-1.166) at lag 1, respectively.

Conclusions

These findings suggest that NO2 and O3 ambient air concentrations may adversely affect cardiovascular health, as measured by the dispensing of glyceryl trinitrates for angina pectoris. Further, the findings suggest that data on the dispensing of medication may be a valuable health indicator when studying the effect of air pollution on cardiovascular morbidity.
Analytical modelling of monolayer graphene-based ion-sensitive FET to pH changes
Authors: Kiani Mohammad Javad , Ahmadi Mohammad Taghi , Karimi Feiz Abadi Hediyeh , Rahmani Meisam , Hashim Amin , Che harun Fauzan Khairi
Published: April 2013

Graphene has attracted great interest because of unique properties such as high sensitivity, high mobility, and biocompatibility. It is also known as a superior candidate for pH sensing. Graphene-based ion-sensitive field-effect transistor (ISFET) is currently getting much attention as a novel material with organic nature and ionic liquid gate that is intrinsically sensitive to pH changes. pH is an important factor in enzyme stabilities which can affect the enzymatic reaction and broaden the number of enzyme applications. More accurate and consistent results of enzymes must be optimized to realize their full potential as catalysts accordingly. In this paper, a monolayer graphene-based ISFET pH sensor is studied by simulating its electrical measurement of buffer solutions for different pH values. Electrical detection model of each pH value is suggested by conductance modelling of monolayer graphene. Hydrogen ion (H+) concentration as a function of carrier concentration is proposed, and the control parameter (Ƥ) is defined based on the electro-active ions absorbed by the surface of the graphene with different pH values. Finally, the proposed new analytical model is compared with experimental data and shows good overall agreement.
A DFT-based approximate eigenvalue and singular value decomposition of polynomial matrices
Authors: Tohidian Mahdi , Amindavar Hamidreza , Reza Ali M.
Published: April 2013

In this article, we address the problem of singular value decomposition of polynomial matrices and eigenvalue decomposition of para-Hermitian matrices. Discrete Fourier transform enables us to propose a new algorithm based on uniform sampling of polynomial matrices in frequency domain. This formulation of polynomial matrix decomposition allows for controlling spectral properties of the decomposition. We set up a nonlinear quadratic minimization for phase alignment of decomposition at each frequency sample, which leads to a compact order approximation of decomposed matrices. Compact order approximation of decomposed matrices makes it suitable in filterbank and multiple-input multiple-output (MIMO) precoding applications or any application dealing with realization of polynomial matrices as transfer function of MIMO systems. Numerical examples demonstrate the versatility of the proposed algorithm provided by relaxation of paraunitary constraint, and its configurability to select different properties.