bluuebunny/crossref_metadata_2025 huggingface dataset:
Highly fluorescent GFPm2+‐based genome integration‐proficient promoter probe vector to study Mycobacterium tuberculosis promoters in infected macrophages
Authors: Roy Sougata , Narayana Yeddula , Narayanaswamy Balaji Kithiganahalli , Ajitkumar Parthasarathi
Published: September 2011

Study of activity of cloned promoters in slow‐growing Mycobacterium tuberculosis during long‐term growth conditions in vitro or inside macrophages, requires a genome‐integration proficient promoter probe vector, which can be stably maintained even without antibiotics, carrying a substrate‐independent, easily scorable and highly sensitive reporter gene. In order to meet this requirement, we constructed pAKMN2, which contains mycobacterial codon‐optimized gfpm2+ gene, coding for GFPm2+ of highest fluorescence reported till date, mycobacteriophage L5 attP‐int sequence for genome integration, and a multiple cloning site. pAKMN2 showed stable integration and expression of GFPm2+ from M. tuberculosis and M. smegmatis genome. Expression of GFPm2+, driven by the cloned minimal promoters of M. tuberculosis cell division gene, ftsZ (MtftsZ), could be detected in the M. tuberculosis/pAKMN2‐promoter integrants, growing at exponential phase in defined medium in vitro and inside macrophages. Stable expression from genome‐integrated format even without antibiotic, and high sensitivity of detection by flow cytometry and fluorescence imaging, in spite of single copy integration, make pAKMN2 useful for the study of cloned promoters of any mycobacterial species under long‐term in vitro growth or stress conditions, or inside macrophages.
Cyclic di‐nucleotides: new era for small molecules as adjuvants
Authors: Libanova Rimma , Becker Pablo D. , Guzmán Carlos A.
Published: September 2011

The implementation of vaccination as an empiric strategy to protect against infectious diseases was introduced even before the advent of hygiene and antimicrobials in the medical practice. Nevertheless, it was not until a few decades ago that we really started understanding the underlying mechanisms of protection triggered by vaccination. Vaccines were initially based on attenuated or inactivated organisms. Subunit vaccines were then introduced as more refined formulations, exhibiting improved safety profiles. However, purified antigens tend to be poorly immunogenic and often require the use of adjuvants to achieve adequate stimulation of the immune system. Vaccination strategies, such as mucosal administration, also require potent adjuvants to improve performance. In the 1990s, immunologists found that pathogens could be sensed as ‘danger signals’ by receptors recognizing conserved motifs. Although our knowledge is still limited, tremendous advances were made in the understanding of host defence mechanisms regulated by these evolutionary conserved receptors, and the molecular structures which are recognized by them. This opened a new era in adjuvant development. Some of the latest players arrived to this field are the cyclic di‐nucleotides, which are ubiquitous prokaryotic intracellular signalling molecules. This review is focused on their potential for the development of vaccines and immunotherapies.
Prevalence of diabetic retinopathy in Norway: report from a screening study
Authors: Kilstad Hilde Nygaard , Sjølie Anne Katrine , Gøransson Lasse , Hapnes Rune , Henschien Hans Jørgen , Alsbirk Knud Erik , Fossen Kristian , Bertelsen Geir , Holstad Gro , Bergrem Harald
Published: September 2011

Purpose:  The purpose of the present study was to investigate the prevalence of diabetic retinopathy (DR) in Norway and adherence to the Norwegian Guidelines for screening for diabetic eye disease.

Methods:  Two hundred and ninety‐nine people with diabetes were randomly recruited from the patient lists of randomly selected general practitioners from three different regions in Norway. Retinopathy was evaluated from retinal photographs after dilation of the pupils using a red‐free digital camera and visual acuity was measured using the Snellen chart. The patients were interviewed about their ophthalmological and general diabetes control, duration and type of diabetes and medical treatment.

Results:  The prevalence of any DR was 28%, 66% for type 1 and 24% for type 2 diabetes. The prevalence of proliferative retinopathy was 38% in type 1 and 1.5% in type 2 diabetes. Two patients (one type 1 and one insulin‐treated type 2) were visually impaired (visual acuity 0.3 or worse in the better eye) because of proliferative DR. Twenty‐six per cent of the patients had never been to an eye examination, and only 69% attended routine eye examinations. Patients who did not attend regular eye screenings were mostly people with type 2 diabetes.

Conclusion:  The prevalence of DR was higher than previously reported in Norway. Screening for DR did not follow guidelines in a considerable proportion of the patients with type 2 diabetes. There is place for improvement in the implementation of guidelines for screening for DR for people with type 2 diabetes in Norway.
Intraocular pressure changes following 20G pars‐plana vitrectomy
Authors: Framme Carsten , Klotz Susanne , Wolf‐Schnurrbusch Ute E.K. , Wiedemann Peter , Wolf Sebastian
Published: September 2011

Purpose:  To observe the excursions of short‐term intraocular pressure (IOP) after 20‐G pars‐plana vitrectomy (ppV).

Material and methods:  In a prospective study, 851 patients (age: mean 63 ± 15 years) underwent unilateral ppV for various vitreoretinal diseases using different endotamponades [Balanced Salt Solution (BSS) 33.1%, Air 7.2%, SF6 33.6%, silicon oil 5000 cst 26.1%]. Intraocular pressure was measured in all patients before and at 3, 6, 24 and 48 hr after surgery. Survival analysis was performed to determine the cumulative hazard of IOP changes depending on endotamponade and time point after ppV (Log‐Rang ‐ Mantel Cox; p < 0.0001).

Results:  At baseline, IOP ranged from 0 to 50 mmHg (mean IOP: 15.3 ± 5.3 mmHg). Mean IOP after surgery revealed a slight elevation (3 hr: 16.5 ± 11.0 mmHg; 6 hr 16.9 ± 9.8 mmHg; 24 hr 19.7 ± 8.0 mmHg; 48 hr 17.3 ± 6.2 mmHg; range: 0–64 mmHg). Silicon oil filling revealed highest mean values at already 3 hr after surgery (21.8 mmHg). Also, BSS filling showed a peak after 3 hr; however, mean values were lower. Equivalent high IOP values as for silicon oil tamponade were found for gas filling; however, maximal peak was reached after 24 hr but not after 3 hr post‐treatment. The cumulative hazard in all patients to reach IOP ≥ 30 mmHg after 24 hr was 23.9%; (IOP ≥ 40 mmHg = 8.2%). Herein, oil filling revealed highest risk at all time points after surgery. The risk of suffering from IOP < 5 mmHg lasting longer than 6 hr was only 1.2% after 20 G vitrectomy.

Conclusion:  Intraocular pressure measurements after ppV are important to prevent unintentional high IOP, especially within the early phase (3 hr post‐treatment) in eyes with silicon oil filling. Gas filling leads to prolonged IOP increase (24 hr post‐treatment). Long‐lasting hypotony (≥6 hr) is very rare after 20G vitrectomy.
Nickel abundance in stony cosmic spherules: Constraining precursor material and formation mechanisms
Authors: CORDIER Carole , Van GINNEKEN Matthias , FOLCO Luigi
Published: September 2011

Abstract–We report bulk and olivine compositions in 66 stony cosmic spherules (Na2O < 0.76 wt%), 200–800 μm in size, from the Transantarctic Mountains, Antarctica. In porphyritic cosmic spherules, relict olivines that survived atmospheric entry heating are always Ni‐poor and similar in composition to the olivines in carbonaceous or unequilibrated ordinary chondrites (18 spherules), and equilibrated ordinary chondrites (one spherule). This is consistent with selective survival of high temperature, Mg‐rich olivines during atmospheric entry. Olivines that crystallized from the melts produced during atmospheric entry have NiO contents that increase with increasing NiO in the bulk spherule, and that range from values similar to those observed in chondritic olivines (NiO generally <0.5 wt%) to values characteristic of olivines in meteoritic ablation spheres (NiO > 2 wt%). Thus, NiO content in olivine cannot be used alone to distinguish meteoritic ablation spheres from cosmic spherules, and the volatile element contents have to be considered. We propose that the variation in NiO contents in cosmic spherules and their olivines is the result of variable content of Fe, Ni metal in the precursor. NiO contents in olivines and in cosmic spherules can thus be used to discuss their parent body. Ni‐poor spherules can be derived from C‐rich and/or metal‐poor precursors, either related to CM, CI, CR chondrites or to chondritic fragments dominated by silicates, regardless of the parent body. Ni‐rich spherules (NiO > 0.7 wt%) that represent 55% of the 47 barred‐olivine spherules we studied, were derived from the melting of C‐poor, metal‐rich precursors, compatible with ordinary chondrite or CO, CV, CK carbonaceous chondrite parentages.
A numerical comparison with the Ceplecha analytical meteoroid orbit determination method
Authors: CLARK David L. , WIEGERT Paul A.
Published: September 2011

Abstract– Analytic methods by Ceplecha have long been used for the determination of meteoroid heliocentric orbits. These methods include both the derivation of an initial atmospheric contact position and velocity state, and the calculation of an orbit at infinity based on zenithal attraction assumptions. Herein, we describe a numerical integration‐based verification for a portion of the Ceplecha methods, a verification driven by the need for an accurate meteoroid ephemeris in the hours before atmospheric contact. We show a close correspondence in analytic and numerical results, with a previously undocumented minor correction to a meteoroid’s longitude of the ascending node.
The effects of an advanced uterine environment on embryonic survival in the mare
Authors: WILSHER S. , LEFRANC A.‐C. , ALLEN W. R.
Published: September 2011

Reasons for performing the study:During embryo transfer (ET) the equine embryo can tolerate a wide degree of negative asynchrony but positive asynchrony of >2 days usually results in embryonic death. There is still confusion over whether this is due to the inability of the embryo to induce luteostasis or to an inappropriate uterine environment.

Objectives:To assess embryo survival and development in an advanced uterine environment.

Hypothesis:Embryo–uterine asynchrony, not the embryo's inability to induce luteostasis, is responsible for embryonic death in recipient mares with a >2 days chronologically advanced uterus.

Methods:Experiment 1: Thirteen Day 7 embryos were transferred to the uteri of recipient mares with luteal prolongation, occasioned by manual crushing of their own conceptus, such that donor–recipient asynchrony was between +13 and +49 days.Experiment 2: Day 7 embryos were transferred to recipient mares carrying their own conceptus at Days 18 (n = 2), 15 (n = 2), 14 (n = 4), 12 (n = 4) or 11 (n = 4) of gestation. In addition, Day 8 embryos were transferred to 4 pregnant recipient mares on Day 11 of gestation.

Results:No pregnancies resulted following transfer of Day 7 embryos to recipients in prolonged dioestrus with asynchronies between +13 and +49 days. However, the use of early pregnant mares as recipients resulted in 5/20 (25%) twin pregnancies, 4 of which came from the transfer of a Day 8 embryo to a Day 11 recipient. All transferred embryos showed retarded growth, with death occurring in 4/5 (80%).

Conclusions and potential relevance:The results emphasise the importance of an appropriate uterine environment for embryo growth and the inability of equine embryos to survive transfer to a uterus >2 days advanced even when luteostasis is achieved. It is possible that in normal, non‐ET equine pregnancy, embryo–uterine asynchrony may account for some cases of embryonic death.
In-vitro and in-vivo transdermal iontophoretic delivery of tramadol, a centrally acting analgesic
Authors: Takasuga Shinri , Yamamoto Rie , Mafune Shoichi , Sutoh Chiyo , Kominami Katsuya , Yoshida Yoshimasa , Ito Masao , Kinoshita Mine
Published: September 2011

Objectives

The feasibility of transdermal delivery of tramadol, a centrally acting analgesic, by anodal iontophoresis using Ag/AgCl electrodes was investigated in vitro and in vivo.

Methods

To examine the effect of species variation and current strength on skin permeability of tramadol, in-vitro skin permeation studies were performed using porcine ear skin, guinea-pig abdominal skin and hairless mouse abdominal skin as the membrane. In an in-vivo pharmacokinetic study, an iontophoretic patch system was applied to the abdominal skin of conscious guinea pigs with a constant current supply (250 µA/cm2) for 6 h. An intravenous injection group to determine the pharmacokinetic parameters for estimation of the transdermal absorption rate in guinea pigs was also included.

Key findings

The in-vitro steady-state skin permeation flux of tramadol current-dependently increased without significant differences among the three different skin types. In the in-vivo pharmacokinetic study, plasma concentrations of tramadol steadily increased and reached steady state (336 ng/ml) 3 h after initiation of current supply, and the in-vivo steady-state transdermal absorption rate was 499 µg/cm2 per h as calculated by a constrained numeric deconvolution method.

Conclusions

The present study reveals that anodal iontophoresis provides current-controlled transdermal delivery of tramadol without significant interspecies differences, and enables the delivery of therapeutic amounts of tramadol.
Spray-dried oil-in-water emulsion to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac
Authors: Zhang Jianjun , Zheng Zengjuan , Gao Yuan , Zhang Yihua
Published: September 2011

Objectives

Spray-dried emulsion (SDE) was prepared and characterized to improve the intestinal absorption and oral bioavailability of ZLR-8, a nitric oxide-releasing derivative of diclofenac, currently under preclinical development.

Methods

The intestinal absorption of ZLR-8 was characterized by single pass intestinal perfusion technique to obtain its absorption and permeability parameters. SDE of ZLR-8 was prepared and characterized by particle size measurements and in-vitro release study. Accurate and precise RP-HPLC methods for the detection of ZLR-8 and its metabolite diclofenac were constructed to perform the bioavailability study.

Key findings

It was demonstrated that ZLR-8 was absorbed in the whole intestine, of which the duodenum segment exhibited the largest absorption ability. ZLR-8 can be classified into BCS Class 2. SDE significantly enhanced the intestinal absorption rate of ZLR-8 in duodenum and jejunum but had indistinctive effect on permeability. All concentrations of ZLR-8 in rat plasma was lower than the limit of detection. A bicompartment model gave the best fit to the plasma diclofenac concentration–time curves. Calculated on AUC0–12h, the mean relative bioavailability of SDE was 105.4-fold that of ZLR-8 suspension.

Conclusions

SDE significantly improved the intestinal absorption of ZLR-8 and resulted in a dramatic improvement in its bioavailability.
Quantifying the Anisotropy in Biological Materials
Authors: Ranganathan Shivakumar I. , Ostoja-Starzewski Martin , Ferrari Mauro
Published: September 2011

Anisotropy is an essential attribute exhibited by most biological materials. Based on the recent work on anisotropy of a wide range of crystals and polycrystals, we propose an appropriate measure (A) to quantify the extent of elastic anisotropy in biomaterials by accounting the tensorial nature (both stiffness-based and compliance-based) of their elastic properties. Next, we derive a relationship between A and an empirically defined existing measure. Also, the preceding measure is used to quantify the extent of anisotropy in select biological materials that include bone, dentitional tissues, and a variety of woods. Our results indicate that woods are an order of magnitude more anisotropic than hard tissues and apatites. Finally, based on the available data, it is found that the anisotropy in human femur increases by over 40% when measured between 30% and 70% of the total femur length.
Steerable Mechanical Joint for High Load Transmission in Minimally Invasive Instruments
Authors: Yan Nai Tin , Herder Just L. , Tuijthof Gabriëlle J. M.
Published: September 2011

As minimally invasive operations are performed through small portals, the limited manipulation capability of straight surgical instruments is an issue. Access to the pathology site can be challenging, especially in confined anatomic areas with few available portals, such as the knee joint. The goal in this paper is to present and evaluate a new sideways-steerable instrument joint that fits within a small diameter and enables transmission of relative high forces (e.g., for cutting of tough tissue). Meniscectomy was selected as a target procedure for which quantitative design criteria were formulated. The steering mechanism consists of a crossed configuration of a compliant rolling-contact element that forms the instrument joint, which is rotated by flexural steering beams that are configured in a parallelogram mechanism. The actuation of cutting is performed by steel wire that runs through the center of rotation of the instrument joint. A prototype of the concept was fabricated and evaluated technically. The prototype demonstrated a range of motion between −22° and 25° with a steering stiffness of 17.6 Nmm/rad (min 16.9 – max 18.2 Nmm/rad). Mechanical tests confirmed that the prototype can transmit an axial load of 200 N on the tip with a maximum parasitic deflection of 4.4°. A new sideways steerable mechanical instrument joint was designed to improve sideways range of motion while enabling the cutting of strong tissues in a minimally invasive procedure. Proof of principle was achieved for the main criteria, which encourages the future development of a complete instrument.
Cardiac Assist With a Twist: Apical Torsion as a Means to Improve Failing Heart Function
Authors: Trumble Dennnis R. , McGregor Walter E. , Kerckhoffs Roy C. P. , Waldman Lewis K.
Published: September 2011

Changes in muscle fiber orientation across the wall of the left ventricle (LV) cause the apex of the heart to turn 10–15 deg in opposition to its base during systole and are believed to increase stroke volume and lower wall stress in healthy hearts. Studies show that cardiac torsion is sensitive to various disease states, which suggests that it may be an important aspect of cardiac function. Modern imaging techniques have sparked renewed interest in cardiac torsion dynamics, but no work has been done to determine whether mechanically augmented apical torsion can be used to restore function to failing hearts. In this report, we discuss the potential advantages of this approach and present evidence that turning the cardiac apex by mechanical means can displace a clinically significant volume of blood from failing hearts. Computational models of normal and reduced-function LVs were created to predict the effects of applied apical torsion on ventricular stroke work and wall stress. These same conditions were reproduced in anesthetized pigs with drug-induced heart failure using a custom apical torsion device programmed to rotate over various angles during cardiac systole. Simulations of applied 90 deg torsion in a prolate spheroidal computational model of a reduced-function pig heart produced significant increases in stroke work (25%) and stroke volume with reduced fiber stress in the epicardial region. These calculations were in substantial agreement with corresponding in vivo measurements. Specifically, the computer model predicted torsion-induced stroke volume increases from 13.1 to 14.4 mL (9.9%) while actual stroke volume in a pig heart of similar size and degree of dysfunction increased from 11.1 to 13.0 mL (17.1%). Likewise, peak LV pressures in the computer model rose from 85 to 95 mm Hg (11.7%) with torsion while maximum ventricular pressures in vivo increased in similar proportion, from 55 to 61 mm Hg (10.9%). These data suggest that: (a) the computer model of apical torsion developed for this work is a fair and accurate predictor of experimental outcomes, and (b) supra-physiologic apical torsion may be a viable means to boost cardiac output while avoiding blood contact that occurs with other assist methods.
Evaluating Foot Kinematics Using Magnetic Resonance Imaging: From Maximum Plantar Flexion, Inversion, and Internal Rotation to Maximum Dorsiflexion, Eversion, and External Rotation
Authors: Fassbind Michael J. , Rohr Eric S. , Hu Yangqiu , Haynor David R. , Siegler Sorin , Sangeorzan Bruce J. , Ledoux William R.
Published: September 2011

The foot consists of many small bones with complicated joints that guide and limit motion. A variety of invasive and noninvasive means [mechanical, X-ray stereophotogrammetry, electromagnetic sensors, retro-reflective motion analysis, computer tomography (CT), and magnetic resonance imaging (MRI)] have been used to quantify foot bone motion. In the current study we used a foot plate with an electromagnetic sensor to determine an individual subject’s foot end range of motion (ROM) from maximum plantar flexion, internal rotation, and inversion to maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation. We then used a custom built MRI-compatible device to hold each subject’s foot during scanning in eight unique positions determined from the end ROM data. The scan data were processed using software that allowed the bones to be segmented with the foot in the neutral position and the bones in the other seven positions to be registered to their base positions with minimal user intervention. Bone to bone motion was quantified using finite helical axes (FHA). FHA for the talocrural, talocalcaneal, and talonavicular joints compared well to published studies, which used a variety of technologies and input motions. This study describes a method for quantifying foot bone motion from maximum plantar flexion, inversion, and internal rotation to maximum dorsiflexion, eversion, and external rotation with relatively little user processing time.
Anthropogenic Aerosols and the Weakening of the South Asian Summer Monsoon
Authors: Bollasina Massimo A. , Ming Yi , Ramaswamy V.
Published: September 2011

Changes in monsoon rainfall are caused by human-produced aerosols slowing the tropical atmospheric circulation.
Late Interleukin-6 Escalates T Follicular Helper Cell Responses and Controls a Chronic Viral Infection
Authors: Harker James A. , Lewis Gavin M. , Mack Lauren , Zuniga Elina I.
Published: September 2011

A persisting wave of the cytokine interleukin-6 allows control of chronic viral infections.
Bidirectional Control of Social Hierarchy by Synaptic Efficacy in Medial Prefrontal Cortex
Authors: Wang Fei , Zhu Jun , Zhu Hong , Zhang Qi , Lin Zhanmin , Hu Hailan
Published: September 2011

Manipulation of the neural circuit determining social status allows subordinate mice to move up the hierarchy and dominant mice to go down.
Direct intraoperative confirmation of penetration of ethylene vinyl alcohol copolymer (Onyx) into the vasa nervosa of the facial nerve
Authors: Chen James , Crane Benjamin , Niparko John , Gandhi Dheeraj
Published: September 2011

The case history is described of a patient referred to our institution with facial nerve palsy following embolization of a middle cranial fossa dural arteriovenous fistula using ethylene vinyl alcohol copolymer (EVOH). Facial nerve decompression was performed which showed evidence of extensive penetration of EVOH into the vasa nervosa of the facial nerve. Facial nerve palsy is a debilitating complication that can be avoided by attention to the lower cranial nerve arterial supply during careful procedural planning and consideration of alternative strategies for fistula obliteration in cases where eloquent feeders are involved.
Prevalence of bisexual behaviour among bridge population of men who have sex with men in China: a meta-analysis of observational studies
Authors: Yun K , Xu J J , Reilly K H , Zhang J , Jiang Y J , Wang N , Shang H
Published: September 2011

Objective

To integrate the empirical estimates of bisexual behaviour among the bridge population of men who have sex with men (MSM) in China and their HIV and syphilis prevalences stratified by sexual behaviour.

Methods

The Pubmed, Chinese Biomedical, Chinese National Knowledge Infrastructure, VIP, Wanfang and Google Scholar databases were searched to January 2011 to identify relevant articles. Data of eligible citations were extracted by two reviewers. All analyses were performed using Stata 10.0.

Results

Forty-nine articles (including 28 739 MSM subjects) met the selection criteria. Aggregated findings indicated that the estimated prevalence of bisexual behaviour among MSM in China is 31.2% (95% CI 28.1% to 34.5%). HIV and syphilis prevalences were 5.4% and 11.4%, respectively, among MSM engaging in bisexual behaviour and 3.8% and 9.3% among MSM only having sex with men. HIV prevalence among MSM engaging in sex with both men and women was significantly higher than in those who only have sex with men (OR 1.30; 95% CI 1.04 to 1.62; p=0.02).

Conclusion

There is a high prevalence of bisexual behaviour among MSM in China and bisexual behaviour is significantly associated with increased HIV infection risk. The results of this meta-analysis highlight a critical pattern of HIV transmission among MSM in China and indicate that targeted interventions aimed at encouraging safe sex practices and promoting societal and family acceptance of MSM are urgently needed.
Effect of synthetic cationic protein on mechanoexcitability of vagal afferent nerve subtypes in guinea pig esophagus
Authors: Yu Shaoyong , Ouyang Ann
Published: September 2011

Eosinophilic esophagitis is characterized by increased infiltration and degranulation of eosinophils in the esophagus. Whether eosinophil-derived cationic proteins regulate esophageal sensory nerve function is still unknown. Using synthetic cationic protein to investigate such effect, we performed extracellular recordings from vagal nodose or jugular neurons in ex vivo esophageal-vagal preparations with intact nerve endings in the esophagus. Nerve excitabilities were determined by comparing action potentials evoked by esophageal distensions before and after perfusion of synthetic cationic protein poly-l-lysine (PLL) with or without pretreatment with poly-l-glutamic acid (PLGA), which neutralized cationic charges of PLL. Perfusion with PLL did not evoke action potentials in esophageal nodose C fibers but increased their responses to esophageal distension. This potentiation effect lasted for 30 min after washing out of PLL. Pretreatment with PLGA significantly inhibited PLL-induced mechanohyperexcitability of esophageal nodose C fibers. In esophageal nodose Aδ fibers, perfusion with PLL did not evoke action potentials. In contrast to nodose C fibers, both the spontaneous discharges and the responses to esophageal distension in nodose Aδ fibers were decreased by perfusion with PLL, which can be restored after washing out PLL for 30–60 min. Pretreatment with PLGA attenuated PLL-induced decrease in spontaneous discharge and mechanoexcitability of esophageal nodose Aδ fibers. In esophageal jugular C fibers, PLL neither evoked action potentials nor changed their responses to esophageal distension. Collectively, these data demonstrated that synthetic cationic protein did not evoke action potential discharges of esophageal vagal afferents but had distinctive sensitization effects on their responses to esophageal distension.
Plane of vertebral movement eliciting muscle lengthening history in the low back influences the decrease in muscle spindle responsiveness of the cat
Authors: Ge Weiqing , Cao Dong-Yuan , Long Cynthia R. , Pickar Joel G.
Published: September 2011

Proprioceptive feedback is thought to play a significant role in controlling both lumbopelvic and intervertebral orientations. In the lumbar spine, a vertebra's positional history along the dorsal-ventral axis has been shown to alter the position, movement, and velocity sensitivity of muscle spindles in the multifidus and longissimus muscles. These effects appear due to muscle history. Because spinal motion segments have up to 6 degrees of freedom for movement, we were interested in whether the axis along which the history is applied differentially affects paraspinal muscle spindles. We tested the null hypothesis that the loading axis, which creates a vertebra's positional history, has no effect on a lumbar muscle spindle's subsequent response to vertebral position or movement. Identical displacements were applied along three orthogonal axes directly at the L6 spinous process using a feedback motor system under displacement control. Single-unit nerve activity was recorded from 60 muscle spindle afferents in teased filaments from L6 dorsal rootlets innervating intact longissimus or multifidus muscles of deeply anesthetized cats. Muscle lengthening histories along the caudal-cranial and dorsal-ventral axis, compared with the left-right axis, produced significantly greater reductions in spindle responses to vertebral position and movement. The spinal anatomy suggested that the effect of a lengthening history is greatest when that history had occurred along an axis lying within the anatomical plane of the facet joint. Speculation is made that the interaction between normal spinal mechanics and the inherent thixotropic property of muscle spindles poses a challenge for feedback and feedforward motor control of the lumbar spine.
Hepatic lipase gene -514C>T variant is associated with exercise training-induced changes in VLDL and HDL by lipoprotein lipase
Authors: Brinkley Tina E. , Halverstadt Amy , Phares Dana A. , Ferrell Robert E. , Prigeon Ronald L. , Hagberg James M. , Goldberg Andrew P.
Published: September 2011

Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene ( LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may affect these responses. Seventy-six sedentary overweight to obese men and women aged 50–75 yr at risk for coronary heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype-specific effects of exercise training on lipoproteins measured enzymatically and by nuclear magnetic resonance, postheparin LPL and HL activities, body composition by dual energy x-ray absorptiometry and computer tomography scan, and aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL-C, HDL2-C, large HDL, HDL particle size, and large LDL than CC homozygotes. Exercise training elicited genotype-specific decreases in VLDL-TG (−22 vs. +7%; P < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in HDL-C (7 vs. 4%; P < 0.03) and HDL3-C with significant genotype×sex interactions for the changes in HDL-C and HDL3-C ( P values = 0.01–0.02). There were also genotype-specific changes in LPL (+23 vs. −6%; P < 0.05) and HL (+7 vs. −24%; P < 0.01) activities, with LPL increasing only in CC subjects ( P < 0.006) and HL decreasing only in CT subjects ( P < 0.007). Reductions in TG, VLDL-TG, large VLDL, and medium VLDL and increases in HDL3-C and small HDL particles correlated significantly with changes in LPL, but not HL, activity only in CC subjects. This suggests that the LIPC -514C>T variant significantly affects training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL through an association with increased LPL activity in CC subjects, which could guide therapeutic strategies to reduce CHD risk.
Pulse arrival time is not an adequate surrogate for pulse transit time as a marker of blood pressure
Authors: Zhang Guanqun , Gao Mingwu , Xu Da , Olivier N. Bari , Mukkamala Ramakrishna
Published: September 2011

Pulse transit time (PTT) is a proven, simple to measure, marker of blood pressure (BP) that could potentially permit continuous, noninvasive, and cuff-less BP monitoring (after an initial calibration). However, pulse arrival time (PAT), which is equal to the sum of PTT and the pre-ejection period, is gaining popularity for BP tracking, because it is even simpler to measure. The aim of this study was to evaluate the hypothesis that PAT is an adequate surrogate for PTT as a marker of BP. PAT and PTT were estimated through the aorta using high-fidelity invasive arterial waveforms obtained from six dogs during wide BP changes induced by multiple interventions. These time delays and their reciprocals were evaluated in terms of their ability to predict diastolic, mean, and systolic BP (DBP, MBP, and SBP) per animal. The root mean squared error (RMSE) between the BP parameter predicted via the time delay and the measured BP parameter was specifically used as the evaluation metric. Taking the reciprocals of the time delays tended to reduce the RMSE values. The DBP, MBP, and SBP RMSE values for 1/PAT were 9.8 ± 5.2, 10.4 ± 5.6, and 11.9 ± 6.1 mmHg, whereas the corresponding values for 1/PTT were 5.3 ± 1.2, 4.8 ± 1.0, and 7.5 ± 2.2 mmHg ( P < 0.05). Thus tracking BP via PAT was not only markedly worse than via PTT but also unable to meet the FDA BP error limits. In contrast to previous studies, our results quantitatively indicate that PAT is not an adequate surrogate for PTT in terms of detecting challenging BP changes.
Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse
Authors: Borges João Batista , Suarez-Sipmann Fernando , Bohm Stephan H. , Tusman Gerardo , Melo Alexandre , Maripuu Enn , Sandström Mattias , Park Marcelo , Costa Eduardo L. V. , Hedenstierna Göran , Amato Marcelo
Published: September 2011

The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was −0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.
Clinical Decision Making of Nurses Working in Hospital Settings
Authors: Bjørk Ida Torunn , Hamilton Glenys A.
Published: September 2011

This study analyzed nurses' perceptions of clinical decision making (CDM) in their clinical practice and compared differences in decision making related to nurse demographic and contextual variables. A cross-sectional survey was carried out with 2095 nurses in four hospitals in Norway. A 24-item Nursing Decision Making Instrument based on cognitive continuum theory was used to explore how nurses perceived their CDM when meeting an elective patient for the first time. Data were analyzed with descriptive frequencies,t-tests, Chi-Square test, and linear regression. Nurses' decision making was categorized into analytic-systematic, intuitive-interpretive, and quasi-rational models of CDM. Most nurses reported the use of quasi-rational models during CDM thereby supporting the tenet that cognition most often includes properties of both analysis and intuition. Increased use of intuitive-interpretive models of CDM was associated with years in present job, further education, male gender, higher age, and working in predominantly surgical units.
Toxicity of Methylated Bismuth Compounds Produced by Intestinal Microorganisms toBacteroides thetaiotaomicron, a Member of the Physiological Intestinal Microbiota
Authors: Bialek Beatrix , Diaz-Bone Roland A. , Pieper Dominik , Hollmann Markus , Hensel Reinhard
Published: September 2011

Methanoarchaea have an outstanding capability to methylate numerous metal(loid)s therefore producing toxic and highly mobile derivatives. Here, we report that the production of methylated bismuth species by the methanoarchaeumMethanobrevibacter smithii, a common member of the human intestine, impairs the growth of members of the beneficial intestinal microbiota at low concentrations. The bacteriumBacteroides thetaiotaomicron, which is of great importance for the welfare of the host due to its versatile digestive abilities and its protective function for the intestine, is highly sensitive against methylated, but not against inorganic, bismuth species. The level of methylated bismuth species produced by the methanoarchaeumM. smithiiin a coculture experiment causes a reduction of the maximum cell density ofB. thetaiotaomicron. This observation suggests that the production of methylated organometal(loid) species in the human intestine, caused by the activity of methanoarchaea, may affect the health of the host. The impact of the species to reduce the number of the physiological intestinal microbiota brings an additional focus on the potentially harmful role of methanoarchaea in the intestine of a higher organism.
Optimal Bounded Control for Stationary Response of Strongly Nonlinear Oscillators under Combined Harmonic and Wide‐Band Noise Excitations
Authors: Wu Yongjun , Feng Changshui , Huan Ronghua
Published: September 2011

We study the stochastic optimal bounded control for minimizing the stationary response of strongly nonlinear oscillators under combined harmonic and wide‐band noise excitations. The stochastic averaging method and the dynamical programming principle are combined to obtain the fully averaged Itô stochastic differential equations which describe the original controlled strongly nonlinear system approximately. The stationary joint probability density of the amplitude and phase difference of the optimally controlled systems is obtained from solving the corresponding reduced Fokker‐Planck‐Kolmogorov (FPK) equation. An example is given to illustrate the proposed procedure, and the theoretical results are verified by Monte Carlo simulation.
Spacecraft Formation Orbit Estimation Using WLPS-Based Localization
Authors: Goh Shu Ting , Abdelkhalik Ossama , Zekavat Seyed A. (Reza)
Published: September 2011

This paper studies the implementation of a novel wireless local positioning system (WLPS) for spacecraft formation flying to maintain high-performance spacecraft relative and absolute position estimation. A WLPS equipped with antenna arrays allows each spacecraft to measure the relative range and coordinate angle(s) of other spacecraft located in its coverage area. The dynamic base station and the transponder of WLPS enable spacecraft to localize each other in the formation. Because the signal travels roundtrip in WLPS, and due to the high spacecraft velocities, the signal transmission time delay reduces the localization performance. This work studies spacecraft formation positions estimation performance assuming that only WLPS is available onboard. The feasibility of estimating the spacecraft absolute position using only one-dimensional antenna array is also investigated. The effect of including GPS measurements in addition to WLPS is studied and compared to a GPS standalone system.
Evaluation of Epstein-Barr Virus Latent Membrane Protein 2 Specific T-Cell Receptors Driven by T-Cell Specific Promoters Using Lentiviral Vector
Authors: Yang Dongchang , Shao Qing , Sun Hua , Mu Xiaoxin , Gao Yun , Jiang Runqiu , Hou Jiajie , Yao Kun , Chen Yun , Sun Beicheng
Published: September 2011

Transduction of latent membrane protein 2 (LMP2)-specific T-cell receptors into activated T lymphocytes may provide a universal, MHC-restricted mean to treat EBV-associated tumors in adoptive immunotherapy. We compared TCR-specific promoters of distinct origin in lentiviral vectors, that is, Vβ6.7, delta, luria, and Vβ5.1 to evaluate TCR gene expression in human primary peripheral blood monocytes and T cell line HSB2. Vectors containing Vβ6.7 promoter were found to be optimal for expression in PBMCs, and they maintained expression of the transduced TCRs for up to 7 weeks. These cells had the potential to recognize subdominant EBV latency antigens as measured by cytotoxicity and IFN-γsecretion. The nude mice also exhibited significant resistance to the HLA-A2 and LMP2-positive CNE tumor cell challenge after being infused with lentiviral transduced CTLs. In conclusion, LMP2-specific CTLs by lentiviral transduction have the potential use for treatment of EBV-related tumors.
Fabrication of Photofunctional Nanoporous Membrane and Its Photoinactivation Effect of Vesicular Stomatitis Virus
Authors: Wang Kang-Kyun , Kim Bong-Jin , Ko Si-Hwan , Choi Dong Hoon , Kim Yong-Rok
Published: September 2011

Fabrication and photophysical study of photofunctional nanoporous alumina membrane (PNAM) were performed, and its application of photodynamic antimicrobial chemotherapy (PACT) was investigated. Nanoporous alumina membrane (NAM) was fabricated by two‐step aluminium anodic oxidation process. Surface of the fabricated NAM was modified with organo‐silane agent to induce covalent bonding between NAM and a photosensitizer (PtCP: [5,10,15‐triphenyl‐20‐(4‐methoxycarbonylphenyl)‐porphyrin] platinum). PtCP was covalently bonded to the surface of the modified NAM by nucleophilic acyl substitution reaction process. The morphology and the photophysical properties of the fabricated PNAM were confirmed with field emission scanning electron microscope (FE‐SEM), steady‐state spectroscopies, and nanosecond laser‐induced time‐resolved spectroscopy. For the efficacy study of PNAM in PACT, an enveloped animal virus, vesicular stomatitis virus (VSV), was utilized as a target organism. Antiviral effect of the PNAM‐PACT was measured by the extent of suppression of plaque‐forming units (PFU) after the light irradiation. In the cultures inoculated with PACT‐treated VSV, the suppression of PFU was prominent, which demonstrates that PNAM is a potential bio clean‐up tool.
Adaptive Immunity in Ankylosing Spondylitis: Phenotype and Functional Alterations of T-Cells before and during Infliximab Therapy
Authors: Szalay Balázs , Mészáros Gergő , Cseh Áron , Ács Lilla , Deák Magdolna , Kovács László , Vásárhelyi Barna , Balog Attila
Published: September 2011

Our aim was to assess the phenotype of T-cell subsets in patients with ankylosing spondylitis (AS), a chronic inflammatory rheumatic disease. In addition, we also tested short-term T-cell activation characteristics. Measurements were done in 13 AS patients before and during the intravenous therapy with anti-TNF agent infliximab (IFX). Flow cytometry was used to determine T-cell subsets in peripheral blood and their intracellular signaling during activation. The prevalence of Th2 and Th17 cells responsible for the regulation of adaptive immunity was higher in AS than in 9 healthy controls. Although IFX therapy improved patients' condition, immune phenotype did not normalize. Cytoplasmic and mitochondrial calcium responses of CD4+ and CD8+ cells to a specific activation were delayed, while NO generation was increased in AS. NO generation normalized sooner upon IFX than calcium response. These results suggest an abnormal immune phenotype with functional disturbances of CD4+ and CD8+ cells in AS.
Cetuximab Pharmacokinetics Influences Progression-Free Survival of Metastatic Colorectal Cancer Patients
Authors: Azzopardi Nicolas , Lecomte Thierry , Ternant David , Boisdron-Celle Michelle , Piller Friedrich , Morel Alain , Gouilleux-Gruart Valérie , Vignault-Desvignes Céline , Watier Hervé , Gamelin Erick , Paintaud Gilles
Published: September 2011

Purpose: An ancillary phase II study was conducted to study interindividual variability in cetuximab pharmacokinetics and its influence on progression-free survival (PFS) in metastatic colorectal cancer patients cotreated with irinotecan and 5-fluorouracil.

Experimental Design: Ninety-six patients received cetuximab as an infusion loading dose of 400 mg/m2 followed by weekly infusions of 250 mg/m2. Doses of irinotecan and 5-fluorouracil were adjusted individually. Cetuximab concentrations were measured by ELISA. Compartmental pharmacokinetic parameters were estimated by a population approach, and PFS was analyzed using a Cox model.

Results: Cetuximab pharmacokinetics was best described using a two-compartment model with both first-order and saturable (zero-order) elimination. Estimated pharmacokinetic parameters (% standard error) were as follows: central volume of distribution V1 = 2.96 L (4%), peripheral volume of distribution V2 = 4.65 L (6%), elimination clearance CL = 0.497 L/d (4%), distribution clearance Q = 0.836 L/d (8%), and zero-order elimination rate k0 = 8.71 mg/d (10%). Body surface area influenced V1, V2, and k0. Pretreatment serum albumin influenced CL. Risk of disease progression decreased with cetuximab global clearance (cumulative dose/cumulative area under the concentration versus time curve; P = 0.00016). Median PFS of patients with a cetuximab residual concentration on day 14 below median value was 3.3 months as compared with 7.8 months for the other patients (P = 0.004).

Conclusions: Cetuximab pharmacokinetics in colorectal cancer patients can be described using a model combining linear and nonlinear elimination rates. PFS is influenced by global clearance of cetuximab, a parameter that can be estimated using cetuximab residual concentration on day 14. Clin Cancer Res; 17(19); 6329–37. ©2011 AACR.
The Evolutionary History of TLR4 Polymorphisms in Europe
Authors: Plantinga Theo S. , Ioana Mihai , Alonso Santos , Izagirre Neskuts , Hervella Montserrat , Joosten Leo A.B. , van der Meer Jos W.M. , de la Rúa Concepcion , Netea Mihai G.
Published: September 2011

Infections exert important evolutionary pressures shaping the human genome, especially on genes involved in host defense. A crucial step for host defense is recognition of pathogens by pattern recognition receptors on innate immune cells, among which Toll-like receptor 4 (TLR4) is one of the best known. Genetic variation in TLR4 (Asp299Gly, Thr399Ile) has been recently described. Haplotype frequencies of these polymorphisms differ among African, Asian and European populations, suggesting evolutionary pressures exerted by local infections. The TLR4 299Gly/399Ile haplotype, characteristic mainly of European populations, has relatively high frequency in the Iberian peninsula. This region is also described as refuge area during the last glacial maximum 20,000 years ago, from which repopulation of Europe took place. We speculate that a genetic bottleneck in the Iberian peninsula could have promoted the increased frequency of this haplotype by genetic drift. This hypothesis is supported by three arguments: (1) the West-East gradient of prevalence in the haplotype among European populations; (2) ancient DNA from Neolithic burials in the Iberian peninsula, dated 6,600–4,500 years before present, confirmed the relatively high frequency of this haplotype in the region, and (3) no functional differences between this haplotype and wild-type TLR4 have been found. In contrast, the disappearance of the 299Gly/399Thr haplotype in Europe is most likely due to negative selection due to sepsis. In conclusion, differences in distribution of TLR4 polymorphisms Asp299Gly and Thr399Ile in European populations are most likely due to a combination of population migration events combined with selection due to sepsis.