bluuebunny/crossref_metadata_2025 huggingface dataset:
Ultraviolet radiation therapy and UVR dose models
Authors: Grimes David Robert
Published: December 2014

Ultraviolet radiation (UVR) has been an effective treatment for a number of chronic skin disorders, and its ability to alleviate these conditions has been well documented. Although nonionizing, exposure to ultraviolet (UV) radiation is still damaging to deoxyribonucleic acid integrity, and has a number of unpleasant side effects ranging from erythema (sunburn) to carcinogenesis. As the conditions treated with this therapy tend to be chronic, exposures are repeated and can be high, increasing the lifetime probability of an adverse event or mutagenic effect. Despite the potential detrimental effects, quantitative ultraviolet dosimetry for phototherapy is an underdeveloped area and better dosimetry would allow clinicians to maximize biological effect whilst minimizing the repercussions of overexposure. This review gives a history and insight into the current state of UVR phototherapy, including an overview of biological effects of UVR, a discussion of UVR production, illness treated by this modality, cabin design and the clinical implementation of phototherapy, as well as clinical dose estimation techniques. Several dose models for ultraviolet phototherapy are also examined, and the need for an accurate computational dose estimation method in ultraviolet phototherapy is discussed.
Modeling of human blood rheology in transient shear flows
Authors: Apostolidis Alex J. , Armstrong Matthew J. , Beris Antony N.
Published: December 2014

We offer here an extension of our previous work [Apostolidis and Beris, J. Rheol. 58, 607–633 (2014)] of modeling blood flow rheology in simple shear steady state flows to time-dependent conditions. The basis of our model is a scalar, structural, parameter thixotropic model. More specifically, we show that a modified version of the “Delaware model” [A. Mujumdar et al., J. Non-Newtonian Fluid Mech. 102, 157–178 (2002)] is capable of predicting the time-dependent shear flow rheology of blood at low and moderate values of shear rate. At steady state, the model reduces to the Casson constitutive model for low and moderate shear rate values consistent to the findings of our previously mentioned work. At high shear rates it reduces to a Newtonian model, correcting our previous model and consistent to data from the literature [Merrill and Pelletier, J. Appl. Physiol. 23, 178–182 (1967)]. Exploiting the existing parameterization developed before for the steady state Casson model and the Merrill and Pelletier steady state data, the transient thixotropic model introduces only three additional parameters. Each one of these parameters has a specific physical meaning: A zero-shear rate maximum strain, and two kinematic parameters governing the relaxation of the structural parameter and the elastic modulus, respectively. The model is able to naturally account for the additional yield strengthening effect attributable to the red blood cell rouleaux structures developed within blood. The proposed model can fit excellently the experimental data of Bureau et al. [Biorheology 17, 191–203 (1980)], on simple triangular steps in shear flow at low shear rates. The predictions of the present model are then validated comparing them against additional experimental data, collected on the same samples, either on triangular steps in shear flow but at higher shear rates or on rectangular step-up and step-down experiments. The model is further validated by comparing its predictions against recent large amplitude oscillatory shear data [P. C. Sousa et al., Biorheology 50, 269–282 (2013)]. In all these comparisons there is good, at least semiquantitative, agreement, with the observed discrepancies only appearing at the higher shear rates, where the isotropic description resulting from the use of a single scalar internal parameter to describe the blood microstructure naturally breaks down.
LocZ Is a New Cell Division Protein Involved in Proper Septum Placement in Streptococcus pneumoniae
Authors: Holečková Nela , Doubravová Linda , Massidda Orietta , Molle Virginie , Buriánková Karolína , Benada Oldřich , Kofroňová Olga , Ulrych Aleš , Branny Pavel
Published: December 2014

How bacteria control proper septum placement at midcell, to guarantee the generation of identical daughter cells, is still largely unknown. Although different systems involved in the selection of the division site have been described in selected species, these do not appear to be widely conserved. Here, we report that LocZ (Spr0334), a newly identified cell division protein, is involved in proper septum placement in
Streptococcus pneumoniae
. We show that
locZ
is not essential but that its deletion results in cell division defects and shape deformation, causing cells to divide asymmetrically and generate unequally sized, occasionally anucleated, daughter cells. LocZ has a unique localization profile. It arrives early at midcell, before FtsZ and FtsA, and leaves the septum early, apparently moving along with the equatorial rings that mark the future division sites. Consistently, cells lacking LocZ also show misplacement of the Z-ring, suggesting that it could act as a positive regulator to determine septum placement. LocZ was identified as a substrate of the Ser/Thr protein kinase StkP, which regulates cell division in S. pneumoniae. Interestingly, homologues of LocZ are found only in streptococci, lactococci, and enterococci, indicating that this close phylogenetically related group of bacteria evolved a specific solution to spatially regulate cell division.

IMPORTANCE
Bacterial cell division is a highly ordered process regulated in time and space. Recently, we reported that the Ser/Thr protein kinase StkP regulates cell division in Streptococcus pneumoniae, through phosphorylation of several key proteins. Here, we characterized one of the StkP substrates, Spr0334, which we named LocZ. We show that LocZ is a new cell division protein important for proper septum placement and likely functions as a marker of the cell division site. Consistently, LocZ supports proper Z-ring positioning at midcell. LocZ is conserved only among streptococci, lactococci, and enterococci, which lack homologues of the Min and nucleoid occlusion effectors, indicating that these bacteria adapted a unique mechanism to find their middle, reflecting their specific shape and symmetry.
A 2-Pyridone-Amide Inhibitor Targets the Glucose Metabolism Pathway of Chlamydia trachomatis
Authors: Engström Patrik , Krishnan K. Syam , Ngyuen Bidong D. , Chorell Erik , Normark Johan , Silver Jim , Bastidas Robert J. , Welch Matthew D. , Hultgren Scott J. , Wolf-Watz Hans , Valdivia Raphael H. , Almqvist Fredrik , Bergström Sven
Published: December 2014

In a screen for compounds that inhibit infectivity of the obligate intracellular pathogen
Chlamydia trachomatis
, we identified the 2-pyridone amide KSK120. A fluorescent KSK120 analogue was synthesized and observed to be associated with the C. trachomatis surface, suggesting that its target is bacterial. We isolated KSK120-resistant strains and determined that several resistance mutations are in genes that affect the uptake and use of glucose-6-phosphate (G-6P). Consistent with an effect on G-6P metabolism, treatment with KSK120 blocked glycogen accumulation. Interestingly, KSK120 did not affect
Escherichia coli
or the host cell. Thus, 2-pyridone amides may represent a class of drugs that can specifically inhibit C. trachomatis infection.

IMPORTANCE
Chlamydia trachomatis
is a bacterial pathogen of humans that causes a common sexually transmitted disease as well as eye infections. It grows only inside cells of its host organism, within a parasitophorous vacuole termed the inclusion. Little is known, however, about what bacterial components and processes are important for C. trachomatis cellular infectivity. Here, by using a visual screen for compounds that affect bacterial distribution within the chlamydial inclusion, we identified the inhibitor KSK120. As hypothesized, the altered bacterial distribution induced by KSK120 correlated with a block in C. trachomatis infectivity. Our data suggest that the compound targets the glucose-6-phosphate (G-6P) metabolism pathway of C. trachomatis, supporting previous indications that G-6P metabolism is critical for C. trachomatis infectivity. Thus, KSK120 may be a useful tool to study chlamydial glucose metabolism and has the potential to be used in the treatment of C. trachomatis infections.
Exploration and confirmation of factors associated with uncomplicated pregnancy in nulliparous women: prospective cohort study
Authors: Chappell Lucy C , Seed Paul T , Myers Jenny , Taylor Rennae S , Kenny Louise C , Dekker Gustaaf A , Walker James J , McCowan Lesley M E , North Robyn A , Poston Lucilla
Published: December 2014

STUDY QUESTION

Which variables at 15 and 20 weeks' gestation, particularly those amenable to modification before pregnancy, are associated with a subsequent uncomplicated pregnancy?

SUMMARY ANSWER

Normalising body mass index, increasing fruit intake before pregnancy, reducing blood pressure, stopping misuse of drugs, and being in paid employment are all associated with subsequent uncomplicated pregnancy outcomes.
Prevalence and determinants of caesarean section in private and public health facilities in underserved South Asian communities: cross-sectional analysis of data from Bangladesh, India and Nepal
Authors: Neuman Melissa , Alcock Glyn , Azad Kishwar , Kuddus Abdul , Osrin David , More Neena Shah , Nair Nirmala , Tripathy Prasanta , Sikorski Catherine , Saville Naomi , Sen Aman , Colbourn Tim , Houweling Tanja A J , Seward Nadine , Manandhar Dharma S , Shrestha Bhim P , Costello Anthony , Prost Audrey
Published: December 2014

Objectives

To describe the prevalence and determinants of births by caesarean section in private and public health facilities in underserved communities in South Asia.

Design

Cross-sectional study.

Setting

81 community-based geographical clusters in four locations in Bangladesh, India and Nepal (three rural, one urban).

Participants

45 327 births occurring in the study areas between 2005 and 2012.

Outcome measures

Proportion of caesarean section deliveries by location and type of facility; determinants of caesarean section delivery by location.

Results

Institutional delivery rates varied widely between settings, from 21% in rural India to 90% in urban India. The proportion of private and charitable facility births delivered by caesarean section was 73% in Bangladesh, 30% in rural Nepal, 18% in urban India and 5% in rural India. The odds of caesarean section were greater in private and charitable health facilities than in public facilities in three of four study locations, even when adjusted for pregnancy and delivery characteristics, maternal characteristics and year of delivery (Bangladesh: adjusted OR (AOR) 5.91, 95% CI 5.15 to 6.78; Nepal: AOR 2.37, 95% CI 1.62 to 3.44; urban India: AOR 1.22, 95% CI 1.09 to 1.38). We found that highly educated women were particularly likely to deliver by caesarean in private facilities in urban India (AOR 2.10; 95% CI 1.61 to 2.75) and also in rural Bangladesh (AOR 11.09, 95% CI 6.28 to 19.57).

Conclusions

Our results lend support to the hypothesis that increased caesarean section rates in these South Asian countries may be driven in part by the private sector. They also suggest that preferences for caesarean delivery may be higher among highly educated women, and that individual-level and provider-level factors interact in driving caesarean rates higher. Rates of caesarean section in the private sector, and their maternal and neonatal health outcomes, require close monitoring.
Moxibustion for the treatment of pressure ulcers: study protocol for a pilot, multicentre, randomised controlled trial
Authors: Zhang Qin-hong , Yue Jin-huan , Li Chao-ran , Sun Zhong-ren
Published: December 2014

Introduction

Pressure ulcers are common in the elderly and immobile. Currently, there are few proven effective treatments for pressure ulcers. This trial aims to evaluate the feasibility, efficacy and safety of moxibustion for pressure ulcers.

Methods/analysis

This is a multicentre, two-armed, parallel-design randomised controlled trial (RCT). 30 eligible patients with pressure ulcers will be randomised in a ratio of 1:1 to the treatment group and control group. The participants in the treatment group will undergo indirect moxibustion for 30 min before application of a dressing, one session daily, five sessions weekly for 4 weeks. The patients in the control group will only receive a dressing, applied in the same way as in the treatment group. Both groups will be followed up for 3 months. The primary outcome measures will be wound surface area (WSA) and proportion of ulcers healed within trial period (PUHTP). The secondary outcomes will be the Pressure Ulcer Scale for Healing (PUSH Tool), visual analogue scale (VAS) and adverse events. All outcomes will be evaluated at the beginning of the study, at the end of the second week, at 4 weeks after randomisation and at 1 and 3 months after treatment cessation.

Ethics/dissemination

This trial has undergone ethical scrutiny and been approved by the ethics review boards of First Affiliated Hospital of Heilongjiang University of Chinese Medicine and Second Affiliated Hospital of Heilongjiang University of Chinese Medicine (Permission number: HZYEYLP2014). The results of this study will provide clinical evidence for the feasibility, efficacy and safety of moxibustion for pressure ulcers.

Trial registration number

ChiCTR-TRC-13003959.
Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild-to-moderate COPD exacerbations
Authors: Brusse-Keizer Marjolein , VanderValk Paul , Hendrix Ron , Kerstjens Huib , van der Palen Job
Published: December 2014

Background

The effectiveness of antibiotics in chronic obstructive pulmonary disease (COPD) exacerbations is still a matter of debate, especially in outpatients with an intermediate probability of bacterial infection.

Methods

In this study, 35 COPD outpatients diagnosed by their chest physician with moderately severe COPD exacerbation, but without pneumonia, were randomised in a double blind, placebo-controlled study. Patients had one or two of the following characteristics: a positive Gram's stain of the sputum, 2 or more exacerbations in the previous year, a decrease in lung function of>200 mL and>12%. Patients received amoxicillin clavulanic acid (500/125 mg three times daily) or placebo for 7 days, always combined with a course of prednisolone (30 mg/day) for 7 days. Primary outcome was duration of the exacerbation. Additionally, we measured severity of the exacerbation, health-related quality of life, sputum parameters, number of relapses within 28 days and the number of re-exacerbations within 4 months after the study.

Results

There was no difference observed in time to resolution of the exacerbation between the two groups (HR=1.12; (95% CI 0.5 to 2.3; p=0.77)), nor in any other treatment parameter.

Conclusions

We detected no evidence for the effectiveness of addition of antibiotics to prednisolone for COPD exacerbations of moderate severity and with intermediate probability of bacterial infection in this underpowered study. More placebo-controlled studies are needed to properly define subgroups of COPD outpatients in which antibiotics are of additional value.

Trials registration number

clinical trial registered withhttp://www.trialregister.nl/(NTR351).
Publication rate of abstracts presented at the emergency medicine congresses held by the European Society for Emergency Medicine (EUSEM) in 2011 and 2012
Authors: Kalkan Asim , Kose Ozkan , Bilir Ozlem , Ersunan Gokhan , Ozel Deniz , Guler Ferhat
Published: December 2014

Purpose

The purpose of this study was to assess the publication rate of the abstracts presented at the 6th Mediterranean Emergency Medicine Congress, 2011 and the 7th European Congress on Emergency Medicine, 2012.

Materials and methods

All abstracts, both posters and oral presentations, from the international emergency medicine congresses held by the European Society for Emergency Medicine (EUSEM) in 2011 and 2012 were identified. To establish whether these abstracts were subsequently published in peer-reviewed medical journals, the names of all the authors and the title of the abstracts were searched for in the databases of Clinical Key/Elsevier, EBSCO Discovery Service, MD Consult, Science Direct, Scopus, EMBASE, Medscape, Google Scholar and local ULAKBIM. The year of publication, consistency of author names and titles, the type of study, the journals in which papers were published and countries from which reports were submitted were all recorded.

Results

A total of 1721 abstracts were examined; 626 from 2011 (307 oral presentations and 319 posters) and 1095 from 2012 (154 oral presentations and 941 posters). Of all abstracts in 2011, 172 (27.5%) and of all abstracts in 2012, 265 (24.2%) were subsequently published as full-text reports in peer-reviewed journals. Of the 172 papers published in 2011, 152 (88.4%) were accepted by Science Citation Index (SCI) and/or SCI Expanded (SCI-E) journals and 155 (58.5%) of 265 papers were accepted by SCI and/or SCI-E journals in 2012 (p=0.0001).

Conclusions

The publication rate of abstracts submitted to international emergency medicine congresses held by EUSEM over those 2 years was low compared with that of abstracts presented in other emergency medicine congresses. Presenters should be encouraged to send their studies to peer-reviewed journals. During the selection process by the scientific panel, constructive critics should be notified to the presenters instead of simply accepting or rejecting the studies that submitted to the congress, which may increase the subsequent publication rate.
Are estimates of socioeconomic inequalities in chronic disease artefactually narrowed by self-reported measures of prevalence in low-income and middle-income countries? Findings from the WHO-SAGE survey
Authors: Vellakkal Sukumar , Millett Christopher , Basu Sanjay , Khan Zaky , Aitsi-Selmi Amina , Stuckler David , Ebrahim Shah
Published: December 2014

Background

The use of self-reported measures of chronic disease may substantially underestimate prevalence in low-income and middle-income country settings, especially in groups with lower socioeconomic status (SES). We sought to determine whether socioeconomic inequalities in the prevalence of non-communicable chronic diseases (NCDs) differ if estimated by using symptom-based or criterion-based measures compared with self-reported physician diagnoses.

Methods

Using population-representative data sets of the WHO Study of Global Ageing and Adult Health (SAGE), 2007–2010 (n=42 464), we calculated wealth-related and education-related concentration indices of self-reported diagnoses and symptom-based measures of angina, hypertension, asthma/chronic lung disease, visual impairment and depression in three ‘low-income and lower middle-income countries’—China, Ghana and India—and three ‘upper-middle-income countries’—Mexico, Russia and South Africa.

Results

SES gradients in NCD prevalence tended to be positive for self-reported diagnoses compared with symptom-based/criterion-based measures. In China, Ghana and India, SES gradients were positive for hypertension, angina, visual impairment and depression when using self-reported diagnoses, but were attenuated or became negative when using symptom-based/criterion-based measures. In Mexico, Russia and South Africa, this distinction was not observed consistently. For example, concentration index of self-reported versus symptom-based angina were: in China: 0.07 vs −0.11, Ghana: 0.04 vs −0.21, India: 0.02 vs −0.16, Mexico: 0.19 vs −0.22, Russia: −0.01 vs −0.02 and South Africa: 0.37 vs 0.02.

Conclusions

Socioeconomic inequalities in NCD prevalence tend to be artefactually positive when using self-report compared with symptom-based or criterion-based diagnostic criteria, with greater bias occurring in low-income countries. Using standardised, symptom-based measures would provide more valid estimates of NCD inequalities.
Hip fractures sustained in hospital: comorbidities and outcome
Authors: Shabani Farzad , Farrier Adam J , Smith Robert , Venkatesan Murali , Thomas Christopher , Uzoigwe Chika Edward , Isaac Sheriff , Chami George
Published: December 2014

Background

Guidelines on the management of hip fracture in the elderly focus on fractures suffered in the community. Between 4% and 7% of hip fractures occur in hospital. Mortality is higher in those who sustain hip fracture in hospital than those who sustain a fracture in the community. However, it is not known if sustaining a nosocomial fracture is an independent risk factor for a poor outcome.

Objective

To compare outcomes of hip fracture sustained in the community and sustained while in hospital for another reason. After adjusting for confounders, we sought to determine if sustaining a fracture in hospital was an independent risk factor for a poor outcome.

Methods

Using the National Hip Fracture Database, we identified all patients admitted to Leicester Royal Infirmary with hip fracture between July 2009 and February 2013. We extracted demographic data, details of comorbidity, and 30-day and long-term mortality. Age, gender, American Society of Anaesthesiologists (ASA) grade, time to surgery, and survival were compared between patients with hospital-acquired and those with community-acquired hip fracture.

Results

During the study period, 2987 patients were treated for hip fracture; 2984 were included in the study. Of these, 261 (8.7%) sustained the fracture while in hospital. Those who sustained the fracture in hospital were more commonly men (106/261 (41%)) than those with a community-acquired fracture (738/2723 (27%)) and had a worse ASA grade (III or IV, 215/230 (93%) vs 1647/2573 (64%)). Thirty-day mortality was higher in those with a hospital-acquired fracture (48/261 (18%)) than in those with a community-acquired fracture (212/2723 (7.8%)) (p<0.001). However, after adjustment for confounding variables, the association between hip fracture, in-hospital and 30-day mortality was not significant: OR 1.2 (95% CI 0.8 to 2.0), p=0.40. Longer-term mortality was associated with hip fracture in hospital after adjustment for confounding variables in multivariate proportional hazards regression: HR 1.5 (95% CI 1.2 to 1.8), p<0.001.

Conclusions

Patients who sustain hip fractures in hospital are unsurprisingly sicker than those who sustain hip fractures in the community. Although being in hospital is not an independent risk factor, this easily identifiable group of patients are at particular risk of a poor outcome. We suggest that it might be appropriate to consider modifying the guidelines for treatment of hip fracture for this group in an attempt to improve outcome.
Efficacy of treatment of cattle for liver fluke at housing: influence of differences in flukicidal activity against juvenile Fasciola hepatica
Authors: Forbes A. B. , Reddick D. , Stear M. J.
Published: December 2014

Flukicides are commonly administered at housing to cattle that have grazed fluke‐infected pastures or that have been purchased from endemic areas. The choice of product is determined by numerous factors, one of which is the stages of Fasciola hepatica that are killed. Flukicides can be categorised into three main groups: (A) those that kill all juvenile stages and adults; (B) those that kill juveniles from six to eight weeks of age and adults and (C) those that kill adults only. This study was conducted on a commercial beef farm in Scotland and was designed to compare the efficacy of flukicides from each of these three classes in terms of their effects on faecal egg output, coproantigen and liveweight gain. The majority of animals in the untreated control group were positive for coproantigen, fluke eggs or both throughout the study duration of 16 weeks. Egg reappearance interval following housing treatment was eight weeks for clorsulon and 13 weeks for nitroxynil, though patent infections in both groups developed in only a small minority of animals; no fluke eggs were recovered from cattle treated with triclabendazole. Coproantigen was detected four weeks before the reappearance of fluke eggs in the dung. Animals treated with flukicides had significantly fewer faecal samples positive for eggs (P<0.006) and coproantigen (P<0.05) following treatment compared with the controls. Despite differences in the efficacy profiles among the flukicide‐treated groups, there were no significant differences (P>0.05) in growth rates among any of the four treatment groups. There was, however, a significant negative association (P<0.001) between fluke positivity at housing and subsequent growth performance, irrespective of treatment group.
Online Monitoring Systems for Performance Fault Detection
Authors: Gioiosa Roberto , Kestor Gokcen , Kerbyson Darren J.
Published: December 2014

To achieve the exaFLOPS performance within a contained power budget, next generation supercomputers will feature hundreds of millions of components operating at low- and near-threshold voltage. As the probability that at least one of these components fails during the execution of an application approaches certainty, it seems unrealistic to expect that any run of a scientific application will not experience some performance faults. We believe that there is need of a new generation of light-weight performance and debugging tools that can be used online even during production runs of parallel applications and that can identify performance anomalies during the application execution. In this work we propose the design and implementation of a monitoring system that continuously inspects the evolution of running applications and the health of the system. To achieve minimum runtime overhead while maintaining the desired level of flexibility, we propose a decoupled approach in which accurate monitoring is performed at kernel-level while performance anomaly disambiguation and corrective actions are performed at user-level.

We evaluate our monitoring system on a 128-core AMD Interlagos system: First, we show that the runtime overhead of the monitoring system is negligible (0-2%). Then we show how our system can be used to precisely identify performance faults in three different scenarios: OS noise, application co-scheduling and dynamic power capping.
Towards Extreme-Scale Simulations for Low Mach Fluids with Second-Generation Trilinos
Authors: Lin Paul , Bettencourt Matthew , Domino Stefan , Fisher Travis , Hoemmen Mark , Hu Jonathan , Phipps Eric , Prokopenko Andrey , Rajamanickam Sivasankaran , Siefert Christopher , Kennon Stephen
Published: December 2014

Trilinos is an object-oriented software framework for the solution of large-scale, complex multi-physics engineering and scientific problems. While Trilinos was originally designed for scalable solutions of large problems, the fidelity needed by many simulations is significantly greater than what one could have envisioned two decades ago. When problem sizes exceed a billion elements even scalable applications and solver stacks require a complete revision. The second-generation Trilinos employs C++ templates in order to solve arbitrarily large problems. We present a case study of the integration of Trilinos with a low Mach fluids engineering application (SIERRA low Mach module/Nalu). Through the use of improved algorithms and better software engineering practices, we demonstrate good weak scaling for up to a nine billion element large eddy simulation (LES) problem on unstructured meshes with a 27 billion row matrix on 524,288 cores of an IBM Blue Gene/Q platform.
Sampling of bosonic qubits
Authors: Tamma Vincenzo
Published: December 2014

The boson sampling problem has brought a lot of attention in the quantum information field because it is not efficiently solvable with a classical computer; nonetheless it can be implementable with linear optical interferometers with single-boson sources. Recently, we introduced a more general problem, the multi-boson correlation sampling problem, which allows to take advantage of the muti-mode spectral distribution of the bosonic sources together with time-correlated measurements in order to achieve a sampling not only over the output channels of the interferometer but also over the joint detection times. This problem was analyzed for both single-photon sources and thermal sources. In this work, we demonstrate that it is possible to use single qubit bosonic sources in order to sample not only in the described "space-time" degree of freedom but also over all the possible exponential number of multi-qubit output states.
Interaction between hydrogen sulfide-induced sulfhydration and tyrosine nitration in the KATP channel complex
Authors: Kang Minho , Hashimoto Atsushi , Gade Aravind , Akbarali Hamid I.
Published: December 2014

Hydrogen sulfide (H2S) is an endogenous gaseous mediator affecting many physiological and pathophysiological conditions. Enhanced expression of H2S and reactive nitrogen/oxygen species (RNS/ROS) during inflammation alters cellular excitability via modulation of ion channel function. Sulfhydration of cysteine residues and tyrosine nitration are the posttranslational modifications induced by H2S and RNS, respectively. The objective of this study was to define the interaction between tyrosine nitration and cysteine sulfhydration within the ATP-sensitive K+ (KATP) channel complex, a significant target in experimental colitis. A modified biotin switch assay was performed to determine sulfhydration of the KATP channel subunits, Kir6.1, sulphonylurea 2B (SUR2B), and nitrotyrosine measured by immunoblot. NaHS (a donor of H2S) significantly enhanced sulfhydration of SUR2B but not Kir6.1 subunit. 3-Morpholinosydnonimine (SIN-1) (a donor of peroxynitrite) induced nitration of Kir6.1 subunit but not SUR2B. Pretreatment with NaHS reduced the nitration of Kir6.1 by SIN-1 in Chinese hamster ovary cells cotransfected with the two subunits, as well as in enteric glia. Two specific mutations within SUR2B, C24S, and C1455S prevented sulfhydration by NaHS, and these mutations prevented NaHS-induced reduction in tyrosine nitration of Kir6.1. NaHS also reversed peroxynitrite-induced inhibition of smooth muscle contraction. These studies suggest that posttranslational modifications of the two subunits of the KATP channel interact to alter channel function. The studies described herein demonstrate a unique mechanism by which sulfhydration of one subunit modifies tyrosine nitration of another subunit within the same channel complex. This interaction provides a mechanistic insight on the protective effects of H2S in inflammation.
Mitochondrial depolarization and asystole in the globally ischemic rabbit heart: coordinated response to interventions affecting energy balance
Authors: Venable Paul W. , Sciuto Katie J. , Warren Mark , Taylor Tyson G. , Garg Vivek , Shibayama Junko , Zaitsev Alexey V.
Published: December 2014

Mitochondrial membrane potential (ΔΨm) depolarization has been implicated in the loss of excitability (asystole) during global ischemia, which is relevant for the success of defibrillation and resuscitation after cardiac arrest. However, the relationship between ΔΨm depolarization and asystole during no-flow ischemia remains unknown. We applied spatial Fourier analysis to confocally recorded fluorescence emitted by ΔΨm-sensitive dye tetramethylrhodamine methyl ester. The time of ischemic ΔΨm depolarization ( tmito_depol) was defined as the time of 50% decrease in the magnitude of spectral peaks reflecting ΔΨm. The time of asystole ( tasys) was determined as the time when spontaneous and induced ventricular activity ceased to exist. Interventions included tachypacing (150 ms), myosin II ATPase inhibitor blebbistatin (heart immobilizer), and the combination of blebbistatin and the inhibitor of glycolysis iodoacetate. In the absence of blebbistatin, confocal images were obtained during brief perfusion with hyperkalemic solution and after the contraction failed between 7 and 15 min of ischemia. In control, tmito_depol and tasys were 24.4 ± 6.0 and 26.0 ± 5.0 min, respectively. Tachypacing did not significantly affect either parameter. Blebbistatin dramatically delayed tmito_depol and tasys (51.4 ± 8.6 and 45.7 ± 5.3 min, respectively; both P < 0.0001 vs. control). Iodoacetate combined with blebbistatin accelerated both events ( tmito_depol, 12.7 ± 1.8 min; and tasys, 6.5 ± 1.1 min; both P < 0.03 vs. control). In all groups pooled together, tasys was strongly correlated with tmito_depol ( R2 = 0.845; P < 0.0001). These data may indicate a causal relationship between ΔΨm depolarization and asystole or a similar dependence of the two events on energy depletion during ischemia. Our results urge caution against the use of blebbistatin in studies addressing pathophysiology of myocardial ischemia.
Working with nitric oxide and hydrogen sulfide in biological systems
Authors: Yuan Shuai , Patel Rakesh P. , Kevil Christopher G.
Published: December 2014

Nitric oxide (NO) and hydrogen sulfide (H2S) are gasotransmitter molecules important in numerous physiological and pathological processes. Although these molecules were first known as environmental toxicants, it is now evident that that they are intricately involved in diverse cellular functions with impact on numerous physiological and pathogenic processes. NO and H2S share some common characteristics but also have unique chemical properties that suggest potential complementary interactions between the two in affecting cellular biochemistry and metabolism. Central among these is the interactions between NO, H2S, and thiols that constitute new ways to regulate protein function, signaling, and cellular responses. In this review, we discuss fundamental biochemical principals, molecular functions, measurement methods, and the pathophysiological relevance of NO and H2S.
Morg1 heterozygous deficiency ameliorates hypoxia-induced acute renal injury
Authors: Loeffler Ivonne , Wolf Gunter
Published: December 2014

Acute kidney injury is a common complication of critically ill patients and may occur as a result of various factors and coexisting previous illnesses. Some pathophysiological responses seen in critical illness can be similar to the human physiological response to extreme environmental challenges, such as hypoxia from reduced oxygen availability at high altitudes (systemic hypoxia). Due to oxygen deficiency, mammalian cells activate the transcriptional factor hypoxia-inducible factor (HIF); its degradation is regulated by prolyl hydroxylase 3 (PHD3) in interaction with the scaffold protein MAPK organizer 1 (Morg1). While homozygous Morg1−/−mice are embryonically lethal, the kidneys of heterozygous Morg1+/−mice reveal elevated HIF protein levels and increased serum erythropoietin compared with wild-type Morg1+/+mice. In this study, we exposed wild-type and Morg1+/−mice to 10% oxygen in a hypoxic chamber for 3 days. This reduced oxygen concentration leads to a deterioration of renal function, an increase in renal inflammation, and significantly more tubular damage and apoptosis in the kidneys of wild-type (Morg1+/+) mice. In sharp contrast, Morg1+/−kidneys were protected against systemic hypoxia. They show significantly less renal lesions, reduced or no inflammation, and less tubular damage and apoptosis. Thus short-term systemic and subsequently renal hypoxia which may occur in many patients in the intensive care unit induces in wild-type mice renal injury, which is ameliorated by Morg1 deficiency. Our findings suggest that therapeutical manipulation of Morg1 may be an interesting novel target to prevent hypoxia-associated renal damage.
Very long apnea events in preterm infants
Authors: Mohr Mary A. , Vergales Brooke D. , Lee Hoshik , Clark Matthew T. , Lake Douglas E. , Mennen Anne C. , Kattwinkel John , Sinkin Robert A. , Moorman J. Randall , Fairchild Karen D. , Delos John B.
Published: December 2014

Apnea is nearly universal among very low birth weight (VLBW) infants, and the associated bradycardia and desaturation may have detrimental consequences. We describe here very long (>60 s) central apnea events (VLAs) with bradycardia and desaturation, discovered using a computerized detection system applied to our database of over 100 infant years of electronic signals. Eighty-six VLAs occurred in 29 out of 335 VLBW infants. Eighteen of the 29 infants had a clinical event or condition possibly related to the VLA. Most VLAs occurred while infants were on nasal continuous positive airway pressure, supplemental oxygen, and caffeine. Apnea alarms on the bedside monitor activated in 66% of events, on average 28 s after cessation of breathing. Bradycardia alarms activated late, on average 64 s after cessation of breathing. Before VLAs oxygen saturation was unusually high, and during VLAs oxygen saturation and heart rate fell unusually slowly. We give measures of the relative severity of VLAs and theoretical calculations that describe the rate of decrease of oxygen saturation. A clinical conclusion is that very long apnea (VLA) events with bradycardia and desaturation are not rare. Apnea alarms failed to activate for about one-third of VLAs. It appears that neonatal intensive care unit (NICU) personnel respond quickly to bradycardia alarms but not consistently to apnea alarms. We speculate that more reliable apnea detection systems would improve patient safety in the NICU. A physiological conclusion is that the slow decrease of oxygen saturation is consistent with a physiological model based on assumed high values of initial oxygen saturation.
No redistribution of lung blood flow by inhaled nitric oxide in endotoxemic piglets pretreated with an endothelin receptor antagonist
Authors: Trachsel Sebastien , Hambraeus-Jonzon Kristina , Bergquist Maria , Martijn Cecile , Chen Luni , Hedenstierna Göran
Published: December 2014

Inhaled nitric oxide (INO) improves ventilation-perfusion matching and alleviates pulmonary hypertension in patients with acute respiratory distress syndrome. However, outcome has not yet been shown to improve, and nonresponse is common. A better understanding of the mechanisms by which INO acts may guide in improving treatment with INO in patients with severe respiratory failure. We hypothesized that INO may act not only by vasodilation in ventilated lung regions, but also by causing vasoconstriction via endothelin (ET-1) in atelectatic, nonventilated lung regions. This was studied in 30 anesthetized, mechanically ventilated piglets. The fall in oxygenation and rise in pulmonary artery pressure during a sepsislike condition (infusion of endotoxin) were blunted by INO 40 ppm. Endotoxin infusion increased serum ET-1, and INO almost doubled the ratio between mRNA expression of endothelin receptor A (mediating vasoconstriction) and B (mediating vasodilation and clearance of ET-1) (ET-A/ET-B) in atelectatic lung regions. INO caused a shift in blood flow away from atelectatic lung regions in the endotoxemic piglets, but not during ET receptor antagonism. We conclude that INO in short-term experiments, in addition to causing selective pulmonary vasodilation in ventilated lung regions, increases the ET-A/ET-B mRNA expression ratio in lung tissue. This might augment the vasoconstriction in atelectatic lung regions, enhancing the redistribution of pulmonary blood flow to ventilated lung regions which are reached by INO. Such vasoconstriction may be an important additional factor explaining the effect of INO.
Combined Prediction Model of Death Toll for Road Traffic Accidents Based on Independent and Dependent Variables
Authors: Zhong-xiang Feng , Shi-sheng Lu , Wei-hua Zhang , Nan-nan Zhang
Published: December 2014

In order to build a combined model which can meet the variation rule of death toll data for road traffic accidents and can reflect the influence of multiple factors on traffic accidents and improve prediction accuracy for accidents, the Verhulst model was built based on the number of death tolls for road traffic accidents in China from 2002 to 2011; and car ownership, population, GDP, highway freight volume, highway passenger transportation volume, and highway mileage were chosen as the factors to build the death toll multivariate linear regression model. Then the two models were combined to be a combined prediction model which has weight coefficient. Shapley value method was applied to calculate the weight coefficient by assessing contributions. Finally, the combined model was used to recalculate the number of death tolls from 2002 to 2011, and the combined model was compared with the Verhulst and multivariate linear regression models. The results showed that the new model could not only characterize the death toll data characteristics but also quantify the degree of influence to the death toll by each influencing factor and had high accuracy as well as strong practicability.
Asynchronous H∞ Dynamic Output Feedback Control of Switched Time‐Delay Systems with Sensor Nonlinearity and Missing Measurements
Authors: Wen Jiwei , Peng Li
Published: December 2014

The H∞ dynamic output feedback control problem for a class of discrete‐time switched time‐delay systems under asynchronous switching is investigated in this paper. Sensor nonlinearity and missing measurements are considered when collecting output knowledge of the system. Firstly, when there exists asynchronous switching between the switching modes and the candidate controllers, new results on the regional stability and l2 gain analysis for the underlying system are given by allowing the Lyapunov‐like function (LLF) to increase with a random probability. Then, a mean square stabilizing output feedback controller and a switching law subject to average dwell time (ADT) are obtained with a given disturbance attenuation level. Moreover, the mean square domain of attraction could be estimated by a convex combination of a set of ellipsoids, the number of which depends on the number of switching modes. Finally, a numerical example is given to illustrate the effectiveness of the proposed method.
Spatial Distribution and Temporal Variability of Ammonium-Nitrogen, Phosphorus, and Potassium in a Rice Field in Corrientes, Argentina
Authors: Morales Luis Alberto , Vidal Vázquez Eva , Paz-Ferreiro Jorge
Published: December 2014

Proper and effective management of soil nutrients requires assessment of their variability at the field scale. We compare the effects of lime amendment rate on the spatial variability of three macronutrient forms (NH4+-N, Olsen P, and Mehlich-1 K) in a paddy soil at three different dates during the growth period of a rice crop. The field work was carried out near Corrientes, Argentina. Lime treatments were 0, 625, and 1250 kg ha−1dolomite, and each liming dose was applied to a 1.7 ha field. Ninety-three soil samples per treatment were first collected in aerobic conditions and then two more times after flooding, at bunch formation and flowering. SoilNH4+-N increased along time, whereas P was highest at bunch formation and K steadily decreased along the rice growth period. Dolomite addition increased macronutrient availability at the first and second samplings, but its effects at the third sampling depended on the element. The three soil nutrients analyzed displayed strong patterns of spatial dependence for the three lime treatments and at the three periods studied. The areas with relative high or low macronutrient concentrations within each field were not stable throughout the rice growth period. Seasonality in the spatial distribution of macronutrients may be of agronomic value for site specific management.
Stop Flow Lithography Synthesis and Characterization of Structured Microparticles
Authors: Baah David , Donnell Tobias , Srinivasan Sesha , Floyd-Smith Tamara
Published: December 2014

In this study, the synthesis of nonspherical composite particles of poly(ethylene glycol) diacrylate (PEG‐DA)/SiO2 and PEG‐DA/Al2O3 with single or multiple vias and the corresponding inorganic particles of SiO2 and Al2O3 synthesized using the Stop Flow Lithography (SFL) method is reported. Precursor suspensions of PEG‐DA, 2‐hydroxy‐2‐methylpropiophenone, and SiO2 or Al2O3 nanoparticles were prepared. The precursor suspension flows through a microfluidic device mounted on an upright microscope and is polymerized in an automated process. A patterned photomask with transparent geometric features masks UV light to synthesize the particles. Composite particles with vias were synthesized and corresponding inorganic SiO2 and Al2O3 particles were obtained through polymer burn‐off and sintering of the composites. The synthesis of porous inorganic particles of SiO2 and Al2O3 with vias and overall dimensions in the range of ~35–90 µm was achieved. BET specific surface area measurements for single via inorganic particles were 56–69 m2/g for SiO2 particles and 73–81 m2/g for Al2O3 particles. Surface areas as high as 114 m2/g were measured for multivia cubic SiO2 particles. The findings suggest that, with optimization, the particles should have applications in areas where high surface area is important such as catalysis and sieving.
Design, Synthesis, and Molecular Docking of 1-(1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine as Potent Nonazole Anticandidal Agent
Authors: Ghabbour Hazem A. , Qabeel Maha M. , Eldehna Wagdy M. , Al-Dhfyan Abdullah , Abdel-Aziz Hatem A.
Published: December 2014

1-(1-(4-Chlorophenyl)-2-(phenylsulfonyl)ethylidene)-2-phenylhydrazine (13) was designed and synthesized as potential nonazole anticandidal agent and precisely characterized by IR,1H NMR,13C NMR, and ESI-MS. The anti-Candidaactivity of13was evaluated against fourCandidaspecies (C. albicans, C. krusei, C. parapsilosis, andC. glabrata). Compound13displayed good anticandidal activities (MIC=0.39, 0.195, 0.39, and 1.56 μmol/mL, resp.) in comparison with that of the standard drug fluconazole (MIC=0.195, inactive, 1.56, and 1.56 μmol/mL, resp.) againstC. albicans, C. krusei, C. parapsilosis, andC. glabrata, respectively. A molecular modeling of the newly synthesized compound13was built in order to investigate its mode of action towards the prospective target cytochrome P450-dependent enzyme lanosterol 14α-demethylase (PDB-code: 1EA1). The docking results showed a similar binding interaction of13and fluconazole at the active site of CYT P450 14α-sterol demethylase. Furthermore, compound13showed no cytotoxicity against normal human breast cell line MCF10A.
Effects of pH, Photoperiod, and Nutrient on Germination and Growth of Calymperes erosum C. Muell. Gemmaling
Authors: Ogbimi Anthony Zinno , Owoeye Yetunde Biodun , Ibiyemi Victor Oluwaseyi , Bofede Akpos Valentino
Published: December 2014

Effects of pH, photoperiod, and substrate nutrient concentration on the rate of germination of the gemmae and primary protonema growth of Calymperes erosum C. Muell. were studied. There was a statistically significant difference in germination of C. erosum gemmae and protonema growth among the different substrate pH levels, photoperiod treatments, and substrate nutrient conditions, respectively (P<0.01). Gemmae germination and protonemal growth peaked at pH 4 and 5. Protonemal growth was retarded at pH 2, 3, 6, and 7. No germination was observed in continuous darkness. Germination and protonema growth increased significantly (P<0.01) within the first 3 and 6 hours of daylight but not again until after 9 and 12 hours of exposure, respectively. No statistical (P>0.05) increase in germination and protonemal growth was observed when the nutrient concentration was increased from 25% to 200%. Results indicate the moss is adapted to low nutrients and that it may germinate well at substrate pH as low as 2 howbeit the probability of establishment will remain limited until pH levels improve to 4 or 5. Furthermore, the moss is able to achieve net photosynthetic carbon gain during morning hours. Recovery from photoinhibition is likely by evening.