bluuebunny/crossref_metadata_2025 huggingface dataset:
Axis IV – psychosocial and environmental problems – in the DSM‐IV
Authors: Ramirez A. , Ekselius L. , Ramklint M.
Published: April 2013

Accessible summary

The aim of this study was to extensively explore the properties of the revised axis IV of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM‐IV).

Psychosocial and environmental problems, which are believed to exacerbate current mental disorders, were evaluated by using a questionnaire and through clinical interviews. The reliability between self‐assessment and professional assessment was also examined.

The results showed that the revised axis IV according to DSM‐IV seems to have concurrent validity, but is still hampered by limited reliability.

These findings could be useful for the upcoming DSM‐V revision as well as help clinicians and patients to better identify mental health problems.

The aim of this study was to further explore the properties of axis IV in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM‐IV). In a naturalistic cross‐sectional design, a group (n = 163) of young (18–25 years old) Swedish psychiatric outpatients was assessed according to DSM‐IV. Psychosocial and environmental problems/axis IV were evaluated through structured interviewing by a social worker and by self‐assessment on a questionnaire. Reliability between professional assessment and self‐assessment of axis IV was examined. Concurrent validity of axis IV was also examined. Reliability between professional and self‐assessed axis IV was fair to almost perfect, 0.31–0.83, according to prevalence and bias‐adjusted kappa. Categories of psychosocial stress and environmental problems were related to the presence of axis I disorders, co‐morbidity, personality disorders and decreasing Global Assessment of Functioning (GAF) values. The revised axis IV according to DSM‐IV seems to have concurrent validity, but is still hampered by limited reliability.
Early Morphea Mimicking Acquired Port‐Wine Stain
Authors: Pickert Amanda J. , Carpentieri David , Price Harper , Hansen Ronald C.
Published: April 2013

We report the case of a 2.5‐year‐old girl with linear morphea initially diagnosed as an acquired port‐wine stain (PWS). She underwent three treatments to the right face using the pulsed dye laser (PDL) before sclerotic changes were observed and the correct diagnosis was confirmed with histopathology. Treatment using the PDL reduced the skin erythema but did not prevent subsequent sclerosis. The sclerosis became most prominent superior to the patient's right ear in an area not treated using the laser. A review of the English‐language medical literature identified no cases of morphea triggered using a PDL, but there were several reports of early morphea misdiagnosed as an acquired PWS. Briefly, we review those cases, as well as morphea subtypes, and comment on how the pathophysiology of morphea may lend itself to an early underrecognized inflammatory presentation, delaying diagnosis.
Development and Evaluation of an International Service Learning Program for Nursing Students
Authors: Curtin Alicia J. , Martins Diane C. , Schwartz‐Barcott Donna , DiMaria Lisa , Ogando Béliga Milagros Soler
Published: April 2013

Objectives

(1) Using Riner's framework, the development of an international service learning program in the Dominican Republic (DR) for Baccalaureate nursing students will be described, and (2) an initial impact of the students' experiences will be examined.

Design and Sample

A qualitative descriptive research design was used to examine its impact. The international service learning program included (1) didactic (five, 2 hr and one full day educational sessions) prior to (2) immersion (2 weeks in country), and (3) posttrip debriefing session. Ten females, senior nursing students participated in the program. Students' daily journals were examined using thematic analysis.

Results

Five major themes that emerged were as follows adapting physically, encountering frustration in their inability to fully meet patients' needs, increasing confidence in speaking Spanish and assessing health problems, and increasing cultural awareness. Students were descriptive regarding their daily activities, and did some, but limited, critical reflection.

Conclusions

Models of reflection need to be explored to select the most appropriate technique to facilitate students' critical reflection in meeting the goals and objectives of the experience. Curriculum integration of global learning, social consciousness, and global cultural competence development is needed.
Population Density, Distance to Public Transportation, and Health of Women in Low‐Income Neighborhoods
Authors: DeGuzman Pamela B. , Merwin Elizabeth I. , Bourguignon Cheryl
Published: April 2013

Objectives

The purpose of this research was to determine the impact of two neighborhood walkability (the extent to which the built environment is pedestrian friendly) metrics on health outcomes of women living in low‐income urban neighborhoods, both before and after accounting for individual and neighborhood factors.

Design and Sample

A cross‐sectional, retrospective design was used. The sample of 1800 low‐income women was drawn from Welfare, Children and Families: A Three‐City Study (a study of low‐income women from three U.S. cities).

Measures

Using multilevel modeling and geographic information systems, the study sought to determine the effect of distance to public transportation and residential density on health status, mental health symptoms, and health‐related limitations.

Results

No significant relationship was found between the two walkability metrics and health outcomes. Instead, neighborhood problems that affect crime and safety impacted health status and mental health symptoms.

Conclusions

As cities make changes to the built environment with the hope of affecting residents' health outcomes, public health nurses need to be aware that changing walkability characteristics in a neighborhood may not affect the health of residents of high crime, low‐income neighborhoods. Without first addressing neighborhood crime, efforts to improve walkability in low‐income neighborhoods may fail.
Socioeconomic Factors Affecting Infant Sleep‐Related Deaths in St. Louis
Authors: Hogan Cathy
Published: April 2013

Objective

Though the Back to Sleep Campaign that began in 1994 caused an overall decrease in sudden infant death syndrome (SIDS) rates, racial disparity has continued to increase in St. Louis. Though researchers have analyzed and described various sociodemographic characteristics of SIDS and infant deaths by unintentional suffocation in St. Louis, they have not simultaneously controlled for contributory risk factors to racial disparity such as race, poverty, maternal education, and number of children born to each mother (parity). To determine whether there is a relationship between maternal socioeconomic factors and sleep‐related infant death.

Design and Sample

This quantitative case‐control study used secondary data collected by the Missouri Department of Health and Senior Services between 2005 and 2009. The sample includes matched birth/death certificates and living birth certificates of infants who were born/died within time frame.

Measures

Descriptive analysis, Chi‐square, and logistic regression.

Results

The controls were birth records of infants who lived more than 1 year. Chi‐square and logistic regression analyses confirmed that race and poverty have significant relationships with infant sleep‐related deaths.

Conclusions

The social significance of this study is that the results may lead to population‐specific modifications of prevention messages that will reduce infant sleep‐related deaths.
Immunobiology of Plasmodium in liver and brain
Authors: Frevert U. , Nacer A.
Published: April 2013

Malaria remains one of the most serious health problems globally, but our understanding of the biology of the parasite and the pathogenesis of severe disease is still limited. Multiple cellular effector mechanisms that mediate parasite elimination from the liver have been described, but how effector cells use classical granule‐mediated cytotoxicity to attack infected hepatocytes and how cytokines and chemokines spread via the unique fluid pathways of the liver to reach the parasites over considerable distances remains unknown. Similarly, a wealth of information on cerebral malaria (CM), one of the most severe manifestations of the disease, was gained from post‐mortem analyses of human brain and murine disease models, but the cellular processes that ultimately cause disease are not fully understood. Here, we discuss how imaging of the local dynamics of parasite infection and host response as well as consideration of anatomical and physiological features of liver and brain can provide a better understanding of the initial asymptomatic hepatic phase of the infection and the cascade of events leading to CM. Given the increasing drug resistance of both parasite and vector and the unavailability of a protective vaccine, the urgency to reduce the tremendous morbidity and mortality associated with severe malaria is obvious.
Expression of Cyclins and Cyclin‐Dependent Kinase Inhibitors in Granulosa Cells from Bovine Ovary
Authors: Shimizu T , Hirai Y , Miyamoto A
Published: April 2013

Contents

The regulation of granulosa cell proliferation is complex, and it is essential for normal follicular development in mammals. The aim of this study was to examine the expression of cyclins and their inhibitors in the granulosa cells of follicles at different developmental stages. Follicles were classified into three groups: oestrogen‐inactive dominant follicles (EIDs), oestrogen‐active dominant follicles (EADs) and pre‐ovulatory follicles (POs). The expression of CCND2 (cyclin D2) mRNA was significantly higher in granulosa cells from EADs and POs than in those from EIDs. The expression of CCND3 (cyclin D3) mRNA was significantly higher in granulosa cells from EADs than in those from other follicles. CCND1 (cyclin D1), CCNE1 (cyclin E1) and CCNE2 (cyclin E2) mRNA expression did not differ among the different follicular stages. The expression of CDKN1A (p21cip1) and CDKN1B (p27kip1) mRNA was significantly higher in granulosa cells from EIDs and POs, respectively, than in those from other follicles. Expression of CDKN2D (p19INK4d) mRNA did not differ among the different follicular stages. Taken together, our study suggested that cyclins and their inhibitors are associated with granulosa cell proliferation at specific follicular developmental stages.
Smoking cessation practice and research in China: What's history and culture got to do with it?
Authors: Dean Elizabeth , Bodner Michael , Al‐Bannay Hana , Li Zhenyi
Published: April 2013

See article, page 790
Ambient wood smoke, traffic pollution and adult asthma prevalence and severity
Authors: Bui D. Son , Burgess John A. , Matheson Melanie C. , Erbas Bircan , Perret Jennifer , Morrison Stephen , Giles Graham G. , Hopper John L. , Thomas Paul S. , Markos James , Abramson Michael J. , Walters E. Haydn , Dharmage Shyamali C.
Published: April 2013

Background and objective

The impact of ambient wood smoke and traffic‐related air pollution on adult asthma has not been well studied. This paper aims to investigate associations between exposure to ambient wood smoke, traffic‐related air pollution and current asthma/asthma severity in middle age, and whether any associations are modified by atopic status.

Methods

Using data from the Tasmanian Longitudinal Health Study, associations between ambient wood smoke and two indices of traffic‐related air pollution (frequency of heavy vehicles near the home and frequency of intense traffic noise) and current asthma/asthma severity were investigated. Unconditional logistic regression to examine current asthma and ordinal logistic regression to examine asthma severity was used.

Results

For asthmatics, both exposure to ambient wood smoke (odds ratio 1.11; 95% confidence interval 1.02–1.20) and being frequently exposed to heavy vehicles (odds ratio 1.80; 95% confidence interval 1.09–2.96) were associated with increased asthma severity. Neither association varied by atopic status.

Conclusions

In middle‐aged adults, ambient wood smoke and traffic pollution were associated with increased asthma severity. These findings suggest that avoiding or limiting exposure to traffic pollution and wood smoke may help to reduce asthma. Future studies to replicate this finding are recommended and should examine specific biological mechanisms for this effect.
Cretaceous and Cenozoic cooling history of the eastern Qilian Shan, north‐eastern margin of the Tibetan Plateau: evidence from apatite fission‐track analysis
Authors: Baotian Pan , Qingyang Li , Xiaofei Hu , Haopeng Geng , Zibian Liu , Shaofei Jiang , Wanming Yuan
Published: April 2013

The exhumation history and tectonic evolution of the Qilian Shan at the north‐eastern margin of the Tibetan Plateau has been widely debated. Here, we present apatite fission‐track (AFT) data for 12 Ordovician granodiorite samples along a vertical transect in the eastern Qilian Shan. These thermochronometry data indicate that the eastern Qilian Shan experienced a three‐stage cooling history, including: (i) rapid initial cooling in the late Cretaceous; (ii) a stage of quasi isothermal quiescence from ~ 80 to 24 Ma; and (iii) rapid subsequent cooling beginning in the early Miocene. The inferred cooling rates for the three stages are 6.8 ± 4.9 °C Ma−1, 0.6 ± 0.2 °C Ma−1 and 2.7 ± 0.9 °C Ma−1 respectively (±1 σ). Assuming a geothermal gradient of 25 °C km−1, the exhumation rates for the three stages are 0.27 ± 0.20 mm a−1, 0.017 ± 0.007 mm a−1 and 0.11 ± 0.04 mm a−1 respectively (±1 σ). We suggest that the late Cretaceous cooling records collision of the Lhasa block with the Eurasian continent and that the Miocene cooling represents uplift/exhumation of the Qilian Shan.
Modeling and Experimental Studies on Oscillating Inclined-Bed Solar Dryer
Authors: Shanmugam S. , Kumar P. , Veerappan AR.
Published: April 2013

This paper presents a mathematical model for drying agricultural produce using a solar dryer capable of oscillating its bed while kept at an inclined position with respect to vertical. A model of the solar dryer with double-pass flat plate collector and an oscillating-bed has been fabricated and tested for drying agricultural produce (sunflower seeds). The model can predict the change in the absolute humidity of air across the bed, the temperature of the air, the moisture content, and the dryer thermal efficiency. Sunflower seeds were dried on a physical model of the solar dryer with its bed tilted at different angles and oscillated at different frequencies. The predicted and the experimental results are in good agreement. The average error and standard deviation for the absolute humidity of air across the bed is 1.74 and 1.55%, the exit temperature of air leaving the bed is 1.11and 1.21%, and the dryer thermal efficiency is 0.78 and 1.33%, respectively.
The High Inertance Free Piston Engine Compressor—Part II: Design and Experimental Evaluation
Authors: Willhite Joel A. , Yong Chao , Barth Eric J.
Published: April 2013

Pneumatically actuated robotic systems are attractive alternatives to traditional electromechanical systems due to the power density advantage of pneumatic actuators. This assumes that a power source is available to provide the pneumatic supply at a sufficient energy density to compete with batteries. To this end, a high inertance free liquid piston compressor (HIFLPC) was developed as a portable, efficient, compact power supply for pneumatically actuated systems. This paper presents the model-based design and operation of the HIFLPC, as well as the fabrication and evaluation of an experimental prototype of the device. Efficiency, power output, and other operational characteristics of the prototype are experimentally assessed. A validation of the dynamic model developed for the HIFLPC is conducted, and model-based studies are performed to investigate the influence on system performance by varying liquid piston dynamics.
Investigation on the Stability and Bifurcation of a 3D Rotor-Bearing System
Authors: Liu Yi , Liu Heng , Yi Jun , Jing Minqing
Published: April 2013

The stability and bifurcation of a flexible 3D rotor system are investigated in this paper. The rotor is discretized by 3D elements and reduced by using component mode synthesis. Periodic motions and stability margins are obtained by using the shooting method and path-following technique, and the local stability of the periodic motions is determined by using the Floquet theory. Comparisons indicate that 3D and 1D systems have a general resemblance in the bifurcation characteristics while mass eccentricity and rotating speed are changed. For both systems, the orbit size of the periodic motions has the same order of magnitude, and the vibration response has identical frequency components when typical bifurcations occur. The stress distribution and location of the maximum stress spot are determined by the bending mode of the rotor. The type of 3D element has a slight effect on the stability and bifurcation of the rotor system. Generally, this paper presents a feasible method for analyzing the stability and bifurcation of complex rotors without much structural simplification.
Kinematic Analysis of a Three-Degree of Freedom Compliant Platform
Authors: Correa Julio C. , Crane Carl
Published: April 2013

This paper addresses the kinematic analysis of a three-degree of freedom (DOF) compliant platform able to move in three dimensional space. The device is formed by the actuators, a central moving platform, and compliant joints. The actuators are three binary links. The moving platform is an equilateral plate. Springs connect the free end of each actuator with each vertex of the central platform. In this way, the motion of the actuators is transmitted to the moving platform. Compliant joints increase the complexity of the motion of the central platform and few studies have been carried out. This paper focuses on the forward and reverse analyses for the platform and the derivation of equations that relate the velocity of the moving platform with the velocity of the actuators.
Design Fixation and Its Mitigation: A Study on the Role of Expertise
Authors: Viswanathan Vimal K. , Linsey Julie S.
Published: April 2013

Engineering idea generation plays a vital role in the development of novel products. Prior studies have shown that designers fixate to the features of example solutions and replicate these features in their ideas. This type of fixation acts as a major hindrance in idea generation, as it restricts the solution space where designers search for their ideas. Building upon the study by Linsey et al. [2010, “A Study of Design Fixation, Its Mitigation and Perception in Engineering Design Faculty,” ASME Trans. J. Mech. Des., 132, 041003], this study hypothesizes that designers fixate to example features and this fixation can be mitigated using certain defixation materials including alternate representations of the design problem. To investigate this, the experiment conducted by Linsey et al. [2010] with engineering design faculty is replicated with novice designers. Participants generate ideas for a design problem in three groups: one group working with a fixating example, a second group working with the same example along with alternate representations of the design problem and a control group. The obtained results show that both the novice designers and design faculty fixate to the same extent, whereas the defixation materials have differential effect on the two groups. This result indicates that design researchers need to be very careful in developing methods and guidelines that are formulated and tested with studies on novice designers. The effectiveness of such measures may vary with the level of expertise of the designer.
Po‐Poster ‐ 07: Commissioning of virtual linacs for Monte Carlo simulations by optimizing photon source characteristics
Authors: Bush K , Popescu T
Published: April 2013

In conjunction with rapidly expanding clinical Monte Carlo (MC) implementation, MC users are faced with the difficult and time consuming commissioning process of their virtual linac. After accurately configuring the treatment head according to manufacturer specifications, a rigorous and extensive benchmarking process is required to ensure that the MC virtual linac produces beams of essentially the same quality as those of the real treatment unit being modeled. Often, even after systematically varying the input parameters over a suitably chosen range, it is found that the shape of the measured profiles cannot be exactly matched. This limitation is attributed to the lack of accurate knowledge of the geometry and materials of some linac components, especially, the flattening filter. We have developed an automatic optimization method that allows a user with an arbitrary linear accelerator to commission a MC dose calculation engine that accurately reproduces the measured output of the accelerator in water. Using a simulated annealing optimization algorithm our method converges MC dose distributions to experimental measurements by optimizing the weights of particles in a phase space. To achieve this, a phase space is divided up using LATCH variable assignment, each beamlet is transported into a water tank phantom, and the dose deposition is scored separately. Individual beamlet weights are then optimized such that the weighted sum of beamlet dose depositions converge toward our target dose distribution. The resulting beamlet weights are then assigned to all particles in the original phase space where they are incorporated into all future simulations.
Sci‐YIS Fri ‐ 03: Calculation of singlet oxygen dose from photosensitizer photobleaching during mTHPC or Photofrin photodynamic therapy in vitro
Authors: Dysart J , Singh G , Patterson M
Published: April 2013

Photodynamic therapy (PDT) is emerging as a treatment option for various malignant conditions. PDT damage is caused by the generation of singlet oxygen. This process is dependent on the complex interaction between the photosensitizer (PS), treatment light, and oxygen. Since these parameters may be highly variable among patients and may change during treatment, it is difficult to predict therapeutic outcome based on administered PS and delivered light dose alone. An implicit dose metric model has been proposed in which singlet oxygen dose is monitored by the decrease in PS fluorescence during treatment caused by reactions between PS and singlet oxygen. To investigate this, MatLyLu (MLL) rat prostate adenocarcinoma cells were incubated with Foscan (mTHPC) or Photofrin and treated with the appropriate wavelength of light. Fluorescence was monitored during treatment and, at selected fluence levels, cell viability was determined using a colony formation assay. Singlet oxygen dose models were developed based on measurements of PS fluorescence and reaction kinetics. Cell survival correlated well to calculated singlet oxygen dose, independent of initial PS concentration, treatment fluence rate, and oxygenation. These results indicate that investigation of photobleaching is warranted as an in vivo dose metric. We found 1.5 ± 0.3 and 0.45 ± 0.09 mM of singlet oxygen was required to reduce the survival fraction by 1/e for mTHPC and Photofrin respectively.
Sci‐AM1 Sat ‐ 03: Comparison of chest radiographs, fluoroscopy and seed‐migration detector for the detection of embolized seeds to the lung
Authors: Morrier J , Chrétien M , Beaulieu L
Published: April 2013

To evaluate the efficacy of a seed‐migration detector and to compare it to fluoroscopy and to the postoperative chest radiographs generally recommended. A gamma scintillation survey meter was converted to a seed‐migration detector. It was used to perform a chest evaluation on 155 patients (8717 seeds) at their first postoperative visit. When the detector showed activity around a patient's chest, it was confirmed by taking an antero‐posterior chest radiograph and by looking at the region with fluoroscopy. 3 patients (21.3%) present at least one embolized seed. That is a 0.47% seed migration rate (41/8717). 37 (90%) of the seeds were visible under fluoroscopy and 28 (68%) appeared on x‐rays. Rapid movement of the seeds, due to breathing or to a location close to the heart, makes nine seeds to be visible with fluoroscopy but not on the radiograph. Moreover, four seeds were not visible with fluoroscopy neither with radiograph. In comparison to the seed‐migration detector, detection based on fluoroscopy would have led to four false‐negative detections (out of 33 or 12.1%) while the radiograph would have resulted in thirteen or 39.4%. Moreover, x‐ray would have required extra radiation dose to lung to 100% of the patients rather than the 21.3% who needed it in this study. The recommendation to perform chest radiographs should be revised because of superior efficacy of the seed‐migration detector. X‐rays should only remain for documentation purposes. Finally, the detector is convenient, cost‐effective and non‐invasive: it does not require any additional radiation to the patient.
Sci‐AM1 Sat ‐ 07: Monte Carlo simulation of large electron fields at extended distances: Total skin electron treatment optimization
Authors: Shokrani P , Elson H
Published: April 2013

Development of a Total Skin Electron Therapy (TSET) procedure and acquiring all of the necessary parameters by measurement is difficult tedious and time consuming. To produce large fields for TSET, an external scatterer is usually attached to treatment head. Selection of scatterer's properties would be influenced by the requirements of angular spread, minimum energy loss and bremsstrahlung contamination. The goal of this research was to select properties of an optimal scatterer (z and thickness) in order to achieve an optimum single large electron field at extended SSD, as a first step in development of a TSET optimization process. A 6 MeV electron beam from a Philips SL‐20 unit, scattered by a control copper scatterer, was simulated using EGS4 code (12 hours CPU time for transport of particles from scatterer into a cylindrical phantom, r=50 cm, at 300 SSD for 10E5 initial electrons). For optimization process, a group of 10 materials were selected as candidate materials, using the radiation length concept. Comparison of field characteristics calculated for candidate materials and control scatterer resulted in selection of a 0.059 mm lead foil as the optimal scatterer: a uniformity index of 93%, a d80% of 1.8–2.1 cm and a 30% increase in output compared to control scatterer. This simulation showed that in large scattered electron fields, energy loss and dose rate are controlled by scatterer's atomic number and thickness respectively. For the same energy loss, however, field uniformity and bremsstrahlung contamination are not influenced noticeably by the properties of the scatterer.
Reconstituting Angiogenesis in Vitro
Authors: Gough Nancy R.
Published: April 2013

An in vitro 3D system enables testing of pro- and anti-angiogenic factors.
Exacerbating Autoimmune Disease with Salt
Authors: VanHook Annalisa M.
Published: April 2013

Sodium chloride promotes the production of pathogenic T
H
17 cells and exacerbates autoimmune disease.
Surviving Glutamine Deprivation
Authors: Wong Wei
Published: April 2013

The PP2A subunit B55α triggers the activation of p53 to enable cells to survive glutamine deprivation.
Steady-State Pharmacokinetics of Oral Voriconazole and Its Primary Metabolite,
N
-Oxide Voriconazole, Pre- and Post-Autologous Peripheral Stem Cell Transplantation
Authors: Amsden Jarrett R. , Gubbins Paul O. , McConnell Scott , Anaissie Elias
Published: April 2013

Voriconazole (VCZ) is frequently utilized for prevention and treatment of invasive fungal infections in peripheral stem cell transplant (PSCT) patients. We performed an open-label pharmacokinetic study to compare VCZ and
N
-oxide voriconazole (
N
-oxide VCZ) pharmacokinetics in patients pre- and post-PSCT. Ten patients completed both sampling periods. The pharmacokinetics of VCZ were unchanged; however, those of
N
-oxide VCZ were significantly different pre- and post-PSCT.
Dormancy Is Not Necessary or Sufficient for Bacterial Persistence
Authors: Orman Mehmet A. , Brynildsen Mark P.
Published: April 2013

The antibiotic tolerances of bacterial persisters have been attributed to transient dormancy. While persisters have been observed to be growth inhibited prior to antibiotic exposure, we sought to determine whether such a trait was essential to the phenotype. Furthermore, we sought to provide direct experimental evidence of the persister metabolic state so as to determine whether the common assumption of metabolic inactivity was valid. Using fluorescence-activated cell sorting (FACS), a fluorescent indicator of cell division, a fluorescent measure of metabolic activity, and persistence assays, we found that bacteria that are rapidly growing prior to antibiotic exposure can give rise to persisters and that a lack of replication or low metabolic activity prior to antibiotic treatment simply increases the likelihood that a cell is a persister. Interestingly, a lack of significant growth or metabolic activity does not guarantee persistence, as the majority of even “dormant” subpopulations (>99%) were not persisters. These data suggest that persistence is far more complex than dormancy and point to additional characteristics needed to define the persister phenotype.
Gentamicin-Loaded Borate Bioactive Glass Eradicates Osteomyelitis Due to Escherichia coli in a Rabbit Model
Authors: Xie Zongping , Cui Xu , Zhao Cunju , Huang Wenhai , Wang Jianqiang , Zhang Changqing
Published: April 2013

The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus
Escherichia coli
. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated
in vitro
and
in vivo
for the treatment of osteomyelitis induced by
Escherichia coli
. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.
In Vitro
and
In Vivo
Antimalarial Efficacies of Optimized Tetracyclines
Authors: Draper Michael P. , Bhatia Beena , Assefa Haregewein , Honeyman Laura , Garrity-Ryan Lynne K. , Verma Atul K. , Gut Jiri , Larson Kelley , Donatelli Janice , Macone Ann , Klausner Kevin , Leahy Raina G. , Odinecs Aleksandrs , Ohemeng Kwasi , Rosenthal Philip J. , Nelson Mark L.
Published: April 2013

With increasing resistance to existing antimalarials, there is an urgent need to discover new drugs at affordable prices for countries in which malaria is endemic. One approach to the development of new antimalarial drugs is to improve upon existing antimalarial agents, such as the tetracyclines. Tetracyclines exhibit potent, albeit relatively slow, action against malaria parasites, and doxycycline is used for both treatment (with other agents) and prevention of malaria. We synthesized 18 novel 7-position modified tetracycline derivatives and screened them for activity against cultured malaria parasites. Compounds with potent
in vitro
activity and other favorable drug properties were further tested in a rodent malaria model. Ten compounds inhibited the development of cultured
Plasmodium falciparum
with a 50% inhibitory concentration (IC
50
) after 96 h of incubation of <30 nM, demonstrating activity markedly superior to that of doxycycline (IC
50
at 96 h of 320 nM). Most compounds showed little mammalian cell cytotoxicity and no evidence of
in vitro
phototoxicity. In a murine
Plasmodium berghei
model, 13 compounds demonstrated improved activity relative to that of doxycycline. In summary, 7-position modified tetracyclines offer improved activity against malaria parasites compared to doxycycline. Optimized compounds may allow lower doses for treatment and chemoprophylaxis. If safety margins are adequate, dosing in children, the group at greatest risk for malaria in countries in which it is endemic, may be feasible.
Characterization and Functional Analysis of AatB, a Novel Autotransporter Adhesin and Virulence Factor of Avian Pathogenic Escherichia coli
Authors: ZhuGe Xiangkai , Wang Shaohui , Fan Hongjie , Pan Zihao , Ren Jianluan , Yi Li , Meng Qingmei , Yang Xuqiu , Lu Chengping , Dai Jianjun
Published: April 2013

Autotransporter (AT) proteins constitute a large family of extracellular proteins that contribute to bacterial virulence. A novel AT adhesin gene,
aatB
, was identified in avian pathogenic
Escherichia coli
(APEC) DE205B via genomic analyses. The open reading frame of
aatB
was 1,017 bp, encoding a putative 36.3-kDa protein which contained structural motifs characteristic for AT proteins: a signal peptide, a passenger domain, and a translocator domain. The predicted three-dimensional structure of AatB consisted of two distinct domains, the C-terminal β-barrel translocator domain and an N-terminal passenger domain. The prevalence analyses of
aatB
in APEC indicated that
aatB
was detected in 26.4% (72/273) of APEC strains and was strongly associated with phylogenetic groups D and B2. Quantitative real-time reverse transcription-PCR analyses revealed that AatB expression was increased during infection
in vitro
and
in vivo
. Moreover, AatB could elicit antibodies in infected ducks, suggesting that AatB is involved in APEC pathogenicity. Thus, APEC DE205B strains with a mutated
aatB
gene and mutated strains complemented with the
aatB
gene were constructed. Inactivation of
aatB
resulted in a reduced capacity to adhere to DF-1 cells, defective virulence capacity
in vivo
, and decreased colonization capacity in lung during systemic infection compared with the capacities of the wild-type strain. Furthermore, these capacities were restored in the complementation strains. These results indicated that AatB makes a significant contribution to APEC virulence through bacterial adherence to host tissues
in vivo
and
in vitro
. In addition, biofilm formation assays with strain AAEC189 expressing AatB indicated that AatB mediates biofilm formation.
Heme Catabolism by Heme Oxygenase-1 Confers Host Resistance to Mycobacterium Infection
Authors: Silva-Gomes Sandro , Appelberg Rui , Larsen Rasmus , Soares Miguel Parreira , Gomes Maria Salomé
Published: April 2013

Heme oxygenases (HO) catalyze the rate-limiting step of heme degradation. The cytoprotective action of the inducible HO-1 isoform, encoded by theHmox1gene, is required for host protection against systemic infections. Here we report that upregulation of HO-1 expression in macrophages (Mϕ) is strictly required for protection against mycobacterial infection in mice. HO-1-deficient (Hmox1−/−) mice are more susceptible to intravenousMycobacterium aviuminfection, failing to mount a protective granulomatous response and developing higher pathogen loads, than infected wild-type (Hmox1+/+) controls. Furthermore,Hmox1−/−mice also develop higher pathogen loads and ultimately succumb when challenged with a low-dose aerosol infection withMycobacterium tuberculosis. The protective effect of HO-1 acts independently of adaptive immunity, as revealed inM. avium-infectedHmox1−/−versusHmox1+/+SCID mice lacking mature B and T cells. In the absence of HO-1, heme accumulation acts as a cytotoxic pro-oxidant in infected Mϕ, an effect mimicked by exogenous heme administration toM. avium-infected wild-type Mϕin vitroor to micein vivo. In conclusion, HO-1 prevents the cytotoxic effect of heme in Mϕ, contributing critically to host resistance toMycobacteriuminfection.
Lipopolysaccharide Modifications of a Cholera Vaccine Candidate Based on Outer Membrane Vesicles Reduce Endotoxicity and Reveal the Major Protective Antigen
Authors: Leitner Deborah R. , Feichter Sandra , Schild-Prüfert Kristina , Rechberger Gerald N. , Reidl Joachim , Schild Stefan
Published: April 2013

The causative agent of the life-threatening gastrointestinal infectious disease cholera is the Gram-negative, facultative human pathogen
Vibrio cholerae
. We recently started to investigate the potential of outer membrane vesicles (OMVs) derived from
V. cholerae
as an alternative approach for a vaccine candidate against cholera and successfully demonstrated the induction of a long-lasting, high-titer, protective immune response upon immunization with OMVs using the mouse model. In this study, we present immunization data using lipopolysaccharide (LPS)-modified OMVs derived from
V. cholerae
, which allowed us to improve and identify the major protective antigen of the vaccine candidate. Our results indicate that reduction of endotoxicity can be achieved without diminishing the immunogenic potential of the vaccine candidate by genetic modification of lipid A. Although the protective potential of anti-LPS antibodies has been suggested many times, this is the first comprehensive study that uses defined LPS mutants to characterize the LPS-directed immune response of a cholera vaccine candidate in more detail. Our results pinpoint the O antigen to be the essential immunogenic structure and provide a protective mechanism based on inhibition of motility, which prevents a successful colonization. In a detailed analysis using defined antisera, we can demonstrate that only anti-O antigen antibodies, but not antibodies directed against the major flagellar subunit FlaA or the most abundant outer membrane protein, OmpU, are capable of effectively blocking the motility by binding to the sheathed flagellum and provide protection in a passive immunization assay.
Improving outcomes for pancreatic cancer: radical surgery with patient-tailored, surgery-specific advanced haemodynamic monitoring
Authors: Weinberg Laurence , Houli Nezor , Nikfarjam Mehrdad
Published: April 2013

Pancreatic cancer has poor prognoses, with a median survival after diagnosis of less than 6 months. For some patients radical surgery remains the only chance of long-term cure. We report the successful outcome of a patient with pancreatic cancer and portal vein encasement that underwent a biliary bypass procedure and chemoradiotherapy. He was reassessed 8 months later where a complete resection of the pancreatic cancer was undertaken. The patient required a total pancreatectomy, splenectomy, subtotal gastrectomy and partial colectomy. Portal and superior mesenteric vein resection was performed, with reconstitution using the splenic vein as conduit with its draining inferior mesenteric vein. We report novel aspects of the surgical technique and describe our institution's patient-tailored, surgery-specific goal-directed strategy that was considered paramount for the successful perioperative outcome in this case.
Localised normocalcaemic tetany secondary to dehydration in an individual with Gitelman syndrome
Authors: Kalsi Hardeep Singh , Kim Michael , Alkhamesi Anmar
Published: April 2013

Dehydration is a common presentation to any emergency department with symptoms ranging from lethargy, confusion, oliguria as well as those specific to the underlying cause. In this case we describe a young patient who following a short history of vomiting and abdominal pain developed carpopedal spasm and distal parasthesia on a background of Gitelman syndrome. Biochemical blood analysis showed a marked hypokalaemia, hypomagnesaemia and mild metabolic alkalosis in addition to a prolonged QTc interval of 592 ms seen on ECG. Following fluid replacement and electrolyte correction his clinical symptoms resolved along with QTc normalisation. This case demonstrates a patient with a rare and interesting renal disorder who presented with typical biochemical and ECG abnormalities in addition to tetany in the presence of normal plasma calcium.
Silastic arthroplasty of the first metatarsophalangeal joint as salvage for failed revisional fusion with interpositional structural bone graft
Authors: Kumar Vishwajeet , Clough Tim
Published: April 2013

Silastic arthroplasty of the first metatarsophalangeal joint should be considered a viable salvage procedure either for cases of previously failed fusion with interpositional tricortical bone grafting, or for cases of painful previous Kellers, as it can restore length back to the toe, power, stability of gait and therefore reduce pain.
Primary intracranial melanoma in a child with a giant congenital melanocytic naevus and normal MRI
Authors: Al-Hadithy Nada , Al-Nakib Khalil , McGurk Simon , Quaba Awf
Published: April 2013

We present a case of a 10-year-old girl with a giant congenital melanocytic naevus, and malignant cerebral melanoma.
Acquired urethral meatal stenosis: a rare sequel of an aggressive form of Behçet's disease
Authors: Ghosh Soumik , Kumar Manish , Kumari Pushpa , Gadpayle Adesh Kumar
Published: April 2013

Behçet's disease (BD) is characterised by the triad of recurrent oral and genital aphthous ulceration, skin lesions and ocular inflammation. This disease frequently affects other systems including neurological, locomotor, cardiac or vascular systems. Recurrent oral and genital aphthous ulcerations are the hallmarks of BD. We hereby report a case of rapidly evolving and aggressive form of BD in a young man presenting with extensive ulcerative lesions in orogenital region leading to obstructive uropathy resulting in acquired urethral meatal stenosis due to inflammatory activity.
Ulcerative colitis: a case of steroid refractory disease
Authors: Lee Lennard , Akhtar Mohammed Majid , Gardezisanjliajk Anjum , Macfaul George
Published: April 2013

A 21-year-old lady was admitted to a hospital with an 8-week history of bloody diarrhoea. She had been diagnosed with ulcerative colitis 2 years previously and had remained in remission until the gradual onset of bloody diarrhoea. Her bowel frequency was 20 times per day and associated with significant abdominal pain and weight loss. She was started on intravenous steroids, topical therapy and anti-tumour necrosis factor therapy; however, this failed to achieve symptom control. Histology of tissue obtained from flexible sigmoidoscopy eventually demonstrated cytomegalovirus (CMV)-associated colitis. Intravenous anti-viral valganciclovir was initiated and the patient made a rapid recovery. This case discusses the differentials for steroid-refractory ulcerative colitis, including the common pitfall of inflammatory bowel disease management and CMV infection. This case also discusses CMV pathophysiology including histological features, appropriate investigations and current management guidelines.
On the economics of Norway spruce stands and carbon storage
Authors: Niinimäki Sami , Tahvonen Olli , Mäkelä Annikki , Linkosalo Tapio
Published: April 2013

We combine a process-based growth model for even-aged Norway spruce (Picea abies (L.) Karst.) with economics and optimization. Carbon storage is subsidized based on stand growth and product decay. We include detailed optimized thinnings and timber quality features and present cost functions for stand-level CO2 storage. In contrast to earlier studies, our results suggest that changing thinning strategies and postponing thinnings are at least as important as lengthening the rotation period when considering economically efficient carbon storage. The role of thinning is most important in less fertile sites. Contrary to the generic Faustmann model, a higher interest rate increases rotation length on our fertile site. Including carbon release from decaying timber products as reductions from carbon subsidies only has minor effects on optimal solutions. The fertile site stores more discounted carbon. However, with a 1% interest rate, the less fertile site is cost-efficient up to 13 CO2 t·ha−1, and with a 3% interest rate, it is cost-efficient up to 14 CO2 t·ha−1. After these points, carbon storage on the fertile site becomes cheaper. The economic costs of carbon storage suggest that it is optimal to apply carbon storage in Norway spruce forests to meet greenhouse gas reduction commitments.
BEHIND THE MAGICAL NUMBERS: HIERARCHICAL CHUNKING AND THE HUMAN WORKING MEMORY CAPACITY
Authors: LI GUOQI , NING NING , RAMANATHAN KIRUTHIKA , HE WEI , PAN LI , SHI LUPING
Published: April 2013

To explore the influence of chunking on the capacity limits of working memory, a model for chunking in sequential working memory is proposed, using hierarchical bidirectional inhibition-connected neural networks with winnerless competition. With the assumption of the existence of an upper bound to the inhibitory weights in neurobiological networks, it is shown that chunking increases the number of memorized items in working memory from the "magical number 7" to 16 items. The optimal number of chunks and the number of the memorized items in each chunk are the "magical number 4".
TEMPERATURE AND STRAIN RATE SENSITIVITY OF ULTRAFINE-GRAINED COPPER UNDER UNIAXIAL COMPRESSION
Authors: SUO TAO , MING LU , ZHAO FENG , LI YULONG , FAN XUELING
Published: April 2013

Uniaxial compressive experiments of ultrafine-grained (UFG) copper fabricated by equal channel angular pressing method were performed at temperatures ranging from 77 K to 573 K under quasi-static and dynamic loading conditions. Based on the experimental results, the influence of temperature on flow stress, strain hardening rate and strain rate sensitivity (SRS) were investigated carefully. The results show that the flow stress of UFG copper displays much larger sensitivity to testing temperature than that of coarse grained copper. Meanwhile, both the strain hardening rate and its sensitivity to temperature of UFG copper are lower than those of its coarse counterpart. The SRS of UFG copper also shows apparent dependence on temperature. Although the estimated activation volume of UFG- Cu is on the order of ~10 b3, which is on the same order with that of grain boundary diffusion processes, these processes should be ruled out as dominant mechanisms for UFG- Cu at our experimental temperature and strain rate range. Instead, it is suggested that the dislocation-grain boundary interactions process might be the dominant thermally activated mechanism for UFG- Cu .