bluuebunny/crossref_metadata_2025 huggingface dataset:
Fatal tracheal aspergillosis during rituximab combined chemotherapy for diffuse large B‐cell lymphoma that developed after lung transplantation
Authors: Kawamoto K. , Shibasaki Y. , Sato S. , Nemoto H. , Takizawa J. , Narita M. , Tsuchida M. , Sone H. , Masuko M.
Published: September 2015

Invasive tracheal aspergillosis (ITA) is an infection that is unique to patients who have undergone lung transplantation (LT). Although the activity of this disease often appears on imaging, we encountered a case of ITA that became exacerbated, despite few computed tomography (CT) findings, during rituximab combined chemotherapy for diffuse large B‐cell lymphoma. ITA developed during immunosuppressive therapy after LT. Because CT findings may show false‐negative results, bronchoscopy is recommended for such cases.
Natural variation in the C‐repeat binding factor cold response pathway correlates with local adaptation of Arabidopsis ecotypes
Authors: Gehan Malia A. , Park Sunchung , Gilmour Sarah J. , An Chuanfu , Lee Chin‐Mei , Thomashow Michael F.
Published: September 2015

The natural range of Arabidopsis thaliana (Arabidopsis) encompasses geographical regions that have greatly differing local climates, including harshness of winter temperatures. A question thus raised is whether differences in freezing tolerance might contribute to local adaptation in Arabidopsis. Consistent with this possibility is that Arabidopsis accessions differ in freezing tolerance and that those collected from colder northern latitudes are generally more tolerant to freezing than those collected from warmer southern latitudes. Moreover, recent studies with Arabidopsis genotypes collected from sites in Sweden (SW) and Italy (IT) have established that the two accessions are locally adapted, that the SW ecotype is more tolerant of freezing than the IT ecotype, and that genetic differences between the two ecotypes that condition local adaptation and freezing tolerance map to a region that includes the C‐repeat binding factor (CBF) locus. The CBF locus includes three genes – CBF1, CBF2 and CBF3 – that are induced by low temperature and encode transcription factors that regulate a group of more than 100 genes, the CBF regulon, which impart freezing tolerance. Here we show that cold induction of most CBF regulon genes is lower in IT plants compared with SW plants, and that this is due to the IT CBF2 gene encoding a non‐functional CBF2 protein. The non‐functional IT CBF2 protein also contributes to the lower freezing tolerance of the IT plants compared with the SW plants. Taken together, studies on the SW and IT ecotypes provide evidence that natural variation in the CBF pathway has contributed to adaptive evolution in these Arabidopsis populations.
Offshoring, Plant Survival and Employment Growth
Authors: Bandick Roger
Published: September 2015

This paper empirically investigates the effects of offshoring on plant survival and employment growth using data on the Danish manufacturing plants during the period 1995–2006. To control for the potential endogeneity of the offshoring decision, the paper uses instrumental variables and propensity score‐matching approaches. The data allow me to control for the heterogeneity between the units by using firm‐level offshoring activities in different regions and performing the empirical analysis on plantlevel aggregation, which is shown to be of crucial importance. Using firm as a unit of observation, the effect of offshoring is, if any, very small. However, using plant as a unit of observation, there are strong indications that offshoring plays a much larger role for the extensive and intensive margin of adjustments. The results reveal that plants survival prospect is higher if the main offshoring is located in high‐wage countries; lower if it is located in low‐wage countries; and not affected if it is located in medium‐wage countries. Finally, the results also reveal that depending on where the main offshoring is located, the growth rate of low‐skilled employment is 2 to 8 per cent lower in plants of offshoring firms.
Causal and Fault Trees Analysis of Proton Exchange Membrane Fuel Cell Degradation
Authors: Brik Kais , Ben Ammar Faouzi , Djerdir Abdesslam , Miraoui Abdellatif
Published: September 2015

This paper presents a reliability approach to analyze the degradation of proton exchange membrane fuel cell. This approach is based on the dependability analysis tools such as the causal and fault trees to establish an analysis of the internal state of the fuel cell energy conversion performance and evaluate its lifetime. The elaboration of causal tree offers powerful tools to a deductive analysis, which consists on seeking the various combinations of events leading to the fuel cell degradation. The parameters of fuel cell model are identified in order to found the degree of degradation. The experimental determination of the variation interval of the parameters is done according to each of degradation modes. A diagnostic method is proposed in order to identify the depth of each aging process of the fuel cell. The diagnosis is done by comparing the experimental output characteristic at beginning of life of the fuel cell with the used fuel cell to qualify and quantify the depth of degradation.
The Role of the Hand During Freestyle Swimming
Authors: Cohen Raymond C. Z. , Cleary Paul W. , Mason Bruce R. , Pease David L.
Published: September 2015

The connections between swimming technique and the fluid dynamical interactions they generate are important for assisting performance improvement. Computational fluid dynamics (CFD) modeling provides a controlled and unobtrusive way for understanding the fundamentals of swimming. A coupled biomechanical–smoothed particle hydrodynamics (SPH) fluid model is used to analyze the thrust and drag generation of a freestyle swimmer. The swimmer model was generated using a three-dimensional laser body scan of the athlete and digitization of multi-angle video footage. Two large distinct peaks in net streamwise thrust are found during the stroke, which coincide with the underwater arm strokes. The hand motions generate vortical structures that travel along the body toward the kicking legs and the hands are shown to produce thrust using both lift and drag. These findings advance understanding of the freestyle stroke and may be used to improve athlete technique.
Kinematics and Enumeration of Combined Harmonic Drive Gearing
Authors: Pennestrì Ettore , Valentini Pier Paolo
Published: September 2015

The combined harmonic drive (HD) gearing is a class of differential gears composed of traditional and HD gears. In this paper, the kinematic analysis and enumeration of these less known gear devices are discussed. In particular, a new graph-based method of kinematic analysis has been developed. In order to stimulate the diffusion and applications of combined HD gearing, an atlas of structurally nonisomorphic gear trains has been compiled.
Estimating patient‐specific and anatomically correct reference model for craniomaxillofacial deformity via sparse representation
Authors: Wang Li , Ren Yi , Gao Yaozong , Tang Zhen , Chen Ken‐Chung , Li Jianfu , Shen Steve G. F. , Yan Jin , Lee Philip K. M. , Chow Ben , Xia James J. , Shen Dinggang
Published: September 2015

Purpose:

A significant number of patients suffer from craniomaxillofacial (CMF) deformity and require CMF surgery in the United States. The success of CMF surgery depends on not only the surgical techniques but also an accurate surgical planning. However, surgical planning for CMF surgery is challenging due to the absence of a patient‐specific reference model. Currently, the outcome of the surgery is often subjective and highly dependent on surgeon's experience. In this paper, the authors present an automatic method to estimate an anatomically correct reference shape of jaws for orthognathic surgery, a common type of CMF surgery.

Methods:

To estimate a patient‐specific jaw reference model, the authors use a data‐driven method based on sparse shape composition. Given a dictionary of normal subjects, the authors first use the sparse representation to represent the midface of a patient by the midfaces of the normal subjects in the dictionary. Then, the derived sparse coefficients are used to reconstruct a patient‐specific reference jaw shape.

Results:

The authors have validated the proposed method on both synthetic and real patient data. Experimental results show that the authors’ method can effectively reconstruct the normal shape of jaw for patients.

Conclusions:

The authors have presented a novel method to automatically estimate a patient‐specific reference model for the patient suffering from CMF deformity.
Increasing efficiency of BEAMnrc‐simulated Co‐60 beams using directional source biasing
Authors: Walters B. R. B.
Published: September 2015

Purpose:

This study describes the implementation of a directional source biasing (DSB) scheme for efficiently simulating Cobalt‐60 treatment heads using the BEAMnrc Monte Carlo code. Previous simulation of Co‐60 beams with BEAMnrc was impractical because of the time required to track photons not directed into the treatment field and to simulate secondary charged particles.

Methods:

In DSB, efficiency is increased by splitting each photon emitted by the Co‐60 source a user‐defined number of times. Only those split primary photons directed into a user‐defined splitting field (encompassing the treatment field) are sampled, yielding many low‐weight photons directed into the field. Efficiency can be further increased by taking advantage of radial symmetry at the top of the treatment head to reduce the number of split primary photons tracked in this portion. There is also an option to generate contaminant electrons in DSB.

Results:

The DSB scheme in BEAMnrc increases the photon fluence calculation efficiency in a 10 × 10 cm2 Co‐60 beam by a factor of 1800 with a concurrent increase in contaminant electron fluence calculation efficiency by a factor of 1200. Implementation of DSB in beampp, a C++ code for accelerator simulations based on EGSnrc and the C++ class library, egspp, increases photon fluence efficiency by a factor of 2800 and contaminant electron fluence efficiency by a factor of 1600. Optimum splitting numbers are in the range of 20 000–40 000. For dose calculations in a water phantom (0.5 × 0.5 × 0.5 cm3 voxels) this translates into a factor of ∼400 increase in dose calculation efficiency (all doses > 0.5 × Dmax). An example calculation of the ratio of dose to water to dose to chamber (the basis of the beam quality correction factor) to within 0.2% in a realistic chamber using a full simulation of a Co‐60 treatment head as a source indicates the practicality of Co‐60 simulations with DSB.

Conclusions:

The efficiency improvement resulting from DSB makes Monte Carlo commissioning of Co‐60 beams and calculation of beam quality correction factors feasible.
Echolocation of insects using intermittent frequency-modulated sounds
Authors: Matsuo Ikuo , Takanashi Takuma
Published: September 2015

Using echolocation influenced by Doppler shift, bats can capture flying insects in real three-dimensional space. On the basis of this principle, a model that estimates object locations using frequency modulated (FM) sound was proposed. However, no investigation was conducted to verify whether the model can localize flying insects from their echoes. This study applied the model to estimate the range and direction of flying insects by extracting temporal changes from the time-frequency pattern and interaural range difference, respectively. The results obtained confirm that a living insect's position can be estimated using this model with echoes measured while emitting intermittent FM sounds.
Quantifying Habitual Levels of Physical Activity According to Impact in Older People: Accelerometry Protocol for the VIBE Study
Authors: Deere Kevin C. , Hannam Kimberly , Coulson Jessica , Ireland Alex , McPhee Jamie S. , Moss Charlotte , Edwards Mark H. , Dennison Elaine , Cooper Cyrus , Sayers Adrian , Lipperts Matthijs , Grimm Bernd , Tobias Jon H.
Published: September 2015

Physical activity (PA) may need to produce high impacts to be osteogenic. The aim of this study was to identify threshold(s) for defining high impact PA for future analyses in the VIBE (Vertical Impact and Bone in the Elderly) study, based on home recordings with triaxial accelerometers. Recordings were obtained from 19 Master Athlete Cohort (MAC; mean 67.6 years) and 15 Hertfordshire Cohort Study (HCS; mean 77.7 years) participants. Data cleaning protocols were developed to exclude artifacts. Accelerations expressed in g units were categorized into three bands selected from the distribution of positive Y-axis peak accelerations. Data were available for 6.6 and 4.4 days from MAC and HCS participants respectively, with approximately 14 hr recording daily. Three-fold more 0.5−1.0g impacts were observed in MAC versus HCS, 20-fold more 1.0−1.5g impacts, and 140-fold more impacts ≥ 1.5g. Our analysis protocol successfully distinguishes PA levels in active and sedentary older individuals.
Exercise and Depressive Symptoms in Older Adults: A Systematic Meta-Analytic Review
Authors: Rhyner Kathleen T. , Watts Amber
Published: September 2015

Depressive symptoms are common in older adults, but antidepressant medications may be contraindicated or poorly tolerated in this population. Intervention studies demonstrate that exercise may be an effective alternative. This meta-analysis included 41 randomized controlled trials of aerobic and nonaerobic exercise interventions investigating the effect of exercise on depressive symptoms in adults aged 60 or older. A random effects model demonstrated that exercise was associated with significantly lower depression severity (SMD = 0.57, 95% CI 0.36–0.78). This effect was not significantly different for different ages of participants, types of control groups, or types of exercise interventions. Studies requiring a diagnosis of depression had significantly greater mean effect sizes than studies that did not require a depression diagnosis (Qbet = 6.843, df = 1, p = .009). These findings suggest that exercise is an effective treatment option for older individuals with depressive symptoms.
A metabolite rescues DNA damage
Authors: Prabakaran Sudhakaran
Published: September 2015

Nuclear fumarate, a TCA cycle metabolic intermediate, aids in DNA double-stranded break repair.
Uridylylation of PBL2 triggers plant immune responses
Authors: VanHook Annalisa M.
Published: September 2015

Uridylylating activity of a plant pathogen inhibits one form of the plant immune response but triggers another.
Changing properties of interneurons
Authors: Gough Nancy R.
Published: September 2015

The transcriptional regulator Er81 enables activity-dependent changes in the properties of delay-type fast-spiking interneurons.
A leak in the dike
Authors: LaMarco Kelly
Published: September 2015

Dengue virus NS1 triggers endothelial permeability and is a TLR4 agonist, suggesting NS1 as a component of dengue vaccines.
Harnessing cellular stress to kill myeloma
Authors: Ferrarelli Leslie K.
Published: September 2015

Combining an oxidative stress inducer and an inhibitor of the kinase ATR to increase DNA damage may kill multiple myeloma cells.
Limiting S1P production with Nogo-B
Authors: Gough Nancy R.
Published: September 2015

Proper control of sphingolipid biosynthesis in endothelial cells is essential for regulation of blood pressure.
Evaluation of VT-1161 for Treatment of Coccidioidomycosis in Murine Infection Models
Authors: Shubitz Lisa F. , Trinh Hien T. , Galgiani John N. , Lewis Maria L. , Fothergill Annette W. , Wiederhold Nathan P. , Barker Bridget M. , Lewis Eric R. G. , Doyle Adina L. , Hoekstra William J. , Schotzinger Robert J. , Garvey Edward P.
Published: September 2015

Coccidioidomycosis, or valley fever, is a growing health concern endemic to the southwestern United States. Safer, more effective, and more easily administered drugs are needed especially for severe, chronic, or unresponsive infections. The novel fungal CYP51 inhibitor VT-1161 demonstrated
in vitro
antifungal activity, with MIC
50
and MIC
90
values of 1 and 2 μg/ml, respectively, against 52
Coccidioides
clinical isolates. In the initial animal study, oral doses of 10 and 50 mg/kg VT-1161 significantly reduced fungal burdens and increased survival time in a lethal respiratory model in comparison with treatment with a placebo (
P
< 0.001). Oral doses of 25 and 50 mg/kg VT-1161 were similarly efficacious in the murine central nervous system (CNS) model compared to placebo treatment (
P
< 0.001). All comparisons with the positive-control drug, fluconazole at 50 mg/kg per day, demonstrated either statistical equivalence or superiority of VT-1161. VT-1161 treatment also prevented dissemination of infection from the original inoculation site to a greater extent than fluconazole. Many of these
in vivo
results can be explained by the long half-life of VT-1161 leading to sustained high plasma levels. Thus, the efficacy and pharmacokinetics of VT-1161 are attractive characteristics for long-term treatment of this serious fungal infection.
Antibiotic Selection Pressure Determination through Sequence-Based Metagenomics
Authors: Willmann Matthias , El-Hadidi Mohamed , Huson Daniel H. , Schütz Monika , Weidenmaier Christopher , Autenrieth Ingo B. , Peter Silke
Published: September 2015

The human gut forms a dynamic reservoir of antibiotic resistance genes (ARGs). Treatment with antimicrobial agents has a significant impact on the intestinal resistome and leads to enhanced horizontal transfer and selection of resistance. We have monitored the development of intestinal ARGs over a 6-day course of ciprofloxacin (Cp) treatment in two healthy individuals by using sequenced-based metagenomics and different ARG quantification methods. Fixed- and random-effect models were applied to determine the change in ARG abundance per defined daily dose of Cp as an expression of the respective selection pressure. Among various shifts in the composition of the intestinal resistome, we found in one individual a strong positive selection for class D beta-lactamases which were partly located on a mobile genetic element. Furthermore, a trend to a negative selection has been observed with class A beta-lactamases (−2.66 hits per million sample reads/defined daily dose;
P
= 0.06). By 4 weeks after the end of treatment, the composition of ARGs returned toward their initial state but to a different degree in both subjects. We present here a novel analysis algorithm for the determination of antibiotic selection pressure which can be applied in clinical settings to compare therapeutic regimens regarding their effect on the intestinal resistome. This information is of critical importance for clinicians to choose antimicrobial agents with a low selective force on their patients' intestinal ARGs, likely resulting in a diminished spread of resistance and a reduced burden of hospital-acquired infections with multidrug-resistant pathogens.
Treatment of Experimental Candida Sepsis with a Janus Kinase Inhibitor Controls Inflammation and Prolongs Survival
Authors: Tsirigotis P. , Papanikolaou N. , Elefanti A. , Konstantinou P. , Gkirkas K. , Rontogianni D. , Siafakas N. , Karakitsos P. , Roilides E. , Dimitriadis G. , Zerva L. , Meletiadis J.
Published: September 2015

Janus kinases (JAK) are intracellular tyrosine kinases that transduce cytokine-mediated signals to the nucleus, promoting gene expression. Cytokines play a major role in microbial sepsis, which is often associated with uncontrolled inflammation leading to death. JAK inhibitors have been used for the treatment of several autoimmune diseases by modulating immune response, but they have never been tested against microbial sepsis. Ruxolitinib is a small-molecule inhibitor of JAK1/2 proteins, which are involved in the downstream signaling pathway of the vast majority of proinflammatory and anti-inflammatory cytokines. We therefore studied the effect of ruxolitinib in a mouse model of sepsis due to
Candida albicans
. When ruxolitinib therapy (50 mg/kg [of body weight]/day) was started 1 day before infection, the median survival time was reduced by 3 days, the fungal loads in all organs were higher, the inflammation was significantly less, and serum tumor necrosis factor alpha (TNF-α) and interleukin 10 (IL-10) levels and IL-10/TNF-α ratios were higher than in controls. When ruxolitinib therapy (50 to 1.5 mg/kg/day) was started 1 day after infection, an inverted-U relationship was found, with 6.25 mg/kg/day prolonging median survival time by 6 days, resulting in similar fungal loads, less inflammation, and similar cytokine levels but higher IL-10/TNF-α ratios than the controls. The optimal dose of ruxolitinib controlled infection and prolonged survival with less inflammation than in control animals. Administration of JAK inhibitors may be a promising therapeutic adjunct that needs further investigation.
Elucidating the Role of Residue 67 in IMP-Type Metallo-β-Lactamase Evolution
Authors: LaCuran Alecander E. , Pegg Kevin M. , Liu Eleanor M. , Bethel Christopher R. , Ai Ni , Welsh William J. , Bonomo Robert A. , Oelschlaeger Peter
Published: September 2015

Antibiotic resistance in bacteria is ever changing and adapting, as once-novel β-lactam antibiotics are losing their efficacy, primarily due to the production of β-lactamases. Metallo-β-lactamases (MBLs) efficiently inactivate a broad range of β-lactam antibiotics, including carbapenems, and are often coexpressed with other antibacterial resistance factors. The rapid dissemination of MBLs and lack of novel antibacterials pose an imminent threat to global health. In an effort to better counter these resistance-conferring β-lactamases, an investigation of their natural evolution and resulting substrate specificity was employed. In this study, we elucidated the effects of different amino acid substitutions at position 67 in IMP-type MBLs on the ability to hydrolyze and confer resistance to a range of β-lactam antibiotics. Wild-type β-lactamases IMP-1 and IMP-10 and mutants IMP-1-V67A and IMP-1-V67I were characterized biophysically and biochemically, and MICs for
Escherichia coli
cells expressing these enzymes were determined. We found that all variants exhibited catalytic efficiencies (
k
cat
/

K
m

) equal to or higher than that of IMP-1 against all tested β-lactams except penicillins, against which IMP-1 and IMP-1-V67I showed the highest
k
cat
/

K
m

values. The substrate-specific effects of the different amino acid substitutions at position 67 are discussed in light of their side chain structures and possible interactions with the substrates. Docking calculations were employed to investigate interactions between different side chains and an inhibitor used as a β-lactam surrogate. The differences in binding affinities determined experimentally and computationally seem to be governed by hydrophobic interactions between residue 67 and the inhibitor and, by inference, the β-lactam substrates.
Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2 and Human Papillomavirus
Authors: Levendosky Keith , Mizenina Olga , Martinelli Elena , Jean-Pierre Ninochka , Kizima Larisa , Rodriguez Aixa , Kleinbeck Kyle , Bonnaire Thierry , Robbiani Melissa , Zydowsky Thomas M. , O'Keefe Barry R. , Fernández-Romero José A.
Published: September 2015

Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC
50
) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC
50
= 0.429 to 1.39 μM). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through α
6
integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (
P
= 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (
P
< 0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (
P
< 0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide.
Assessment of Antiviral Properties of Peramivir against H7N9 Avian Influenza Virus in an Experimental Mouse Model
Authors: Farooqui Amber , Huang Linxi , Wu Suwu , Cai Yingmu , Su Min , Lin Pengzhou , Chen Weihong , Fang Xibin , Zhang Li , Liu Yisu , Zeng Tiansheng , Paquette Stephane G. , Khan Adnan , Kelvin Alyson A. , Kelvin David J.
Published: September 2015

The H7N9 influenza virus causes a severe form of disease in humans. Neuraminidase inhibitors, including oral oseltamivir and injectable peramivir, are the first choices of antiviral treatment for such cases; however, the clinical efficacy of these drugs is questionable. Animal experimental models are essential for understanding the viral replication kinetics under the selective pressure of antiviral agents. This study demonstrates the antiviral activity of peramivir in a mouse model of H7N9 avian influenza virus infection. The data show that repeated administration of peramivir at 30 mg/kg of body weight successfully eradicated the virus from the respiratory tract and extrapulmonary tissues during the acute response, prevented clinical signs of the disease, including neuropathy, and eventually protected mice against lethal H7N9 influenza virus infection. Early treatment with peramivir was found to be associated with better disease outcomes.
Nanoscale Plasma Coating Inhibits Formation of Staphylococcus aureus Biofilm
Authors: Xu Yuanxi , Jones John E. , Yu Haiqing , Yu Qingsong , Christensen Gordon D. , Chen Meng , Sun Hongmin
Published: September 2015

Staphylococcus aureus
commonly infects medical implants or devices, with devastating consequences for the patient. The infection begins with bacterial attachment to the device, followed by bacterial multiplication over the surface of the device, generating an adherent sheet of bacteria known as a biofilm. Biofilms resist antimicrobial therapy and promote persistent infection, making management difficult to futile. Infections might be prevented by engineering the surface of the device to discourage bacterial attachment and multiplication; however, progress in this area has been limited. We have developed a novel nanoscale plasma coating technology to inhibit the formation of
Staphylococcus aureus
biofilms. We used monomeric trimethylsilane (TMS) and oxygen to coat the surfaces of silicone rubber, a material often used in the fabrication of implantable medical devices. By quantitative and qualitative analysis, the TMS/O
2
coating significantly decreased the
in vitro
formation of
S. aureus
biofilms; it also significantly decreased
in vivo
biofilm formation in a mouse model of foreign-body infection. Further analysis demonstrated TMS/O
2
coating significantly changed the protein adsorption, which could lead to reduced bacterial adhesion and biofilm formation. These results suggest that TMS/O
2
coating can be used to effectively prevent medical implant-related infections.
Neither Classical nor Alternative Macrophage Activation Is Required for Pneumocystis Clearance during Immune Reconstitution Inflammatory Syndrome
Authors: Zhang Zhuo-Qian , Wang Jing , Hoy Zachary , Keegan Achsah , Bhagwat Samir , Gigliotti Francis , Wright Terry W.
Published: September 2015

Pneumocystisis a respiratory fungal pathogen that causes pneumonia (Pneumocystispneumonia [PcP]) in immunocompromised patients. Alveolar macrophages are critical effectors for CD4+T cell-dependent clearance ofPneumocystis, and previous studies found that alternative macrophage activation accelerates fungal clearance during PcP-related immune reconstitution inflammatory syndrome (IRIS). However, the requirement for either classically or alternatively activated macrophages forPneumocystisclearance has not been determined. Therefore, RAG2−/−mice lacking either the interferon gamma (IFN-γ) receptor (IFN-γR) or interleukin 4 receptor alpha (IL-4Rα) were infected withPneumocystis. These mice were then immune reconstituted with wild-type lymphocytes to preserve the normal T helper response while preventing downstream effects of Th1 or Th2 effector cytokines on macrophage polarization. As expected, RAG2−/−mice developed severe disease but effectively clearedPneumocystisand resolved IRIS. Neither RAG/IFN-γR−/−nor RAG/IL-4Rα−/−mice displayed impairedPneumocystisclearance. However, RAG/IFN-γR−/−mice developed a dysregulated immune response, with exacerbated IRIS and greater pulmonary function deficits than those in RAG2 and RAG/IL-4Rα−/−mice. RAG/IFN-γR−/−mice had elevated numbers of lung CD4+T cells, neutrophils, eosinophils, and NK cells but severely depressed numbers of lung CD8+T suppressor cells. Impaired lung CD8+T cell responses in RAG/IFN-γR−/−mice were associated with elevated lung IFN-γ levels, and neutralization of IFN-γ restored the CD8 response. These data demonstrate that restricting the ability of macrophages to polarize in response to Th1 or Th2 cytokines does not impairPneumocystisclearance. However, a cell type-specific IFN-γ/IFN-γR-dependent mechanism regulates CD8+T suppressor cell recruitment, limits immunopathogenesis, preserves lung function, and enhances the resolution of PcP-related IRIS.
Host Contributions to Construction of Three Device-Associated Candida albicans Biofilms
Authors: Nett Jeniel E. , Zarnowski Robert , Cabezas-Olcoz Jonathan , Brooks Erin G. , Bernhardt Jörg , Marchillo Karen , Mosher Deane F. , Andes David R.
Published: September 2015

Among the most fascinating virulence attributes of
Candida
is the ability to transition to a biofilm lifestyle. As a biofilm,
Candida
cells adhere to a surface, such as a vascular catheter, and become encased in an extracellular matrix. During this mode of growth,
Candida
resists the normal immune response, often causing devastating disease. Based on scanning electron microscopy images, we hypothesized that host cells and proteins become incorporated into clinical biofilms. As a means to gain an understanding of these host-biofilm interactions, we explored biofilm-associated host components by using microscopy and liquid chromatography-mass spectrometry. Here we characterize the host proteins associated with several
in vivo
rat
Candida albicans
biofilms, including those from vascular catheter, denture, and urinary catheter models as well as uninfected devices. A conserved group of 14 host proteins were found to be more abundant during infection at each of the niches. The host proteins were leukocyte and erythrocyte associated and included proteins involved in inflammation, such as C-reactive protein, myeloperoxidase, and alarmin S100-A9. A group of 59 proteins were associated with both infected and uninfected devices, and these included matricellular and inflammatory proteins. In addition, site-specific proteins were identified, such as amylase in association with the denture device. Cellular analysis revealed neutrophils as the predominant leukocytes associating with biofilms. These experiments demonstrate that host cells and proteins are key components of
in vivo
Candida
biofilms, likely with one subset associating with the device and another being recruited by the proliferating biofilm.
Periodontal Pathogens Invade Gingiva and Aortic Adventitia and Elicit Inflammasome Activation in αvβ6 Integrin-Deficient Mice
Authors: Velsko Irina M. , Chukkapalli Sasanka S. , Rivera-Kweh Mercedes F. , Zheng Donghang , Aukhil Ikramuddin , Lucas Alexandra R. , Larjava Hannu , Kesavalu Lakshmyya
Published: September 2015

The American Heart Association supports an association between periodontal diseases and atherosclerosis but not a causal association. This study explores the use of the integrin β6
−/−
mouse model to study the causality. We investigated the ability of a polymicrobial consortium of
Porphyromonas gingivalis
,
Treponema denticola
,
Tannerella forsythia
, and
Fusobacterium nucleatum
to colonize the periodontium and induce local and systemic inflammatory responses. Polymicrobially infected
Itgβ6
−/−
mice demonstrate greater susceptibility to gingival colonization/infection, with severe gingival inflammation, apical migration of the junctional epithelium, periodontal pocket formation, alveolar bone resorption, osteoclast activation, bacterial invasion of the gingiva, a greater propensity for the bacteria to disseminate hematogenously, and a strong splenic T cell cytokine response. Levels of atherosclerosis risk factors, including serum nitric oxide, oxidized low-density lipoprotein, serum amyloid A, and lipid peroxidation, were significantly altered by polybacterial infection, demonstrating an enhanced potential for atherosclerotic plaque progression. Aortic gene expression revealed significant alterations in specific Toll-like receptor (TLR) and nucleotide-binding domain- and leucine-rich-repeat-containing receptor (NLR) pathway genes in response to periodontal bacterial infection. Histomorphometry of the aorta demonstrated larger atherosclerotic plaques in
Itgβ6
−/−
mice than in wild-type (WT) mice but no significant difference in atherosclerotic plaque size between mice with polybacterial infection and mice with sham infection. Fluorescence
in situ
hybridization demonstrated active invasion of the aortic adventitial layer by
P. gingivalis
. Our observations suggest that polybacterial infection elicits distinct aortic TLR and inflammasome signaling and significantly increases local aortic oxidative stress. These results are the first to demonstrate the mechanism of the host aortic inflammatory response induced by polymicrobial infection with well-characterized periodontal pathogens.
Death by Cystine: an Adverse Emergent Property from a Beneficial Series of Reactions
Authors: Reitzer Larry
Published: September 2015

In this issue of the
Journal of Bacteriology
, Chonoles Imlay et al. (K. R. Chonoles Imlay, S. Korshunov, and J. A. Imlay, J Bacteriol 197:3629–3644, 2015,
http://dx.doi.org/10.1128/JB.00277-15
) show that oxidative stress kills sulfur-restricted
Escherichia coli
grown with sublethal H
2
O
2
when challenged with cystine. Killing requires rapid and seemingly unregulated cystine transport and equally rapid cystine reduction to cysteine. Cysteine export completes an energy-depleting futile cycle. Each reaction of the cycle could be beneficial. Together, a cystine-mediated vulnerability emerges during the transition from a sulfur-restricted to a sulfur-replete environment, perhaps because of complexities of sulfur metabolism.
An atypical presentation of colonic malignancy:Clostridium septicumaortitis
Authors: Tabasum Arshiya , Bleehen Robert , Healy Brendan , George Lindsay
Published: September 2015

Clostridium septicum(CS) is a rare organism that accounts for only 1.3% of all clostridial infections. However, its detection is of great clinical significance, as over 80% of cases are associated with malignancy, often occult; the most common primary sites are the ascending colon and caecum, and the most common cause is haematological malignancy. We report a case of a 79-year-old woman, admitted with shortness of breath and left-sided chest pain, who, following subsequent investigations, was found to have CS aortitis. She was further evaluated with CT of the abdomen followed by colonoscopy and biopsy, which revealed adenocarcinoma of the caecum with liver metastasis. The CS aortitis has a reported mortality of 100% if left untreated. Therefore prompt intervention and surgical debridement is recommended. Despite these recommendations, our patient had some delays in her treatment and did not undergo surgical debridement due to frailty. We believe that it is highly unusual for a patient such as ours to have survived both the aortitis and the colonic malignancy, after undergoing endovascular radiological intervention and antibiotic therapy, without surgical debridement.
A unique case of gliomatosis peritonei in a man, following a retroperitoneal teratoma
Authors: Chauhan Meera , Kockelbergh Roger , Faust Guy
Published: September 2015

We present an unusual case of a 56- year-old man presenting with abdominal swelling. Imaging revealed a large abdominal 23 cm cystic mass, which radiologically appeared to be related to the small bowel. There was an attempted surgical removal by the general surgeons. It was histologically confirmed as a retroperitoneal cystic teratoma with immature neural elements with incomplete resection margins. Residual disease was found at re-imaging 3 months later and a further block dissection was performed, with histology confirming recurrence. Thirteen months later, imaging revealed recurrent disease with peritoneal involvement. At laparoscopic exploration, there was peritoneal seeding, and biopsies confirmed a diagnosis of gliomatosis peritonei, secondary to the retroperitoneal teratoma. The patient proceeded to have combination chemotherapy to achieve stable disease on imaging. A month after completion, sadly, the disease progressed; the patient received best supportive care.
Does the Finnish intervention prevent obstetric anal sphincter injuries? A systematic review of the literature
Authors: Poulsen Mette Østergaard , Madsen Mia Lund , Skriver-Møller Anne-Cathrine , Overgaard Charlotte
Published: September 2015

Objectives

A rise in obstetric anal sphincter injuries (OASIS) has been observed and a preventive approach, originating in Finland, has been introduced in several European hospitals. The aim of this paper was to systematically evaluate the evidence behind the ‘Finnish intervention’.

Design

A systematic review of the literature conducted according to the Preferred Reporting for Systematic Reviews and Meta-analyses (PRISMA) guidelines.

Outcome measures

The primary outcome was OASIS. Secondary outcomes were (perinatal): Apgar scores, pH and standard base excess in the umbilical cord, and (maternal): episiotomy, intact perineum, first and second-degree perineal lacerations, duration of second stage, birth position and women's perceptions/birth experiences.

Methods

Multiple databases (Cochrane, Embase, Pubmed and SveMed) were systematically searched for studies published up to December 2014. Both randomised controlled trials and observational studies were eligible for inclusion. Studies were excluded if a full-text article was not available. Studies were evaluated by use of international reporting guidelines (eg, STROBE).

Results

Overall, 1042 articles were screened and 65 retrieved for full-text evaluation. Seven studies, all observational and with a level of evidence at 2c or lower, were included and consistently reported a significant reduction in OASIS. All evaluated episiotomy and found a significant increase. Three studies evaluated perinatal outcomes and reported conflicting results. No study reported on other perineal outcomes, duration of the second stage, birth positions or women's perceptions.

Conclusions

A reduction in OASIS has been contributed to the Finnish intervention in seven observational studies, all with a low level of evidence. Knowledge about the potential perinatal and maternal side effects and women's perceptions of the intervention is extremely limited and the biological mechanisms underlying the Finnish intervention are not well documented. Studies with a high level of evidence are needed to assess the effects of the intervention before implementation in clinical settings can be recommended.
Individual-level and community-level effect modifiers of the temperature–mortality relationship in 66 Chinese communities
Authors: Huang Zhengjing , Lin Hualiang , Liu Yunning , Zhou Maigeng , Liu Tao , Xiao Jianpeng , Zeng Weilin , Li Xing , Zhang Yonghui , Ebi Kristie L , Tong Shilu , Ma Wenjun , Wang Lijun
Published: September 2015

Objectives

To examine the modification of temperature-mortality association by factors at the individual and community levels.

Design and methods

This study investigated this issue using a national database comprising daily data of 66 Chinese communities for 2006–2011. A ‘threshold-natural cubic spline’ distributed lag non-linear model was utilised to estimate the mortality effects of daily mean temperature, and then examined the modification of the relationship by individual factors (age, sex, education level, place of death and cause of death) using a meta-analysis approach and community-level factors (annual temperature, population density, sex ratio, percentage of older population, health access, household income and latitude) using a meta-regression method.

Results

We found significant effects of high and low temperatures on mortality in China. The pooled excess mortality risk was 1.04% (95% CI 0.90% to 1.18%) for a 1°C temperature decrease below the minimum mortality temperature (MMT), and 3.44% (95% CI 3.00% to 3.88%) for a 1°C temperature increase above MMT. At the individual level, age and place of death were found to be significant modifiers of cold effect, while age, sex, place of death, cause of death and education level were effect modifiers of heat effect. At the community level, communities with lower socioeconomic status and higher annual temperature were generally more vulnerable to the mortality effects of high and low temperatures.

Conclusions

This study identifies susceptibility based on both individual-level and community-level effect modifiers; more attention should be given to these vulnerable individuals and communities to reduce adverse health effects of extreme temperatures.
Initial factors affecting the clinical outcome after successful recanalization via MR-based mechanical thrombectomy in patients with acute ischemic stroke due to basilar artery occlusion
Authors: Son Seungnam , Kim Yong-Won , Oh Min Kyun , Kim Soo-Kyoung , Park Ki-Jong , Choi Nack-Cheon , Kwon Oh-Young , Lim Byeong Hoon , Choi Ho Cheol , Choi Dae Seob
Published: September 2015

Background and purpose

To determine the initial factors, including patient characteristics, stroke etiology and severity, time factors, and imaging findings, that could affect the clinical outcome of patients with acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) where successful recanalization was achieved via mechanical thrombectomy.

Methods

Between March 2011 and December 2014, 35 patients with AIS caused by BAO received MRI/MR angiography-based mechanical thrombectomies, and recanalization was achieved with a Thrombolysis In Cerebral Infarction score of >2b. The patients were divided into a good outcome group (n=19), defined as those with a modified Rankin Scale (mRS) score of 0–2 at 3 months after stroke onset, and a poor outcome group (n=16), defined as a mRS score of 3–6. The differences between the groups were analyzed.

Results

Initial National Institutes of Health Stroke Scale (NIHSS) score (good vs poor: 17.9±8.9 vs 27.6±8.5, p=0.003), posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) based on initial diffusion-weighted images (DWI) (good vs poor: 7.8±1.6 vs 5.4±1.8, p=0.001), pc-ASPECTS based on contrast staining on the post-thrombectomy control CT (good vs poor: 9.2±1.5 vs 6.3±2.2, p<0.001), and presence of contrast staining in the brainstem on that CT (good vs poor: 15.8% vs 81.6%, p<0.001) were significantly different between the groups.

Conclusions

Patients with AIS caused by BAO with a lower initial NIHSS score, fewer lesions on initial DWI, and less contrast staining on the post-thrombectomy control CT have higher probabilities of a good clinical outcome after successful recanalization via a mechanical thrombectomy.
Characterizing the ageing of a geosynthetic clay liner through electrical resistivity
Authors: Sirieix C. , Genelle F. , Barral C. , Touze-Foltz N. , Riss J. , Bégassat B.
Published: September 2015

In closed hazardous waste landfills, impermeable layered covers mainly composed of clays, geosynthetic clay liner (GCL) or geomembrane, etc. are used to seal in the waste to minimize water infiltration and accumulation of leachate inside the waste. An experimental site of landfill cap was realized with sodium-activated calcium bentonite GCL at a depth of 0.45 m covered by gravels and top soil. The monitoring of this site was performed during 32 months with measurements of weather conditions, and electrical resistivity tomography (ERT) and geotechnical measurements at the end of the monitoring. The two different methods underlined that the GCL’s electrical resistivity decreased after 22 months subsequent to its installation; moreover, it was possible to detect the defects that had been made in the GCL prior to closure, to simulate factors affecting GCL performance. Thereby the analyses made on the GCL samples taken at two locations in the vicinity of the ERT profile highlighted changes in the intrinsic properties of the material. Changes in the proportion of sodium and calcium cations occurred and its hydraulic conductivity increased from 5 × 10−11 to 3 × 10−6 m/s. Thus, this study shows that electrical resistivity is suitable to characterize the ageing of a GCL.
Non-central potentials in the cosmic string space–time
Authors: Afshardoost A. , Hassanabadi H.
Published: September 2015

We investigate the behavior of quantum particles in the cosmic string space–time in the presence of Pöschl–Teller double-ring-shaped Coulomb and double-ring-shaped oscillator potentials. We obtain energy levels and finally compare the results with the Minkowski space–time. To do this, we solve the Schrödinger equation in spherical coordinates.
Effects of habitat quality and anthropogenic disturbance on grizzly bear (Ursus arctos horribilis) home-range fidelity
Authors: Sorensen A.A. , Stenhouse G.B. , Bourbonnais M.L. , Nelson T.A.
Published: September 2015

In the Rocky Mountain eastern slopes of Alberta, Canada, grizzly bears (Ursus arctos horribilis Ord, 1815) live in a landscape heavily impacted by industrial development and human disturbance. We characterized the role of changing habitat quality and new disturbance features on patterns of grizzly bear seasonal home-range fidelity and drift by comparing consecutive-year seasonal home ranges. We relied on the geographic technique “spatial–temporal analysis of moving polygons” (STAMP) to examine changes in habitat quality and new development between zones of home-range fidelity, expansion, and contraction. Areas considered to be high-quality habitat were selected at a greater frequency than available and retained in zones of home-range fidelity, but also vacated during home-range contraction. Areas of decreasing habitat quality were equally present in zones of contraction, expansion, and stability. The proportion of new forest harvest areas and roads developed within the past year did not differ between zones of home-range change, but the proportion of new well sites was higher in contraction zones than in stability zones. Our results showed that while considerable drift occurs, changes in habitat quality and recent anthropogenic disturbances cannot account for annual variation in home ranges, suggesting other important factors influencing behaviour and movement.