bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondrial function/dysfunction in white adipose tissue
Authors: Boudina Sihem , Graham Timothy E.
Published: August 2014

New Findings

What is the topic of this review?

The review covers basic knowledge about the role of mitochondria in the homeostatic function of adipose tissue. It also provide a comprehensive analysis of how mitochondrial function is affected during obesity and lipoatrophies and discuss the results of recent studies that targeted mitochondrial function specifically in adipose tissue or in fat cells and how these interventions affected whole body adiposity and peripheral insulin sensitivity.

What advances does it highlight?

The review provides specific highlights of the major roles of mitochondria in key metabolic processes that occur in adipose tissue including its role in adipogenesis, adipokine secretion, lipogenesis, fatty acid esterification, branched‐chain amino acid catabolism and lipolysis. Furthermore, we provide the reader with an update on the specific defects that affect mitochondrial function in adipose tissue during obesity and lipoatrophies. Finally, we discuss the latest mouse studies that specifically targeted mitochondrial function in adipose tissue to assess its contribution to the pathogenesis of obesity and insulin resistance.

The role of mitochondria in white adipocytes has long been neglected due in part to their lower abundance in these cells. However, accumulating evidence suggests that mitochondria are vital for maintaining metabolic homeostasis in white adipocytes because of their involvement in adipogenesis, fatty acid synthesis and esterification, branched‐chain amino acid catabolism and lipolysis. It is therefore not surprising that white adipose tissue function can be perturbed by altering mitochondrial components or oxidative capacity. Moreover, studies in humans and animals with significantly altered fat mass, such as in obesity or lipoatrophy, indicate that impaired mitochondrial function in adipocytes may be linked directly to the development of metabolic diseases such as diabetes and insulin resistance. However, recent studies that specifically targeted mitochondrial function in adipocytes indicated dissociation between impaired mitochondrial oxidative capacity and systemic insulin sensitivity.
Effect of Varying Jet Diameter on the Heat Transfer Distributions of Narrow Impingement Channels
Authors: Terzis Alexandros , Ott Peter , Cochet Magali , von Wolfersdorf Jens , Weigand Bernhard
Published: August 2014

The development of integrally cast turbine airfoils allows the production of narrow impingement channels in a double-wall configuration, where the coolant is practically injected within the wall of the airfoil providing increased heat transfer capabilities. This study examines the cooling performance of narrow impingement channels with varying jet diameters using a single exit design in an attempt to regulate the generated crossflow. The channel consists of a single row of five inline jets tested at two different channel heights and over a range of engine representative Reynolds numbers. Detailed heat transfer coefficient distributions are evaluated over the complete interior surfaces of the channel using the transient liquid crystal technique. Additionally, local jet discharge coefficients are determined by probe traversing measurements for each individual jet. A 10%-increasing and a 10%-decreasing jet diameter pattern are compared with a baseline geometry of uniform jet size distribution, indicating a considerable effect of varying jet diameter on the heat transfer level and the development of the generated crossflow.
Comparison Between a Wideband Fractal-Inspired and a Traditional Multicantilever Piezoelectric Energy Converter
Authors: Castagnetti Davide
Published: August 2014

Harvesting energy from ambient vibrations in order to power autonomous sensors is a challenging issue. The aim of this work is to compare the power output from an innovative wideband fractal-inspired piezoelectric converter to that from a traditional multicantilever piezoelectric energy converter. In a given frequency range, the converters are tuned on the same eigenfrequencies. The effect of the input acceleration and of the resistive load applied to the converters is investigated experimentally for each of the three eigenfrequencies in the range between 0 and 120 Hz. The fractal-inspired converter exhibits a significantly higher specific output power at the first and third of the eigenfrequencies investigated.
Modeling, Control, and Validation of Electrohydrostatic Shock Absorbers
Authors: Galluzzi Renato , Tonoli Andrea , Amati Nicola
Published: August 2014

The implementation of variable damping systems to increase the adaptability of mechanical structures to their working environment has been gaining increasing scientific interest, and numerous attempts have been devoted to address vibration control by means of active and semi-active devices. Although research results seem promising in some cases, the proposed solutions are often not able to fulfill requirements in terms of compactness and simplicity on one hand, and dynamic performance on the other. In this context, the present paper discusses the modeling and control of an electrohydrostatic actuation (EHA) system for its implementation as a damping device. A model of the device is proposed and analyzed for design purposes. Subsequently, a damping control strategy is presented. Finally, a case study introduces and validates an EHA prototype for helicopter rotor blade lead–lag damping.
Fast and Accurate Evaluation of Cooling in Data Centers
Authors: Bhagwat Harshad , Singh Umesh , Deodhar Anirudh , Singh Amarendra , Sivasubramaniam Anand
Published: August 2014

Cooling is a major component in the enormous energy consumption in data centers. Accurate evaluation of cooling inside a data center forms the backbone of all the attempts for improving cooling efficiency. Models based on computational fluid dynamics (CFD) are typically used for accurate evaluation, but have a drawback of high computation time. This paper presents a novel thermal predictor to evaluate data center cooling in seconds. The key idea is to extract information from a single instance of CFD simulation using metrics called as influence indices to build the fast thermal predictor. Then, this predictor can evaluate the cooling for altered operation of data center with comparable accuracy in seconds without the need for repetitive CFD simulations. This paper demonstrates the accuracy of the thermal predictor by comparing with CFD simulations for a sample, but realistic data center. The fast thermal predictor then successfully passed more challenging tests in a real production data center and proved its practical utility. The results of the thermal predictor compared with measurements carried out in the production data center are also presented. This fast thermal predictor is an important milestone in the development of a method for model-based real time control of data center cooling.
New Micro Tube Hydroforming System Based on Floating Die Assembly Concept
Authors: Ngaile Gracious , Lowrie James
Published: August 2014

The advancement of micro tube hydroforming (THF) technology has been hindered by, among others, the lack of robust microdie systems that could facilitate hydroforming of complex parts that require both expansion and feeding. This paper proposes a new micro-THF die assembly that is based on floating a microdie-assembly in a pressurized chamber. The fluid pressure inside the chamber which surrounds the dies and punches is the same as the pressure required to hydroform the tube. The fluid pressure intensity in the chamber varies in accordance with the predetermined pressure loading path required to successfully hydroform the part. The system was built, and hydroforming experiments were carried out for various micro- and meso-scale shapes, including bulge-shapes, Y-shapes, and T-shapes.
Advanced Natural Convection Cooling Designs for Light-Emitting Diode Bulb Systems
Authors: Petroski James
Published: August 2014

The movement to light-emitting diode (LED) lighting systems worldwide is accelerating quickly as energy savings and reduction in hazardous materials increase in importance. Government regulations and rapidly lowering prices help to further this trend. Today's strong drive is to replace light bulbs of common outputs (60 W, 75 W, and 100 W) without resorting to compact fluorescent (CFL) bulbs containing mercury while maintaining the standard industry bulb size and shape referred to as A19. For many bulb designs, this A19 size and shape restriction forces a small heat sink which is barely capable of dissipating heat for 60 W equivalent LED bulbs with natural convection for today's LED efficacies. 75 W and 100 W equivalent bulbs require larger sizes, some method of forced cooling, or some unusual liquid cooling system; generally none of these approaches are desirable for light bulbs from a consumer point of view. Thus, there is interest in developing natural convection cooled A19 light bulb designs for LEDs that cool far more effectively than today's current designs. Current A19 size heat sink designs typically have thermal resistances of 5–7 °C/W. This paper presents designs utilizing the effects of chimney cooling, well developed for other fields that reduce heat sink resistances by significant amounts while meeting all other requirements for bulb system design. Numerical studies and test data show performance of 3–4 °C/W for various orientations including methods for keeping the chimney partially active in horizontal orientations. Significant parameters are also studied with effects upon performance. The simulations are in good agreement with the experimental data. Such chimney-based designs are shown to enable 75 W and 100 W equivalent LED light bulb designs critical for faster penetration of LED systems into general lighting applications.
Four-Wire Bridge Measurements of Silicon van der Pauw Stress Sensors
Authors: Jaeger Richard C. , Motalab Mohammad , Hussain Safina , Suhling Jeffrey C.
Published: August 2014

Under the proper orientations and excitations, the transverse output of rotationally symmetric four-contact van der Pauw (VDP) stress sensors depends upon only the in-plane shear stress or the difference of the in-plane normal stresses on (100) silicon. In bridge-mode, each sensor requires only one four-wire measurement and produces an output voltage with a sensitivity that is 3.16 times that of the equivalent resistor rosettes or bridges, just as in the normal VDP sensor mode that requires two separate measurements. Both numerical and experimental results are presented to validate the conjectured behavior of the sensor. Similar results apply to sensors on (111) silicon. The output voltage results provide a simple mathematical expression for the offset voltage in Hall effect devices or the response of pseudo Hall-effect sensors. Bridge operation facilitates use of the VDP structure in embedded stress sensors in integrated circuits.
A Model for an Acoustically Driven Microbubble Inside a Rigid Tube
Authors: Qamar Adnan , Samtaney Ravi
Published: August 2014

A theoretical framework to model the dynamics of acoustically driven microbubble inside a rigid tube is presented. The proposed model is not a variant of the conventional Rayleigh–Plesset category of models. It is derived from the reduced Navier–Stokes equation and is coupled with the evolving flow field solution inside the tube by a similarity transformation approach. The results are computed, and compared with experiments available in literature, for the initial bubble radius of Ro = 1.5 μm and 2 μm for the tube diameter of D = 12 μm and 200 μm with the acoustic parameters as utilized in the experiments. Results compare quite well with the existing experimental data. When compared to our earlier basic model, better agreement on a larger tube diameter is obtained with the proposed coupled model. The model also predicts, accurately, bubble fragmentation in terms of acoustic and geometric parameters.
Precision Microscopic Actuations of Parabolic Cylindrical Shell Reflectors
Authors: Hu S. D. , Li H. , Tzou H. S.
Published: August 2014

An open parabolic cylindrical shell panel plays a key role in radial signal collection, reflection, and/or transmission applied to radar antennas, space reflectors, solar collectors, etc. Active vibration control can suppress unexpected fluctuation and maintain its precision surface and operations. This study aims to investigate the distributed active actuation behavior of adaptive open parabolic cylindrical shell panels using piezoelectric actuator patches. Dynamic equations of parabolic cylindrical shells laminated with piezoelectric actuator patches are presented first. Then, the actuator induced modal control force is defined based on a newly derived mode shape function. As the actuator area varies due to the curvature change, the normalized actuation effectiveness (i.e., modal control force per unit actuator area) is further evaluated. When the actuator area shrinks to infinitesimal, the expression of microscopic local modal control force is obtained to predict the spatial microscopic actuation behavior on parabolic cylindrical shells. The total control force and its three components exhibit distinct characteristics with respect to shell geometries, modes, and actuator properties. Analyzes suggest that the control force contributed by the membrane force component dominates the total actuation effect. The bending-contributed component increases with the corresponding mode number, while the membrane-contributed component decreases. Actuation effectiveness of two shell geometries, from shallow to deep, and actuator sizes are evaluated. Analysis of optimal actuator locations reveals that actuators placed at the maximal shell curvature are more effective and maximize the control effects.
Measurement of Fatigue Crack Growth Relationships in Hydrogen Gas for Pressure Swing Adsorber Vessel Steels
Authors: Somerday Brian P. , Barney Monica
Published: August 2014

Hydrogen-assisted fatigue crack growth rates (da/dN) were measured for SA516 Grade 70 steel as a function of stress-intensity factor range (ΔK) and load-cycle frequency to provide life-prediction data relevant to pressure swing adsorber (PSA) vessels. For ΔK values up to 18.5 MPa m1/2, the baseline da/dN versus ΔK relationship measured at 1 Hz in 2.8 MPa hydrogen gas represents an upper bound with respect to crack growth rates measured at lower frequency. However, at higher ΔK values, baseline da/dN data must be corrected to account for modestly higher crack growth rates at the lower frequencies relevant to PSA vessel operation.
Disregarding RBE variation in treatment plan comparison may lead to bias in favor of proton plans
Authors: Wedenberg Minna , Toma‐Dasu Iuliana
Published: August 2014

Purpose:

Currently in proton radiation therapy, a constant relative biological effectiveness (RBE) equal to 1.1 is assumed. The purpose of this study is to evaluate the impact of disregarding variations in RBE on the comparison of proton and photon treatment plans.

Methods:

Intensity modulated treatment plans using photons and protons were created for three brain tumor cases with the target situated close to organs at risk. The proton plans were optimized assuming a standard RBE equal to 1.1, and the resulting linear energy transfer (LET) distribution for the plans was calculated. In the plan evaluation, the effect of a variable RBE was studied. The RBE model used considers the RBE variation with dose, LET, and the tissue specific parameter α/β of photons. The plan comparison was based on dose distributions, DVHs and normal tissue complication probabilities (NTCPs).

Results:

Under the assumption of RBE = 1.1, higher doses to the tumor and lower doses to the normal tissues were obtained for the proton plans compared to the photon plans. In contrast, when accounting for RBE variations, the comparison showed lower doses to the tumor and hot spots in organs at risk in the proton plans. These hot spots resulted in higher estimated NTCPs in the proton plans compared to the photon plans.

Conclusions:

Disregarding RBE variations might lead to suboptimal proton plans giving lower effect in the tumor and higher effect in normal tissues than expected. For cases where the target is situated close to structures sensitive to hot spot doses, this trend may lead to bias in favor of proton plans in treatment plan comparisons.
Impact of extraneous mispositioned events on motion‐corrected brain SPECT images of freely moving animals
Authors: Angelis Georgios I. , Ryder William J. , Bashar Rezaul , Fulton Roger R. , Meikle Steven R.
Published: August 2014

Purpose:

Single photon emission computed tomography (SPECT) brain imaging of freely moving small animals would allow a wide range of important neurological processes and behaviors to be studied, which are normally inhibited by anesthetic drugs or precluded due to the animal being restrained. While rigid body motion of the head can be tracked and accounted for in the reconstruction, activity in the torso may confound brain measurements, especially since motion of the torso is more complex (i.e., nonrigid) and not well correlated with that of the head. The authors investigated the impact of mispositioned events and attenuation due to the torso on the accuracy of motion corrected brain images of freely moving mice.

Methods:

Monte Carlo simulations of a realistic voxelized mouse phantom and a dual compartment phantom were performed. Each phantom comprised a target and an extraneous compartment which were able to move independently of each other. Motion correction was performed based on the known motion of the target compartment only. Two SPECT camera geometries were investigated: a rotating single head detector and a stationary full ring detector. The effects of motion, detector geometry, and energy of the emitted photons (hence, attenuation) on bias and noise in reconstructed brain regions were evaluated.

Results:

The authors observed two main sources of bias: (a) motion‐related inconsistencies in the projection data and (b) the mismatch between attenuation and emission. Both effects are caused by the assumption that the orientation of the torso is difficult to track and model, and therefore cannot be conveniently corrected for. The motion induced bias in some regions was up to 12% when no attenuation effects were considered, while it reached 40% when also combined with attenuation related inconsistencies. The detector geometry (i.e., rotating vs full ring) has a big impact on the accuracy of the reconstructed images, with the full ring detector being more advantageous.

Conclusions:

Motion‐induced inconsistencies in the projection data and attenuation/emission mismatch are the two main causes of bias in reconstructed brain images when there is complex motion. It appears that these two factors have a synergistic effect on the qualitative and quantitative accuracy of the reconstructed images.
Evaluation of adaptive dynamic range optimization in adverse listening conditions for cochlear implants
Authors: Ali Hussnain , Hazrati Oldooz , Tobey Emily A. , Hansen John H. L
Published: August 2014

The aim of this study is to investigate the effect of Adaptive Dynamic Range Optimization (ADRO) on speech identification for cochlear implant (CI) users in adverse listening conditions. In this study, anechoic quiet, noisy, reverberant, noisy reverberant, and reverberant noisy conditions are evaluated. Two scenarios are considered when modeling the combined effects of reverberation and noise: (a) noise is added to the reverberant speech, and (b) noisy speech is reverberated. CI users were tested in different listening environments using IEEE sentences presented at 65 dB sound pressure level. No significant effect of ADRO processing on speech intelligibility was observed.
Manipulation of receptor oligomerization as a strategy to inhibit signaling by TNF superfamily members
Authors: Warren Julia T. , Nelson Christopher A. , Decker Corinne E. , Zou Wei , Fremont Daved H. , Teitelbaum Steven L.
Published: August 2014

A three-in-one cytokine engineered to bind to its receptor with high affinity, but prevent receptor activation, may be an effective therapy for osteoporosis.
Science Signaling
Podcast: 19 August 2014
Authors: Ghosh Sourav , Rothlin Carla V. , VanHook Annalisa M.
Published: August 2014

Atypical protein kinase C is a promising target for treating glioblastoma.
A Leg Up for Transplant
Authors: Colmone Angela C.
Published: August 2014

Tacrolimus-encapsulated hydrogels improve long-term survival of a vascularized composite allograft.
Synchronizing Metabolism, Physiology, and Behavior Through mTORC1 and FGF21
Authors: Berndt Jason D.
Published: August 2014

Liver glutamine metabolism stimulates production of FGF21 to link metabolism with organismal physiology and behavior.
Macromolecular assembly of the adaptor SLP-65 at intracellular vesicles in resting B cells
Authors: Engelke Michael , Pirkuliyeva Sona , Kühn Julius , Wong Leo , Boyken Janina , Herrmann Nadine , Becker Stefan , Griesinger Christian , Wienands Jürgen
Published: August 2014

Optimal B cell activation requires the recruitment of a vesicle-associated adaptor protein to the B cell receptor complex.
Changes in Pneumococcal Serotypes and Antimicrobial Resistance after Introduction of the 13-Valent Conjugate Vaccine in the United States
Authors: Richter Sandra S. , Diekema Daniel J. , Heilmann Kristopher P. , Dohrn Cassie L. , Riahi Fathollah , Doern Gary V.
Published: August 2014

Ongoing surveillance for
Streptococcus pneumoniae
is needed to assess the impact of the pneumococcal conjugate vaccine introduced in 2010 (PCV13). Forty-two U.S. centers submitted
S. pneumoniae
isolates between 1 October 2012 and 31 March 2013. Susceptibility testing was performed by use of a broth dilution method as recommended by the Clinical and Laboratory Standards Institute. Serotyping was performed by multiplex PCR and the Quellung reaction. Multidrug resistance (MDR) was defined as nonsusceptibility to penicillin (PNSP; MIC ≥ 0.12 μg/ml) combined with resistance to ≥2 non-β-lactam antimicrobials. Penicillin-resistant
S. pneumoniae
(PRSP) was defined as a penicillin MIC of ≥2 μg/ml. For the 1,498 isolates collected during 2012-13, the PRSP and MDR rates were 14.2 and 21.0%, respectively. These percentages were lower than rates obtained in a surveillance study conducted 4 years earlier in 2008-09 (17.0 and 26.6%, respectively). The most common serotypes identified in 2012-13 were 3, 35B, and 19A, each representing 9 to 10% of all isolates. The largest percentage of PNSP in 2012-13 were found in serotypes 35B (24.8%), 19A (23.5%), and 15A (10.3%). Predominant PRSP serotypes were 19A (54.5%), 35B (28.2%), and 19F (7.0%). Major MDR serotypes were 19A (38.5%), 15A (16.9%), 6C (8.3%), and 35B (6.4%). The change in prevalence of PCV13 serotypes (43.4 to 27.1%) was primarily due to a decrease in serotype 19A strains, i.e., 22% of all strains in 2008-09 to 10% of all strains in 2012-13. Among the PNSP subset, serotypes showing a proportional increase were 35B, 15B, and 23B. Among MDR strains, the largest proportional increases were observed in serotypes 35B, 15B, and 23A.
Antimicrobial Resistance in Salmonella enterica Serovar Typhi Isolates from Bangladesh, Indonesia, Taiwan, and Vietnam
Authors: Chiou Chien-Shun , Lauderdale Tsai-Ling , Phung Dac Cam , Watanabe Haruo , Kuo Jung-Che , Wang Pei-Jen , Liu Yen-Yi , Liang Shiu-Yun , Chen Pei-Chen
Published: August 2014

We characterized
Salmonella enterica
serovar Typhi isolates from Bangladesh, Indonesia, Taiwan, and Vietnam to investigate their genetic relatedness and antimicrobial resistance. The isolates from Bangladesh and Vietnam were genetically closely related but were distant from those from Indonesia and Taiwan. All but a few isolates from Indonesia and Taiwan were susceptible to all antimicrobials tested. The majority of isolates from Bangladesh and Vietnam were multidrug resistant (MDR) and belonged to the widespread haplotype H58 clone. IncHI1 plasmids were detected in all MDR
S
. Typhi isolates from Vietnam but in only 15% of MDR isolates from Bangladesh. Resistance genes in the majority of MDR
S
. Typhi isolates from Bangladesh should reside in the chromosome. Among the isolates from Bangladesh, 82% and 40% were resistant to various concentrations of nalidixic acid and ciprofloxacin, respectively. Several resistance mechanisms, including alterations in gyrase A, the presence of QnrS, and enhanced efflux pumps, were involved in the reduced susceptibility and resistance to fluoroquinolones. Intensive surveillance is necessary to monitor the spread of chromosome-mediated MDR and fluoroquinolone-resistant
S
. Typhi emerging in Bangladesh.
Association between Vancomycin Trough Concentration and Area under the Concentration-Time Curve in Neonates
Authors: Frymoyer Adam , Hersh Adam L. , El-Komy Mohammed H. , Gaskari Shabnam , Su Felice , Drover David R. , Van Meurs Krisa
Published: August 2014

National treatment guidelines for invasive methicillin-resistant
Staphylococcus aureus
(MRSA) infections recommend targeting a vancomycin 24-h area under the concentration-time curve (AUC
0–24
)-to-MIC ratio of >400. The range of vancomycin trough concentrations that best predicts an AUC
0–24
of >400 in neonates is not known. This understanding would help clarify target trough concentrations in neonates when treating MRSA. A retrospective chart review from a level III neonatal intensive care unit was performed to identify neonates treated with vancomycin over a 5-year period. Vancomycin concentrations and clinical covariates were utilized to develop a one-compartment population pharmacokinetic model and examine the relationships between trough and AUC
0–24
in the study neonates. Monte Carlo simulations were performed to examine the effect of dose, postmenstrual age (PMA), and serum creatinine level on trough and AUC
0–24
achievement. A total of 1,702 vancomycin concentrations from 249 neonates were available for analysis. The median (interquartile range) PMA was 39 weeks (32 to 42 weeks) and weight was 2.9 kg (1.6 to 3.7 kg). Vancomycin clearance was predicted by weight, PMA, and serum creatinine level. At a trough of 10 mg/liter, 89% of the study neonates had an AUC
0–24
of >400. Monte Carlo simulations demonstrated that troughs ranging from 7 to 11 mg/liter were highly predictive of an AUC
0–24
of >400 across a range of PMA, serum creatinine levels, and vancomycin doses. However, a trough of ≥10 mg/liter was not readily achieved in most simulated subgroups using routine starting doses. Higher starting doses frequently resulted in troughs of >20 mg/liter. A vancomycin trough of ∼10 mg/liter is likely adequate for most neonates with invasive MRSA infections based on considerations of the AUC
0–24
. Due to pharmacokinetic and clinical heterogeneity in neonates, consistently achieving this target vancomycin exposure with routine starting doses is difficult. More robust clinical dosing support tools are needed to help clinicians with dose individualization.
Validation of a Model To Predict the Risk of Nephrotoxicity in Patients Receiving Colistin
Authors: Phe Kady , Johnson Michael L. , Palmer Hannah R. , Tam Vincent H.
Published: August 2014

Despite concerns about its nephrotoxicity, colistin often remains the only effective agent for treating multidrug-resistant Gram-negative infections. Published studies have reported a wide range of nephrotoxicity risk factors. To assess the clinical utility of various models, we compared their performances for predicting the risk of nephrotoxicity. We identified a model demonstrating reasonable overall risk assessment, with an observed/expected ratio of 1.29 (95% confidence interval [CI], 0.68 to 1.90) and a positive predictive value of 87.5% for identifying patients at high risk of developing nephrotoxicity.
EUCAST Testing of Isavuconazole Susceptibility in Aspergillus: Comparison of Results for Inoculum Standardization Using Conidium Counting versus Optical Density
Authors: Arendrup Maiken Cavling , Howard Susan , Lass-Flörl Cornelia , Mouton Johan W. , Meletiadis Joseph , Cuenca-Estrella Manuel
Published: August 2014

The EUCAST E.DEF9.1 standard recommends standardization of the inoculum concentration by conidium counting using a hemocytometer rather than a spectrophotometer. In this study, we investigated whether the choice of these methods influenced isavuconazole MICs. A blinded collection of 30 molecularly characterized azole-resistant isolates and 10 wild-type
Aspergillus fumigatus
isolates was shared with four different laboratories. Additionally, each laboratory selected approximately 100
A. fumigatus
isolates and 50 isolates each of
A. flavus
,
A. nidulans
,
A. niger
, and
A. terreus
(1,237 isolates in total). Three laboratories (laboratories 1 to 3) used conidium counting. One laboratory standardized the inoculum using a spectrophotometer (that is, by use of the optical density [OD]) and is referred to as the OD laboratory. Correlation coefficients, intraclass correlation coefficients, and essential agreement were calculated, and 2-log-unit differences were assessed (paired
t
test). The MIC range for the blinded collection was 0.25 to 16 mg/liter, and a 1-dilution-step difference between the MIC
50
and MIC
90
across the four laboratories was detected and a 2-dilution-step difference between the modal MICs was detected. Compared to the results for laboratories 1 and 2, a significant correlation was found for the OD laboratory MIC data (correlation coefficients, 0.85 and 0.93, respectively; intraclass correlation coefficients, 0.88 and 0.96, respectively). The number of mutant isolates whose MICs overlapped those of the wild-type isolates was the lowest for the OD laboratory (14/30 [46.7%] mutant isolates), whereas the numbers were 18/30 (60%) isolates for laboratory 1, 17/30 (56.7%) isolates for laboratory 2, and 21/30 (70%) isolates for laboratory 3. For the
A. flavus
,
A. fumigatus
,
A. nidulans
,
A. niger
, and
A. terreus
isolates, comparative analysis again defined the MIC distributions from the OD laboratory to be in excellent agreement with those from laboratories 1 and 2 across all five
Aspergillus
spp. The findings suggest that EUCAST testing using OD determination is an appropriate alternative for standardization of
Aspergillus
inoculum concentrations.
Silver Resistance Genes Are Overrepresented among Escherichia coli Isolates with CTX-M Production
Authors: Sütterlin Susanne , Edquist Petra , Sandegren Linus , Adler Marlen , Tängdén Thomas , Drobni Mirva , Olsen Björn , Melhus Åsa
Published: August 2014

Members of the
Enterobacteriaceae
with extended-spectrum beta-lactamases (ESBLs) of the CTX-M type have disseminated rapidly in recent years and have become a threat to public health. In parallel with the CTX-M type expansion, the consumption and widespread use of silver-containing products has increased. To determine the carriage rates of silver resistance genes in different
Escherichia coli
populations, the presence of three silver resistance genes (
silE
,
silP
, and
silS
) and genes encoding CTX-M-, TEM-, and SHV-type enzymes were explored in
E. coli
isolates of human (
n
= 105) and avian (
n
= 111) origin. The antibiotic profiles were also determined. Isolates harboring CTX-M genes were further characterized, and phenotypic silver resistance was examined. The
silE
gene was present in 13 of the isolates. All of them were of human origin. Eleven of these isolates harbored ESBLs of the CTX-M type (
P
= 0.007), and eight of them were typed as CTX-M-15 and three as CTX-M-14. None of the
silE
-positive isolates was related to the O25b-ST131 clone, but 10 out of 13 belonged to the ST10 or ST58 complexes. Phenotypic silver resistance (silver nitrate MIC > 512 mg/liter) was observed after silver exposure in 12 of them, and a concomitant reduced susceptibility to piperacillin-tazobactam developed in three. In conclusion, 12% of the human
E. coli
isolates but none of the avian isolates harbored silver resistance genes. This indicates another route for or level of silver exposure for humans than that caused by common environmental contamination. Since
silE
-positive isolates were significantly more often found in CTX-M-positive isolates, it is possible that silver may exert a selective pressure on CTX-M-producing
E. coli
isolates.
Surveillance of Viruses in Wild Fish Populations in Areas around the Gulf of Cadiz (South Atlantic Iberian Peninsula)
Authors: Moreno Patricia , Olveira José G. , Labella Alejandro , Cutrín Juan Manuel , Baro Jorge C. , Borrego Juan Jose , Dopazo Carlos P.
Published: August 2014

This report describes a viral epidemiological study of wild fish around the Gulf of Cadiz (southwestern Iberian Peninsula) and is focused on infectious pancreatic necrosis virus (IPNV), viral hemorrhagic septicemia virus (VHSV), and viral nervous necrosis virus (VNNV). One fish species (
Chelon labrosus
) was sampled inside the gulf, at the mouth of the San Pedro River. Another 29 were sampled, in three oceanographic campaigns, at sites around the Bay of Cadiz. The fish were processed individually and subjected to isolation in cell culture and molecular diagnosis. VHSV was not isolated from any species. Thirteen IPNV-type isolates were obtained from barracuda (
Sphyraena sphyraena
), axillary seabream (
Pagellus acarne
), common two-banded seabream (
Diplodus vulgaris
), common pandora (
P. erythrinus
), Senegal seabream (
D. bellottii
), and surmullet (
Mullus surmuletus
). Six VNNV isolates were obtained from axillary seabream, common pandora, black seabream (
Spondyliosoma cantharus
), red mullet (
Mullet barbatus
), Lusitanian toadfish (
Halobatrachus didactylus
), and tub gurnard (
Chelidonichtys lucerna
). In the river mouth, viruses were detected only after reamplification, obtaining prevalence percentages of IPNV and VNNV (44.4 and 63.0%, respectively) much higher than those observed in the oceanographic campaigns (25.7 and 19.6%, respectively). The opposite results were obtained in the case of VHSV after reamplification: 11.1% in the river mouth and 43.6% in the oceanic locations. Analyzing the results with respect to the proximity of the sampling sites to the coast, an anthropogenic influence on wild fish is suggested and discussed. The type of viruses and the presence of natural reassortants are also discussed.
Homeostasis of N-α-Terminal Acetylation of EsxA Correlates with Virulence in Mycobacterium marinum
Authors: Mba Medie Felix , Champion Matthew M. , Williams Emily A. , Champion Patricia A. DiGiuseppe
Published: August 2014

The mycobacterial Esx-1 (ESAT-6 system 1) exporter translocates virulence factors across the cytoplasmic membrane to the cell wall, cell surface, and the bacteriological medium
in vitro
. The mechanisms underlying substrate targeting to distinct locations are unknown. Several Esx-1 substrates are N-α-terminally acetylated. The role of this rare modification in bacteria is unclear. We sought to identify genes required for Esx-1 substrate modification, transport, and localization. Pathogenic mycobacteria lyse
Acanthamoeba castellanii
in an Esx-1-dependent manner. We conducted a genetic screen to identify
Mycobacterium marinum
strains which failed to lyse amoebae. We identified a noncytotoxic
M. marinum
strain with a transposon insertion in a predicted N-α-terminal acetyltransferase not previously linked to mycobacterial pathogenesis. Disruption of this gene led to attenuation of virulence, failure to induce a type I interferon response during macrophage infection, and loss of hemolytic activity. The major Esx-1 substrates, EsxA and EsxB, were exported to the cell surface, but only low levels were released into the bacteriological medium. The balance of EsxA N-α-terminal acetylation was disrupted, resulting in a mycobacterial strain in which surface-associated EsxA was hyperacetylated. Genetic complementation completely restored Esx-1 function and the levels of N-α-terminally acetylated EsxA on the surface but restored only low levels of Esx-1 substrates in the bacteriological medium. Our results reveal a novel gene required for mycobacterial Esx-1 export. Our findings indicate that maintaining the homeostasis of Esx-1 substrate N-α-terminal acetylation is essential for Esx-1-mediated virulence. We propose an inverse correlation between EsxA acetylation and virulence.
Dynamic Changes in the Streptococcus pneumoniae Transcriptome during Transition from Biofilm Formation to Invasive Disease upon Influenza A Virus Infection
Authors: Pettigrew Melinda M. , Marks Laura R. , Kong Yong , Gent Janneane F. , Roche-Hakansson Hazeline , Hakansson Anders P.
Published: August 2014

Streptococcus pneumoniae
is a leading cause of infectious disease globally. Nasopharyngeal colonization occurs in biofilms and precedes infection. Prior studies have indicated that biofilm-derived pneumococci are avirulent. However, influenza A virus (IAV) infection releases virulent pneumococci from biofilms
in vitro
and
in vivo
. Triggers of dispersal include IAV-induced changes in the nasopharynx, such as increased temperature (fever) and extracellular ATP (tissue damage). We used whole-transcriptome shotgun sequencing (RNA-seq) to compare the
S. pneumoniae
transcriptome in biofilms, bacteria dispersed from biofilms after exposure to IAV, febrile-range temperature, or ATP, and planktonic cells grown at 37°C. Compared with biofilm bacteria, actively dispersed
S. pneumoniae
, which were more virulent in invasive disease, upregulated genes involved in carbohydrate metabolism. Enzymatic assays for ATP and lactate production confirmed that dispersed pneumococci exhibited increased metabolism compared to those in biofilms. Dispersed pneumococci also upregulated genes associated with production of bacteriocins and downregulated colonization-associated genes related to competence, fratricide, and the transparent colony phenotype. IAV had the largest impact on the pneumococcal transcriptome. Similar transcriptional differences were also observed when actively dispersed bacteria were compared with avirulent planktonic bacteria. Our data demonstrate complex changes in the pneumococcal transcriptome in response to IAV-induced changes in the environment. Our data suggest that disease is caused by pneumococci that are primed to move to tissue sites with altered nutrient availability and to protect themselves from the nasopharyngeal microflora and host immune response. These data help explain pneumococcal virulence after IAV infection and have important implications for studies of
S. pneumoniae
pathogenesis.
Psychosis with Huntington's disease: role of antipsychotic medications
Authors: Ding Jonathan , Gadit Amin Muhammad
Published: August 2014

This is a case of a 60-year-old man who presented with a 6-month history of increasing agitation and emotional volatility. His family brought him to the emergency room as they were concerned about his threatening and aggressive behaviour. The patient was initially incoherent and uncooperative. During the interview, the patient's family revealed that he had a previous diagnosis of Huntington's disease; there was also a family history of personality changes preceding Huntington's chorea. The patient was admitted to the psychiatric inpatient unit and started on low-dose risperidone. Consequently, there was marked improvement in his symptoms. Subsequent cognitive tests revealed deficits in multiple domains. After a month, the patient was discharged to a community home in stable state.
Parathyroid carcinoma, a rare cause of primary hyperparathyroidism
Authors: Alperstein Adam , Bhayani Rajendra
Published: August 2014

A 45 year-old woman who presented with non-specific neck and shoulder pain, was found to have mild hypercalcaemia, markedly elevated parathyroid hormone levels, and an irregular parathyroid gland on imaging. The patient underwent a parathyroidectomy and the pathology report came back positive for parathyroid carcinoma with muscular invasion. Parathyroid carcinoma is an exceptionally rare cause of primary hyperparathyroidism and can have a poor prognosis due to metastases and a high propensity to recur after resection. Reports of non-functioning parathyroid carcinomas tend to behave even more aggressively. Repeat imaging on this patient showed residual cancer present, so the patient underwent a second surgery with radical neck dissection and has since been doing very well postoperatively. Diagnosis and treatment is challenging and it is critical to continuously follow-up for recurrent disease.
Transient cefuroxime/metronidazole treatment induced factor V antibodies
Authors: Van den Berg Sjoerd Adrianus Antonius , Verwer Patricia E , Idema René N , Van Guldener Coen
Published: August 2014

A 29-year-old patient presented with an appendicular infiltrate, initially treated with intravenous antibiotics, but later requiring percutaneous drainage. Both prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged on 3 days of antibiotic treatment and unresponsive to vitamin K or prothrombin complex concentrate. Laboratory investigation ultimately showed reduced factor V activity and factor V antibodies. In contrast to previously described cases of factor V antibodies, PT and aPTT were only mildly prolonged and residual factor V activity was still >20%. Draining of the abscess did not induce significant bleeding. Afterwards, no haemostatic medication was required. The patient was discharged from the hospital without complications. One week after cessation of the antibiotic treatment, PT and aPTT were within normal range again, with a factor V activity level of 36%. In conclusion, we present a patient with transient factor V antibodies, induced by antibiotics, without clinical bleeding tendency.
Post-traumatic iridodialysis, crystalline dislocation and vitreous haemorrhage: how to manage
Authors: Loiudice Pasquale , Casini Giamberto
Published: August 2014

A 66-year-old man, while taking care of his horse, sustained a blunt, non-penetrating injury to the right side of his face, which damaged his eye. On slit lamp examination, iris dialysis and crystalline dislocation in the vitreous chamber were observed. On presentation, his best correct visual acuity was hand motion. A 23 G vitrectomy and subsequently an iris reconstruction and a glued intraocular lens implant were performed. Visual acuity reached +0.1 logMAR 1 month after surgery and remained stable after 12 months’ follow-up.
Haemophagocytic lymphohistiocytosis associated with coccidiomycosis
Authors: Ramsi Musaab , Alvira Cristina , Purohit Prashant , Cornfield David
Published: August 2014

Haemophagocytic lymphohistiocytosis (HLH) is a rapidly fatal disease caused by dysregulated histiocytes leading to an excessive inflammatory reaction. While genetic forms of HLH exist, the most common form is acquired, frequently associated with infection. Here we report the first case of HLH associated with a coccidiomycosis infection. This patient is a 13-year-old previously healthy boy who presented with a flu-like illness, which rapidly progressed to refractory shock, severe ARDS, multiorgan failure and death despite maximal medical therapy, including broad-spectrum antibiotics to treat well-established causes of acquired HLH. Autopsy findings revealed the diagnosis of HLH in the setting of pulmonary coccidiomycosis. Antifungal therapy should be considered in cases of acquired HLH when the underlying aetiology is not clear.
Mislaid dentures: a cause for unusual presentation of bilateral vocal cord palsy
Authors: Vallamkondu Vamsidhar , Gatenby Andrew , Shakeel Muhammad , Hussain Akhtar
Published: August 2014

An 81-year-old man was referred urgently to the head and neck clinic with symptoms of worsening dysphagia, dysphonia and weight loss. He had a history of chronic lymphocytic leukaemia. On full ear, nose and throat examination, he was found to have fixed vocal cords with pooling of saliva in the bilateral pyriform fossa. Hypopharyngeal malignancy was suspected and further imaging was performed. Imaging also raised the suspicion of malignancy in the hypopharynx. Rigid endoscopic examination under general anaesthesia was carried out which revealed an impacted denture in the cricopharynx and upper oesophagus. The patient was aware of his loss of dentures 3 months ago (corresponds to the onset of his symptoms) but felt that he had mislaid them and had never mentioned this to anyone. We present a case highlighting a delay in diagnosis, a missed diagnosis on CT scan and an unusual presentation leading to bilateral vocal cord paresis.
Mid- and long-term outcomes of carotid-cavernous fistula endovascular management with Onyx and n-BCA: experience of a single tertiary center
Authors: Barber Sean M , Rangel-Castilla Leonardo , Zhang Y Jonathan , Klucznik Richard , Diaz Orlando
Published: August 2014

Introduction

Endovascular therapy is the preferred treatment for most carotid-cavernous fistulas (CCFs). Early reports have documented excellent initial clinical and radiographic outcomes after embolization of CCFs with Onyx or n-butyl cyanoacrylate (n-BCA), but little evidence is available about the long-term durability of this technique.

Objective

To characterize the long-term durability of CCF liquid embolization.

Methods

The authors retrospectively reviewed a database of 24 CCFs in 21 consecutive patients who underwent Onyx or n-BCA embolization of a CCF from 2006 to 2013 at our institution.

Results

A total of 25 Onyx or n-BCA embolization procedures were attempted and 24 successfully completed during the study, resulting in complete or near-complete occlusion by the end of the study in all 24 CCFs (obliteration success, 100%). Attempted embolization in a single CCF failed initially, but was performed successfully at a later date by a different approach. None of the 24 CCFs recanalized, regrew, or required any further treatment subsequent to Onyx or n-BCA embolization throughout a mean 12.4 months of angiographic follow-up (range 1–36 months). Clinically significant complications were seen in three embolization procedures, including cranial nerve palsies (n=1), embolic infarct (n=1), and intraperitoneal hemorrhage (n=1).

Conclusions

Early evidence has indicated that endovascular embolization with Onyx is relatively safe and effective at achieving an initial angiographic cure for CCFs. Results of our series suggest that angiographic and clinical outcomes of Onyx and n-BCA embolization remain stable at mid- and long-term follow-up.