bluuebunny/crossref_metadata_2025 huggingface dataset:
PtaRHE1, a Populus tremula × Populus alba RING‐H2 protein of the ATL family, has a regulatory role in secondary phloem fibre development
Authors: Baldacci‐Cresp Fabien , Moussawi Jihad , Leplé Jean‐Charles , Van Acker Rebecca , Kohler Annegret , Candiracci Julie , Twyffels Laure , Spokevicius Antanas V. , Bossinger Gerd , Laurans Françoise , Brunel Nicole , Vermeersch Marjorie , Boerjan Wout , El Jaziri Mondher , Baucher Marie
Published: April 2015

REALLY INTERESTING NEW GENE (RING) proteins play important roles in the regulation of many processes by recognizing target proteins for ubiquitination. Previously, we have shown that the expression of PtaRHE1, encoding a Populus tremula × Populus alba RING‐H2 protein with E3 ubiquitin ligase activity, is associated with tissues undergoing secondary growth. To further elucidate the role of PtaRHE1 in vascular tissues, we have undertaken a reverse genetic analysis in poplar. Within stem secondary vascular tissues, PtaRHE1 and its corresponding protein are expressed predominantly in the phloem. The downregulation of PtaRHE1 in poplar by artificial miRNA triggers alterations in phloem fibre patterning, characterized by an increased portion of secondary phloem fibres that have a reduced cell wall thickness and a change in lignin composition, with lower levels of syringyl units as compared with wild‐type plants. Following an RNA‐seq analysis, a biological network involving hormone stress signalling, as well as developmental processes, could be delineated. Several candidate genes possibly associated with the altered phloem fibre phenotype observed in amiRPtaRHE1 poplar were identified. Altogether, our data suggest a regulatory role for PtaRHE1 in secondary phloem fibre development.
Efficacy of Mechanical versus Non‐Mechanical Sterile Preoperative Skin Preparation With Chlorhexidine Gluconate 4% Solution
Authors: Davids Benjamin I. , Davidson Megan J. , TenBroeck Saundra H. , Colahan Patrick T. , Oli Monika W.
Published: April 2015

Objective

To compare the efficacy of sterile preoperative skin antisepsis using either a 5‐minute mechanical preparation or 5‐minute non‐mechanical preparation with chlorhexidine gluconate 4% solution.

Study Design

Matched design, ANOVA.

Animals

Healthy adult Thoroughbred horses (n = 30).

Methods

Each horse had both surgical preparation methods randomly assigned to identical sites on the left or right upper thigh. Prepared sites were sampled and cultured for bacteria after each preparation step.

Results

Mechanical and non‐mechanical preparation techniques significantly reduced bacteria isolated from surface swab samples compared with samples taken from unprepared skin and after the preliminary rough prepared skin (P < 0.05). No difference in the number of skin‐associated bacteria was detected between the mechanical and non‐mechanical sterile preoperative preparation techniques (P = 0.77). Ten species of bacteria were identified by 16s PCR after final skin preparation.

Conclusions

Pre‐surgical skin preparation without repeated mechanical scrubbing using chlorhexidine gluconate 4% solution (total contact time, 225 seconds) is effective in reducing bacterial counts.
Pseudomonas aeruginosa uses T3SS to inhibit diabetic wound healing
Authors: Goldufsky Josef , Wood Stephen J. , Jayaraman Vijayakumar , Majdobeh Omar , Chen Lin , Qin Shanshan , Zhang Chunxiang , DiPietro Luisa A. , Shafikhani Sasha H.
Published: April 2015

Diabetic foot ulcers are responsible for more hospitalizations than any other complication of diabetes. Bacterial infection is recognized as an important factor associated with impaired healing in diabetic ulcers. Pseudomonas aeruginosa is the most frequently detected Gram‐negative pathogen in diabetic ulcers. P. aeruginosa infection has been shown to impair healing in diabetic wounds in a manner that correlates with its ability to form biofilm. While the majority of infections in diabetic ulcers are biofilm associated, 33% of infections are nonbiofilm in nature. P. aeruginosa is the most prevalent Gram‐negative pathogen in all diabetic wound types, which suggests that the deleterious impact of P. aeruginosa on healing in diabetic wounds goes beyond its ability to form biofilm and likely involves other factors. The Type III Secretion System (T3SS) virulence structure is required for the pathogenesis of all P. aeruginosa clinical isolates, suggesting that it may also play a role in the inhibition of wound repair in diabetic skin ulcers. We evaluated the role of T3SS in mediating P. aeruginosa–induced tissue damage in the wounds of diabetic mice. Our data demonstrate that P. aeruginosa establishes a robust and persistent infection in diabetic wounds independent of its ability to form biofilm and causes severe wound damage in a manner that primarily depends on its T3SS.
Online updating of context‐aware landmark detectors for prostate localization in daily treatment CT images
Authors: Dai Xiubin , Gao Yaozong , Shen Dinggang
Published: April 2015

Purpose:

In image guided radiation therapy, it is crucial to fast and accurately localize the prostate in the daily treatment images. To this end, the authors propose an online update scheme for landmark‐guided prostate segmentation, which can fully exploit valuable patient‐specific information contained in the previous treatment images and can achieve improved performance in landmark detection and prostate segmentation.

Methods:

To localize the prostate in the daily treatment images, the authors first automatically detect six anatomical landmarks on the prostate boundary by adopting a context‐aware landmark detection method. Specifically, in this method, a two‐layer regression forest is trained as a detector for each target landmark. Once all the newly detected landmarks from new treatment images are reviewed or adjusted (if necessary) by clinicians, they are further included into the training pool as new patient‐specific information to update all the two‐layer regression forests for the next treatment day. As more and more treatment images of the current patient are acquired, the two‐layer regression forests can be continually updated by incorporating the patient‐specific information into the training procedure. After all target landmarks are detected, a multiatlas random sample consensus (multiatlas RANSAC) method is used to segment the entire prostate by fusing multiple previously segmented prostates of the current patient after they are aligned to the current treatment image. Subsequently, the segmented prostate of the current treatment image is again reviewed (or even adjusted if needed) by clinicians before including it as a new shape example into the prostate shape dataset for helping localize the entire prostate in the next treatment image.

Results:

The experimental results on 330 images of 24 patients show the effectiveness of the authors’ proposed online update scheme in improving the accuracies of both landmark detection and prostate segmentation. Besides, compared to the other state‐of‐the‐art prostate segmentation methods, the authors’ method achieves the best performance.

Conclusions:

By appropriate use of valuable patient‐specific information contained in the previous treatment images, the authors’ proposed online update scheme can obtain satisfactory results for both landmark detection and prostate segmentation.
Abacavir, an anti–HIV-1 drug, targets TDP1-deficient adult T cell leukemia
Authors: Tada Kohei , Kobayashi Masayuki , Takiuchi Yoko , Iwai Fumie , Sakamoto Takashi , Nagata Kayoko , Shinohara Masanobu , Io Katsuhiro , Shirakawa Kotaro , Hishizawa Masakatsu , Shindo Keisuke , Kadowaki Norimitsu , Hirota Kouji , Yamamoto Junpei , Iwai Shigenori , Sasanuma Hiroyuki , Takeda Shunichi , Takaori-Kondo Akifumi
Published: April 2015

An anti–HIV-1 drug is found to destroy leukemia cells in adults.
Characteristic signatures of quantum criticality driven by geometrical frustration
Authors: Tokiwa Yoshifumi , Stingl Christian , Kim Moo-Sung , Takabatake Toshiro , Gegenwart Philipp
Published: April 2015

Thermodynamic measurements on the Kondo lattice CeRhSn indicate a quantun critical point driven by geometrical frustration.
The matrikine N-α-PGP couples extracellular matrix fragmentation to endothelial permeability
Authors: Hahn Cornelia S. , Scott David W. , Xu Xin , Roda Mojtaba Abdul , Payne Gregory A. , Wells J. Michael , Viera Liliana , Winstead Colleen J. , Bratcher Preston , Sparidans Rolf W. , Redegeld Frank A. , Jackson Patricia L. , Folkerts Gert , Blalock J. Edwin , Patel Rakesh P. , Gaggar Amit
Published: April 2015

Organ tissue breakdown can induce vascular leak in lung injury.
Evaluation of the Ion Torrent Personal Genome Machine for Gene-Targeted Studies Using Amplicons of the Nitrogenase Gene
nifH
Authors: Zhang Bangzhou , Penton C. Ryan , Xue Chao , Wang Qiong , Zheng Tianling , Tiedje James M.
Published: April 2015

The sequencing chips and kits of the Ion Torrent Personal Genome Machine (PGM), which employs semiconductor technology to measure pH changes in polymerization events, have recently been upgraded. The quality of PGM sequences has not been reassessed, and results have not been compared in the context of a gene-targeted microbial ecology study. To address this, we compared sequence profiles across available PGM chips and chemistries and with 454 pyrosequencing data by determining error types and rates and diazotrophic community structures. The PGM was then used to assess differences in
nifH
-harboring bacterial community structure among four corn-based cropping systems. Using our suggested filters from mock community analyses, the overall error rates were 0.62, 0.36, and 0.39% per base for chips 318 and 314 with the 400-bp kit and chip 318 with the Hi-Q chemistry, respectively. Compared with the 400-bp kit, the Hi-Q kit reduced indel rates by 28 to 59% and produced one to seven times more reads acceptable for downstream analyses. The PGM produced higher frameshift rates than pyrosequencing that were corrected by the RDP FrameBot tool. Significant differences among platforms were identified, although the diversity indices and overall site-based conclusions remained similar. For the cropping system analyses, a total of 6,182 unique NifH operational taxonomic units at 5% amino acid dissimilarity were obtained. The current crop type, as well as the crop rotation history, significantly influenced the composition of the soil diazotrophic community detected.
Effects of Colonization of the Roots of Domestic Rice (Oryza sativa L. cv. Amaroo) by Burkholderia pseudomallei
Authors: Prasertsincharoen Noppadol , Constantinoiu Constantin , Gardiner Christopher , Warner Jeffrey , Elliman Jennifer
Published: April 2015

Burkholderia pseudomallei
is a saprophytic bacterium that causes melioidosis and is often isolated from rice fields in Southeast Asia, where the infection incidence is high among rice field workers. The aim of this study was to investigate the relationship between this bacterium and rice through growth experiments where the effect of colonization of domestic rice (
Oryza sativa
L. cv Amaroo) roots by
B. pseudomallei
could be observed. When
B. pseudomallei
was exposed to surface-sterilized seeds, the growth of both the root and the aerosphere was retarded compared to that in controls. The organism was found to localize in the root hairs and endodermis of the plant. A biofilm formed around the root and root structures that were colonized. Growth experiments with a wild rice species (
Oryza meridionalis
) produced similar retardation of growth, while another domestic cultivar (
O. sativa
L. cv Koshihikari) did not show retarded growth. Here we report
B. pseudomallei
infection and inhibition of
O. sativa
L. cv Amaroo, which might provide insights into plant interactions with this important human pathogen.
Recent Emergence of Escherichia coli with Cephalosporin Resistance Conferred by
bla
CTX-M
on Washington State Dairy Farms
Authors: Davis Margaret A. , Sischo William M. , Jones Lisa P. , Moore Dale A. , Ahmed Sara , Short Diana M. , Besser Thomas E.
Published: April 2015

Enterobacteriaceae
-associated
bla
CTX-M
genes have become globally widespread within the past 30 years. Among isolates from Washington State cattle,
Escherichia coli
strains carrying
bla
CTX-M
(CTX-M
E. coli
strains) were absent from a set of 2008 isolates but present in a set of isolates from 2011. On 30 Washington State dairy farms sampled in 2012, CTX-M
E. coli
prevalence was significantly higher on eastern than on northwestern Washington farms, on farms with more than 3,000 adult cows, and on farms that recently received new animals. The addition of fresh bedding to calf hutches at least weekly and use of residual fly sprays were associated with lower prevalence of CTX-M
E. coli
. In Washington State, the occurrence of human pathogens carrying
bla
CTX-M
genes preceded the emergence of
bla
CTX-M
-associated
E. coli
in cattle, indicating that these resistance determinants and/or their bacterial hosts may have emerged in human populations prior to their dissemination to cattle populations.
Dynamics of Escherichia coli Virulence Factors in Dairy Herds and Farm Environments in a Longitudinal Study in the United States
Authors: Lambertini Elisabetta , Karns Jeffrey S. , Van Kessel Jo Ann S. , Cao Huilin , Schukken Ynte H. , Wolfgang David R. , Smith Julia M. , Pradhan Abani K.
Published: April 2015

Pathogenic
Escherichia coli
or its associated virulence factors have been frequently detected in dairy cow manure, milk, and dairy farm environments. However, it is unclear what the long-term dynamics of
E. coli
virulence factors are and which farm compartments act as reservoirs. This study assessed the occurrence and dynamics of four
E. coli
virulence factors (
eae
,
stx
1
,
stx
2
, and the gamma allele of the
tir
gene [γ-
tir
]) on three U.S. dairy farms. Fecal, manure, water, feed, milk, and milk filter samples were collected from 2004 to 2012. Virulence factors were measured by postenrichment quantitative PCR (qPCR). All factors were detected in most compartments on all farms. Fecal and manure samples showed the highest prevalence, up to 53% for
stx
and 21% for γ-
tir
in fecal samples and up to 84% for
stx
and 44% for γ-
tir
in manure. Prevalence was low in milk (up to 1.9% for
stx
and 0.7% for γ-
tir
). However, 35% of milk filters were positive for
stx
and 20% were positive for γ-
tir
. All factors were detected in feed and water. Factor prevalence and levels, expressed as qPCR cycle threshold categories, fluctuated significantly over time, with no clear seasonal signal independent from year-to-year variability. Levels were correlated between fecal and manure samples, and in some cases autocorrelated, but not between manure and milk filters. Shiga toxins were nearly ubiquitous, and 10 to 18% of the lactating cows were potential shedders of
E. coli
O157 at least once during their time in the herds.
E. coli
virulence factors appear to persist in many areas of the farms and therefore contribute to transmission dynamics.
Photoautotrophic Polyhydroxybutyrate Granule Formation Is Regulated by Cyanobacterial Phasin PhaP in Synechocystis sp. Strain PCC 6803
Authors: Hauf Waldemar , Watzer Björn , Roos Nora , Klotz Alexander , Forchhammer Karl
Published: April 2015

Cyanobacteria are photoautotrophic microorganisms which fix atmospheric carbon dioxide via the Calvin-Benson cycle to produce carbon backbones for primary metabolism. Fixed carbon can also be stored as intracellular glycogen, and in some cyanobacterial species like
Synechocystis
sp. strain PCC 6803, polyhydroxybutyrate (PHB) accumulates when major nutrients like phosphorus or nitrogen are absent. So far only three enzymes which participate in PHB metabolism have been identified in this organism, namely, PhaA, PhaB, and the heterodimeric PHB synthase PhaEC. In this work, we describe the cyanobacterial PHA surface-coating protein (phasin), which we term PhaP, encoded by
ssl2501
. Translational fusion of Ssl2501 with enhanced green fluorescent protein (eGFP) showed a clear colocalization to PHB granules. A deletion of
ssl2501
reduced the number of PHB granules per cell, whereas the mean PHB granule size increased as expected for a typical phasin. Although deletion of
ssl2501
had almost no effect on the amount of PHB, the biosynthetic activity of PHB synthase was negatively affected. Secondary-structure prediction and circular dichroism (CD) spectroscopy of PhaP revealed that the protein consists of two α-helices, both of them associating with PHB granules. Purified PhaP forms oligomeric structures in solution, and both α-helices of PhaP contribute to oligomerization. Together, these results support the idea that Ssl2501 encodes a cyanobacterial phasin, PhaP, which regulates the surface-to-volume ratio of PHB granules.
Aerobic Hydrogen Production via Nitrogenase in Azotobacter vinelandii CA6
Authors: Noar Jesse , Loveless Telisa , Navarro-Herrero José Luis , Olson Jonathan W. , Bruno-Bárcena José M.
Published: April 2015

The diazotroph
Azotobacter vinelandii
possesses three distinct nitrogenase isoenzymes, all of which produce molecular hydrogen as a by-product. In batch cultures,
A. vinelandii
strain CA6, a mutant of strain CA, displays multiple phenotypes distinct from its parent: tolerance to tungstate, impaired growth and molybdate transport, and increased hydrogen evolution. Determining and comparing the genomic sequences of strains CA and CA6 revealed a large deletion in CA6's genome, encompassing genes related to molybdate and iron transport and hydrogen reoxidation. A series of iron uptake analyses and chemostat culture experiments confirmed iron transport impairment and showed that the addition of fixed nitrogen (ammonia) resulted in cessation of hydrogen production. Additional chemostat experiments compared the hydrogen-producing parameters of different strains: in iron-sufficient, tungstate-free conditions, strain CA6's yields were identical to those of a strain lacking only a single hydrogenase gene. However, in the presence of tungstate, CA6 produced several times more hydrogen.
A. vinelandii
may hold promise for developing a novel strategy for production of hydrogen as an energy compound.
Rich Medium Composition Affects Escherichia coli Survival, Glycation, and Mutation Frequency during Long-Term Batch Culture
Authors: Kram Karin E. , Finkel Steven E.
Published: April 2015

Bacteria such as
Escherichia coli
are frequently grown to high density to produce biomolecules for study in the laboratory. To achieve this, cells can be incubated in extremely rich media that increase overall cell yield. In these various media, bacteria may have different metabolic profiles, leading to changes in the amounts of toxic metabolites produced. We have previously shown that stresses experienced during short-term growth can affect the survival of cells during the long-term stationary phase (LTSP). Here, we incubated cells in LB, 2× yeast extract-tryptone (YT), Terrific Broth, or Super Broth medium and monitored survival during the LTSP, as well as other reporters of genetic and physiological change. We observe differential cell yield and survival in all media studied. We propose that differences in long-term survival are the result of changes in the metabolism of components of the media that may lead to increased levels of protein and/or DNA damage. We also show that culture pH and levels of protein glycation, a covalent modification that causes protein damage, affect long-term survival. Further, we measured mutation frequency after overnight incubation and observed a correlation between high mutation frequencies at the end of the log phase and loss of viability after 4 days of LTSP incubation, indicating that mutation frequency is potentially predictive of long-term survival. Since glycation and mutation can be caused by oxidative stress, we measured expression of the
oxyR
oxidative stress regulator during log-phase growth and found that higher levels of
oxyR
expression during the log phase are consistent with high mutation frequency and lower cell density during the LTSP. Since these complex rich media are often used when producing large quantities of biomolecules in the laboratory, the observed increase in damage resulting in glycation or mutation may lead to production of a heterogeneous population of plasmids or proteins, which could affect the quality of the end products yielded in some laboratory experiments.
The Xanthomonas oryzae pv. oryzae PilZ Domain Proteins Function Differentially in Cyclic di-GMP Binding and Regulation of Virulence and Motility
Authors: Yang Fenghuan , Tian Fang , Chen Huamin , Hutchins William , Yang Ching-Hong , He Chenyang
Published: April 2015

The PilZ domain proteins have been demonstrated to be one of the major types of receptors mediating cyclic di-GMP (c-di-GMP) signaling pathways in several pathogenic bacteria. However, little is known about the function of PilZ domain proteins in c-di-GMP regulation of virulence in the bacterial blight pathogen of rice
Xanthomonas oryzae
pv. oryzae. Here, the roles of PilZ domain proteins PXO_00049 and PXO_02374 in c-di-GMP binding, regulation of virulence and motility, and subcellular localization were characterized in comparison with PXO_02715, identified previously as an interactor with the c-di-GMP receptor Filp to regulate virulence. The c-di-GMP binding motifs in the PilZ domains were conserved in PXO_00049 and PXO_02374 but were less well conserved in PXO_02715. PXO_00049 and PXO_02374 but not PXO_02715 proteins bound to c-di-GMP with high affinity
in vitro
, and the R
141
and R
10
residues in the PilZ domains of PXO_00049 and PXO_02374, respectively, were crucial for c-di-GMP binding. Gene deletion of PXO_00049 and PXO_02374 resulted in significant increases in virulence and
hrp
gene transcription, indicating their negative regulation of virulence via type III secretion system expression. All mutants showed significant changes in sliding motility but not exopolysaccharide production and biofilm formation. In
trans
expression of the full-length open reading frame (ORF) of each gene in the relevant mutants led to restoration of the phenotype to wild-type levels. Moreover, PXO_00049 and PXO_02374 displayed mainly multisite subcellular localizations, whereas PXO_02715 showed nonpolar distributions in the
X. oryzae
pv. oryzae cells. Therefore, this study demonstrated the different functions of the PilZ domain proteins in mediation of c-di-GMP regulation of virulence and motility in
X. oryzae
pv. oryzae.
Distribution and Characterization of Salmonella enterica Isolates from Irrigation Ponds in the Southeastern United States
Authors: Luo Zhiyao , Gu Ganyu , Ginn Amber , Giurcanu Mihai C. , Adams Paige , Vellidis George , van Bruggen Ariena H. C. , Danyluk Michelle D. , Wright Anita C.
Published: April 2015

Irrigation water has been implicated as a likely source of produce contamination by
Salmonella enterica
. Therefore, the distribution of
S. enterica
was surveyed monthly in irrigation ponds (
n
= 10) located within a prime agricultural region in southern Georgia and northern Florida. All ponds and 28.2% of all samples (
n
= 635) were positive for
Salmonella
, with an overall geometric mean concentration (0.26 most probable number [MPN]/liter) that was relatively low compared to prior reports for rivers in this region.
Salmonella
peaks were seasonal; the levels correlated with increased temperature and rainfall (
P
< 0.05). The numbers and occurrence were significantly higher in water (0.32 MPN/liter and 37% of samples) than in sediment (0.22 MPN/liter and 17% of samples) but did not vary with depth. Representative isolates (
n
= 185) from different ponds, sample types, and seasons were examined for resistance to 15 different antibiotics; most strains were resistant to streptomycin (98.9%), while 20% were multidrug resistant (MDR) for 2 to 6 antibiotics. DiversiLab repetitive extragenic palindromic-element sequence-based PCR (rep-PCR) revealed genetic diversity and showed 43 genotypes among 191 isolates, as defined by >95% similarity. The genotypes did not partition by pond, season, or sample type. Genetic similarity to known serotypes indicated Hadar, Montevideo, and Newport as the most prevalent. All ponds achieved the current safety standards for generic
Escherichia coli
in agricultural water, and regression modeling showed that the
E. coli
level was a significant predictor for the probability of
Salmonella
occurrence. However, persistent populations of
Salmonella
were widely distributed in irrigation ponds, and the associated risks for produce contamination and subsequent human exposure are unknown, supporting continued surveillance of this pathogen in agricultural settings.
The Aspergillus fumigatus sitA Phosphatase Homologue Is Important for Adhesion, Cell Wall Integrity, Biofilm Formation, and Virulence
Authors: Bom Vinícius Leite Pedro , de Castro Patrícia Alves , Winkelströter Lizziane K. , Marine Marçal , Hori Juliana I. , Ramalho Leandra Naira Zambelli , dos Reis Thaila Fernanda , Goldman Maria Helena S. , Brown Neil Andrew , Rajendran Ranjith , Ramage Gordon , Walker Louise A. , Munro Carol A. , Rocha Marina Campos , Malavazi Iran , Hagiwara Daisuke , Goldman Gustavo H.
Published: April 2015

Aspergillus fumigatusis an opportunistic pathogenic fungus able to infect immunocompromised patients, eventually causing disseminated infections that are difficult to control and lead to high mortality rates. It is important to understand how the signaling pathways that regulate these factors involved in virulence are orchestrated. Protein phosphatases are central to numerous signal transduction pathways. Here, we characterize theA. fumigatusprotein phosphatase 2A SitA, theSaccharomyces cerevisiaeSit4p homologue. ThesitAgene is not an essential gene, and we were able to construct anA. fumigatusnull mutant. The ΔsitAstrain had decreased MpkA phosphorylation levels, was more sensitive to cell wall-damaging agents, had increased β-(1,3)-glucan and chitin, was impaired in biofilm formation, and had decreased protein kinase C activity. The ΔsitAstrain is more sensitive to several metals and ions, such as MnCl2, CaCl2, and LiCl, but it is more resistant to ZnSO4. The ΔsitAstrain was avirulent in a murine model of invasive pulmonary aspergillosis and induces an augmented tumor necrosis factor alpha (TNF-α) response in mouse macrophages. These results stress the importance ofA. fumigatusSitA as a possible modulator of PkcA/MpkA activity and its involvement in the cell wall integrity pathway.
Single-Blinded, Randomised Preliminary Study Evaluating the Effects of 2 hz Electroacupuncture for Postoperative Pain in Patients with Total Knee Arthroplasty
Authors: Tzeng Chung-Yuh , Chang Shih-Liang , Wu Chih-Cheng , Chang Chu-Ling , Chen Wen-Gii , Tong Kwok-Man , Huang Kui-Chou , Hsieh Ching-Liang
Published: April 2015

Objective

To explore the point-specific clinical effect of 2 Hz electroacupuncture (EA) in treating postoperative pain in patients undergoing total knee arthroplasty (TKA),

Methods

In a randomised, partially single-blinded preliminary study, 47patients with TKA were randomly divided into three groups: control group (CG, n=17) using only patient-controlled analgesia (PCA); EA group (EAG, n=16) with 2 Hz EA applied at ST36 ( Zusanli) and GB34 ( Yanglingquan) contralateral to the operated leg for 30 min on the first two postoperative days, also receiving PCA; and non-point group (NPG, n=14), with EA identical to the EAG except given 1 cm lateral to both ST36 and GB34. The Mann–Whitney test was used to show the difference between two groups and the Kruskal–Wallis test to show the difference between the three groups.

Results

The time until patients first required PCA in the CG was 34.1±22.0 min, which was significantly shorter than the 92.0±82.7 min in the EAG (p<0.001) and 90.7±94.8 min in the NPG (p<0.001); there was no difference between the EAG and NPG groups (p>0.05). The total dosage of PCA solution given was 4.6±0.9 mL/kg body weight in the CG, 4.2±1.0 mL/kg in the EAG and 4.5±1.0 mL/kg in the NPG; there were no significant differences (p>0.05) among the three groups.

Conclusions

In this small preliminary study, EA retarded the first demand for PCA in comparison with no EA. No effect was seen on the total dosage of PCA required and no point-specific effect was seen.
Lower levels of 25-hydroxyvitamin D3are associated with a higher prevalence of microvascular complications in patients with type 2 diabetes
Authors: Zoppini Giacomo , Galletti Anna , Targher Giovanni , Brangani Corinna , Pichiri Isabella , Trombetta Maddalena , Negri Carlo , De Santi Francesca , Stoico Vincenzo , Cacciatori Vittorio , Bonora Enzo
Published: April 2015

Objective

Low levels of serum 25-hydroxyvitamin D [25(OH)D] are commonly found in type 2 diabetes. We examined whether there is an association between circulating 25(OH)D concentrations and the presence of microvascular complications in people with type 2 diabetes.

Research design and methods

We studied 715 outpatients with type 2 diabetes who regularly attended our clinic. Participants were evaluated for the presence of microvascular complications (namely retinopathy and/or nephropathy) by clinical evaluation, fundus examination, urine examination and biochemical tests. Serum 25(OH)D levels were also measured for each participant.

Results

Hypovitaminosis D (ie, a serum 25(OH)D level <30 ng/mL) was found in 75.4%, while deficiency (ie, a 25(OH)D level <20 ng/mL) was found in 36.6% of these patients. Serum 25(OH)D levels decreased significantly in relation to the severity of either retinopathy or nephropathy or both. In multivariate logistic regression analysis, lower 25(OH)D levels were independently associated with the presence of microvascular complications (considered as a composite end point; OR 0.758; 95% CI 0.607 to 0.947, p=0.015). Notably, this association remained significant even after excluding those with an estimated glomerular filtration rate <60 mL/min/1.73 m2.

Conclusions

We found an inverse and independent relationship between circulating 25(OH)D levels and the prevalence of microvascular complications in patients with type 2 diabetes. However, vitamin D may be simply a marker and causality cannot be implied from our cross-sectional study. Whether vitamin D supplementation in patients with type 2 diabetes may have beneficial effects on the risk of microvascular complications remains to be investigated.
Diabetic muscle infarction: a systematic review
Authors: Horton William B , Taylor Jeremy S , Ragland Timothy J , Subauste Angela R
Published: April 2015

Context

Diabetic muscle infarction (DMI) is a rare complication associated with poorly controlled diabetes mellitus. Less than 200 cases have been reported in the literature since it was first described over 45 years ago. There is no clear ‘standard of care’ for managing these patients.

Evidence acquisition

PubMed searches were conducted for ‘diabetic muscle infarction’ and ‘diabetic myonecrosis’ from database inception through July 2014. All articles identified by these searches were reviewed in detail if the article text was available in English.

Evidence synthesis

The current literature exists as case reports or small case series, with no prospective or higher-order treatment studies available. Thus, an evidence-based approach to data synthesis was difficult. The available literature is presented objectively with an attempt to describe clinically relevant trends and findings in the diagnosis and management of DMI.

Conclusions

Early recognition of DMI is key, so appropriate treatment can be initiated. MRI is the radiological study of choice. A combination of bed rest, glycemic control, and non-steroidal anti-inflammatory drug therapy appears to yield the shortest time to symptom resolution and the lowest risk of recurrence.
The association of hospital prevention processes and patient risk factors with the risk ofClostridium difficileinfection: a population-based cohort study
Authors: Daneman N , Guttmann A , Wang X , Ma X , Gibson D , Stukel TA
Published: April 2015

Background

Clostridium difficileis the most common cause of healthcare-acquired infection; the real-world impacts of some proposedC. difficileprevention processes are unknown.

Methods

We conducted a population-based retrospective cohort study of all patients admitted to acute care hospitals between April 2011 and March 2012 in Ontario, Canada. Hospital prevention practices were determined by survey of infection control programmes; responses were linked to patient-level risk factors andC. difficileoutcomes in Ontario administrative databases. Multivariable generalised estimating equation (GEE) regression models were used to assess the impact of selected understudied hospital prevention processes on the patient-level risk ofC. difficileinfection, accounting for patient risk factors, baselineC. difficilerates and structural hospital characteristics.

Results

C. difficileinfections complicated 2341 of 653 896 admissions (3.6 per 1000 admissions). Implementation of the selectedC. difficileprevention practices was variable across the 159 hospitals with isolation of all patients at onset of diarrhoea reported by 43 (27%), auditing of antibiotic stewardship compliance by 26 (16%), auditing of cleaning practices by 115 (72%), on-site diagnostic testing by 74 (47%), vancomycin as first-line treatment by 24 (15%) and reporting rates to senior leadership by 52 (33%). None of these processes were associated with a significantly reduced risk ofC. difficileafter adjustment for baselineC. difficilerates, structural hospital characteristics and patient-level factors. Patient-level factors were strongly associated withC. difficilerisk, including age, comorbidities, non-elective and medical admissions.

Conclusions

In the largest study to date, selected hospital prevention strategies were not associated with a statistically significant reduction in patients’ risk ofC. difficileinfection. These prevention strategies have either limited effectiveness or were ineffectively implemented during the study period.
Mother's education and the risk of preterm and small for gestational age birth: a DRIVERS meta-analysis of 12 European cohorts
Authors: Ruiz Milagros , Goldblatt Peter , Morrison Joana , Kukla Lubomír , Švancara Jan , Riitta-Järvelin Marjo , Taanila Anja , Saurel-Cubizolles Marie-Josèphe , Lioret Sandrine , Bakoula Chryssa , Veltsista Alexandra , Porta Daniela , Forastiere Francesco , van Eijsden Manon , Vrijkotte Tanja G M , Eggesbø Merete , White Richard A , Barros Henrique , Correia Sofia , Vrijheid Martine , Torrent Maties , Rebagliato Marisa , Larrañaga Isabel , Ludvigsson Johnny , Olsen Faresjö Åshild , Hryhorczuk Daniel , Antipkin Youriy , Marmot Michael , Pikhart Hynek
Published: April 2015

Background

A healthy start to life is a major priority in efforts to reduce health inequalities across Europe, with important implications for the health of future generations. There is limited combined evidence on inequalities in health among newborns across a range of European countries.

Methods

Prospective cohort data of 75 296 newborns from 12 European countries were used. Maternal education, preterm and small for gestational age births were determined at baseline along with covariate data. Regression models were estimated within each cohort and meta-analyses were conducted to compare and measure heterogeneity between cohorts.

Results

Mother's education was linked to an appreciable risk of preterm and small for gestational age (SGA) births across 12 European countries. The excess risk of preterm births associated with low maternal education was 1.48 (1.29 to 1.69) and 1.84 (0.99 to 2.69) in relative and absolute terms (Relative/Slope Index of Inequality, RII/SII) for all cohorts combined. Similar effects were found for SGA births, but absolute inequalities were greater, with an SII score of 3.64 (1.74 to 5.54). Inequalities at birth were strong in the Netherlands, the UK, Sweden and Spain and marginal in other countries studied.

Conclusions

This study highlights the value of comparative cohort analysis to better understand the relationship between maternal education and markers of fetal growth in different settings across Europe.
Guilt by association: paradigm for detecting a silent killer (thoracic aortic aneurysm)
Authors: Elefteriades John A , Sang Adam , Kuzmik Gregory , Hornick Matthew
Published: April 2015

Recent studies have confirmed a close association between various medical conditions (intracranial aneurysm, abdominal aortic aneurysm, temporal arteritis, autoimmune disorder, renal cysts), certain aortic anatomic variants (bovine aortic arch, direct origin of left vertebral artery from aortic arch, bicuspid aortic valve), and family history of aneurysm disease with thoracic aortic aneurysm and dissection. This paper reviews these associations. We propose to capitalise on these associations as powerful and expanding opportunities to diagnose the virulent but silent disease of thoracic aortic aneurysm. This can be accomplished by recognition of this ‘guilt by association’ with the other conditions. Thus, patients with associated diseases and anatomic variants should be investigated for silent aortic aneurysms. Such a paradigm holds substantial potential for reducing death from the silent killer represented by thoracic aortic aneurysm disease.
Preparing to take the USMLE Step 1: a survey on medical students’ self-reported study habits
Authors: Kumar Andre D , Shah Monisha K , Maley Jason H , Evron Joshua , Gyftopoulos Alex , Miller Chad
Published: April 2015

Background

The USA Medical Licensing Examination Step 1 is a computerised multiple-choice examination that tests the basic biomedical sciences. It is administered after the second year in a traditional four-year MD programme. Most Step 1 scores fall between 140 and 260, with a mean (SD) of 227 (22). Step 1 scores are an important selection criterion for residency choice. Little is known about which study habits are associated with a higher score.

Objective

To identify which self-reported study habits correlate with a higher Step 1 score.

Methods

A survey regarding Step 1 study habits was sent to third year medical students at Tulane University School of Medicine every year between 2009 and 2011. The survey was sent approximately 3 months after the examination.

Results

256 out of 475 students (54%) responded. The mean (SD) Step 1 score was 229.5 (22.1). Students who estimated studying more than 8–11 h per day had higher scores (p<0.05), but there was no added benefit with additional study time. Those who reported studying <40 days achieved higher scores (p<0.05). Those who estimated completing >2000 practice questions also obtained higher scores (p<0.01). Students who reported studying in a group, spending the majority of study time on practice questions or taking >40 preparation days did not achieve higher scores.

Conclusions

Certain self-reported study habits may correlate with a higher Step 1 score compared with others. Given the importance of achieving a high Step 1 score on residency choice, it is important to further identify which characteristics may lead to a higher score.
Styles, origins and implications of syndepositional deformation structures in Ediacaran microbial carbonates (Nama Basin, Namibia)
Authors: Winterleitner G. , Le Heron D. P. , Mapani B. , Vining B. A. , McCaffrey K. J. W.
Published: April 2015

Outstanding exposures of Ediacaran-aged thrombolite–stromatolite bioherms and biostromes crop out in the Nama Basin, SW Namibia. Fieldwork, dovetailed with remote sensing and a terrestrial laser scanning (LiDAR) survey, allow the fracture network of this succession to be characterized, and the relative age of fracture sets and families to be determined. The results show that the microbial carbonates were affected by intense syndepositional brittle and ductile deformation. Early brittle fracturing was favoured where early lithification of microbialites took place upon deposition. Such deposits were prone to gravitational collapse due to internal weaknesses during early lithification. Timing of syndepositional fracturing of bioherms and biostromes is demonstrated by contemporaneous microbial overgrowth over brecciated material in open-mode fractures. Ductile deformation occurs preferentially around massive thrombolite domes and columns, represented by folding of mud-dominated sediments in inter-column fill. Secondary fractures developed during the long-lived structural history of the Nama Basin, resulting in a complex fracture network of syndepositional fractures overprinted by secondary fractures. These findings have important implications for carbonate reservoir characterization in microbial reservoirs and subsurface fluid-flow estimations. The observed syndepositional fractures form due to body forces that are intrinsic to the microbial system and thus do not require an external tectonic driver.
Tectonic setting and stratigraphic architecture of an Early Cretaceous lacustrine carbonate platform, Sugar Loaf High, Santos Basin, Brazil
Authors: Buckley J. P. , Bosence D. , Elders C.
Published: April 2015

The Sugar Loaf High is an extensive basement structure within the Santos Basin, offshore Brazil, in which all of the elements of the pre-salt hydrocarbon play are present. Following a clastic-dominated early synrift phase, the later synrift and sag phases are characterized by an extensive non-marine carbonate platform over the basement high. The study area within this new 3D seismic dataset contains carbonates stratigraphically equivalent to the reservoirs within the Lula and Sapinhoá fields. Analysis of the 3D seismic data shows that the pre-salt carbonates onlap the basement of the Sugar Loaf High and form aggradational geometries on a platform that has a proximal to distal width of about 100 km and an interpreted relief of some 900 m. The carbonate platform has an aggradational and mounded basinward-facing gullied margin with slope deposits. Progradational units are imaged on the platform top that may be either carbonate or clastic in composition. The platform is preserved beneath evaporites that form the regional seal within the Santos Basin. Platforms of this size are previously unknown from lacustrine settings outside the pre-salt stratigraphy of the Santos and Campos Basins, Brazil.
Role played by interleukin-6 in evoking the exercise pressor reflex in decerebrate rats: effect of femoral artery ligation
Authors: Copp Steven W. , Stone Audrey J. , Li Jianhua , Kaufman Marc P.
Published: April 2015

IL-6 signaling via the soluble IL-6 receptor (sIL-6r) has been shown to increase primary afferent responsiveness to noxious stimuli. This finding prompted us to test the hypothesis that IL-6 and sIL-6r would increase the exercise pressor reflex in decerebrate rats with freely perfused femoral arteries. We also tested the hypothesis that soluble glycoprotein (sgp)130, an inhibitor of IL-6/sIL-6r signaling, would decrease the exaggerated exercise pressor reflex that is found in decerebrate rats with ligated femoral arteries. In rats with freely perfused femoral arteries, coinjection of 50 ng of IL-6 and sIL-6r into the arterial supply of the hindlimb significantly increased the peak pressor response to static (control: 14 ± 3 mmHg and IL-6/sIL-6r: 17 ± 2 mmHg, P = 0.03) and intermittent isometric (control: 10 ± 2 mmHg and IL-6/sIL-6r: 15 ± 4 mmHg, P = 0.03) hindlimb muscle contraction. In rats with ligated femoral arteries, injection of 50 ng of sgp130 into the arterial supply of the hindlimb reduced the peak pressor response to static (control: 24 ± 2 mmHg and sgp130: 16 ± 3 mmHg, P = 0.01) and intermittent isometric (control: 16 ± 2 mmHg and sgp130: 13 ± 2 mmHg, P = 0.04) hindlimb muscle contraction, whereas there was no effect of sgp130 on the exercise pressor reflex in rats with freely perfused femoral arteries. We conclude that coinjection of exogenous IL-6 and sIL-6r increased the exercise pressor reflex in rats with freely perfused femoral arteries. More importantly, we also conclude that IL-6 and sIL-6r play an endogenous role in evoking the exercise pressor reflex in rats with ligated femoral arteries but not in rats with freely perfused femoral arteries.
Lungs at high-altitude: genomic insights into hypoxic responses
Authors: Mishra Aastha , Mohammad Ghulam , Norboo Tsering , Newman John H. , Pasha M. A. Qadar
Published: April 2015

Hypobaric hypoxia at high altitude (HA) results in reduced blood arterial oxygen saturation, perfusion of organs with hypoxemic blood, and direct hypoxia of lung tissues. The pulmonary complications in the cells of the pulmonary arterioles due to hypobaric hypoxia are the basis of the pathophysiological mechanisms of high-altitude pulmonary edema (HAPE). Some populations that have dwelled at HA for thousands of years have evolutionarily adapted to this environmental stress; unadapted populations may react with excessive physiological responses that impair health. Individual variations in response to hypoxia and the mechanisms of HA adaptation provide insight into physiological responses. Adaptive and maladaptive responses include alterations in pathways such as oxygen sensing, hypoxia signaling, K+- and Ca2+-gated channels, redox balance, and the renin-angiotensin-aldosterone system. Physiological imbalances are linked with genetic susceptibilities, and nonhomeostatic responses in gene regulation that occur by small RNAs, histone modification, and DNA methylation predispose susceptible humans to these HA illnesses. Elucidation of the interaction of these factors will lead to a more comprehensive understanding of HA adaptations and maladaptations and will lead to new therapeutics for HA disorders related to hypoxic lungs.
A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis
Authors: Choi Seo-Hyun , Hong Zhen-Yu , Nam Jae-Kyung , Lee Hae-June , Jang Junho , Yoo Ran Ji , Lee Yong Jin , Lee Chang Young , Kim Kyung Hwan , Park Seungwoo , Ji Young Hoon , Lee Yun-Sil , Cho Jaeho , Lee Yoon-Jin
Published: April 2015

Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF.

Experimental Design/Results: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-to-mesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)–specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFβ-R1/Smad signaling was dependent on HIF1α expression. A novel HIF1α inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1α-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1α-related EndMT was observed also in human RIPF tissues.

Conclusions: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage. Clin Cancer Res; 21(16); 3716–26. ©2015 AACR.