bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma HMGB‐1 after the initial dose of epirubicin/docetaxel in cancer
Authors: Arnold Tobias , Michlmayr Anna , Baumann Suzann , Burghuber Christopher , Pluschnig Ursula , Bartsch Rupert , Steger Guenther , Gnant Michael , Bergmann Michael , Bachleitner‐Hofmann Thomas , Oehler Rudolf
Published: January 2013

Background

The response of breast cancer patients to neoadjuvant chemotherapy (NCT) is highly heterogeneous, and reliable predictive instruments remain to be defined. High‐mobility group box‐1 (HMGB‐1) protein is a cell death marker, which is easily detectable in plasma. We hypothesized that the initial dose of NCT with epirubicin/docetaxel induces changes in plasma HMGB‐1 which could allow for an early prediction of response to therapy.

Materials and methods

First, we analysed whether epirubicin/docetaxel releases HMGB‐1 from HCC1143 breast cancer cells in vitro. Thereafter, plasma HMGB‐1 levels before and 1–4 days after the first dose of epirubicin/docetaxel‐based NCT were determined in 41 breast cancer patients and correlated with pathological response to treatment.

Results

Treatment of HCC1143 cells with epirubicin/docetaxel resulted in a significant HMGB‐1 release in vitro. In vivo, HMGB‐1 levels increased significantly only in responders (pathological complete response or partial remission, n = 22) but not in nonresponders (stable or progressive disease, n = 19).

Conclusion

Our data suggest that early dynamic changes of plasma HMGB1 could be a promising biomarker to predict the final response to NCT in breast cancer patients.
Class III phosphatidylinositol 3–kinase and its catalytic product PtdIns3P in regulation of endocytic membrane traffic
Authors: Raiborg Camilla , Schink Kay O. , Stenmark Harald
Published: January 2013

Endocytosis and subsequent membrane traffic through endosomes are cellular processes that are integral to eukaryotic evolution, and numerous human diseases are associated with their dysfunction. Consequently, it is important to untangle the molecular machineries that regulate membrane dynamics and protein flow in the endocytic pathway. Central in this context is class III phosphatidylinositol 3–kinase, an evolutionarily conserved enzyme complex that phosphorylates phosphatidylinositol into phosphatidylinositol 3–phosphate. Phosphatidylinositol 3–phosphate recruits specific effector proteins, most of which contain FYVE or PX domains, to promote endocytosis, endosome fusion, endosome motility and endosome maturation, as well as cargo sorting to lysosomes, the biosynthetic pathway or the plasma membrane. Here we review the functions of key phosphatidylinositol 3–phosphate effectors in regulation of endocytic membrane dynamics and protein sorting.
Development of an integrated transcript sequence database and a gene expression atlas for gene discovery and analysis in switchgrass (Panicum virgatum L.)
Authors: Zhang Ji‐Yi , Lee Yi‐Ching , Torres‐Jerez Ivone , Wang Mingyi , Yin Yanbin , Chou Wen‐Chi , He Ji , Shen Hui , Srivastava Avinash C. , Pennacchio Christa , Lindquist Erika , Grimwood Jane , Schmutz Jeremy , Xu Ying , Sharma Manoj , Sharma Rita , Bartley Laura E. , Ronald Pamela C. , Saha Malay C. , Dixon Richard A. , Tang Yuhong , Udvardi Michael K.
Published: January 2013

Switchgrass (Panicum virgatum L.) is a perennial C4 grass with the potential to become a major bioenergy crop. To help realize this potential, a set of RNA‐based resources were developed. Expressed sequence tags (ESTs) were generated from two tetraploid switchgrass genotypes, Alamo AP13 and Summer VS16. Over 11.5 million high‐quality ESTs were generated with 454 sequencing technology, and an additional 169 079 Sanger sequences were obtained from the 5′ and 3′ ends of 93 312 clones from normalized, full‐length‐enriched cDNA libraries. AP13 and VS16 ESTs were assembled into 77 854 and 30 524 unique transcripts (unitranscripts), respectively, using the Newbler and pave programs. Published Sanger‐ESTs (544 225) from Alamo, Kanlow, and 15 other cultivars were integrated with the AP13 and VS16 assemblies to create a universal switchgrass gene index (PviUT1.2) with 128 058 unitranscripts, which were annotated for function. An Affymetrix cDNA microarray chip (Pvi_cDNAa520831) containing 122 973 probe sets was designed from PviUT1.2 sequences, and used to develop a Gene Expression Atlas for switchgrass (PviGEA). The PviGEA contains quantitative transcript data for all major organ systems of switchgrass throughout development. We developed a web server that enables flexible, multifaceted analyses of PviGEA transcript data. The PviGEA was used to identify representatives of all known genes in the phenylpropanoid–monolignol biosynthesis pathway.
OsCYP2, a chaperone involved in degradation of auxin‐responsive proteins, plays crucial roles in rice lateral root initiation
Authors: Kang Bo , Zhang Zhongchen , Wang Lingling , Zheng Libin , Mao Weihua , Li Meifei , Wu Yunrong , Wu Ping , Mo Xiaorong
Published: January 2013

Auxin plays a pivotal role in many facets of plant development. It acts by inducing the interaction between auxin‐responsive [auxin (AUX)/indole‐3‐acetic acid (IAA)] proteins and the ubiquitin protein ligase SCFTIR to promote the degradation of the AUX/IAA proteins. Other cofactors and chaperones that participate in auxin signaling remain to be identified. Here, we characterized rice (Oryza sativa) plants with mutations in a cyclophilin gene (OsCYP2). cyp2 mutants showed defects in auxin responses and exhibited a variety of auxin‐related growth defects in the root. In cyp2 mutants, lateral root initiation was blocked after nuclear migration but before the first anticlinal division of the pericycle cell. Yeast two‐hybrid and in vitro pull‐down results revealed an association between OsCYP2 and the co‐chaperone Suppressor of G2 allele of skp1 (OsSGT1). Luciferase complementation imaging assays further supported this interaction. Similar to previous findings in an Arabidopsis thaliana SGT1 mutant (atsgt1b), degradation of AUX/IAA proteins was retarded in cyp2 mutants treated with exogenous 1‐naphthylacetic acid. Our results suggest that OsCYP2 participates in auxin signal transduction by interacting with OsSGT1.
Overexpression of a soybean nuclear localized type–III DnaJ domain‐containing HSP40 reveals its roles in cell death and disease resistance
Authors: Liu Jian‐Zhong , Whitham Steven A.
Published: January 2013

Heat‐shock proteins such as HSP70 and HSP90 are important molecular chaperones that play critical roles in biotic and abiotic stress responses; however, the involvement of their co‐chaperones in stress biology remains largely uninvestigated. In a screen for candidate genes stimulating cell death in Glycine max (soybean), we transiently overexpressed full‐length cDNAs of soybean genes that are highly induced during soybean rust infection in Nicotiana benthamiana leaves. Overexpression of a type‐III DnaJ domain‐containing HSP40 (GmHSP40.1), a co‐chaperone of HSP70, caused hypersensitive response (HR)‐like cell death. The HR‐like cell death was dependent on MAPKKKα and WIPK, because silencing each of these genes suppressed the HR. Consistent with the presence of a nuclear localization signal (NLS) motif within the GmHSP40.1 coding sequence, GFP‐GmHSP40.1 was exclusively present in nuclear bodies or speckles. Nuclear localization of GmHSP40.1 was necessary for its function, because deletion of the NLS or addition of a nuclear export signal abolished its HR‐inducing ability. GmHSP40.1 co‐localized with HcRed‐SE, a protein involved in pri‐miRNA processing, which has been shown to be co‐localized with SR33‐YFP, a protein involved in pre‐mRNA splicing, suggesting a possible role for GmHSP40.1 in mRNA splicing or miRNA processing, and a link between these processes and cell death. Silencing GmHSP40.1 enhanced the susceptibility of soybean plants to Soybean mosaic virus, confirming its positive role in pathogen defense. Together, the results demonstrate a critical role of a nuclear‐localized DnaJ domain‐containing GmHSP40.1 in cell death and disease resistance in soybean.
The rice faded green leaf locus encodes protochlorophyllide oxidoreductase B and is essential for chlorophyll synthesis under high light conditions
Authors: Sakuraba Yasuhito , Rahman Md Lutfor , Cho Sung‐Hwan , Kim Ye‐Sol , Koh Hee‐Jong , Yoo Soo‐Cheul , Paek Nam‐Chon
Published: January 2013

NADPH:protochlorophyllide oxidoreductase (POR) catalyzes photoreduction of protochlorophyllide (Pchlide) to chlorophyllide in chlorophyll (Chl) synthesis, and is required for prolamellar body (PLB) formation in etioplasts. Rice faded green leaf (fgl) mutants develop yellow/white leaf variegation and necrotic lesions during leaf elongation in field‐grown plants. Map‐based cloning revealed that FGL encodes OsPORB, one of two rice POR isoforms. In fgl, etiolated seedlings contained smaller PLBs in etioplasts, and lower levels of total and photoactive Pchlide. Under constant or high light (HL) conditions, newly emerging green leaves rapidly turned yellow and formed lesions. Increased levels of non‐photoactive Pchlide, which acts as a photosensitizer, may cause reactive oxygen accumulation and lesion formation. OsPORA expression is repressed by light and OsPORB expression is regulated in a circadian rhythm in short‐day conditions. OsPORA was expressed at high levels in developing leaves and decreased dramatically in fully mature leaves, whereas OsPORB expression was relatively constant throughout leaf development, similar to expression patterns of AtPORA and AtPORB in Arabidopsis. However, OsPORB expression is rapidly upregulated by HL treatment, similar to the fluence rate‐dependent regulation of AtPORC. This suggests that OsPORB function is equivalent to both AtPORB and AtPORC functions. Our results demonstrate that OsPORB is essential for maintaining light‐dependent Chl synthesis throughout leaf development, especially under HL conditions, whereas OsPORA mainly functions in the early stages of leaf development. Developmentally and physiologically distinct roles of monocot OsPORs are discussed by comparing with those of dicot AtPORs.
Mechanisms responsible for beneficial and adverse effects of rosiglitazone in a rat model of acute cardiac ischaemia–reperfusion
Authors: Palee Siripong , Weerateerangkul Punate , Chinda Kroekkiat , Chattipakorn Siriporn C. , Chattipakorn Nipon
Published: January 2013

New Findings

What is the central question of this study?

Controversy exists regarding the beneficial and adverse effects of rosiglitazone. We sought to determine the effects of rosiglitazone in the heart during ischaemia–reperfusion injury.

What is the main finding and what is its importance?

We demonstrated that rosiglitazone simultaneously exerted both beneficial and adverse effects on the heart during ischaemia–reperfusion. These findings provided new mechanistic insights into the effects of this drug, and elucidate the possibility of its undesirable effects in patients taking this drug.

Despite debate regarding its cardioprotective and pro‐arrhythmic effects, the precise mechanisms of action of rosiglitazone on the heart are still unclear. We determined the mechanistic effects of rosiglitazone on cardiac function, arrhythmias and infarct size during cardiac ischaemia–reperfusion. Twenty‐six rats were used. In each rat, either rosiglitazone or saline solution was administered intravenously prior to a 30 min left anterior descending coronary artery ligation and a 120 min reperfusion. Cardiac function, infarct size, myocardial levels of connexin43, Bax/Bcl‐2, cytochrome c, caspase‐3, caspase‐8, Akt, tumour necrosis factor‐α and interleukin‐4 and cardiac mitochondrial function were determined. Isolated cardiomyocytes were used for studying intracellular calcium. Rosiglitazone did not alter cardiac function during the ischaemia–reperfusion periods, but increased the arrhythmia score and mortality rate, decreased the time to onset of ventricular fibrillation and prolonged the Ca2+ decay rate, in comparison to the saline‐injected group (P < 0.05). However, the infarct size in the rosiglitazone‐injected group was reduced (P < 0.05). Rosiglitazone decreased the levels of connexin43 phosphorylation, active caspase‐8 and tumour necrosis factor‐α, but increased the level of procaspase‐3. However, levels of Bax/Bcl‐2, cytochrome c, Akt and interleukin‐4 and the cardiac mitochondrial function were not different between the two groups. Rosiglitazone simultaneously exerted both beneficial and adverse cardiac effects in the heart exposed to ischaemia–reperfusion. Although it decreased the infarct size via the extrinsic anti‐apoptotic pathway and anti‐inflammatory effects, rosiglitazone facilitated a fatal arrhythmia by decreasing connexin43 phosphorylation and prolonging the Ca2+ decay rate in ischaemia–reperfusion. The higher mortality rate in the rosiglitazone‐injected group suggests that its undesirable effect was more pronounced than its benefit on infarct size reduction.
A review of breast tomosynthesis. Part II. Image reconstruction, processing and analysis, and advanced applications
Authors: Sechopoulos Ioannis
Published: January 2013

Many important post‐acquisition aspects of breast tomosynthesis imaging can impact its clinical performance. Chief among them is the reconstruction algorithm that generates the representation of the three‐dimensional breast volume from the acquired projections. But even after reconstruction, additional processes, such as artifact reduction algorithms, computer aided detection and diagnosis, among others, can also impact the performance of breast tomosynthesis in the clinical realm. In this two part paper, a review of breast tomosynthesis research is performed, with an emphasis on its medical physics aspects. In the companion paper, the first part of this review, the research performed relevant to the image acquisition process is examined. This second part will review the research on the post‐acquisition aspects, including reconstruction, image processing, and analysis, as well as the advanced applications being investigated for breast tomosynthesis.
3D image‐guided robotic needle positioning system for small animal interventions
Authors: Bax Jeffrey S. , Waring Christopher S. R. , Sherebrin Shi , Stapleton Shawn , Hudson Thomas J. , Jaffray David A. , Lacefield James C. , Fenster Aaron
Published: January 2013

Purpose:

This paper presents the design of a micro‐CT guided small animal robotic needle positioning system. In order to simplify the robotic design and maintain a small targeting error, a novel implementation of the remote center of motion is used in the system. The system has been developed with the objective of achieving a mean targeting error of <200 μm while maintaining a high degree of user friendliness.

Methods:

The robot is compact enough to operate within a 25 cm diameter micro‐CT bore. Small animals can be imaged and an intervention performed without the need to transport the animal from one workspace to another. Not requiring transport of the animal reduces opportunities for targets to shift from their localized position in the image and simplifies the workflow of interventions. An improved method of needle calibration is presented that better characterizes the calibration using the position of the needle tip in photographs rather than the needle axis. A calibration fixture was also introduced, which dramatically reduces the time requirements of calibration while maintaining calibration accuracy. Two registration modes have been developed to correspond the robot coordinate system with the coordinate system of the micro‐CT scanner. The two registration modes offer a balance between the time required to complete a registration and the overall registration accuracy. The development of slow high accuracy and fast low accuracy registration modes provides users with a degree of flexibility in selecting a registration mode best suited for their application.

Results:

The target registration error (TRE) of the higher accuracy primary registration was TREprimary = 31 ± 12 μm. The error in the lower accuracy combined registration was TREcombined = 139 ± 63 μm. Both registration modes are therefore suitable for small‐animal needle interventions. The targeting accuracy of the robotic system was characterized using targeting experiments in tissue‐mimicking gelatin phantoms. The results of the targeting experiments were combined with the known calibration and needle deflection errors to provide a more meaningful measure of the needle positioning accuracy of the system. The combined targeting errors of the system were 149 ± 41 μm and 218 ± 38 μm using the primary and combined registrations, respectively. Finally, pilot in vivo experiments were successfully completed to demonstrate the performance of the system in a biomedical application.

Conclusions:

The device was able to achieve the desired performance with an error of <200 μm and improved repeatability when compared to other designs. The device expands the capabilities of image‐guided interventions for preclinical biomedical applications.
Proton Therapy Physics.
Authors: Fontenot Jonas
Published: January 2013

Proton Therapy Physics., Paganetti H., CRC Press, Taylor & Francis Group, Boca Raton, FL, 2012. 704 pp. Price: $129.95. ISBN: 9781439836446 (hardcover).
Gafchromic EBT2 film dosimetry in reflection mode with a novel plan‐based calibration method
Authors: Méndez I. , Hartman V. , Hudej R. , Strojnik A. , Casar B.
Published: January 2013

Purpose:

A dosimetric system formed by Gafchromic EBT2 radiochromic film and Epson Expression 10000XL flatbed scanner was commissioned for dosimetry. In this paper, several open questions concerning the commissioning of radiochromic films for dosimetry were addressed: (a) is it possible to employ this dosimetric system in reflection mode; (b) if so, can the methods used in transmission mode also be used in reflection mode; (c) is it possible to obtain accurate absolute dose measurements with Gafchromic EBT2 films; (d) which calibration method should be followed; (e) which calibration models should be used; and (f) does three‐color channel dosimetry offer a significant improvement over single channel dosimetry. The purpose of this paper is to help clarify these questions.

Methods:

In this study, films were scanned in reflection mode, the effect of surrounding film was evaluated and the feasibility of EBT2 film dosimetry in reflection mode was studied. EBT2's response homogeneity has been reported to lead to excessive dose uncertainties. To overcome this problem, a new plan‐based calibration method was implemented. Plan‐based calibration can use every pixel and each of the three color channels of the scanned film to obtain the parameters of the calibration model. A model selection analysis was conducted to select lateral correction and sensitometric curve models. The commonly used calibration with fragments was compared with red‐channel plan‐based calibration and with three‐channel plan‐based calibration.

Results:

No effect of surrounding film was found in this study. The film response inhomogeneity in EBT2 films was found to be important not only due to differences in the fog but also due to differences in sensitivity. The best results for lateral corrections were obtained using absolute corrections independent of the dose. With respect to the sensitometric curves, an empirical polynomial fit of order 4 was found to obtain results equivalent to a gamma‐distributed single hit model based on physical assumptions. Three‐channel dosimetry was found to be substantially superior to red‐channel dosimetry.

Conclusions:

Reflection mode with Gafchromic EBT2 radiochromic film was found to be a viable alternative to transmission mode. The same methods that are used in transmission mode can be followed in reflection mode. A novel plan‐based method was developed for calibration and multichannel dosimetry. This novel method offers increased robustness against film response inhomogeneities and reduces considerably the time required for calibration.
A comparative study of small field total scatter factors and dose profiles using plastic scintillation detectors and other stereotactic dosimeters: The case of the CyberKnife
Authors: Morin Jonathan , Béliveau‐Nadeau Dominic , Chung Eunah , Seuntjens Jan , Thériault Dany , Archambault Louis , Beddar Sam , Beaulieu Luc
Published: January 2013

Purpose:

Small‐field dosimetry is challenging, and the main limitations of most dosimeters are insufficient spatial resolution, water nonequivalence, and energy dependence. The purpose of this study was to compare plastic scintillation detectors (PSDs) to several commercial stereotactic dosimeters by measuring total scatter factors and dose profiles on a CyberKnife system.

Methods:

Two PSDs were developed, having sensitive volumes of 0.196 and 0.785 mm3, and compared with other detectors. The spectral discrimination method was applied to subtract Čerenkov light from the signal. Both PSDs were compared to four commercial stereotactic dosimeters by measuring total scatter factors, namely, an IBA dosimetry stereotactic field diode (SFD), a PTW 60008 silicon diode, a PTW 60012 silicon diode, and a microLion. The measured total scatter factors were further compared with those of two independent Monte Carlo studies. For the dose profiles, two commercial detectors were used for the comparison, i.e., a PTW 60012 silicon diode and Gafchromics EBT2. Total scatter factors for a CyberKnife system were measured in circular fields with diameters from 5 to 60 mm. Dose profiles were measured for the 5‐ and 60‐mm cones. The measurements were performed in a water tank at a 1.5‐cm depth and an 80‐cm source‐axis distance.

Results:

The total scatter factors measured using all the detectors agreed within 1% with the Monte Carlo values for cones of 20 mm or greater in diameter. For cones of 10–20 mm in diameter, the PTW 60008 silicon diode was the only dosimeter whose measurements did not agree within 1% with the Monte Carlo values. For smaller fields (<10 mm), each dosimeter type showed different behaviors. The silicon diodes over‐responded because of their water nonequivalence; the microLion and 1.0‐mm PSD under‐responded because of a volume‐averaging effect; and the 0.5‐mm PSD was the only detector within the uncertainties of the Monte Carlo simulations for all the cones. The PSDs, the PTW 60012 silicon diode, and the Gafchromics EBT2 agreed within 2% and 0.2 mm (gamma evaluation) for the measured dose profiles except in the tail of the 60‐mm cone.

Conclusions:

Silicon diodes can be used to accurately measure small‐field dose profiles but not to measure total scatter factors, whereas PSDs can be used to accurately measure both. The authors' measurements show that the use of a 1.0‐mm PSD resulted in a negligible volume‐averaging effect (under‐response of ≈1%) down to a field size of 5 mm. Therefore, PSDs are strong candidates to become reference radiosurgery detectors for beam characterization and quality assurance measurements.
A system for MRI‐guided transperineal delivery of needles to the prostate for focal therapy
Authors: Cepek Jeremy , Chronik Blaine A. , Lindner Uri , Trachtenberg John , Davidson Sean R. H. , Bax Jeffrey , Fenster Aaron
Published: January 2013

Purpose:

To demonstrate the capabilities of a new magnetic resonance imaging (MRI)‐guided system for delivering needles to the prostate for focal therapy. Included is a presentation of the design of the system and its user interface, evaluation of MR‐compatibility, and quantitative evaluation of guidance accuracy and repeatability within the bore of a clinical MRI scanner.

Methods:

The use of MRI for visualization of tumors, intraoperative visualization of interventional tools, and thermometry for controlled ablation of lesions is becoming increasingly prevalent. In this work, the authors present a prototype system for guiding needles to prostate tumors within the bore of an MRI scanner for use in focal laser thermal ablation of prostate tumors. The system consists of a manually actuated trajectory alignment device that allows a physician to precisely align a set of needle guides with an intended target in the prostate within the bore of a clinical closed‐bore MRI scanner. Needle insertion is then performed transperineally, with the patient in the bore of the MRI, and custom software provides monitoring of thermal ablative procedures.

Results:

The system is shown to have a minimal effect on image distortion, and only a 6% decrease in image signal‐to‐noise ratio. Through needle insertion tests in tissue‐mimicking phantoms, the system's potential for reliably guiding needles to intra‐MR targets within 2.64 mm has been demonstrated. Use of the system to deliver focal laser ablation therapy to two patients showed that it can be used to deliver needles with minimal disruption of workflow, and in less time than when insertions are performed freehand or with a fixed grid template.

Conclusions:

A system for delivering needles to a patient's prostate for focal therapy within the bore of an MRI scanner has been developed. Results from needle insertion tests in phantoms suggest that the system has the potential to provide accurate delivery of focal therapy to prostate tumors of the smallest clinically significant size. Initial tests in two patients showed that needle deflection was larger than in phantoms, but methods of manually compensating for this effect were employed and needles were delivered to treatment sites with sufficient accuracy to deliver effective treatment. In addition, the treatment was delivered in less time than with a fixed grid template or freehand insertions. Despite this success, methods of reducing needle deflection are needed in order to fully utilize the potential of this system, and further reduce total procedure time.
Specificity between Lactobacilli and Hymenopteran Hosts Is the Exception Rather than the Rule
Authors: McFrederick Quinn S. , Cannone Jamie J. , Gutell Robin R. , Kellner Katrin , Plowes Robert M. , Mueller Ulrich G.
Published: January 2013

Lactobacilli (
Lactobacillales
:
Lactobacillaceae
) are well known for their roles in food fermentation, as probiotics, and in human health, but they can also be dominant members of the microbiota of some species of Hymenoptera (ants, bees, and wasps). Honey bees and bumble bees associate with host-specific lactobacilli, and some evidence suggests that these lactobacilli are important for bee health. Social transmission helps maintain associations between these bees and their respective microbiota. To determine whether lactobacilli associated with social hymenopteran hosts are generally host specific, we gathered publicly available
Lactobacillus
16S rRNA gene sequences, along with
Lactobacillus
sequences from 454 pyrosequencing surveys of six other hymenopteran species (three sweat bees and three ants). We determined the comparative secondary structural models of 16S rRNA, which allowed us to accurately align the entire 16S rRNA gene, including fast-evolving regions. BLAST searches and maximum-likelihood phylogenetic reconstructions confirmed that honey and bumble bees have host-specific
Lactobacillus
associates. Regardless of colony size or within-colony oral sharing of food (trophallaxis), sweat bees and ants associate with lactobacilli that are closely related to those found in vertebrate hosts or in diverse environments. Why honey and bumble bees associate with host-specific lactobacilli while other social Hymenoptera do not remains an open question. Lactobacilli are known to inhibit the growth of other microbes and can be beneficial whether they are coevolved with their host or are recruited by the host from environmental sources through mechanisms of partner choice.
Characterization of the MSMEG_2631 Gene (
mmp
) Encoding a Multidrug and Toxic Compound Extrusion (MATE) Family Protein in Mycobacterium smegmatis and Exploration of Its Polyspecific Nature Using Biolog Phenotype MicroArray
Authors: Mishra Mukti Nath , Daniels Lacy
Published: January 2013

In
Mycobacterium
, multidrug efflux pumps can be associated with intrinsic drug resistance. Comparison of putative mycobacterial transport genes revealed a single annotated open reading frame (ORF) for a multidrug and toxic compound extrusion (MATE) family efflux pump in all sequenced mycobacteria except
Mycobacterium leprae
. Since MATE efflux pumps function as multidrug efflux pumps by conferring resistance to structurally diverse antibiotics and DNA-damaging chemicals, we studied this gene (MSMEG_2631) in
M. smegmatis
mc
2
155 and determined that it encodes a MATE efflux system that contributes to intrinsic resistance of
Mycobacterium
. We propose that the MSMEG_2631 gene be named
mmp
, for
m
ycobacterial
M
ATE
p
rotein. Biolog Phenotype MicroArray data indicated that
mmp
deletion increased susceptibility for phleomycin, bleomycin, capreomycin, amikacin, kanamycin, cetylpyridinium chloride, and several sulfa drugs. MSMEG_2619 (
efpA
) and MSMEG_3563 mask the effect of
mmp
deletion due to overlapping efflux capabilities. We present evidence that
mmp
is a part of an MSMEG_2626-2628-2629-2630-2631 operon regulated by a strong constitutive promoter, initiated from a single transcription start site. All together, our results show that
M. smegmatis
constitutively encodes an Na
+
-dependent MATE multidrug efflux pump from
mmp
in an operon with putative genes encoding proteins for apparently unrelated functions.
Regulatory Twist and Synergistic Role of Metabolic Coinducer- and Response Regulator-Mediated CbbR-

cbb
I

Interactions in Rhodopseudomonas palustris CGA010
Authors: Joshi Gauri S. , Zianni Michael , Bobst Cedric E. , Tabita F. Robert
Published: January 2013

Rhodopseudomonas palustris
assimilates CO
2
by the Calvin-Benson-Bassham (CBB) reductive pentose phosphate pathway. Most genes required for a functional CBB pathway are clustered into the

cbb
I

and cbb
II

operons, with the

cbb
I

operon subject to control by a LysR transcriptional activator, CbbR, encoded by
cbbR
, which is divergently transcribed from the
cbbLS
genes (encoding form I RubisCO) of the

cbb
I

operon. Juxtaposed between the genes encoding CbbR and CbbLS are genes that encode a three-protein two-component system (CbbRRS system) that functions to modify the ability of CbbR to regulate
cbbLS
expression. Previous studies indicated that the response regulators, as well as various coinducers (effectors), specifically influence CbbR-promoter interactions. In the current study, it was shown via several experimental approaches that the response regulators and coinducers act synergistically on CbbR to influence
cbbLS
transcription. Synergistic effects on the formation of specific CbbR-DNA complexes were quantified using surface plasmon resonance (SPR) procedures. Gel mobility shift and DNA footprint analyses further indicated structural changes in the DNA arising from the presence of response regulators and coinducer molecules binding to CbbR. Based on previous studies, and especially emphasized by the current investigation, it is clear that protein complexes influence promoter activity and the
cbbLS
transcription machinery.
A Qualitative Study of the Experiences of Patients with Knee Osteoarthritis Undergoing Moxibustion
Authors: Son Haeng-Mi , Kim Duck Hee , Kim Eunjeong , Jung So-Young , Kim Ae-Ran , Kim Tae-Hun
Published: January 2013

Objective

To explore and understand how patients with knee osteoarthritis (OA) experience moxibustion.

Method

This qualitative research was conducted as part of a larger clinical trial of the effectiveness of moxibustion for the treatment of knee OA by qualitative content analysis. Sixteen patients with mild knee OA who participated in a 12-week moxibustion treatment as part of the trial were interviewed using open-ended questions.

Results

The participants recognised knee OA as a normal ageing process that caused physical and emotional discomfort in daily life. Regardless of any adverse effects of moxibustion, most of the participants were interested in continuous moxibustion treatment as a long-term management strategy and for general health.

Conclusions

This study suggests that moxibustion can be helpful in managing symptoms related to knee OA. Patients’ attitudes towards moxibustion can affect the treatment result and those who prefer it want to continue the treatment for a long time because they understand that knee OA is a chronic condition which needs continuous care. However, practitioners need to pay more attention to those who are very enthusiastic because they tend to endure treatment-related adverse events in their desire for better effects.
Gastrointestinal presentation and outcome of perinatal cytomegalovirus infection
Authors: Hendriks Gillian , McPartland Jo , El-Matary Wael
Published: January 2013

A term infant presented at birth with bilious vomiting and abdominal distension. Multiple investigations were undertaken, including two laparotomies and a rectal biopsy, as no obvious cause for his symptoms could be found. This included testing for human cytomegalovirus (CMV) infection as part of a TORCH screen, which was negative at 10 days of age. However, a repeat screen at 3 weeks of age demonstrated positive findings of CMV in both urine and blood PCR. This subsequently led to the diagnosis of gastrointestinal pseudoobstruction associated with perinatal CMV infection. This case is of interest though there is limited information regarding the recognition of gastrointestinal symptoms in relation to CMV infection. This report aims to highlight our experience with an infant with perinatal CMV infection and severe gastrointestinal symptoms.
The impact of the 2011 Great East Japan Earthquake on hospitalisation for respiratory disease in a rapidly aging society: a retrospective descriptive and cross-sectional study at the disaster base hospital in Ishinomaki
Authors: Yamanda Shinsuke , Hanagama Masakazu , Kobayashi Seiichi , Satou Hikari , Tokuda Shinsaku , Niu Kaijun , Yanai Masaru
Published: January 2013

Objective

To investigate the impact in an aging society of the 2011 Great East Japan earthquake on hospitalisation for respiratory disease at the disaster base hospital.

Design

Descriptive and cross-sectional study.

Setting

Emergency care in Japanese Red Cross Ishinomaki Hospital, a regional disaster base hospital in Miyagi, Japan.

Participants

322 emergency patients who were hospitalised for respiratory disease from 11 March to 9 May 2011, and 99 and 105 emergency patients who were hospitalised in the corresponding periods in 2009 and 2010, respectively.

Main outcome measures

Description and comparison of patient characteristics and disease distribution in terms of age, time after the disaster and activities of daily living (ADL).

Results

1769 patients were admitted to our hospital during the study period (compared to 850 in 2009 and 1030 in 2010), among whom 322 were hospitalised for respiratory disease (compared to 99 in 2009 and 105 in 2010). Pneumonia (n=190, 59.0%) was the most frequent cause of admission for pulmonary disease, followed by acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) (n=53, 16.5%), asthma attacks (n=27, 8.4%) and progression of lung cancer (n=22, 6.8%). Compared with the corresponding periods in 2009 and 2010, the increase in the absolute numbers of admissions was highest for pneumonia, followed by AE-COPD and asthma attacks. At hospitalisation, 195 patients were ‘dependent’ and 54 patients were ‘partially dependent’. Respiratory admissions accompanied by deterioration of ADL after the disaster were more frequent in elderly and female patients.

Conclusions

After the Great East Japan Earthquake, admissions for pneumonia and exacerbation of chronic respiratory disease in the elderly increased at the disaster base hospital.
Chronic health problems and health-related quality of life in Chinese children and adolescents: a population-based study in Hong Kong
Authors: Lee S L , Cheung Y F , Wong H S W , Leung T H , Lam T H , Lau Y L
Published: January 2013

Objective

We examined the association of different chronic physical and mental conditions, individually or comorbidly on health-related quality of life (QoL) in Chinese children aged ≤14 years in Hong Kong.

Design

Population-based cross-sectional survey.

Participants

Approximately 7500 Chinese children aged <14 years in Hong Kong.

Interventions

Nil.

Primary and secondary outcome measures

Various health concepts of validated Chinese version of Child Health Questionnaire (CHQ), a health-related QoL questionnaire in children.

Result

There was significant association of physical and mental health conditions, either individually or comorbidly, on the various concepts of CHQ. Children with mental health problems were apparently more affected than those with physical health problems. Chronic renal disease and congenital malformation were the physical health conditions associated with the lowest scores in CHQ concepts in children aged 5–10 years and aged 10–14 years, respectively. Behavioural problem was the mental health condition associated with the lowest score in CHQ concepts in both age groups.

Conclusions

Our study shows important information concerning the prevalence of different health conditions and its association, either individually or comorbidly on the QoL in a representative sample of Chinese children in HK.
Characteristics of people with low health literacy on coronary heart disease GP registers in South London: a cross-sectional study
Authors: Rowlands Gillian P , Mehay Anita , Hampshire Sally , Phillips Rachel , Williams Paul , Mann Anthony , Steptoe Andrew , Walters Paul , Tylee Andre T
Published: January 2013

Objective

To explore characteristics associated with, and prevalence of, low health literacy in patients recruited to investigate the role of depression in patients on General Practice (GP) Coronary Heart Disease (CHD) registers (the Up-Beat UK study).

Design

Cross-sectional cohort. The health literacy measure was the Rapid Estimate of Health Literacy in Medicine (REALM). Univariable analyses identified characteristics associated with low health literacy and compared health service use between health literacy statuses. Those variables where there was a statistically significant/borderline significant difference between health literacy statuses were entered into a multivariable model.

Setting

16 General Practices in South London, UK.

Participants

Inclusion: patients >18 years, registered with a GP and on a GP CHD register. Exclusion: patients temporarily registered.

Primary outcome measure

REALM.

Results

Of the 803 Up-Beat cohort participants, 687 (85.55%) completed the REALM of whom 106 (15.43%) had low health literacy. Twenty-eight participants could not be included in the multivariable analysis due to missing predictor variable data, leaving a sample of 659. The variables remaining in the final model were age, gender, ethnicity, Indices of Multiple Deprivation score, years of education, employment; body mass index and alcohol intake, and anxiety scores (Hospital Anxiety and Depression Scale). Univariable analysis also showed that people with low health literacy may have more, and longer, practice nurse consultations than people with adequate health literacy.

Conclusions

There is a disadvantaged group of people on GP CHD registers with low health literacy. The multivariable model showed that patients with low health literacy have significantly higher anxiety levels than people with adequate health literacy. In addition, the univariable analyses show that such patients have more, and longer, consultations with practice nurses. We will collect 4-year longitudinal cohort data to explore the impact of health literacy in people on GP CHD registers and the impact of health literacy on health service use.
A systematic review of evidence on the links between patient experience and clinical safety and effectiveness
Authors: Doyle Cathal , Lennox Laura , Bell Derek
Published: January 2013

Objective

To explore evidence on the links between patient experience and clinical safety and effectiveness outcomes.

Design

Systematic review.

Setting

A wide range of settings within primary and secondary care including hospitals and primary care centres.

Participants

A wide range of demographic groups and age groups.

Primary and secondary outcome measures

A broad range of patient safety and clinical effectiveness outcomes including mortality, physical symptoms, length of stay and adherence to treatment.

Results

This study, summarising evidence from 55 studies, indicates consistent positive associations between patient experience, patient safety and clinical effectiveness for a wide range of disease areas, settings, outcome measures and study designs. It demonstrates positive associations between patient experience and self-rated and objectively measured health outcomes; adherence to recommended clinical practice and medication; preventive care (such as health-promoting behaviour, use of screening services and immunisation); and resource use (such as hospitalisation, length of stay and primary-care visits). There is some evidence of positive associations between patient experience and measures of the technical quality of care and adverse events. Overall, it was more common to find positive associations between patient experience and patient safety and clinical effectiveness than no associations.

Conclusions

The data presented display that patient experience is positively associated with clinical effectiveness and patient safety, and support the case for the inclusion of patient experience as one of the central pillars of quality in healthcare. It supports the argument that the three dimensions of quality should be looked at as a group and not in isolation. Clinicians should resist sidelining patient experience as too subjective or mood-oriented, divorced from the ‘real’ clinical work of measuring safety and effectiveness.
Identifying geographical regions serviced by hospitals to assess laboratory-based outcomes
Authors: Gandhi Sonja , Shariff Salimah Z , Beyea Michael M , Weir Matthew A , Hands Theresa , Kearns Glen , Garg Amit X
Published: January 2013

Objective

To define geographical regions (forward sortation areas; FSAs) in Southwestern Ontario, Canada from which patients would reliably present to a hospital with linked laboratory data if they developed adverse events related to medications dispensed in outpatient pharmacies.

Design

Descriptive research.

Setting

Forty-five hospitals in Southwestern Ontario, Canada, from 2003 to 2009.

Participants

Patients aged 66 years and older who received an outpatient prescription for any drug and presented to the emergency department in the subsequent 120 days.

Main outcome measure

The proportion of patients in a given FSA presenting to an emergency department at a hospital with linked laboratory data versus a hospital without linked laboratory data. To be included in the catchment area at least 90% of emergency department visits in an FSA must have occurred at laboratory-linked hospitals in a given year.

Results

Over the study period, there were 649 713 emergency department visits by patients with recent prescription claims from pharmacies in 1 of 118 FSAs. In total, 141 302 of these patients presented to an emergency department at a laboratory-linked hospital. For the year 2003, 12 FSAs met our criteria to be in the catchment area and this number grew to 25 FSAs by the year 2009.

Conclusions

The relevant geographical regions for hospitals with linked laboratory data have been successfully identified. Studies can now be conducted using these well-defined areas to obtain reliable information on the incidence and absolute risk of presenting to hospital with laboratory abnormalities in older adults dispensed commonly prescribed medications in outpatient pharmacies.
Errors as allies: error management training in health professions education
Authors: King Aimee , Holder Michael G , Ahmed Rami A
Published: January 2013

This paper adopts methods from the organisational team training literature to outline how health professions education can improve patient safety. We argue that health educators can improve training quality by intentionally encouraging errors during simulation-based team training. Preventable medical errors are inevitable, but encouraging errors in low-risk settings like simulation can allow teams to have better emotional control and foresight to manage the situation if it occurs again with live patients. Our paper outlines an innovative approach for delivering team training.
Interprofessional education in team communication: working together to improve patient safety
Authors: Brock Douglas , Abu-Rish Erin , Chiu Chia-Ru , Hammer Dana , Wilson Sharon , Vorvick Linda , Blondon Katherine , Schaad Douglas , Liner Debra , Zierler Brenda
Published: January 2013

Background

Communication failures in healthcare teams are associated with medical errors and negative health outcomes. These findings have increased emphasis on training future health professionals to work effectively within teams. The Team Strategies and Tools to Enhance Performance and Patient Safety (TeamSTEPPS) communication training model, widely employed to train healthcare teams, has been less commonly used to train student interprofessional teams. The present study reports the effectiveness of a simulation-based interprofessional TeamSTEPPS training in impacting student attitudes, knowledge and skills around interprofessional communication.

Methods

Three hundred and six fourth-year medical, third-year nursing, second-year pharmacy and second-year physician assistant students took part in a 4 h training that included a 1 h TeamSTEPPS didactic session and   three 1 h team simulation and feedback sessions. Students worked in groups balanced by a professional programme in a self-selected focal area (adult acute, paediatric, obstetrics). Preassessments and postassessments were used for examining attitudes, beliefs and reported opportunities to observe or participate in team communication behaviours.

Results

One hundred and forty-nine students (48.7%) completed the preassessments and postassessments. Significant differences were found for attitudes toward team communication (p<0.001), motivation (p<0.001), utility of training (p<0.001) and self-efficacy (p=0.005). Significant attitudinal shifts for TeamSTEPPS skills included, team structure (p=0.002), situation monitoring (p<0.001), mutual support (p=0.003) and communication (p=0.002). Significant shifts were reported for knowledge of TeamSTEPPS (p<0.001), advocating for patients (p<0.001) and communicating in interprofessional teams (p<0.001).

Conclusions

Effective team communication is important in patient safety. We demonstrate positive attitudinal and knowledge effects in a large-scale interprofessional TeamSTEPPS-based training involving four student professions.