bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antihypertensive Medications in End‐Stage Renal Disease
Authors: Denker Matthew G. , Cohen Debbie L. 
Published: April 2015

AbstractHypertension is almost universal in end‐stage renal disease (ESRD) and contributes to the substantial cardiovascular (CV) morbidity and mortality observed in these patients. The management of blood pressure (BP) in ESRD is complicated by a number of factors, including missed dialysis treatments, intradialytic changes in BP, medication removal with dialysis, and poor correlation of BPs obtained in the dialysis unit with those at home and with CV outcomes. Control of extracellular volume with ultrafiltration and dietary sodium restriction represents the principal strategy to manage hypertension in ESRD, and antihypertensive medications are subsequently added if this strategy is inadequate. While reduction in BP with medication improves CV outcomes, few head‐to‐head clinical trials have been performed to firmly establish the superiority of one antihypertensive medication class over another. Therefore, individualization of therapy is necessary, and patient comorbidities must be considered. Angiotensin‐converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and beta‐blockers are reasonable first‐line agents for most patients. ACE inhibitors and ARBs exert cardioprotective effects that are independent of BP reduction. Medications that are removed with dialysis may be preferred in patients who are prone to develop intradialytic hypotension. Intradialytic hypertension can be managed with challenging the patient's dry weight and using nondialyzable medications. Within a class of antihypertensive medications, there may be large variability in drug removal with dialysis, which must be considered upon medication selection. Studies demonstrate that even thrice‐weekly dosing of medication after dialysis has robust BP‐lowering effects, which may be a useful regimen in nonadherent patients.
Effect of sorbitol, single, and multidose activated charcoal administration on carprofen absorption following experimental overdose in dogs
Authors: Koenigshof Amy M. , Beal Matthew W. , Poppenga Robert H. , Jutkowitz L. Ari 
Published: April 2015

AbstractObjectiveTo compare the effectiveness of single dose activated charcoal, single dose activated charcoal with sorbitol, and multidose activated charcoal in reducing plasma carprofen concentrations following experimental overdose in dogs.DesignRandomized, four period cross‐over study.SettingUniversity research setting.AnimalsEight healthy Beagles.InterventionsA 120 mg/kg of carprofen was administered orally to each dog followed by either (i) a single 2 g/kg activated charcoal administration 1 hour following carprofen ingestion (AC); (ii) 2 g/kg activated charcoal with 3.84 g/kg sorbitol 1 hour following carprofen ingestion (ACS); (iii) 2 g/kg activated charcoal 1 hour after carprofen ingestion and repeated every 6 hours for a total of 4 doses (MD); (iv) no treatment (control).Measurements and Main ResultsPlasma carprofen concentrations were obtained over a 36‐hour period following carprofen ingestion for each protocol. Pharmacokinetic modeling was performed and time versus concentration, area under the curve, maximum plasma concentration, time to maximum concentration, and elimination half‐life were calculated and compared among the groups using ANOVA followed by Tukey's multiple comparisons test. Activated charcoal, activated charcoal with sorbitol (ACS), and multiple‐dose activated charcoal (MD) significantly reduced the area under the curve compared to the control group. AC and MD significantly reduced the maximum concentration when compared to the control group. MD significantly reduced elimination half‐life when compared to ACS and the control group. There were no other significant differences among the treatment groups.ConclusionsActivated charcoal and ACS are as effective as MD in reducing serum carprofen concentrations following experimental overdose in dogs. Prospective studies are warranted to evaluate the effectiveness of AC, ACS, and MD in the clinical setting.
Neural‐network based autocontouring algorithm for intrafractional lung‐tumor tracking using Linac‐MR
Authors: Yun Jihyun , Yip Eugene , Gabos Zsolt , Wachowicz Keith , Rathee Satyapal , Fallone B. G. 
Published: April 2015

Purpose:To develop a neural‐network based autocontouring algorithm for intrafractional lung‐tumor tracking using Linac‐MR and evaluate its performance with phantom and in‐vivo MR images.Methods:An autocontouring algorithm was developed to determine both the shape and position of a lung tumor from each intrafractional MR image. A pulse‐coupled neural network was implemented in the algorithm for contrast improvement of the tumor region. Prior to treatment, to initiate the algorithm, an expert user needs to contour the tumor and its maximum anticipated range of motion in pretreatment MR images. During treatment, however, the algorithm processes each intrafractional MR image and automatically generates a tumor contour without further user input. The algorithm is designed to produce a tumor contour that is the most similar to the expert's manual one. To evaluate the autocontouring algorithm in the author's Linac‐MR environment which utilizes a 0.5 T MRI, a motion phantom and four lung cancer patients were imaged with 3 T MRI during normal breathing, and the image noise was degraded to reflect the image noise at 0.5 T. Each of the pseudo‐0.5 T images was autocontoured using the author's algorithm. In each test image, the Dice similarity index (DSI) and Hausdorff distance (HD) between the expert's manual contour and the algorithm generated contour were calculated, and their centroid positions were compared (Δdcentroid).Results:The algorithm successfully contoured the shape of a moving tumor from dynamic MR images acquired every 275 ms. From the phantom study, mean DSI of 0.95–0.96, mean HD of 2.61–2.82 mm, and mean Δdcentroid of 0.68–0.93 mm were achieved. From the in‐vivo study, the author's algorithm achieved mean DSI of 0.87–0.92, mean HD of 3.12–4.35 mm, as well as Δdcentroid of 1.03–1.35 mm. Autocontouring speed was less than 20 ms for each image.Conclusions:The authors have developed and evaluated a lung tumor autocontouring algorithm for intrafractional tumor tracking using Linac‐MR. The autocontouring performance in the Linac‐MR environment was evaluated using phantom and in‐vivo MR images. From the in‐vivo study, the author's algorithm achieved 87%–92% of contouring agreement and centroid tracking accuracy of 1.03–1.35 mm. These results demonstrate the feasibility of lung tumor autocontouring in the author's laboratory's Linac‐MR environment.
Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains
Authors: Constanzo Julie , Paquette Benoit , Charest Gabriel , Masson‐Côté Laurence , Guillot Mathieu 
Published: April 2015

Purpose:Targeted and whole‐brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain.Methods:Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements.Results:The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose‐profile agreement within 5%, both in X‐ and Z‐axes.Conclusions:The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife.
Development of PET/MRI with insertable PET for simultaneous PET and MR imaging of human brain
Authors: Jung Jin Ho , Choi Yong , Jung Jiwoong , Kim Sangsu , Lim Hyun Keong , Im Ki Chun , Oh Chang Hyun , Park Hyun‐wook , Kim Kyung Min , Kim Jong Guk 
Published: April 2015

Purpose:The purpose of this study was to develop a dual‐modality positron emission tomography (PET)/magnetic resonance imaging (MRI) with insertable PET for simultaneous PET and MR imaging of the human brain.Methods:The PET detector block was composed of a 4 × 4 matrix of detector modules, each consisting of a 4 × 4 array LYSO coupled to a 4 × 4 Geiger‐mode avalanche photodiode (GAPD) array. The PET insert consisted of 18 detector blocks, circularly mounted on a custom‐made plastic base to form a ring with an inner diameter of 390 mm and axial length of 60 mm. The PET gantry was shielded with gold‐plated conductive fabric tapes with a thickness of 0.1 mm. The charge signals of PET detector transferred via 4 m long flat cables were fed into the position decoder circuit. The flat cables were shielded with a mesh‐type aluminum sheet with a thickness of 0.24 mm. The position decoder circuit and field programmable gate array‐embedded DAQ modules were enclosed in an aluminum box with a thickness of 10 mm and located at the rear of the MR bore inside the MRI room. A 3‐T human MRI system with a Larmor frequency of 123.7 MHz and inner bore diameter of 60 cm was used as the PET/MRI hybrid system. A custom‐made radio frequency (RF) coil with an inner diameter of 25 cm was fabricated. The PET was positioned between gradient and the RF coils. PET performance was measured outside and inside the MRI scanner using echo planar imaging, spin echo, turbo spin echo, and gradient echo sequences. MRI performance was also evaluated with and without the PET insert. The stability of the newly developed PET insert was evaluated and simultaneous PET and MR images of a brain phantom were acquired.Results:No significant degradation of the PET performance caused by MR was observed when the PET was operated using various MR imaging sequences. The signal‐to‐noise ratio of MR images was slightly degraded due to the PET insert installed inside the MR bore while the homogeneity was maintained. The change of gain of the 256 GAPD/scintillator elements of a detector block was <3% for 60 min, and simultaneous PET and MR images of a brain phantom were successfully acquired.Conclusions:Experimental results indicate that a compact and lightweight PET insert for hybrid PET/MRI can be developed using GAPD arrays and charge signal transmission method proposed in this study without significant interference.
Quick Detection of
FKS1
Mutations Responsible for Clinical Echinocandin Resistance in Candida albicans
Authors: Dudiuk Catiana , Gamarra Soledad , Jimenez-Ortigosa Cristina , Leonardelli Florencia , Macedo Daiana , Perlin David S. , Garcia-Effron Guillermo 
Published: April 2015

ABSTRACT

A rapid molecular-based assay for the detection of the
Candida albicans FKS1
gene mutations responsible for resistance to echinocandin drugs was designed and evaluated. The assay consisted of a multiplexed PCR set of 5 tubes able to detect the most commonly described resistance mechanism, including
FKS1
hot spot 1 and hot spot 2 mutations. The performance and specificity of the assay was evaluated using a double-blinded panel of 50
C. albicans
strains. The assay showed a sensitivity of 96% and was able to detect all homozygous mutants included in the collection of strains, demonstrating that it is a robust, quick, and labor-saving method that is suitable for a routine clinical diagnostic laboratory.
Urinary Tract Infection Caused by a Capnophilic Proteus mirabilis Strain
Authors: Trapman Maryse , van Ingen Jakko , Keijman Jeroen , Swanink Caroline M. 
Published: April 2015

ABSTRACT

From a urine sample from a patient with a urinary tract infection, a carbon dioxide-dependent
Proteus mirabilis
strain was isolated. It is important to perform urine cultures in 5% carbon dioxide and an anaerobic atmosphere if bacteria prominent in Gram stains do not grow on routine media in ambient air.
Molecular Assay for Detection of Genetic Markers Associated with Decreased Susceptibility to Cephalosporins in Neisseria gonorrhoeae
Authors: Peterson S. W. , Martin I. , Demczuk W. , Bharat A. , Hoang L. , Wylie J. , Allen V. , Lefebvre B. , Tyrrell G. , Horsman G. , Haldane D. , Garceau R. , Wong T. , Mulvey M. R. 
Published: April 2015

ABSTRACT

The incidence of antimicrobial-resistant
Neisseria gonorrhoeae
continues to rise in Canada; however, antimicrobial resistance data are lacking for approximately 70% of gonorrhea infections that are diagnosed directly from clinical specimens by nucleic acid amplification tests (NAATs). We developed a molecular assay for surveillance use to detect mutations in genes associated with decreased susceptibility to cephalosporins that can be applied to both culture isolates and clinical samples. Real-time PCR assays were developed to detect single nucleotide polymorphisms (SNPs) in
ponA
,
mtrR
,
penA
,
porB
, and one
N. gonorrhoeae
-specific marker (
porA
). We tested the real-time PCR assay with 252 gonococcal isolates, 50 nongonococcal isolates, 24
N. gonorrhoeae
-negative NAAT specimens, and 34
N. gonorrhoeae
-positive NAAT specimens. Twenty-four of the
N. gonorrhoeae
-positive NAAT specimens had matched culture isolates. Assay results were confirmed by comparison with whole-genome sequencing data. For 252
N. gonorrhoeae
strains, the agreement between the DNA sequence and real-time PCR was 100% for
porA
,
ponA
, and
penA
, 99.6% for
mtrR
, and 95.2% for
porB
. The presence of ≥2 SNPs correlated with decreased susceptibility to ceftriaxone (sensitivities of >98%) and cefixime (sensitivities of >96%). Of 24 NAAT specimens with matched cultures, the agreement between the DNA sequence and real-time PCR was 100% for
porB
, 95.8% for
ponA
and
mtrR
, and 91.7% for
penA
. We demonstrated the utility of a real-time PCR assay for sensitive detection of known markers for the decreased susceptibility to cephalosporins in
N. gonorrhoeae
. Preliminary results with clinical NAAT specimens were also promising, as they correlated well with bacterial culture results.
Unravelling the Role of the F55 Regulator in the Transition from Lysogeny to UV Induction of Sulfolobus Spindle-Shaped Virus 1
Authors: Fusco Salvatore , She Qunxin , Fiorentino Gabriella , Bartolucci Simonetta , Contursi Patrizia 
Published: April 2015

ABSTRACT

Sulfolobus
spindle-shaped virus 1 represents a model for studying virus-host interaction in harsh environments, and it is so far the only member of the family
Fuselloviridae
that shows a UV-inducible life cycle. Although the virus has been extensively studied, mechanisms underpinning the maintenance of lysogeny as well as those regulating the UV induction have received little attention. Recently, a novel SSV1 transcription factor, F55, was identified. This factor was able to bind
in vitro
to several sequences derived from the early and UV-inducible promoters of the SSV1 genome. The location of these binding sites together with the differential affinity of F55 for these sequences led to the hypothesis that this protein might be involved in the maintenance of the SSV1 lysogeny. Here, we report an
in vivo
survey of the molecular events occurring at the UV-inducible region of the SSV1 genome, with a focus on the binding profile of F55 before and after the UV irradiation. The binding of F55 to the target promoters correlates with transcription repression, whereas its dissociation is paralleled by transcription activation. Therefore, we propose that F55 acts as a molecular switch for the transcriptional regulation of the early viral genes.

IMPORTANCE
Functional genomic studies of SSV1 proteins have been hindered by the lack of similarity with other characterized proteins. As a result, few insights into their
in vivo
roles have been gained throughout the last 3 decades. Here, we report the first
in vivo
investigation of an SSV1 transcription regulator, F55, that plays a key role in the transition from the lysogenic to the induced state of SSV1. We show that F55 regulates the expression of the UV-inducible as well as the early genes. Moreover, the differential affinity of this transcription factor for these targets allows a fine-tuned and temporal coordinated regulation of transcription of viral genes.
Structural Basis for 2′-5′-Oligoadenylate Binding and Enzyme Activity of a Viral RNase L Antagonist
Authors: Ogden Kristen M. , Hu Liya , Jha Babal K. , Sankaran Banumathi , Weiss Susan R. , Silverman Robert H. , Patton John T. , Prasad B. V. Venkataram 
Published: April 2015

ABSTRACT
Synthesis of 2′-5′-oligoadenylates (2-5A) by oligoadenylate synthetase (OAS) is an important innate cellular response that limits viral replication by activating the latent cellular RNase, RNase L, to degrade single-stranded RNA. Some rotaviruses and coronaviruses antagonize the OAS/RNase L pathway through the activity of an encoded 2H phosphoesterase domain that cleaves 2-5A. These viral 2H phosphoesterases are phylogenetically related to the cellular A kinase anchoring protein 7 (AKAP7) and share a core structure and an active site that contains two well-defined HΦ(S/T)Φ (where Φ is a hydrophobic residue) motifs, but their mechanism of substrate binding is unknown. Here, we report the structures of a viral 2H phosphoesterase, the C-terminal domain (CTD) of the group A rotavirus (RVA) VP3 protein, both alone and in complex with 2-5A. The domain forms a compact fold, with a concave β-sheet that contains the catalytic cleft, but it lacks two α-helical regions and two β-strands observed in AKAP7 and other 2H phosphoesterases. The cocrystal structure shows significant conformational changes in the R loop upon ligand binding. Bioinformatics and biochemical analyses reveal that conserved residues and residues required for catalytic activity and substrate binding comprise the catalytic motifs and a region on one side of the binding cleft. We demonstrate that the VP3 CTD of group B rotavirus, but not that of group G, cleaves 2-5A. These findings suggest that the VP3 CTD is a streamlined version of a 2H phosphoesterase with a ligand-binding mechanism that is shared among 2H phosphodiesterases that cleave 2-5A.

IMPORTANCE
The C-terminal domain (CTD) of rotavirus VP3 is a 2H phosphoesterase that cleaves 2′-5′-oligoadenylates (2-5A), potent activators of an important innate cellular antiviral pathway. 2H phosphoesterase superfamily proteins contain two conserved catalytic motifs and a proposed core structure. Here, we present structures of a viral 2H phosphoesterase, the rotavirus VP3 CTD, alone and in complex with its substrate, 2-5A. The domain lacks two α-helical regions and β-strands present in other 2H phosphoesterases. A loop of the protein undergoes significant structural changes upon substrate binding. Together with our bioinformatics and biochemical findings, the crystal structures suggest that the RVA VP3 CTD domain is a streamlined version of a cellular enzyme that shares a ligand-binding mechanism with other 2H phosphodiesterases that cleave 2-5A but differs from those of 2H phosphodiesterases that cleave other substrates. These findings may aid in the future design of antivirals targeting viral phosphodiesterases with cleavage specificity for 2-5A.
Resection of a large carotid paraganglioma in Carney-Stratakis syndrome: a multidisciplinary feat
Authors: Nicholas Rebecca Spenser , Quddus Ayyaz , Topham Charlotte , Baker Daryll 
Published: April 2015

A 39-year-old man was referred to the vascular surgeons with a right-sided cervical mass, palpitations, headaches and sweating. He had presented with abdominal discomfort 12 months earlier. Investigations had revealed a gastrointestinal stromal tumour (GIST) and left adrenalectomy. CT of the neck with contrast demonstrated a large right carotid paraganglioma, extending superiorly from below the carotid bifurcation to encase the internal carotid artery. Genetic screening confirmed the diagnosis of Carney-Stratakis syndrome, an SDH-D germline mutation leading to GIST and multifocal paragangliomas.Successful surgical excision required considerable multidisciplinary teamwork between neuroendocrinologists, anaesthetists and surgeons. The tumour was highly vascular and involved the right carotid body, hypoglossal and vagus nerves. Access was challenging and maxillofacial surgical expertise were required for division of the mandible. The patient made a good recovery following speech and swallowing rehabilitation.
Application of the Safety Attitudes Questionnaire (SAQ) in Albanian hospitals: a cross-sectional study
Authors: Gabrani Adriatik , Hoxha Adrian , Simaku Artan , Gabrani Jonila (Cyco) 
Published: April 2015

ObjectiveTo establish the reliability and validity of the translated version of the Safety Attitudes Questionnaire (SAQ) by evaluating its psychometric properties and to determine possible differences among nurses and physicians regarding safety attitudes.DesignA cross-sectional study utilising the Albanian version of the SAQ and a demographic questionnaire.SettingFour regional hospitals in Albania.Participants341 healthcare providers, including 132 nurses and 209 doctors.Main outcome measure(s)The translation, construct validity and internal validity of the SAQ. The SAQ includes six scales and 30 items.ResultsA total of 341 valid questionnaires were returned, for a response rate of 70%. The confirmatory factor analysis and its goodness-of-fit indices (standardised root mean square residual 0.075, root mean square error of approximation 0.044 and comparative fit index 0.97) showed good model fit. The Cronbach's α values for each of the scales of the SAQ ranged from 0.64 to 0.82. The percentage of hospital healthcare workers who had a positive attitude was 60.3% for the teamwork climate, 57.2% for the safety climate, 58.4% for job satisfaction, 37.4% for stress recognition, 59.3% for the perception of management and 49.5% for working conditions. Intercorrelations showed that the subscales had moderate-to-high correlations with one another. Nurses were more hesitant to admit and report errors; only 55% of physicians and 44% of nurses endorsed this statement (χ2=4.9, p=0.02). Moreover, nurses received lower scores on team work compared with doctors (N 45.7 vs D 52.3, p=0.01). Doctors denied the effects of stress and fatigue on their performance (N 46.7 vs D 39.5, p<0.01), neglecting the workload.ConclusionsThe SAQ is a useful tool for evaluating safety attitudes in Albanian hospitals. In light of the health workforce's poor recognition of stress, establishing patient safety programmes should be a priority among policymakers in Albania.