bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting return to play after hamstring injuries
Authors: Moen M H , Reurink G , Weir A , Tol J L , Maas M , Goudswaard G J
Published: July 2014

Background

Previous studies on the prognostic value of clinical and MRI parameters for the time to return to play (TTRTP) in acute hamstring injuries showed only limited to moderate evidence for the various investigated parameters. Some studies had multiple methodological limitations, including retrospective designs and the use of univariate analysis only. The aim of this study was to assess the prognostic value of clinical and MRI parameters for TTRTP using multivariate analysis.

Methods

28 clinical and MRI parameters were prospectively investigated for an association with TTRTP in 80 non-professional athletes with MRI positive hamstring injuries undergoing a standardised rehabilitation programme. The association between possible prognostic parameters and TTRTP was assessed with a multivariate linear regression model. Parameters that had a p value <0.2 on univariate testing were included in this model.

Results

74 athletes were available for analysis. A total of nine variables met the criteria for the multivariate analysis: intensity of sports, level of sports, self-predicted TTRTP by the athlete, length of discomfort on palpation, deficit in passive straight leg raise, pain score on isometric knee flexion, isometric knee flexion strength deficit and distance of the proximal pole of the MRI hyperintensity to the tuber ischiadicum. Of these, only self-predicted TTRTP by the athlete and a passive straight leg raise deficit remained significantly associated with TTRTP after stepwise logistic regression.

Conclusions

The clinical parameters self-predicted TTRTP and passive straight leg raise deficit are independently associated with the TTRTP. MRI parameters in grade 1 and 2 hamstring injuries, as described in the literature, are not associated with TTRTP. For clinical practice, prognosis of the TTRTP in these injuries should better be based on clinical parameters.
Prevalence of birefringent crystals in cardiac and prostatic tissues, an observational study
Authors: Park Jane J , Roudier Martine P , Soman Divya , Mokadam Nahush A , Simkin Peter A
Published: July 2014

Introduction

The prevalence of urate crystals in residual tissue samples from coronary arteries, aortic valves and prostate glands was assessed.

Methods

Alcohol-fixed coronary arteries from 55 explanted hearts, alcohol-fixed aortic valves collected from 75 valve replacement surgeries and 40 frozen, unfixed prostate specimens resected during cancer surgery were examined for birefringent crystals with polarising microscopy.

Results

In the 55 explanted hearts, 6 (10.9%) contained a coronary artery with birefringent crystals. One of the 75 aortic valves (1.4%) contained negatively and positively birefringent crystals. Nineteen of the 40 (47.5%) prostates contained birefringent crystals.

Conclusions

We found that a remarkable percentage of coronary arteries and prostate specimens contained birefringent crystals. Crystal presence is an obvious prerequisite for possible crystal induced-inflammation in these tissues, just as similar crystals elicit a gouty inflammatory cascade in synovial joints. Further studies are necessary to determine whether urate crystals may play this role in these tissues and, if so, to establish whether urate-lowering therapy may be beneficial in prostatitis and coronary disease.
‘It sounds like a great idea but…’: a qualitative study of GPs’ attitudes towards the development of a national diabetes register
Authors: Mc Hugh Sheena M , O'Mullane Monica , Perry Ivan J , Bradley Colin
Published: July 2014

Objective

The aim of this study was to investigate the attitudes of general practitioners (GPs) to the development of a national diabetes register as a way of improving the quality of care.

Design

Qualitative study using semistructured interviews.

Setting

General practice, Ireland.

Participants

Purposive sample of 29 GPs and two practice nurses. Participants’ practices varied by (a) location (rural/urban), (b) size (single-handed/group practice) and (c) extent of computerisation.

Methods

The semistructured topic guide focused on experiences of change in the health system at a local and national level and attitudes towards the development of a national diabetes register. Analysis was conducted using the Framework approach.

Results

Participants were sceptical about the development of a national diabetes register. The main advantage was ‘knowing the numbers’ for epidemiological and policy purposes. However, participants questioned the benefits for their practice and patients. There were concerns that it would drain resources from other priorities and distract from patient management. These attitudes were strongly influenced by previous experience of change in the health system. Participants felt that remuneration would be necessary to ensure full engagement, reflecting wider frustrations with payment structures for general practice. There was a sense of wariness towards health service administration which was not specific to diabetes care but which coloured some participants’ attitudes towards a national register. In contrast, participants referred to positive experiences of change at a local level, facilitated by a ‘practice ethos’ and professional leadership.

Conclusions

This study highlights the growing sense of scepticism and inertia towards change within the health system. This inertia stems from previous experience and the competing demands of maintaining versus improving care in a system with dwindling resources.
The WHO surgical safety checklist: survey of patients’ views
Authors: Russ Stephanie Jane , Rout Shantanu , Caris Jochem , Moorthy Krishna , Mayer Erik , Darzi Ara , Sevdalis Nick , Vincent Charles
Published: July 2014

Background

Evidence suggests that full implementation of the WHO surgical safety checklist across NHS operating theatres is still proving a challenge for many surgical teams. The aim of the current study was to assess patients’ views of the checklist, which have yet to be considered and could inform its appropriate use, and influence clinical buy-in.

Method

Postoperative patients were sampled from surgical wards at two large London teaching hospitals. Patients were shown two professionally produced videos, one demonstrating use of the WHO surgical safety checklist, and one demonstrating the equivalent periods of their operation before its introduction. Patients’ views of the checklist, its use in practice, and their involvement in safety improvement more generally were captured using a bespoke 19-item questionnaire.

Results

141 patients participated. Patients were positive towards the checklist, strongly agreeing that it would impact positively on their safety and on surgical team performance. Those worried about coming to harm in hospital were particularly supportive. Views were divided regarding hearing discussions around blood loss/airway before their procedure, supporting appropriate modifications to the tool. Patients did not feel they had a strong role to play in safety improvement more broadly.

Conclusions

It is feasible and instructive to capture patients’ views of the delivery of safety improvements like the checklist. We have demonstrated strong support for the checklist in a sample of surgical patients, presenting a challenge to those resistant to its use.
Teaching medical humanities in the digital world: affordances of technology-enhanced learning
Authors: Kemp Sandra Joy , Day Giskin
Published: July 2014

Medical humanities courses are typically taught in face-to-face teaching environments, but now medical humanities educators, alongside educators from other disciplines, are facing shifts in higher education towards online (and sometimes open) courses. For the medical humanities educator, there is limited guidance regarding how technology-enhanced learning design can support the learning outcomes associated with medical humanities. This article aims to provide useful direction for such educators on how digital technologies can be used through learner-focused pedagogies. Specific examples are provided as to how the affordances of Web 2.0 and other tools can be realised in innovative ways to help achieve skills development within the medical humanities. The guidance, alongside the practical suggestions for implementation, can provide important conceptual background for medical humanities educators who wish to embrace technology-enhanced learning, and reconceptualise or redesign medical humanities for an online or blended teaching environment.
Corynebacterium species nasal carriage in pigs and their farmers in Bavaria, Germany: implications for public health
Authors: Boschert V. , Berger A. , Konrad R. , Huber I. , Hörmansdorfer S. , Zöls S. , Eddicks M. , Ritzmann M. , Sing A.
Published: July 2014

Reports on cases of human diphtheria caused by toxigenic Corynebacterium ulcerans that were linked to occupational swine contact as well as isolation of C ulcerans from wild boars have suggested that pigs might serve as reservoir for human infections. Therefore, a prevalence study on Corynebacterium species nasal carriage in pigs and their farmers was performed between August 1 and December 31, 2009, in 41 swine farms from Bavaria, Germany. All 411 asymptomatic pigs and 29 of 30 healthy farmers were colonised with Corynebacterium strains of up to 11 different species. No potentially toxigenic Corynebacterium strain was isolated either from the pigs or from their farmers, respectively. The patterns of the species composition in the pigs and the farmers were very similar, suggesting a potential transmission of strains between animals and humans.
Multi-Scale Modelling of Nuclear Reactor Core Graphite
Authors: Smith G. E. , Flewitt P. E. J. , Schlangen H.
Published: July 2014

Magnox and Advanced Gas Cooled reactors operated in the UK are cooled by carbon dioxide gas. The graphite moderator bricks in the reactor core lose mass and become more porous during service due to radiolytic oxidation caused by energy deposition, mainly gamma radiation. The microstructure of these graphites comprises filler particles embedded in a graphitised matrix which contains porosity arising from the manufacturing process and subsequent radiolytic oxidation. Computer models have been developed to be representative of the graphite microstructure and these results are used as an input to multi-scale finite element models. These idealised models provide descriptions of the key features that contribute to an understanding of the relationship between the role of filler particles and the amount of porosity on both load-displacement (stress-strain) and fracture characteristics. Two models are considered to span the length-scales: (i) up to millimetre dimensions and (ii) centimetre dimensions. The results are considered with respect to (i) the model length-scale, (ii) the role of the volume percentage of porosity and (iii) the size and distribution of filler particles.
Interaction of arc magmas with subvolcanic hydrothermal systems: insights from compositions and metasomatic textures of olivine crystals in fresh basalts of Daisen and Mengameyama, Western Honshu, Japan
Authors: Zellmer Georg F. , Hwang Shyh-Lung , Sakamoto Naoya , Iizuka Yoshiyuki , Harada Sakiko , Kimura Jun-Ichi , Tamura Yoshihiko , Yurimoto Hisayoshi
Published: July 2014

Pleistocene basalts from Daisen and Mengameyama in the SW Japan volcanic arc of western Honshu are characterized by an abundance of olivine crystals with Fe-rich rims. At Daisen, these have previously been interpreted to have formed from their host melt by equilibrium crystal fractionation and by disequilibrium fractionation during supercooling. Here we use combined electron probe microanalysis, isotopography, transmission electron microscopy and selected area electron diffraction to show that crystal rims are significantly enriched in aluminium (up to
c.
1 wt%) and hydrogen (up to
c.
10 000 ppm) hosted in oriented low-density amorphous domains. These domains are interpreted to have formed by melting of deuteric and/or post-deuteric metasomatic alteration minerals upon uptake of older olivine crystals into fresh, initially aphyric host melts up to a few hours prior to eruption. It is argued that uptake of variably altered crystals into initially aphyric or sparsely phyric melts may be a common process at subduction zones, and can account for typical disequilibrium textures displayed by arc magmas erupted in SW Japan and elsewhere. Analyses of the altered crystal cargo in arc volcanic rocks therefore provides an important tool for understanding subvolcanic hydrothermal systems and the interaction of ascending melts with such systems.

Supplementary material:

Olivine mineral chemistry data from two typical Daisen basalts and one typical Mengameyama basalt, and a figure showing the locations of all focussed ion beam (FIB) sections studied here, are available at
http://www.geolsoc.org.uk/SUP18760
.
Motion-Detecting Circuits in Flies: Coming into View
Authors: Silies Marion , Gohl Daryl M. , Clandinin Thomas R.
Published: July 2014

Visual motion cues provide animals with critical information about their environment and guide a diverse array of behaviors. The neural circuits that carry out motion estimation provide a well-constrained model system for studying the logic of neural computation. Through a confluence of behavioral, physiological, and anatomical experiments, taking advantage of the powerful genetic tools available in the fruit fly Drosophila melanogaster, an outline of the neural pathways that compute visual motion has emerged. Here we describe these pathways, the evidence supporting them, and the challenges that remain in understanding the circuits and computations that link sensory inputs to behavior. Studies in flies and vertebrates have revealed a number of functional similarities between motion-processing pathways in different animals, despite profound differences in circuit anatomy and structure. The fact that different circuit mechanisms are used to achieve convergent computational outcomes sheds light on the evolution of the nervous system.
Uroguanylin inhibits H-ATPase activity and surface expression in renal distal tubules by a PKG-dependent pathway
Authors: da Silva Lima Vanessa , Crajoinas Renato O. , Carraro-Lacroix Luciene R. , Godinho Alana N. , Dias João L. G. , Dariolli Rafael , Girardi Adriana C. C. , Fonteles Manassés C. , Malnic Gerhard , Lessa Lucília M. A.
Published: July 2014

Cumulative evidence suggests that guanylin peptides play an important role on electrolyte homeostasis. We have previously reported that uroguanylin (UGN) inhibits bicarbonate reabsorption in a renal distal tubule. In the present study, we tested the hypothesis that the bicarbonaturic effect of UGN is at least in part attributable to inhibition of H+-ATPase-mediated hydrogen secretion in the distal nephron. By in vivo stationary microperfusion experiments, we were able to show that UGN inhibits H+-ATPase activity by a PKG-dependent pathway because KT5823 (PKG inhibitor) abolished the UGN effect on distal bicarbonate reabsorption and H89 (PKA inhibitor) was unable to prevent it. The in vivo results were confirmed by the in vitro experiments, where we used fluorescence microscopy to measure intracellular pH (pHi) recovery after an acid pulse with NH4Cl. By this technique, we observed that UGN and 8 bromoguanosine-cGMP (8Br-cGMP) inhibited H+-ATPase-dependent pHi recovery and that the UGN inhibitory effect was abolished in the presence of the PKG inhibitor. In addition, by using RT-PCR technique, we verified that Madin-Darby canine kidney (MDCK)-C11 cells express guanylate cyclase-C. Besides, UGN stimulated an increase of both cGMP content and PKG activity but was unable to increase the production of cellular cAMP content and PKA activity. Furthermore, we found that UGN reduced cell surface abundance of H+-ATPase B1 subunit in MDCK-C11 and that this effect was abolished by the PKG inhibitor. Taken together, our data suggest that UGN inhibits H+-ATPase activity and surface expression in renal distal cells by a cGMP/PKG-dependent pathway.
Systemic influences contribute to prolonged microvascular rarefaction after brain irradiation: a role for endothelial progenitor cells
Authors: Ashpole Nicole M. , Warrington Junie P. , Mitschelen Matthew C. , Yan Han , Sosnowska Danuta , Gautam Tripti , Farley Julie A. , Csiszar Anna , Ungvari Zoltan , Sonntag William E.
Published: July 2014

Whole brain radiation therapy (WBRT) induces profound cerebral microvascular rarefaction throughout the hippocampus. Despite the vascular loss and localized cerebral hypoxia, angiogenesis fails to occur, which subsequently induces long-term deficits in learning and memory. The mechanisms underlying the absence of vessel recovery after WBRT are unknown. We tested the hypotheses that vascular recovery fails to occur under control conditions as a result of loss of angiogenic drive in the circulation, chronic tissue inflammation, and/or impaired endothelial cell production/recruitment. We also tested whether systemic hypoxia, which is known to promote vascular recovery, reverses these chronic changes in inflammation and endothelial cell production/recruitment. Ten-week-old C57BL/6 mice were subjected to a clinical series of fractionated WBRT: 4.5-Gy fractions 2 times/wk for 4 wk. Plasma from radiated mice increased in vitro endothelial cell proliferation and adhesion compared with plasma from control mice, indicating that WBRT did not suppress the proangiogenic drive. Analysis of cytokine levels within the hippocampus revealed that IL-10 and IL-12(p40) were significantly increased 1 mo after WBRT; however, systemic hypoxia did not reduce these inflammatory markers. Enumeration of endothelial progenitor cells (EPCs) in the bone marrow and circulation indicated that WBRT reduced EPC production, which was restored with systemic hypoxia. Furthermore, using a bone marrow transplantation model, we determined that bone marrow-derived endothelial-like cells home to the hippocampus after systemic hypoxia. Thus, the loss of production and homing of EPCs have an important role in the prolonged vascular rarefaction after WBRT.
Exercise-mediated vasodilation in human obesity and metabolic syndrome: effect of acute ascorbic acid infusion
Authors: Limberg Jacqueline K. , Kellawan J. Mikhail , Harrell John W. , Johansson Rebecca E. , Eldridge Marlowe W. , Proctor Lester T. , Sebranek Joshua J. , Schrage William G.
Published: July 2014

We tested the hypothesis that infusion of ascorbic acid (AA), a potent antioxidant, would alter vasodilator responses to exercise in human obesity and metabolic syndrome (MetSyn). Forearm blood flow (FBF, Doppler ultrasound) was measured in lean, obese, and MetSyn adults ( n = 39, 32 ± 2 yr). A brachial artery catheter was inserted for blood pressure monitoring and local infusion of AA. FBF was measured during dynamic handgrip exercise (15% maximal effort) with and without AA infusion. To account for group differences in blood pressure and forearm size, and to assess vasodilation, forearm vascular conductance (FVC = FBF/mean arterial blood pressure/lean forearm mass) was calculated. We examined the time to achieve steady-state FVC (mean response time, MRT) and the rise in FVC from rest to steady-state exercise (Δ, exercise − rest) before and during acute AA infusion. The MRT ( P = 0.26) and steady-state vasodilator responses to exercise (ΔFVC, P = 0.31) were not different between groups. Intra-arterial infusion of AA resulted in a significant increase in plasma total antioxidant capacity (174 ± 37%). AA infusion did not alter MRT or steady-state FVC in any group ( P = 0.90 and P = 0.85, respectively). Interestingly, higher levels of C-reactive protein predicted longer MRT ( r = 0.52, P < 0.01) and a greater reduction in MRT with AA infusion ( r = −0.43, P = 0.02). We concluded that AA infusion during moderate-intensity, rhythmic forearm exercise does not alter the time course or magnitude of exercise-mediated vasodilation in groups of young lean, obese, or MetSyn adults. However, systemic inflammation may limit the MRT to exercise, which can be improved with AA.
Balance-corrective responses to unexpected perturbations at the arms during treadmill walking
Authors: Forero Juan , Misiaszek John E.
Published: July 2014

The arms have been shown to be involved in the regulation of balance during walking. The use of a walking aid enhances balance by increasing the base of support and reducing the load on the legs by partly transferring it to the arms. However, when actively engaged during a balance task, perturbations to the arms can destabilize balance. Previous studies have investigated postural adjustments associated with focal arm movements during standing and walking. However, balance-corrective reactions to unexpected perturbations to the arms during walking have not been well studied. In the present study, subjects walked on a treadmill while grasping a pair of handles when sudden perturbations were delivered by displacing the handles in the forward or backward direction. Instructing subjects to oppose the displacement of the handles resulted in strong responses in the arms that were accompanied by activation of muscles in the legs, comparable to those observed in other balance disturbance studies. Conversely, when subjects were instructed to allow the handles to move when displaced, no responses were observed in the arms. However, similar responses were observed in the legs whether subjects opposed the displacement of the handles or not when perturbations were applied at heel strike. The results from this study show that balance reactions can be elicited in the legs in response to perturbations applied at the arms, and that the expression of these responses is affected by the task engaged in by the arms.
A Modified Homotopy Perturbation Transform Method for Transient Flow of a Third Grade Fluid in a Channel with Oscillating Motion on the Upper Wall
Authors: Abdulhameed Mohammed , Roslan Rozaini , Bin Mohamad Mahathir
Published: July 2014

A new analytical algorithm based on modified homotopy perturbation transform method is employed for solving the transient flow of third grade fluid in a porous channel generated by an oscillating upper wall. This method incorporates the He’s polynomial into the HPM, combined with Laplace transform. Comparison with HPM and OHAM analytical solutions reveals that the proposed algorithm is highly accurate. This proves the validity and great potential of the proposed algorithm as a new kind of powerful analytical tool for transient nonlinear problems. Graphs representing the solutions are discussed, and appropriate conclusions are drawn.
Valproate Treatment in an ALS Patient Carrying a c.194G>A Spastin Mutation and SMN2 Homozygous Deletion
Authors: Tremolizzo Lucio , Sala Gessica , Conti Elisa , Rodriguez-Menendez Virginia , Fogli Antonella , Michelucci Angela , Simi Paolo , Penco Silvana , Lunetta Christian , Corbo Massimo , Ferrarese Carlo
Published: July 2014

Here we report the case of an ALS patient found to carry both a novel heterozygous change (c.194G>A) within the spastin gene and a homozygous deletion of the SMN2 gene. The patient was started on valproic acid (VPA, 600 mg/die per os) considering the capacity of this drug of increasing survival motor neuron through an epigenetic mechanism. Patient clinical course and molecular effects of VPA on skin fibroblasts obtained from the proband are described. This c.194G>A spastin mutation might expand the previously known borders of type 4 spastic paraplegia (SPG4) and we suggest the intriguing possibility that the absence of SMN2 might have acted as a contributory risk factor for starting lower motor neuron damage. Exploring the relationship genocopy-phenocopy in selected ALS patients might represent an interesting strategy for understanding its clinical variability.
Synthesis and Crystal Structure of 1-Methyl-3-(2-pyridyl)imidazolium Hexafluorophosphate
Authors: Kandasamy Elango
Published: July 2014

Compound 1-Methyl-3-(2-pyridyl)imidazolium hexafluorophosphate was crystallized in monoclinic system with space group P21/c and unit cell parameters a=7.3740(8) Å, b=15.5931(16) Å, c=10.4787(11) Å, β= 105.3102°, and  ν=1162.12Å3. The obtained solid state structure of 1-Methyl-3-(2-pyridyl)imidazolium hexafluorophosphate shows CH⋯F type weak interactions and was analyzed.
Prediction of Mass Transfer Time Relaxation Parameter for Boiling Simulation on the Shell-Side of LNG Spiral Wound Heat Exchanger
Authors: Wu Zhi-Yong , Cai Wei-Hua , Qiu Guo-Dong , Jiang Yi-Qiang
Published: July 2014

The objective of this present study is to propose an approach to predict mass transfer time relaxation parameter for boiling simulation on the shell-side of LNG spiral wound heat exchanger (SWHE). The numerical model for the shell-side of LNG SWHE was established. For propane and ethane, a predicted value of mass transfer time relaxation parameter was presented through the equivalent evaporation simulations and was validated by the Chisholm void fraction correlation recommended under various testing conditions. In addition, heat transfer deviations between simulations using the predicted value of mass transfer time relaxation parameter and experiments from Aunan were investigated. The boiling characteristics of SWHE shell-side were also visualized based on the simulations with VOF model. The method of predicting mass transfer time relaxation parameter may be well applicable to various phase change simulations.
Vaginal Septoplasty in Septate Uterus with Double Cervix
Authors: Barbanti Samuel , Chiamulera Nara , Botelho Beatriz
Published: July 2014

Fusion defects of the Müllerian ducts occur frequently and they have been described by the American Fertility Society. However, septate uterus with cervical duplication and longitudinal vaginal septum is not described by this classification and has suggested a change in the classical theory of fusion of the Müllerian ducts. This paper describes a rare case report of a patient with complete septate uterus with double cervix and longitudinal vaginal septum, submitted to the vaginal septoplasty for dyspareunia, progressing to clinical improvement. The description of this case is to contribute with all uncommon cases of Müllerian anomalies reports and clinical treatment protocols, which is not yet established.
Locking Compression Plate in Distal Femoral Intra-Articular Fractures: Our Experience
Authors: Kiran Kumar G. N. , Sharma Gaurav , Farooque Kamran , Sharma Vijay , Ratan Ratnav , Yadav Sanjay , Lakhotia Devendra
Published: July 2014

Background. Intra-articular fractures of distal femur present a huge surgical challenge. The aim of this study is to evaluate functional outcome, fracture healing, and the complications of distal femoral intra-articular fractures using locking compression plates. Material and Methods. We reviewed 46 distal femoral fractures treated with distal femoral locking compression plates between 2009 to 2012. There were 36 men and 10 women with mean age of 35 years (range 20–72). More than half of the patients were of type C3 (AO classification) and had been caused by high energy trauma with associated injuries. Results. 2 patients were lost to follow-up. Of the remaining 44 patients, the mean follow-up period was 25 months (range 18–36). The mean time for radiological union was 12 weeks (range 10–18) except 2 patients which had gone for nonunion. At the latest follow up ROM >120∘ is noted in 32 patients, 90–120 in 10 patients, and 70–90 in 2 patients. 38 patients (86%) had good/excellent outcome. Conclusion. Use of standard lateral approach for simple intra-articular distal femoral fractures (C1) and transarticular/minimally invasive techniques for complex intra-articular fractures (C2/C3) results in improved exposure of the knee joint and better union rates with low incidence of bone grafting.
Haematuria: An Imaging Guide
Authors: Moloney Fiachra , Murphy Kevin P. , Twomey Maria , O’Connor Owen J. , Maher Michael M.
Published: July 2014

This paper discusses the current status of imaging in the investigation of patients with haematuria. The physician must rationalize imaging so that serious causes such as malignancy are promptly diagnosed while at the same time not exposing patients to unnecessary investigations. There is currently no universal agreement about the optimal imaging work up of haematuria. The choice of modality to image the urinary tract will depend on individual patient factors such as age, the presence of risk factors for malignancy, renal function, a history of calculus disease and pregnancy, and other factors, such as local policy and practice, cost effectiveness and availability of resources. The role of all modalities, including conventional radiography, intravenous urography/excretory urography, ultrasonography, retrograde pyelography, multidetector computed tomography urography (MDCTU), and magnetic resonance urography, is discussed. This paper highlights the pivotal role of MDCTU in the imaging of the patient with haematuria and discusses issues specific to this modality including protocol design, imaging of the urothelium, and radiation dose. Examination protocols should be tailored to the patient while all the while optimizing radiation dose.
The Effect ofBabesia divergensInfection on the Spleen of Mongolian Gerbils
Authors: Dkhil Mohamed A. , Al-Quraishy Saleh , Al-Khalifa Mohamed S.
Published: July 2014

Babesiosis is caused by intraerythrocytic protozoan parasites transmitted by ticks and affects a wide range of domestic and wild animals and occasionally humans. The current study aimed to investigate the effect ofB. divergensinfected erythrocytes on spleen histopathology, cell cycle alteration, and the presence of oxidative stress. Mongolian gerbils were challenged with 5 × 106  Babesia divergensinfected erythrocytes. Parasitemia reached approximately 77% at day 5 postinfection. Infection also induced injury of the spleen. This was evidenced with (i) increases in cellular damage of the spleen, (ii) decrease in antioxidant capacity as indicated by decreased glutathione, catalase, and superoxide dismutase levels, (iii) increased production of malondialdehyde and nitric oxide derived products (nitrite/nitrate), and (iv) increased lactic acid dehydrogenase activity and protein carbonyl content in the spleen. Infection interfered with normal cell cycle of the spleen cells at G0/G1, S, and G2/M phases. On the basis of the above results it can be hypothesized thatB. divergensinfected erythrocytes could alter the spleen histopathology and cause cell cycle alteration and induce oxidative stress in splenic tissue.
Executive Function and Postural Instability in People with Parkinson’s Disease
Authors: Xu Dong , Cole Michael H. , Mengersen Kerrie , Silburn Peter A. , Qiu Feng , Graepel Cara , Kerr Graham K.
Published: July 2014

The specific aspects of cognition contributing to balance and gait have not been clarified in people with Parkinson’s disease (PD). Twenty PD participants and twenty age- and gender-matched healthy controls were assessed on cognition and clinical mobility tests. General cognition was assessed with the Mini Mental State Exam and Addenbrooke’s Cognitive Exam. Executive function was evaluated using the Trail Making Tests (TMT-A and TMT-B) and a computerized cognitive battery which included a series of choice reaction time (CRT) tests. Clinical gait and balance measures included the Tinetti, Timed Up & Go, Berg Balance, and Functional Reach tests. PD participants performed significantly worse than the controls on the tests of cognitive and executive function, balance, and gait. PD participants took longer on Trail Making Tests, CRT-Location, and CRT-Colour (inhibition response). Furthermore, executive function, particularly longer times on CRT-Distracter and greater errors on the TMT-B, was associated with worse balance and gait performance in the PD group. Measures of general cognition were not associated with balance and gait measures in either group. For PD participants, attention and executive function were impaired. Components of executive function, particularly those involving inhibition response and distracters, were associated with poorer balance and gait performance in PD.
Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?
Authors: Roffi Alice , Filardo Giuseppe , Assirelli Elisa , Cavallo Carola , Cenacchi Annarita , Facchini Andrea , Grigolo Brunella , Kon Elizaveta , Mariani Erminia , Pratelli Loredana , Pulsatelli Lia , Marcacci Maurilio
Published: July 2014

PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1βand HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes.
Optimal Effector Functions in Human Natural Killer Cells Rely upon Autocrine Bone Morphogenetic Protein Signaling
Authors: Robson Neil C. , Hidalgo Laura , McAlpine Tristan , Wei Heng , Martínez Víctor G. , Entrena Ana , Melen Gustavo J. , MacDonald Andrew S. , Phythian-Adams Alexander , Sacedón Rosa , Maraskovsky Eugene , Cebon Jonathan , Ramírez Manuel , Vicente Angeles , Varas Alberto
Published: July 2014

Natural killer (NK) cells are critical for innate tumor immunity due to their specialized ability to recognize and kill neoplastically transformed cells. However, NK cells require a specific set of cytokine-mediated signals to achieve optimal effector function. Th1-associated cytokines promote effector functions that are inhibited by the prototypic Th2 cytokine IL4 and the TGFβ superfamily members TGFβ1 and activin-A. Interestingly, the largest subgroup of the TGFβ superfamily are the bone morphogenetic proteins (BMP), but the effects of BMP signaling on NK cell effector functions have not been evaluated. Here, we demonstrate that blood-circulating NK cells express type I and II BMP receptors, BMP-2 and BMP-6 ligands, and phosphorylated isoforms of Smad-1/-5/-8, which mediate BMP family member signaling. In opposition to the inhibitory effects of TGFβ1 or activin-A, autocrine BMP signaling was supportive to NK cell function. Mechanistic investigations in cytokine and TLR-L–activated NK cells revealed that BMP signaling optimized IFNγ and global cytokine and chemokine production, phenotypic activation and proliferation, and autologous dendritic cell activation and target cytotoxicity. Collectively, our findings identify a novel auto-activatory pathway that is essential for optimal NK cell effector function, one that might be therapeutically manipulated to help eradicate tumors. Cancer Res; 74(18); 5019–31. ©2014 AACR.
Novel Drug Candidates for the Treatment of Metastatic Colorectal Cancer through Global Inverse Gene-Expression Profiling
Authors: van Noort Vera , Schölch Sebastian , Iskar Murat , Zeller Georg , Ostertag Kristina , Schweitzer Christine , Werner Kristin , Weitz Jürgen , Koch Moritz , Bork Peer
Published: July 2014

Drug-induced gene-expression profiles that invert disease profiles have recently been illustrated to be a starting point for drug repositioning. In this study, we validate this approach and focus on prediction of novel drugs for colorectal cancer, for which there is a pressing need to find novel antimetastatic compounds. We computationally predicted three novel and still unknown compounds against colorectal cancer: citalopram (an antidepressant), troglitazone (an antidiabetic), and enilconazole (a fungicide). We verified the compounds by in vitro assays of clonogenic survival, proliferation, and migration and in a subcutaneous mouse model. We found evidence that the mode of action of these compounds may be through inhibition of TGFβ signaling. Furthermore, one compound, citalopram, reduced tumor size as well as the number of circulating tumor cells and metastases in an orthotopic mouse model of colorectal cancer. This study proposes citalopram as a potential therapeutic option for patients with colorectal cancer, illustrating the potential of systems pharmacology. Cancer Res; 74(20); 5690–9. ©2014 AACR.
HSV-sr39TK Positron Emission Tomography and Suicide Gene Elimination of Human Hematopoietic Stem Cells and Their Progeny in Humanized Mice
Authors: Gschweng Eric H. , McCracken Melissa N. , Kaufman Michael L. , Ho Michelle , Hollis Roger P. , Wang Xiaoyan , Saini Navdeep , Koya Richard C. , Chodon Thinle , Ribas Antoni , Witte Owen N. , Kohn Donald B.
Published: July 2014

Engineering immunity against cancer by the adoptive transfer of hematopoietic stem cells (HSC) modified to express antigen-specific T-cell receptors (TCR) or chimeric antigen receptors generates a continual supply of effector T cells, potentially providing superior anticancer efficacy compared with the infusion of terminally differentiated T cells. Here, we demonstrate the in vivo generation of functional effector T cells from CD34-enriched human peripheral blood stem cells modified with a lentiviral vector designed for clinical use encoding a TCR recognizing the cancer/testes antigen NY-ESO-1, coexpressing the PET/suicide gene sr39TK. Ex vivo analysis of T cells showed antigen- and HLA-restricted effector function against melanoma. Robust engraftment of gene-modified human cells was demonstrated with PET reporter imaging in hematopoietic niches such as femurs, humeri, vertebrae, and the thymus. Safety was demonstrated by the in vivo ablation of PET signal, NY-ESO-1-TCR–bearing cells, and integrated lentiviral vector genomes upon treatment with ganciclovir, but not with vehicle control. Our study provides support for the efficacy and safety of gene-modified HSCs as a therapeutic modality for engineered cancer immunotherapy. Cancer Res; 74(18); 5173–83. ©2014 AACR.
Genomic and Transcriptional Alterations in Lung Adenocarcinoma in Relation to Smoking History
Authors: Karlsson Anna , Ringnér Markus , Lauss Martin , Botling Johan , Micke Patrick , Planck Maria , Staaf Johan
Published: July 2014

Purpose: Cigarette smoking is the major pathogenic factor for lung cancer. The precise mechanisms of tobacco-related carcinogenesis and its effect on the genomic and transcriptional landscape in lung cancer are not fully understood.

Experimental Design: A total of 1,398 (277 never-smokers and 1,121 smokers) genomic and 1,449 (370 never-smokers and 1,079 smokers) transcriptional profiles were assembled from public lung adenocarcinoma cohorts, including matched next-generation DNA-sequencing data (n = 423). Unsupervised and supervised methods were used to identify smoking-related copy-number alterations (CNAs), predictors of smoking status, and molecular subgroups.

Results: Genomic meta-analyses showed that never-smokers and smokers harbored a similar frequency of total CNAs, although specific regions (5q, 8q, 16p, 19p, and 22q) displayed a 20% to 30% frequency difference between the two groups. Importantly, supervised classification analyses based on CNAs or gene expression could not accurately predict smoking status (balanced accuracies ∼60% to 80%). However, unsupervised multicohort transcriptional profiling stratified adenocarcinomas into distinct molecular subgroups with specific patterns of CNAs, oncogenic mutations, and mutation transversion frequencies that were independent of the smoking status. One subgroup included approximately 55% to 90% of never-smokers and approximately 20% to 40% of smokers (both current and former) with molecular and clinical features of a less aggressive and smoking-unrelated disease. Given the considerable intragroup heterogeneity in smoking-defined subgroups, especially among former smokers, our results emphasize the clinical importance of accurate molecular characterization of lung adenocarcinoma.

Conclusions: The landscape of smoking-related CNAs and transcriptional alterations in adenocarcinomas is complex, heterogeneous, and with moderate differences. Our results support a molecularly distinct less aggressive adenocarcinoma entity, arising in never-smokers and a subset of smokers. Clin Cancer Res; 20(18); 4912–24. ©2014 AACR.
Cytotoxic T Lymphocyte Antigen-4 Blockade Enhances Antitumor Immunity by Stimulating Melanoma-Specific T-cell Motility
Authors: Pentcheva-Hoang Tsvetelina , Simpson Tyler R. , Montalvo-Ortiz Welby , Allison James P.
Published: July 2014

It is now clear that anti–CTLA-4 (α-CTLA-4) antibodies stimulate tumor immunity either by relieving inhibition of effector T-cell function or by depletion of regulatory T cells (Treg). Several recent reports, however, have suggested that these antibodies may deliver a “go” signal to effector T cells, thus interrupting T-cell receptor signaling and subsequent T-cell activation. We examined the behavior of melanoma-specific CD8+ pmel-1 T cells in the B16/BL6 mouse model using intravital microscopy. Pmel-1 velocities in progressively growing tumors were lower than their velocities in tumors given a therapeutic combination that included α-CTLA-4 antibodies, suggesting that successful immunotherapy correlates with greater T-cell motility. When α-CTLA-4 antibodies were injected during imaging, the velocities of pmel-1 T cells in tumor-draining lymph nodes also increased. Because α-CTLA-4 Fab fragments had the same effect as the intact antibody, the higher T-cell motility does not seem to be due to CTLA-4 inhibitory signaling but rather to the release of nonproductive stable interactions between tumor-infiltrating T cells and tumor targets or antigen-presenting cells subsequent to CTLA-4 blockade. This phenomenon resembles the recently described reversal of the antiviral T-cell motility paralysis by programmed death 1 (PD-1)–specific antibodies during T-cell exhaustion in persistent viral infections. Cancer Immunol Res; 2(10); 970–80. ©2014 AACR.
Utility of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Patients with Fever of Unknown Origin Diagnosed as Lymphoma
Authors: Sheng Zi-Ke , Ye Jin , Li Jun-Jie , Zhao Kui , Sheng Ji-Fang
Published: July 2014

Objective: To assess the efficacy of fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/computed tomography (CT) in the diagnosis of patients with fever of unknown origin (FUO), who were finally diagnosed as lymphoma. Subjects and Methods: A retrospective study was performed in the First Affiliated Hospital, School of Medicine of Zhejiang University, China, from March 2009 to March 2012. The PET/CT images of consecutive patients with FUO were analyzed. Within 1 week of PET/CT scanning, additional histological tests were also performed if clinically needed. Results: A total of 73 consecutive patients were included. Of these, 34 (47%) had a PET/CT finding suggestive of the presence of lymphoma and 29 (85%) had a diagnosis of confirmed lymphoma; 39 (53%) had a PET/CT result revealing the absence of lymphoma and 4 (10%) were diagnosed by biopsy as having lymphoma, . The most frequent lymphoma diagnosis was peripheral T cell lymphoma (n = 16; 55%), followed by diffuse large B cell lymphoma (n = 9; 31%). The accuracy of PET/CT was 88%. Conclusion: In this study, PET/CT had high diagnostic accuracy in patients with FUO resulting from lymphoma, which indicated that PET/CT scanning was a valuable diagnostic tool for these groups of patients with FUO.
Uma carta (quase) americana: o diário de bordo de Sartre
Authors: Lima Adson Cristiano Bozzi Ramatis
Published: July 2014

No ano de 1946 o filósofo francês Jean-Paul Sartre empreendeu uma segunda viagem aos Estados Unidos da América. Como fruto literário desse percurso tivemos a redação dos seguintes ensaios: Individualisme et conformisme aux Etats-Unis, Villes d’Amérique, New York ville coloniale e U.S.A Présentation. O objetivo desse artigo é analisar uma carta endereçada a Simone de Beauvoir, escrita no cargueiro militar que o conduziu ao país norte-americano, na qual ele narra o longo trajeto em alto mar. Acreditamos que a análise dessa missiva pode levar a um melhor esclarecimento dos já citados ensaios, que possuem um caráter bastante pessoal.
Assessorias técnicas no processo autogestionário - possibilidades de atuação
Authors: Barros Mariana Cicuto
Published: July 2014

Com a instituição do Banco Nacional de Habitação (BNH) na década de 1960, passou-se a construir milhares de unidades habitacionais no país, com uma arquitetura padronizada e desqualificada, isenta de preocupações urbanísticas e sociais. Com o fim do BNH tomaram forma discussões e uma nova prática profissional através das assessorias técnicas e dos movimentos de moradia, na busca de um modelo autogestionário para a produção habitacional. Este artigo busca apresentar a trajetória da atuação das assessorias técnicas na cidade de São Paulo através das suas primeiras relações e inserção dos mutirões autogestionários.
Bursaphelenchus penai n. sp. (Tylenchomorpha: Aphelenchoididae), a phoretic associate of ambrosia beetles (Coleoptera: Scolytinae) from avocado in Florida
Authors: Kanzaki Natsumi , Kanzaki Natsumi , Giblin-Davis Robin M. , Kanzaki Natsumi , Giblin-Davis Robin M. , Carrillo Daniel , Kanzaki Natsumi , Giblin-Davis Robin M. , Carrillo Daniel , Duncan Rita , Kanzaki Natsumi , Giblin-Davis Robin M. , Carrillo Daniel , Duncan Rita , Gonzalez Rafael
Published: July 2014

During an experimental host-plant survey for the invasive redbay ambrosia beetle,Xyleborus glabratus, in Homestead, Florida, it and three native species of ambrosia beetle,Xyleborus affinis,X. volvulusandXyleborinus graciliswere found to be associated with aBursaphelenchusspecies. This nematode species, isolated from ambrosia beetles from the tribe Xyleborini, was cultured onMonilinia fructicolaorBotryotinia fuckelianafor further study and was determined to be new to science and a putative sister species toB. kiyoharaibecause of two apomorphic characters in males,viz., possession of a tail spikevsthe typical bursal flap, and the apparent absence of the P1 ventral single papilla, both typically plesiomorphic characters for the genus. Additionally,B. kiyoharaiis associated withX. serriatussuggesting that the host and microbiome associations that are shared between these two species, both of which are carried by ambrosia beetles, may have ecological and biological significance in their evolution and lineage radiation. Molecular phylogenetic analyses of the near-full-length small subunit (SSU: 18S) and the D2/D3 expansion segments of the large subunit (LSU: 28S) confirmed thatB. penain. sp. is very closely related toB. kiyoharaiwhich is a member of theB. fungivorusclade that includesB. thailandaeandB. willibaldi.Bursaphelenchus penain. sp. andB. kiyoharaiboth share very similar overall spicule morphology with theB. fungivorusclade. The new species is described and can be typologically differentiated fromB. kiyoharaiby the position of the hemizonid and excretory pore and its different geographical and host associations.