bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Semiquantitative Histological Score for the Diagnosis of Heaves Using Endobronchial Biopsy Specimens in Horses
Authors: Bullone M. , Hélie P. , Joubert P. , Lavoie J.‐P.
Published: August 2016

Background

Remodeling of the peripheral airways persists during the asymptomatic phase of heaves. Assessing the histology of large bronchi could facilitate the diagnosis of heaves during remission of the disease.

Hypothesis

Airway inflammation and remodeling in endobronchial biopsy (EBB) specimens differentiate horses with heaves from controls, independently of their clinical status (exacerbation or remission).

Animals

Fourteen healthy horses and 24 horses with heaves.

Methods

A 14‐point scoring system assessing central bronchial wall inflammation and remodeling was developed. The score was validated by 2 pathologists using specimens obtained from 18 horses (6 controls, 6 with heaves exacerbation, and 6 with heaves remission) in which lung function had been assessed with impulse oscillometry. Clinical and research application of the score was evaluated using biopsy specimens obtained from 20 additional horses (8 controls, 6 with heaves exacerbation, and 6 with heaves remission).

Results

The score was repeatable (interclass correlation coefficient = 69%). It differentiated horses with heaves in exacerbation (mean ± SD: 6.2 ± 2.2) from those in remission (4.0 ± 1.0) and controls (3.6 ± 1.7, P < 0.0001). The histological scores of horses with heaves correlated with the ratio of respiratory resistance (R) at 5 and 10 Hz (R5 : R10 ratio, r = 0.65, P = 0.03), a parameter assessing airway obstruction.

Conclusions and Clinical Significance

The proposed histological scoring system correlates with the degree of airway obstruction measured by impulse oscillometry. However, it does not discriminate horses with heaves in remission from controls. Evaluation of EBB specimens might be considered in future research and clinical studies of respiratory diseases in horses.
Seizure Disorders in Goats and Sheep
Authors: Chigerwe M. , Aleman M.
Published: August 2016

Background

Goats and sheep are more likely to be presented for examination for seizures than are cattle, possibly as a consequence of their relatively smaller body size. Currently, no reports describing seizure disorders in goats and sheep are available.

Objectives

To describe clinical features and treatment outcomes of sheep and goats presented for seizures.

Animals

A total of 59 goats and 21 sheep presented for seizures.

Methods

Retrospective study. Medical records from 1994 to 2014 at the Veterinary Medical Teaching Hospital, University of California, Davis, were reviewed. Descriptive statistics were used to summarize data. Logistic regression was performed to determine whether variables were associated with mortality.

Results

The majority of seizures in goats and sheep had structural or metabolic causes. Polioencephalomalacia (PEM) secondary to ruminal lactic acidosis or PEM of undetermined cause was the most frequently diagnosed cause of seizures in goats and sheep. The proportions of mortality in goats and sheep were 49.2 and 42.9%, respectively. Age increased the odds mortality (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.07, 2.14) in goats. Goats with structural or metabolic causes of seizures had higher odds for mortality (OR, 37.48; 95% CI, 1.12, 99.10) than those with unknown causes. Age and etiological diagnosis were not significant (P> .05) predictors of mortality in affected sheep.

Conclusions and Clinical Relevance

Seizure disorders in goats and sheep are associated with high mortality, despite treatment. Current treatment in goats and sheep with seizures warrants further investigation to determine whether treatments are beneficial or detrimental to survival.
Readers building fictional worlds: visual representations, poetry and cognition
Authors: Giovanelli Marcello
Published: August 2016

This article explores the complex nature of the literature classroom by drawing on the cognitive linguistic framework Text World Theory to examine the teacher's role as facilitator and mediator of reading. Specifically, the article looks at how one teacher used visual representations as a way of allowing students to engage in a more personal and less teacher‐driven transaction with a poem and to encourage them to reflect on their own roles as active makers of meaning and knowledge in the classroom. The article shows how teachers can be mindful of the various contextual factors that can privilege and legitimise certain kinds of response in the classroom and be wary of external factors and pressures that can promote the idea of preconceived knowledge. The teacher in the case study presented was able to both facilitate the experience of reading poetry in an unmediated way and also develop her students' metacognition in relation to the reading process itself. The article shows how Text World Theory's status as a socio‐cognitive grammar may be of benefit to teachers in understanding the nature of communicative interaction and literary transaction.
Risks factors for severe pain after selective liver transarterial chemoembolization
Authors: Benzakoun Joseph , Ronot Maxime , Lagadec Matthieu , Allaham Wassim , Garcia Alba Carmela , Sibert Annie , Vilgrain Valérie
Published: August 2016

Background & Aims

Post‐procedural pain is frequent after transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), and is only partially prevented by treatment selectivity. Our aim was to determine the risk factors of severe pain after selective TACE for HCC.

Methods

From January 2012 to June 2014, all treatment‐naïve patients undergoing a first selective TACE were included. Risk factors for severe pain, that is, the need for opioid analgesics (grade II–III), were identified by uni‐ and multivariate analysis. Internal validation of a logistic regression model for prediction of opioid intake was done with bootstrapping.

Results

We analysed 335 tumours (mean 47 ± 37 mm) in 159 patients (131 men), mean 63.4 years old (20–92). Twenty‐seven patients (17%) requested opioids. In univariate analysis, opioid intake was associated with young age (P=.021), doxorubicin dose received (P=.031), large HCC (P=.038), absence of chronic liver disease (P<.001) and alpha‐foetoprotein levels (P=.03). In multivariate analysis, opioid intake was associated with young age (OR=0.65 per 10 years increment, P=.048), absence of chronic liver disease (OR=31.7, P<.001) and a higher fraction of the doxorubicin dose (OR=1.32 per 10% increment, P=.009). The optimism‐corrected area under the curve of the prediction model for opioid intake using these three factors was 0.751.

Conclusion

In patients with HCC treated with TACE, selective procedure does not always prevent from severe pain. Young patients without chronic liver disease may be more susceptible to severe pain.
Alteration minerals, fluids, and gases on early Mars: Predictions from 1‐D flow geochemical modeling of mineral assemblages in meteorite ALH 84001
Authors: Melwani Daswani Mohit , Schwenzer Susanne P. , Reed Mark H. , Wright Ian P. , Grady Monica M.
Published: August 2016

Clay minerals, although ubiquitous on the ancient terrains of Mars, have not been observed in Martian meteorite Allan Hills (ALH) 84001, which is an orthopyroxenite sample of the early Martian crust with a secondary carbonate assemblage. We used a low‐temperature (20 °C) one‐dimensional (1‐D) transport thermochemical model to investigate the possible aqueous alteration processes that produced the carbonate assemblage of ALH 84001 while avoiding the coprecipitation of clay minerals. We found that the carbonate in ALH 84001 could have been produced in a process, whereby a low‐temperature (~20 °C) fluid, initially equilibrated with the early Martian atmosphere, moved through surficial clay mineral and silica‐rich layers, percolated through the parent rock of the meteorite, and precipitated carbonates (thereby decreasing the partial pressure of CO2) as it evaporated. This finding requires that before encountering the unweathered orthopyroxenite host of ALH 84001, the fluid permeated rock that became weathered during the process. We were able to predict the composition of the clay minerals formed during weathering, which included the dioctahedral smectite nontronite, kaolinite, and chlorite, all of which have been previously detected on Mars. We also calculated host rock replacement in local equilibrium conditions by the hydrated silicate talc, which is typically considered to be a higher temperature hydrothermal phase on Earth, but may have been a common constituent in the formation of Martian soils through pervasive aqueous alteration. Finally, goethite and magnetite were also found to precipitate in the secondary alteration assemblage, the latter associated with the generation of H2. Apparently, despite the limited water–rock interaction that must have led to the formation of the carbonates ~ 3.9 Ga ago, in the vicinity of the ALH 84001 source rocks, clay formation would have been widespread.
Firms’ Finance in an Experimentally Microfounded Agent‐Based Macroeconomic Model
Authors: Giulioni Gianfranco , Silvestri Marcello , Bucciarelli Edgardo
Published: August 2016

The purpose of this work is twofold. First, we highlight the importance of the finance motive in Keynes and how it has affected the work of Augusto Graziani and Hyman Minsky. Second, we build an agent‐based model where artificial agents replicate heterogeneous financial behavior induced from discovery driven economic experiments. The aggregate and disaggregate outcomes of the model are then investigated to identify the role of entrepreneurs' financial decisions in facing aggregate negative events or in generating endogenous business cycles.
Are Human and Social Capital Linked? Evidence from India
Authors: Alpaslan Barış
Published: August 2016

This paper develops a two‐period Overlapping Generations (OLG) model of endogenous growth in which a two‐way relationship between social capital and human capital is studied. In order to illustrate the impact of public policies, the model is calibrated using the data for a low‐income country, India and a sensitivity analysis is reported under different parameter values. Based on the numerical analysis, this paper focuses on possible trade‐offs in the allocation of government spending between two productive components, that is, social capital‐related activities and education. The results of this paper show that an increase in the share of public spending on social capital‐related activities through a cut in spending on education or vice versa entails trade‐offs. However, the trade‐off fades away and the net impact on long‐run growth turns out to be positive for different parameter values in the case where a higher share of spending on education is financed by a cut in spending on social capital‐related activities but a policy in improving social capital accumulation at the expense of education is always detrimental to long‐run growth.
LaeA regulation of secondary metabolism modulates virulence in Penicillium expansum and is mediated by sucrose
Authors: Kumar Dilip , Barad Shiri , Chen Yong , Luo Xingyu , Tannous Joanna , Dubey Amit , Glam Matana Nofar , Tian Shiping , Li Boqiang , Keller Nancy , Prusky Dov
Published: August 2016

Penicillium expansum, the causal agent of blue mould rot, is a critical health concern because of the production of the mycotoxin patulin in colonized apple fruit tissue. Although patulin is produced by many Penicillium species, the factor(s) activating its biosynthesis are not clear. Sucrose, a key sugar component of apple fruit, was found to modulate patulin accumulation in a dose‐responsive pattern. An increase in sucrose culture amendment from 15 to 175 mm decreased both patulin accumulation and expression of the global regulator laeA by 175‐ and five‐fold, respectively, whilst increasing expression of the carbon catabolite repressor creA. LaeA was found to regulate several secondary metabolite genes, including the patulin gene cluster and concomitant patulin synthesis in vitro. Virulence studies of ΔlaeA mutants of two geographically distant P. expansum isolates (Pe‐21 from Israel and Pe‐T01 from China) showed differential reduction in disease severity in freshly harvested fruit, ranging from no reduction for Ch‐Pe‐T01 strains to 15%–25% reduction for both strains in mature fruit, with the ΔlaeA strains of Is‐Pe‐21 always showing a greater loss in virulence. The results suggest the importance of abiotic factors in LaeA regulation of patulin and other secondary metabolites that contribute to pathogenicity.
Differential control and function of Arabidopsis ProDH1 and ProDH2 genes on infection with biotrophic and necrotrophic pathogens
Authors: Rizzi Yanina Soledad , Cecchini Nicolás Miguel , Fabro Georgina , Alvarez María Elena
Published: August 2016

Arabidopsis contains two proline dehydrogenase (ProDH) genes, ProDH1 and ProDH2, encoding for homologous and functional isoenzymes. Although ProDH1 has been studied extensively, especially under abiotic stress, ProDH2 has only started to be analysed in recent years. These genes display distinctive expression patterns and show weak transcriptional co‐regulation, but are both activated in pathogen‐infected tissues. We have demonstrated previously that Arabidopsis plants with silenced ProDH1/2 expression fail to trigger defences against the hemibiotrophic bacterial pathogen Pseudomonas syringae pv. tomato AvrRpm1 (Pst‐AvrRpm1), and that ProDH1 and ProDH2 are differentially regulated by salicylic acid (SA). In the current work, we used prodh1 and prodh2 single‐mutant plants to assess the particular contribution of each gene to resistance against Pst‐AvrRpm1 and the necrotrophic fungal pathogen Botrytis cinerea. In addition, we studied the sensitivity of ProDH1 and ProDH2 to the jasmonic acid (JA) defence pathway. We found that ProDH1 and ProDH2 are both necessary to achieve maximum resistance against Pst‐AvrRpm1 and B. cinerea. However, ProDH2 has a major effect on early restriction of B. cinerea growth. Interestingly, ProDH1 is up‐regulated by SA and JA, whereas ProDH2 is only activated by JA, and both genes display transcriptional inter‐regulation at basal and infection conditions. These studies provide the first evidence of the contribution of ProDH2 to disease resistance, and describe the differential regulation and non‐redundant but complementary function of both enzyme isoforms in infected tissues, providing support for a fundamental role of ProDH in the control of biotrophic and necrotrophic pathogens.
Turin Shroud, Resurrection and Science: One View of the Cathedral
Authors: Casabianca Tristan
Published: August 2016

In a topic as controversial as the Turin Shroud, it is always surprising to note that there remains a large area of consensus among scholars who hold opposite opinions on the origin of this piece of fabric. According to the consensus view, neither science nor history can prove that the Turin Shroud shows signs of the Resurrection of Jesus of Nazareth. However, the reasons provided for this important claim are not convincing, especially in light of recent developments in historiography and analytic philosophy.
Recent changes in the clinical features of patients with new psychoactive‐substances‐related disorders in Japan: Comparison of the Nationwide Mental Hospital Surveys on Drug‐related Psychiatric Disorders undertaken in 2012 and 2014
Authors: Matsumoto Toshihiko , Tachimori Hisateru , Takano Ayumi , Tanibuchi Yuko , Funada Daisuke , Wada Kiyoshi
Published: August 2016

Aim

The aim of this study was to examine changes in the psychosocial backgrounds and clinical features of patients with psychiatric disorders associated with new psychoactive substances (NPS) between 2012 and 2014 in Japan.

Methods

Clinical features of patients with NPS‐related disorders were compared using data from the Nationwide Mental Hospital Surveys on Drug‐related Psychiatric Disorders undertaken in 2012 and 2014. NPS patients were compared with a control group comprising patients with methamphetamine‐related disorders, using data from the same period.

Results

In NPS patients, changes were observed in the following three areas between 2012 and 2014: (i) a decrease in the number of employed patients; (ii) an increase in the ratio of patients diagnosed with dependence syndrome; and (iii) a decrease in the ratio of patients diagnosed with psychotic disorder. In methamphetamine patients, only one change was observed: protective custody or arrest record relating to the Pharmaceutical Affairs Act.

Conclusion

This study suggests that the number of patients dependent upon NPS, and those exhibiting social dysfunction, increased between 2012 and 2014. There is a need to focus future measures against NPS dependence: not only on stopping the supply of drugs, but also on reducing the demand for them.
Superoxide serves as a putative signal molecule for plant cell division: overexpression of CaRLK1 promotes the plant cell cycle via accumulation of O2− and decrease in H2O2
Authors: Lee Dong Ju , Choi Hyun Jun , Moon Mid‐Eum , Chi Youn‐Tae , Ji Kon‐Young , Choi Doil
Published: August 2016

Reactive oxygen species (ROS) exert both positive and negative effects on plant growth and development and therefore receive a great deal of attention in current research. A hot pepper, Capsicum annuum receptor‐like kinase 1 (CaRLK1) was ectopically expressed in Nicotiana tabacum BY‐2 cell and Nicotiana benthamiana plants. This ectopic expression of CaRLK1 enhanced cell division and proliferation in both heterologous systems. Apparently, CaRLK1 is involved in controlling the cell cycle, possibly by inducing expressions of cyclin B1, cyclin D3, cyclin‐dependent protein kinase 3, condensin complex subunit 2 and anaphase‐promoting complex subunit 11 genes. CaRLK1 overexpression also increased transcript accumulation of NADPH oxidase genes, generation of O2− and catalase (CAT) activity/protein levels. In parallel, it decreased cellular H2O2 levels and cell size. Treatment with Tiron or diphenyleneiodonium (DPI) both decreased the cell division rate and O2− concentrations, but increased cellular H2O2 levels. Tobacco BY‐2 cells overexpressing CaRLK1 were more sensitive to amino‐1,2,4‐triazole (3‐AT), a CAT inhibitor, than control cells, suggesting that the increased H2O2 levels may not function as a signal for cell division and proliferation. Overexpression of CaRLK1 stimulated progression of the cell cycle from G0/G1 phase into the S phase. It is concluded that the CaRLK1 protein plays a pivotal role in controlling the level of O2− as signaling molecule which promotes cell division, concomitant with a reduction in H2O2 by the induction of CAT activity/protein.
Three zinc‐finger RNA‐binding proteins in cabbage (Brassica rapa) play diverse roles in seed germination and plant growth under normal and abiotic stress conditions
Authors: Park Ye Rin , Choi Min Ji , Park Su Jung , Kang Hunseung
Published: August 2016

Despite the increasing understanding of the stress‐responsive roles of zinc‐finger RNA‐binding proteins (RZs) in several plant species, such as Arabidopsis thaliana, wheat (Triticum aestivum) and rice (Oryza sativa), the functions of RZs in cabbage (Brassica rapa) have not yet been elucidated. In this study, the functional roles of the three RZ family members present in the cabbage genome, designated as BrRZ1, BrRZ2 and BrRZ3, were investigated in transgenic Arabidopsis under normal and environmental stress conditions. Subcellular localization analysis revealed that all BrRZ proteins were exclusively localized in the nucleus. The expression levels of each BrRZ were markedly increased by cold, drought or salt stress and by abscisic acid (ABA) treatment. Expression of BrRZ3 in Arabidopsis retarded seed germination and stem growth and reduced seed yield of Arabidopsis plants under normal growth conditions. Germination of BrRZ2‐ or BrRZ3‐expressing Arabidopsis seeds was delayed compared with that of wild‐type seeds under dehydration or salt stress conditions and cold stress conditions, respectively. Seedling growth of BrRZ3‐expressing transgenic Arabidopsis plants was significantly inhibited under salt, dehydration or cold stress conditions. Notably, seedling growth of all three BrRZ‐expressing transgenic Arabidopsis plants was inhibited upon ABA treatment. Importantly, all BrRZs possessed RNA chaperone activity. Taken together, these results indicate that the three cabbage BrRZs harboring RNA chaperone activity play diverse roles in seed germination and seedling growth of plants under abiotic stress conditions as well as in the presence of ABA.
Sources of Mortality on Dialysis with an Emphasis on Microemboli
Authors: Stegmayr Bernd G.
Published: August 2016

Patients on chronic hemodialysis have a shortened survival compared to the general population. There are multiple sources of morbidity and mortality unique to the dialysis population that account for this. Reasons include the effects of blood membrane interactions, intradialytic hypotension, myocardial stunning, excessive interdialytic weight gain, high‐flow arteriovenous fistulae, and impaired lipid break down by anticoagulation administered during HD. Another risk factor, not well appreciated, is the occurrence of microemboli of air (microbubbles) during HD. Such microemboli are not effectively removed by the venous air trap and the safety system provides no warning when these small microbubbles enter the venous bloodline of the extra corporeal circuit and then the venous circulation of the patient. Data indicate that the gas emboli are not fully adsorbed and become embedded by fibrin resulting in a combined clot that causes microemboli in the lung. In addition, these microbubbles (of the size of blood corpuscles) can pass the pulmonary circulation into the left heart and then into the general arterial circulation explaining their detection not only in the lungs but also in the brain and heart of patients. Risk factors for such microbubble appearance include the high blood pump speed associated with high‐efficiency dialyses. This review will discuss these various issues in relation to the better outcome of patients in Japan and also how to reduce some of these risk factors.
Ultrafiltration Rate Clinical Performance Measures: Ready for Primetime?
Authors: Flythe Jennifer E.
Published: August 2016

Mounting evidence supports a strong association between fluid management and outcomes among individuals receiving maintenance hemodialysis. The speed of fluid removal during dialysis (ultrafiltration, UF) is a modifiable aspect of fluid management that has attracted recent attention as a potential performance measure for facility fluid management practices. Observational data support an association between higher UF rates and adverse outcomes. This association is supported by the plausible pathophysiologic rationale of hypoperfusion‐induced ischemic injury to the heart and other end‐organs. However, no published clinical trial has studied the impact of lowering UF rates on clinical and patient‐centered outcomes. Lowering UF rates requires interdialytic weigh gain reduction and/or extension of dialysis time. Weight gain reduction has proven difficult despite nutritional programs focused on salt and fluid restrictions, and patients are generally averse to longer treatment times. Thus, imposition of UF rate limitations may lead to failed target weight achievement and volume expansion over time. Despite these potential unintended consequences, the National Quality Forum endorsed an UF rate clinical performance measure in 2015. Prior to implementation of quality measure‐imposed UF rate limitations, prospective studies of UF rates and outcomes are needed.
In vitro comparison between gamma‐irradiated cryopreserved and Day 7 liquid‐stored buffy coat–derived platelet components
Authors: Crimmins Daryl , Flanagan Peter , Charlewood Richard , Ruggiero Katya
Published: August 2016

BACKGROUND

Cryopreserved platelet (PLT) components stored at −80°C in 5% to 6% dimethyl sulfoxide (DMSO) demonstrate enhanced hemostatic activity. Alterations in PLT surface glycoprotein expression and release of procoagulant microparticles during the freeze/thaw cycle result in PLT activation. Nothing is known of the effect of gamma irradiation on the in vitro quality of reconstituted cryopreserved PLTs.

STUDY DESIGN AND METHODS

Gamma‐irradiated (25‐50 Gy) buffy coat–derived PLT components were either stored at room temperature for 7 days (the current expiry in New Zealand) or cryopreserved at −80°C using 5% to 6% DMSO. Cryopreserved PLTs were thawed at 37°C and reconstituted in ABO‐identical plasma or PAS‐E and compared to Day 7 gamma‐irradiated liquid‐stored PLTs. In vitro assays were performed to assess glycoprotein expression, PLT functionality and soluble cytokine release.

RESULTS

Cryopreserved PLTs after thawing and reconstitution in ABO‐matched plasma or PAS‐E displayed differing recoveries (82.7 and 75.9%, respectively). Key expression levels of glycoproteins GPIbα (CD42b) and GPIIb (CD41a) were reduced. Cryopreserved PLTs retained the ability to form an effective functional clot, while showing accelerated initiation of clot formation (R‐time) compared to Day 7 gamma‐irradiated liquid‐stored PLTs.

CONCLUSION

Gamma‐irradiated buffy coat–derived liquid‐stored and cryopreserved PLTs have distinctly differing phenotypes. Cryopreserved PLTs reconstituted in ABO plasma have enhanced clot strength driven by coagulation factors and fibrinogen levels not present in PAS‐E. Irradiated cryopreserved PLTs maintain a similar in vitro quality profile and hemostatic behavior to previously published, nonirradiated cryopreserved PLTs.
Practical reconstruction protocol for quantitative 90Y bremsstrahlung SPECT/CT
Authors: Siman W. , Mikell J. K. , Kappadath S. C.
Published: August 2016

Purpose:

To develop a practical background compensation (BC) technique to improve quantitative 90Y‐bremsstrahlung single‐photon emission computed tomography (SPECT)/computed tomography (CT) using a commercially available imaging system.

Methods:

All images were acquired using medium‐energy collimation in six energy windows (EWs), ranging from 70 to 410 keV. The EWs were determined based on the signal‐to‐background ratio in planar images of an acrylic phantom of different thicknesses (2–16 cm) positioned below a 90Y source and set at different distances (15–35 cm) from a gamma camera. The authors adapted the widely used EW‐based scatter‐correction technique by modeling the BC as scaled images. The BC EW was determined empirically in SPECT/CT studies using an IEC phantom based on the sphere activity recovery and residual activity in the cold lung insert. The scaling factor was calculated from 20 clinical planar 90Y images. Reconstruction parameters were optimized in the same SPECT images for improved image quantification and contrast. A count‐to‐activity calibration factor was calculated from 30 clinical 90Y images.

Results:

The authors found that the most appropriate imaging EW range was 90–125 keV. BC was modeled as 0.53× images in the EW of 310–410 keV. The background‐compensated clinical images had higher image contrast than uncompensated images. The maximum deviation of their SPECT calibration in clinical studies was lowest (<10%) for SPECT with attenuation correction (AC) and SPECT with AC + BC. Using the proposed SPECT‐with‐AC + BC reconstruction protocol, the authors found that the recovery coefficient of a 37‐mm sphere (in a 10‐mm volume of interest) increased from 39% to 90% and that the residual activity in the lung insert decreased from 44% to 14% over that of SPECT images with AC alone.

Conclusions:

The proposed EW‐based BC model was developed for 90Y bremsstrahlung imaging. SPECT with AC + BC gave improved lesion detectability and activity quantification compared to SPECT with AC only. The proposed methodology can readily be used to tailor 90Y SPECT/CT acquisition and reconstruction protocols with different SPECT/CT systems for quantification and improved image quality in clinical settings.
Influence of medial olivocochlear efferents on the sharpness of cochlear tuning estimates in children
Authors: Mishra Srikanta K. , Dinger Zoë
Published: August 2016

The present study objectively quantified the efferent-induced changes in the sharpness of cochlear tuning estimates and compared these alterations in cochlear tuning between adults and children. Click evoked otoacoustic emissions with and without contralateral broadband noise were recorded from 15 young adults and 14 children aged between 5 and 10 yrs. Time-frequency distributions of click evoked otoacoustic emissions were obtained via the S-transform, and the otoacoustic emission latencies were used to estimate the sharpness of cochlear tuning. Contralateral acoustic stimulation caused a significant reduction in the sharpness of cochlear tuning estimates in the low to mid frequency region, but had no effect in the higher frequencies (3175 and 4000 Hz). The magnitude of efferent-induced changes in cochlear tuning estimates was similar between adults and children. The current evidence suggests that the stimulation of the medial olivocochlear efferent neurons causes similar alterations in cochlear frequency selectivity in adults and children.
Limiting T cell histidine phosphorylation
Authors: Gough Nancy R.
Published: August 2016

Phosphoglycerate mutase 5 (PGAM5) limits T cell activation by dephosphorylating the histidine kinase NDPK-B.
The fat of the (cancer) matter
Authors: Ferrarelli Leslie K.
Published: August 2016

Adipocytes secrete molecules that promote pancreatic and ovarian tumor progression.
Stringent Response Factors PPX1 and PPK2 Play an Important Role in Mycobacterium tuberculosis Metabolism, Biofilm Formation, and Sensitivity to Isoniazid
In Vivo
Authors: Chuang Yu-Min , Dutta Noton K. , Hung Chien-Fu , Wu T.-C. , Rubin Harvey , Karakousis Petros C.
Published: August 2016

Mycobacterium tuberculosis
remains a global health threat largely due to the lengthy duration of curative antibiotic treatment, contributing to medical nonadherence and the emergence of drug resistance. This prolonged therapy is likely due to the presence of
M. tuberculosis
persisters, which exhibit antibiotic tolerance. Inorganic polyphosphate [poly(P)] is a key regulatory molecule in the
M. tuberculosis
stringent response mediating antibiotic tolerance. The polyphosphate kinase PPK1 is responsible for poly(P) synthesis in
M. tuberculosis
, while the exopolyphosphatases PPX1 and PPX2 and the GTP synthase PPK2 are responsible for poly(P) hydrolysis. In the present study, we show by liquid chromatography-tandem mass spectrometry that poly(P)-accumulating
M. tuberculosis
mutant strains deficient in
ppx1
or
ppk2
had significantly lower intracellular levels of glycerol-3-phosphate (G3P) and 1-deoxy-xylulose-5-phosphate. Real-time PCR revealed decreased expression of genes in the G3P synthesis pathway in each mutant. The
ppx1
-deficient mutant also showed a significant accumulation of metabolites in the tricarboxylic acid cycle, as well as altered arginine and NADH metabolism. Each poly(P)-accumulating strain showed defective biofilm formation, while deficiency of
ppk2
was associated with increased sensitivity to plumbagin and meropenem and deficiency of
ppx1
led to enhanced susceptibility to clofazimine. A DNA vaccine expressing
ppx1
and
ppk2
, together with two other members of the
M. tuberculosis
stringent response,
M. tuberculosis
rel
and
sigE
, did not show protective activity against aerosol challenge with
M. tuberculosis
, but vaccine-induced immunity enhanced the killing activity of isoniazid in a murine model of chronic tuberculosis. In summary, poly(P)-regulating factors of the
M. tuberculosis
stringent response play an important role in
M. tuberculosis
metabolism, biofilm formation, and antibiotic sensitivity
in vivo
.
Improved Protection in a Rabbit Model of Community-Associated Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia upon Neutralization of Leukocidins in Addition to Alpha-Hemolysin
Authors: Diep Binh An , Le Vien T. M. , Visram Zehra C. , Rouha Harald , Stulik Lukas , Dip Etyene Castro , Nagy Gábor , Nagy Eszter
Published: August 2016

Community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA), especially the USA300 pulsotype, is a frequent cause of skin and soft tissue infections and severe pneumonia. Despite appropriate antibiotic treatment, complications are common and pneumonia is associated with high mortality.
S. aureus
strains express multiple cytotoxins, including alpha-hemolysin (Hla) and up to five bicomponent leukocidins that specifically target phagocytic cells for lysis. CA-MRSA USA300 strains carry the genes for all six cytotoxins. Species specificity of the leukocidins greatly contributes to the ambiguity regarding their role in
S. aureus
pathogenesis. We performed a comparative analysis of the leukocidin susceptibility of human, rabbit, and mouse polymorphonuclear leukocytes (PMNs) to assess the translational value of mouse and rabbit
S. aureus
models. We found that mouse PMNs were largely resistant to LukSF-PV, HlgAB, and HlgCB and susceptible only to LukED, whereas rabbit and human PMNs were highly sensitive to all these cytotoxins. In the rabbit pneumonia model with a USA300 CA-MRSA strain, passive immunization with a previously identified human monoclonal antibody (MAb), Hla-F#5, which cross-neutralizes Hla, LukSF-PV, HlgAB, HlgCB, and LukED, provided full protection, whereas an Hla-specific MAb was only partially protective. In the mouse USA300 CA-MRSA pneumonia model, both types of antibodies demonstrated full protection, suggesting that Hla, but not leukocidin(s), is the principal virulence determinant in mice. As the rabbit recapitulates the high susceptibility to leukocidins characteristic of humans, this species represents a valuable model for assessing novel, cytotoxin-targeting anti-
S. aureus
therapeutic approaches.
Antistaphylococcal β-Lactams versus Vancomycin for Treatment of Infective Endocarditis Due to Methicillin-Susceptible Coagulase-Negative Staphylococci: a Prospective Cohort Study from the International Collaboration on Endocarditis
Authors: Carugati M. , Petti C. A. , Arnold C. , Miro J. M. , Pericàs J. M. , Garcia de la Maria C. , Kanafani Z. , Durante-Mangoni E. , Baddley J. , Wray D. , Klein J. L. , Delahaye F. , Fernandez-Hidalgo N. , Hannan M. M. , Murdoch D. , Bayer A. , Chu V. H.
Published: August 2016

The phenotypic expression of methicillin resistance among coagulase-negative staphylococci (CoNS) is heterogeneous regardless of the presence of themecAgene. The potential discordance between phenotypic and genotypic results has led to the use of vancomycin for the treatment of CoNS infective endocarditis (IE) regardless of methicillin MIC values. In this study, we assessed the outcome of methicillin-susceptible CoNS IE among patients treated with antistaphylococcal β-lactams (ASB) versus vancomycin (VAN) in a multicenter cohort study based on data from the International Collaboration on Endocarditis (ICE) Prospective Cohort Study (PCS) and the ICE-Plus databases. The ICE-PCS database contains prospective data on 5,568 patients with IE collected between 2000 and 2006, while the ICE-Plus database contains prospective data on 2,019 patients with IE collected between 2008 and 2012. The primary endpoint was in-hospital mortality. Secondary endpoints were 6-month mortality and survival time. Of the 7,587 patients in the two databases, there were 280 patients with methicillin-susceptible CoNS IE. Detailed treatment and outcome data were available for 180 patients. Eighty-eight patients received ASB, while 36 were treated with VAN. In-hospital mortality (19.3% versus 11.1%;P= 0.27), 6-month mortality (31.6% versus 25.9%;P= 0.58), and survival time after discharge (P= 0.26) did not significantly differ between the two cohorts. Cox regression analysis did not show any significant association between ASB use and the survival time (hazard ratio, 1.7;P= 0.22); this result was not affected by adjustment for confounders. This study provides no evidence for a difference in outcome with the use of VAN versus ASB for methicillin-susceptible CoNS IE.
The Single Transmembrane Segment of Minimal Sensor DesK Senses Temperature via a Membrane-Thickness Caliper
Authors: Inda Maria E. , Oliveira Rafael G. , de Mendoza Diego , Cybulski Larisa E.
Published: August 2016

Thermosensors detect temperature changes and trigger cellular responses crucial for survival at different temperatures. The thermosensor DesK is a transmembrane (TM) histidine kinase which detects a decrease in temperature through its TM segments (TMS). Here, we address a key issue: how a physical stimulus such as temperature can be converted into a cellular response. We show that the thickness of
Bacillus
lipid membranes varies with temperature and that such variations can be detected by DesK with great precision. On the basis of genetic studies and measurements of
in vitro
activity of a DesK construct with a single TMS (
m
inimal
s
ensor DesK [MS-DesK]), reconstituted in liposomes, we propose an interplay mechanism directed by a conserved dyad, phenylalanine 8-lysine 10. This dyad is critical to anchor the only transmembrane segment of the MS-DesK construct to the extracellular water-lipid interphase and is required for the transmembrane segment of MS-DesK to function as a caliper for precise measurement of membrane thickness. The data suggest that positively charged lysine 10, which is located in the hydrophobic core of the membrane but is close to the water-lipid interface, pulls the transmembrane region toward the water phase to localize its charge at the interface. Nevertheless, the hydrophobic residue phenylalanine 8, located at the N-terminal extreme of the TMS, has a strong tendency to remain in the lipid phase, impairing access of lysine 10 to the water phase. The outcome of this interplay is a fine-tuned sensitivity to membrane thickness that elicits conformational changes that favor different signaling states of the protein.

IMPORTANCE
The ability to sense and respond to extracellular signals is essential for cell survival. One example is the cellular response to temperature variation. How do cells “sense” temperature changes? It has been proposed that the bacterial thermosensor DesK acts as a molecular caliper measuring membrane thickness variations that would occur as a consequence of temperature changes and activates a pathway to restore membrane fluidity at low temperature. Here, we demonstrated that membrane thickness variations do occur at physiological temperatures by directly measuring
Bacillus
lipid membrane thickness. We also dissected the N-terminal sensing motif of MS-DesK at the molecular-biophysical level and found that the dyad phenylalanine-lysine at the water-lipid phase is critical for achievement of a fine-tuned sensitivity to temperature.
Fortune or misfortune: asymptomatic, delayed presentation of complete dehiscence of mechanical aortic valve conduit and pseudoaneurysm
Authors: Oh Kyung Taek , Derose Joseph , Taub Cynthia
Published: August 2016

Complete dehiscence of a composite aortic valve graft with pseudoaneurysm formation is a rare complication following aortic root replacement. This complication often takes place in the setting of acute graft infection and accompanies symptoms of heart failure, valve insufficiency or sepsis. We present a delayed, asymptomatic presentation of this complication in a young man with distant history of aortic root replacement and medically treated prosthetic valve endocarditis a year postoperatively. He had been non-adherent to warfarin over 10 years, but otherwise maintained a healthy life. After being lost to follow-up, he re-presented 12 years after the initial operation with new-onset seizures. Echocardiogram revealed complete dehiscence of a composite valved conduit at the proximal anastomosis site with a resultant large pseudoaneurysm. The patient underwent an urgent re-operation with resection of the pseudoaneurysm and insertion of a tissue valved conduit. He had an uncomplicated postoperative recovery and promised close follow-up on discharge.
Multimodal imaging of central retinal artery occlusion with retained cilioretinal perfusion
Authors: Walkden Andrew , Kelly Simon P
Published: August 2016

A man aged 59 years old presented with sudden, painless, monocular visual loss due to central retinal artery occlusion. Central vision was retained and peripheral vision lost due to retained cilioretinal perfusion. Increased inner retinal thickening and reflectivity followed by subsequent reduction was documented by sequential imaging. This is the first report of such events monitored with spectral-domain optical coherence tomography where central visual acuity was maintained.
Unlikely culprit: congenital middle aortic syndrome diagnosed in the sixth decade of life
Authors: Ali Muhammad Sajawal , Tchernodrinski Stefan , Mohananey Divyanshu , Ali Ahya Sajawal
Published: August 2016

A 58-year-old woman was admitted with acute heart failure. She had a long history of resistant hypertension, with an unremarkable work up for secondary causes in the past. Her brachial blood pressure was 210/70 mm Hg, with ankle blood pressure of 100/70 mm Hg. CT angiogram revealed marked narrowing of the descending thoracic aorta between the left subclavian artery and the diaphragm, consistent with middle aortic syndrome (MAS). She was initially managed with diuretics and antihypertensives. Subsequently thoracotomy revealed a severely hypoplastic segment of the descending aorta. The diseased segment was resected and aortic reconstruction performed. Histopathology showed fragmentation of the medial elastic fibres and fibrosis of the medial and intimal layers. These findings along with gross aortic hypoplasia and absence of features of Takayasu's arteritis, suggest that our patient had congenital MAS. The patient has done well since her surgery. We believe this is the first case of congenital MAS reported in the sixth decade of life.
Usefulness of sulfasalazine for patients with refractory-ulcerative colits
Authors: Yoshino Takuya , Sono Makoto , Yazumi Shujiro
Published: August 2016

Background

Patients with refractory-ulcerative colitis (UC) require therapy escalation. Sulfasalazine (SASP) could deliver a high concentration of 5-aminosalicylic acid to the colon. The usefulness of SASP for refractory-UC patients, however, is unclear.

Aim

The aim was to evaluate the usefulness of SASP for refractory-UC patients.

Method

We retrospectively analysed 36 (11.4%) of 316 patients with refractory-UC who had been treated with SASP. Clinical and endoscopic activities were evaluated with Lichtiger index and Mayo score, respectively. We analysed the induction-remission rate, predictive factors for the efficacy of SASP, and adverse events.

Results

Of 36 refractory-UC patients, 14 (38.9%) were treated with concomitant mesalazine enemas, 10 (27.8%) with azathiopurine, 4 (11.1%) with tacrolimus and 6 (16.7%) with an antitumour necrosis factor-α agent. After initiating SASP treatment, 25 patients (69.4%) achieved clinical remission. In 9 (64.3%) of 14 patients with UC treated with mesalazine enemas, mesalazine enemas could be discontinued with SASP. In all patients treated with tacrolimus, tacrolimus could be discontinued with SASP. Clinical activity score upon the initiation of SASP was significantly lower (p=0.024) and the number of patients treated with thiopurine was significantly higher (p=0.016) in the clinical remission group than in the non-clinical remission group. These factors might be predictive for the efficacy of SASP, although multivariate analysis demonstrated no statistically significant effect. Adverse events occurred in 7 patients (19.4%), and reduction or discontinuation of SASP led to improvement.

Conclusions

SASP appears to be more effective for refractory-UC patients with low clinical-activity and/or thiopurine-use.

Trial registration number

UMIN000021615; Results.
Paediatric injury from indoor trampoline centres
Authors: Mulligan Christopher S , Adams Susan , Brown Julie
Published: August 2016

Indoor trampoline parks are increasing as a source of injuries among children. We conducted a prospective cohort study, with semi-structured interview and medical record review, of children aged <17 years presenting to a paediatric emergency department following an injury at an indoor trampoline park. In a 6-month period in 2014, 40 such children (55% female) presented to the department. Common mechanisms were individual jumpers falling while attempting a somersault or trick, landing awkwardly on an obstacle such as a ball or protective padding, and multiple users on a single trampoline. Most sustained soft tissue injuries (n=22, 55%) and fractured bones (n=15, 37.5%). One child sustained an unstable cervical fracture/dislocation. Unlike domestic trampolines, where the majority of injuries occur from falling off, most trampoline-park injuries occur on the trampoline surface. These differences require injury prevention strategies that engage children, carers and businesses to meet best practice design and management standards.
Can measures of critical power precisely estimate the maximal metabolic steady-state?
Authors: Mattioni Maturana Felipe , Keir Daniel A. , McLay Kaitlin M. , Murias Juan M.
Published: August 2016

Critical power (CP) conceptually represents the highest power output (PO) at physiological steady-state. In cycling exercise, CP is traditionally derived from the hyperbolic relationship of ∼5 time-to-exhaustion trials (TTE) (CPHYP). Recently, a 3-min all-out test (CP3MIN) has been proposed for estimation of CP as well the maximal lactate steady-state (MLSS). The aim of this study was to compare the POs derived from CPHYP, CP3MIN, and MLSS, and the oxygen uptake and blood lactate concentrations at MLSS. Thirteen healthy young subjects (age, 26 ± 3years; mass, 69.0 ± 9.2 kg; height, 174 ± 10 cm; maximal oxygen uptake, 60.4 ± 5.9 mL·kg−1·min−1) were tested. CPHYP was estimated from 5 TTE. CP3MIN was calculated as the mean PO during the last 30 s of a 3-min all-out test. MLSS was the highest PO during a 30-min ride where the variation in blood lactate concentration was ≤ 1.0 mmol·L−1 during the last 20 min. PO at MLSS (233 ± 41 W; coefficient of variation (CoV), 18%) was lower than CPHYP (253 ± 44 W; CoV, 17%) and CP3MIN (250 ± 51 W; CoV, 20%) (p < 0.05). Limits of agreement (LOA) from Bland–Altman plots between CPHYP and CP3MIN (–39 to 31 W), and CP3MIN and MLSS (–29 to 62 W) were wide, whereas CPHYP and MLSS presented the narrowest LOA (–7 to 48 W). MLSS yielded not only the maximum PO of stable blood lactate concentration, but also stable oxygen uptake. In conclusion, POs associated to CPHYP and CP3MIN were larger than those observed during MLSS rides. Although CPHYP and CP3MIN were not different, the wide LOA between these 2 tests and the discrepancy with PO at MLSS questions the ability of CP measures to determine the maximal physiological steady-state.