bluuebunny/crossref_metadata_2025 huggingface dataset:
Soloist evaluations of six Old Italian and six new violins
Authors: Fritz Claudia , Curtin Joseph , Poitevineau Jacques , Borsarello Hugues , Wollman Indiana , Tao Fan-Chia , Ghasarossian Thierry
Published: April 2014

Significance

Some studies open new fields for investigation; this study attempts to close a perennially fruitless one—the search for the “secrets of Stradivari.” Great efforts have been made to explain why instruments by Stradivari and other Old Italian makers sound better than high-quality new violins, but without providing scientific evidence that this is in fact the case. Doing so requires that experienced violinists demonstrate (under double-blind conditions) both a general preference for Old Italian violins and the ability to reliably distinguish them from new ones. The current study, the second of its kind, again shows that first-rate soloists tend to prefer new instruments and are unable to distinguish old from new at better than chance levels.
Bile salts act as effective protein-unfolding agents and instigators of disulfide stress in vivo
Authors: Cremers Claudia M. , Knoefler Daniela , Vitvitsky Victor , Banerjee Ruma , Jakob Ursula
Published: April 2014

Significance

Bile salts are extremely abundant molecules in the mammalian intestine and play important roles in food digestion. Much less well known is the fact that bile salts are also highly antimicrobial and control bacterial growth in the gut. Here, we report the discovery that bile salts affect bacterial growth by causing widespread unfolding and aggregation of cytosolic proteins in bacteria, while simultaneously triggering a prooxidizing shift in the cellular ratio of reduced to oxidized glutathione. Our studies therefore reveal an important and unrealized property of a set of compounds long known to be important in human physiology, demonstrate how bacteria such as
Escherichia coli
defend themselves against bile salts, and uncover perhaps the first physiological condition that causes disulfide stress in vivo.
What if stock assessment is as simple as a linear model? The a4a
initiative
Authors: Jardim Ernesto , Millar Colin P. , Mosqueira Iago , Scott Finlay , Osio Giacomo Chato , Ferretti Marco , Alzorriz Nekane , Orio Alessandro
Published: April 2014

This manuscript discusses the benefits of having a stock assessment model that is intuitively close to a linear model. It creates a case for the need of such models taking into account the increase in data availability and the expansion of stock assessment requests. We explore ideas around the assessment of large numbers of stocks and the need to make stock assessment easier to run and more intuitive, so that more scientists from diverse backgrounds can be involved. We show, as an example, the model developed under the European Commission Joint Research Center’s ‘Assessment for All’ Initiative (a4a) and how it fits the a4a strategy of making stock assessment simpler and accessible to a wider group of scientists.
AvrA effector protein of Salmonella enterica serovar Enteritidis is expressed and translocated in mesenteric lymph nodes at late stages of infection in mice
Authors: Giacomodonato Mónica N. , Noto Llana Mariángeles , Aya Castañeda María del Rosario , Buzzola Fernanda R. , Sarnacki Sebastián H. , Cerquetti María C.
Published: April 2014

Salmonellosis is a major health problem worldwide. Salmonella
enterica serovar Enteritidis (S. Enteritidis) has been a primary cause of Salmonella outbreaks in many countries. AvrA is an SPI-1 effector protein involved in the enteritis pathway, with critical roles in inhibiting inflammation and apoptosis. In this work, we constructed an AvrA-FLAG-tagged strain of S. Enteritidis to analyse the expression profile of AvrA in vitro, in cell culture and in vivo. AvrA expression and secretion were observed in vitro under culture conditions that mimicked intestinal and intracellular environments. In agreement, bacteria isolated from infected cell monolayers expressed and translocated AvrA for at least 24 h post-inoculation. For in vivo experiments, BALB/c mice were inoculated by the natural route of infection with the AvrA-FLAG strain. Infecting bacteria and infected cells were recovered from mesenteric lymph nodes (MLN). Our results showed that AvrA continues to be synthesized in vivo up to day 8 post-inoculation. Moreover, AvrA translocation was detected in the cytosol of cells isolated from MLN 8 days after infection. Interestingly, we observed that AvrA is secreted by both type three secretion system (T3SS)-1 and T3SS-2. In summary, these findings indicate that AvrA expression is not constrained to the initial host–bacteria encounter in the intestinal environment as defined previously. The AvrA effector may participate also in systemic S. Enteritidis infection.
From food to cell: nutrient exploitation strategies of enteropathogens
Authors: Staib Lena , Fuchs Thilo M.
Published: April 2014

Upon entering the human gastrointestinal tract, foodborne bacterial enteropathogens encounter, among numerous other stress conditions, nutrient competition with the host organism and the commensal microbiota. The main carbon, nitrogen and energy sources exploited by pathogens during proliferation in, and colonization of, the gut have, however, not been identified completely. In recent years, a huge body of literature has provided evidence that most enteropathogens are equipped with a large set of specific metabolic pathways to overcome nutritional limitationsin vivo, thus increasing bacterial fitness during infection. These adaptations include the degradation ofmyo-inositol, ethanolamine cleaved from phospholipids, fucose derived from mucosal glycoconjugates, 1,2-propanediol as the fermentation product of fucose or rhamnose and several other metabolites not accessible for commensal bacteria or present in competition-free microenvironments. Interestingly, the data reviewed here point to common metabolic strategies of enteric pathogens allowing the exploitation of nutrient sources that not only are present in the gut lumen, the mucosa or epithelial cells, but also are abundant in food. An increased knowledge of the metabolic strategies developed by enteropathogens is therefore a key factor to better control foodborne diseases.
Intermediate Migration Yields Optimal Adaptation in Structured, Asexual Populations
Authors: Covert III Arthur , Wilke Claus O
Published: April 2014

Most evolving populations are subdivided into multiple subpopulations connected to each other by varying levels of gene flow. However, how population structure and gene flow (i.e., migration) affect adaptive evolution is not well understood. Here, we studied the impact of migration on asexually reproducing evolving computer programs (digital organisms). We found that digital organisms evolve the highest fitness values at intermediate migration rates, and we tested three hypotheses that could potentially explain this observation: (i) migration promotes passage through fitness valleys, (ii) migration increases genetic variation, and (iii) migration reduces clonal interference through a process called leapfrogging. We found that migration had no appreciable effect on the number of fitness valleys crossed and that genetic variation declined monotonously with increasing migration rates, instead of peaking at the optimal migration rate. However, the number of leapfrogging events, in which a superior beneficial mutation emerges on a genetic background that predates the previously best genotype in the population, did peak at the optimal migration rate. We thus conclude that in structured, asexual populations intermediate migration rates allow for optimal exploration of multiple, distinct fitness peaks, and thus yield the highest long-term adaptive success.
MicroRNAs Regulate the Wnt/Ca2+ Signaling Pathway to Promote the Secretion of Insulin in Pancreatic Nestin-Positive Progenitor Cells
Authors: Bai Chunyu , Li Xiangchen , Gao Yuhua , Lu Taofeng , Wang Kunfu , Li Qian , Xiong Hui , Chen Jia , Zhang Ping , Wang Wenjie , Sun Tingting , Shan Zhiqiang , Sun Bo , Pei Pei , Liu Changqing , Guan Weijun , Ma Yuehui
Published: April 2014

MicroRNAs (miRNAs) are small noncoding RNAs that bind to the 3?-UTR of mRNAs and function mainly in post-transcriptional regulation. MiRNAs have been implicated to play roles in organ development, including that of the pancreas. Many miRNAs, such as miR-375, miR-124, miR-7, miR-21 and miR-221, have been shown to regulate insulin production as well as insulin secretion. However, it is not known whether miRNAs can regulate insulin secretion via the control of intracellular Ca2+ in pancreatic beta cells. In this research, expression profiles of miRNAs and mRNAs were investigated using RNA-sequencing and microarray analysis in chicken pancreatic nestin-positive progenitor cells and differentiated pancreatic beta cells. A number of miRNAs were up-regulated after differentiation of progenitors into beta cells, which regulate cell signaling pathways to control cell function. miR-223 and miR146a were shown to promote insulin secretion from pancreatic beta cells by regulating the concentration of intracellular Ca2+ via the down-regulation of their target genes.
A Limited Role for Carbonic Anhydrase in C4 Photosynthesis as Revealed by a ca1ca2 Double Mutant in Maize
Authors: Studer Anthony J. , Gandin Anthony , Kolbe Allison R. , Wang Lin , Cousins Asaph B. , Brutnell Thomas P.
Published: April 2014

Carbonic anhydrase (CA) catalyzes the first biochemical step of the carbon-concentrating mechanism of C4 plants, and in C4 monocots it has been suggested that CA activity is near limiting for photosynthesis. Here, we test this hypothesis through the characterization of transposon-induced mutant alleles of Ca1 and Ca2 in maize (Zea mays). These two isoforms account for more than 85% of the CA transcript pool. A significant change in isotopic discrimination is observed in mutant plants, which have as little as 3% of wild-type CA activity, but surprisingly, photosynthesis is not reduced under current or elevated CO2 partial pressure (pCO2). However, growth and rates of photosynthesis under subambient pCO2 are significantly impaired in the mutants. These findings suggest that, while CA is not limiting for C4 photosynthesis in maize at current pCO2, it likely maintains high rates of photosynthesis when CO2 availability is reduced. Current atmospheric CO2 levels now exceed 400 ppm (approximately 40.53 Pa) and contrast with the low-pCO2 conditions under which C4 plants expanded their range approximately 10 million years ago, when the global atmospheric CO2 was below 300 ppm (approximately 30.4 Pa). Thus, as CO2 levels continue to rise, selective pressures for high levels of CA may be limited to arid climates where stomatal closure reduces CO2 availability to the leaf.
Identification and Characterization of Maizefloury4as a Novel Semidominant Opaque Mutant That Disrupts Protein Body Assembly
Authors: Wang Guan , Qi Weiwei , Wu Qiao , Yao Dongsheng , Zhang Jushan , Zhu Jie , Wang Gang , Wang Guifeng , Tang Yuanping , Song Rentao
Published: April 2014

Zeins are the major seed storage proteins in maize (Zea mays). They are synthesized on the endoplasmic reticulum (ER) and deposited into protein bodies. Failure of signal peptide cleavage from zeins can cause an opaque endosperm in the mature kernel; however, the cellular and molecular mechanisms responsible for this phenotype are not fully understood. In this study, we report the cloning and characterization of a novel, semidominant opaque mutant, floury4 (fl4). fl4 is caused by a mutated z1A 19-kD α-zein with defective signal peptide cleavage. Zein protein bodies in fl4 endosperm are misshapen and aggregated. Immunolabeling analysis indicated that fl4 participates in the assembly of zeins into protein bodies, disrupting their proper spatial distribution. ER stress is stimulated in fl4 endosperm, as illustrated by dilated rough ER and markedly up-regulated binding protein content. Further analysis confirmed that several ER stress pathways are induced in fl4 endosperm, including ER-associated degradation, the unfolded protein response, and translational suppression by the phosphorylation of eukaryotic translational initiation factor2 α-subunit. Programmed cell death is also elevated, corroborating the intensity of ER stress in fl4. These results provide new insights into cellular responses caused by storage proteins with defective signal peptides.
Light-Harvesting Complex Protein LHCBM9 Is Critical for Photosystem II Activity and Hydrogen Production in Chlamydomonas reinhardtii
Authors: Grewe Sabrina , Ballottari Matteo , Alcocer Marcelo , D’Andrea Cosimo , Blifernez-Klassen Olga , Hankamer Ben , Mussgnug Jan H. , Bassi Roberto , Kruse Olaf
Published: April 2014

Photosynthetic organisms developed multiple strategies for balancing light-harvesting versus intracellular energy utilization to survive ever-changing environmental conditions. The light-harvesting complex (LHC) protein family is of paramount importance for this function and can form light-harvesting pigment protein complexes. In this work, we describe detailed analyses of the photosystem II (PSII) LHC protein LHCBM9 of the microalga Chlamydomonas reinhardtii in terms of expression kinetics, localization, and function. In contrast to most LHC members described before, LHCBM9 expression was determined to be very low during standard cell cultivation but strongly increased as a response to specific stress conditions, e.g., when nutrient availability was limited. LHCBM9 was localized as part of PSII supercomplexes but was not found in association with photosystem I complexes. Knockdown cell lines with 50 to 70% reduced amounts of LHCBM9 showed reduced photosynthetic activity upon illumination and severe perturbation of hydrogen production activity. Functional analysis, performed on isolated PSII supercomplexes and recombinant LHCBM9 proteins, demonstrated that presence of LHCBM9 resulted in faster chlorophyll fluorescence decay and reduced production of singlet oxygen, indicating upgraded photoprotection. We conclude that LHCBM9 has a special role within the family of LHCII proteins and serves an important protective function during stress conditions by promoting efficient light energy dissipation and stabilizing PSII supercomplexes.
Disentangling the effects of exposure and susceptibility on transmission of the zoonotic parasite Schistosoma mansoni
Authors: Civitello David J. , Rohr Jason R.
Published: April 2014

For all parasites, transmission is composed of two processes: host contact with parasites (‘exposure’) and risk of infection given such contact (‘susceptibility’). Classic models, such as mass action (density‐dependent) transmission, lump these processes together.

However, separating these processes could enhance predictions for disease dynamics, especially for free‐living parasites. Here, we outline three transmission models that partition exposure and susceptibility.

Using data from a study of Schistosoma mansoni (trematode) infections in Biomphalaria glabrata snails, we competed these three models against four alternative models, including the mass action model (which lumps exposure and susceptibility).

The models that separately accounted for exposure and susceptibility best predicted prevalence across the density gradients of hosts and parasites, outperforming all other models based on Akaike information criterion. When embedded into a dynamic epidemiological model, the exposure‐explicit models all predicted lower equilibrium densities of infected snails and human‐infectious cercariae.

Thus, population‐level epidemiological models that utilize the classic mass action transmission model might overestimate human risk of schistosomiasis. More generally, the presented approach for disentangling exposure and susceptibility can distinguish between behavioural and immunological resistance, identify mechanisms of ‘disease dilution’ and provide a more complete dissection of drivers of parasite transmission.
Community‐level demographic consequences of urbanization: an ecological network approach
Authors: Rodewald Amanda D. , Rohr Rudolf P. , Fortuna Miguel A. , Bascompte Jordi
Published: April 2014

Ecological networks are known to influence ecosystem attributes, but we poorly understand how interspecific network structure affect population demography of multiple species, particularly for vertebrates. Establishing the link between network structure and demography is at the crux of being able to use networks to understand population dynamics and to inform conservation.

We addressed the critical but unanswered question, does network structure explain demographic consequences of urbanization?

We studied 141 ecological networks representing interactions between plants and nesting birds in forests across an urbanization gradient in Ohio, USA, from 2001 to 2011. Nest predators were identified by video‐recording nests and surveyed from 2004 to 2011.

As landscapes urbanized, bird–plant networks were more nested, less compartmentalized and dominated by strong interactions between a few species (i.e. low evenness). Evenness of interaction strengths promoted avian nest survival, and evenness explained demography better than urbanization, level of invasion, numbers of predators or other qualitative network metrics. Highly uneven networks had approximately half the nesting success as the most even networks. Thus, nest survival reflected how urbanization altered species interactions, particularly with respect to how nest placement affected search efficiency of predators.

The demographic effects of urbanization were not direct, but were filtered through bird–plant networks. This study illustrates how network structure can influence demography at the community level and further, that knowledge of species interactions and a network approach may be requisite to understanding demographic responses to environmental change.
Bipolar disorder in the elderly: a cohort study comparing older and younger patients
Authors: Nivoli A. M. A. , Murru A. , Pacchiarotti I. , Valenti M. , Rosa A. R. , Hidalgo D. , Virdis V. , Strejilevich S. , Vieta E. , Colom F.
Published: April 2014

Objective

The purpose of this study was to analyze differences in clinical and socio‐demographic characteristics between older and younger bipolar outpatients paying special attention to depressive symptoms in a large, naturalistic cohort.

Method

Five hundred and ninety‐three DSM‐IV‐TR bipolar outpatients were enrolled. Clinical characteristics were assessed according to DSM‐IV‐TR (SCID‐I). Subjects were categorized into two groups according to current age (older OBD: age > 65 years; younger‐YBD: age < 65 years).

Results

About 80% of patients were younger (N = 470), and a fifth were older (N = 123), with a mean age of 77.30 years in OBD. Older patients were more likely to be married, not qualified, bipolar II, with depressive polarity of first episode, higher age at illness onset, higher age at first hospitalization. They were more likely to present with depressive predominant polarity, with lifetime history of catatonic, psychotic and melancholic features, age at illness onset >40 years, as well as suffering from more medical comorbidities when compared to younger bipolars.

Conclusion

The clinical presentation of bipolar disorder in late life would be defined more frequently by melancholic depressive features and a predominantly depressive polarity. These results suggest that treatment strategies for elderly bipolar patients should focus in the prevention of depressive episodes.
Quantitative sonoelastography of the uterine cervix prior to induction of labor as a predictor of cervical dilation time
Authors: Hee Lene , Rasmussen Christina K. , Schlütter Jacob M. , Sandager Puk , Uldbjerg Niels
Published: April 2014

Objective

To evaluate how the approximate Young's modulus of the uterine cervix assessed by quantitative sonoelastography in patients undergoing induction of labor is associated with the cervical dilation time and to evaluate the approximate Young's modulus as a predictor of prolonged cervical dilation time.

Design

Cross‐sectional study.

Setting

Aarhus University Hospital, Aarhus, Denmark.

Population

Term‐pregnant women.

Methods

A total of 49 term‐pregnant women were included before induction of labor. The approximate Young's modulus of the anterior cervical lip was determined by the use of a reference cap applied on the end of the transvaginal transducer during sonoelastography.

Main outcome measures

Cervical dilation time during active labor.

Results

The approximate Young's modulus was associated with the cervical dilation time during active labor (R2log = 0.24, p < 0.01) and predicted prolonged duration of cervical dilation time (>330 min) with the area under the receiver operating characteristic (ROC) curve of 0.71, sensitivity 74%, and specificity 69%. Equivalent figures for the Bishop's score were R2log = 0.02 (p = 0.37), the area under the ROC curve 0.53, sensitivity 53%, and specificity 46%. For the cervical length measurements the corresponding results were: R2log = 0.02, p = 0.35, area under the ROC curve 0.57, sensitivity 66% and specificity 54%. The intra‐observer and inter‐observer intraclass correlations were 88% and 58%, respectively, with quantitative elastography.

Conclusions

The approximate Young's modulus is superior to the Bishop score and the cervical length measurements concerning the prediction of cervical dilation time and the risk of prolonged dilation time after induction of labor.
Pathophysiology and potential treatments of pulmonary hypertension due to systolic left heart failure
Authors: Lundgren J. , Rådegran G.
Published: April 2014

Pulmonary hypertension (PH) due to left heart failure is becoming increasingly prevalent and is associated with poor outcome. The precise pathophysiological mechanisms behind PH due to left heart failure are, however, still unclear. In its early course, PH is caused by increased left ventricular filling pressures, without pulmonary vessel abnormalities. Conventional treatment for heart failure may partly reverse such passive PH by optimizing left ventricular function. However, if increased pulmonary pressures persist, endothelial damage, excessive vasoconstriction and structural changes in the pulmonary vasculature may occur. There is, at present, no recommended medical treatment for this active component of PH due to left heart failure. However, as the vascular changes in PH due to left heart failure may be similar to those in pulmonary arterial hypertension (PAH), a selected group of these patients may benefit from PAH treatment targeting the endothelin, nitric oxide or prostacyclin pathways. Such potent pulmonary vasodilators could, however, be detrimental in patients with left heart failure without pulmonary vascular pathology, as selective pulmonary vasodilatation may lead to further congestion in the pulmonary circuit, resulting in pulmonary oedema. The use of PAH therapies is therefore currently not recommended and would require the selection of suitable patients based on the underlying causes of the disease and careful monitoring of their progress. The present review focuses on the following: (i) the pathophysiology behind PH resulting from systolic left heart failure, and (ii) the current evidence for medical treatment of this condition, especially the role of PAH‐targeted therapies in systolic left heart failure.
Contraction‐evoked vasodilation and functional hyperaemia are compromised in branching skeletal muscle arterioles of young pre‐diabetic mice
Authors: Novielli N. M. , Jackson D. N.
Published: April 2014

Aim

To investigate the effects of pre‐diabetes on microvascular network function in contracting skeletal muscle. We hypothesized that pre‐diabetes compromises contraction‐evoked vasodilation of branching second‐order (2A), third‐order (3A) and fourth‐order (4A) arterioles, where distal arterioles would be affected the greatest.

Methods

Intravital video microscopy was used to measure arteriolar diameter (in 2A, 3A and 4A) and blood flow (in 2A and 3A) changes to electrical field stimulation of the gluteus maximus muscle in pre‐diabetic (The Pound Mouse, PD) and control (c57bl6, CTRL) mice.

Results

Baseline diameter and blood flow were similar between groups (2A: ~20 μm, 3A: ~14 μm and 4A: ~8 μm; 2A: ~1 nL s−1 and 3A: ~0.5 nL s−1). Single tetanic contraction (100 Hz; 200, 400, 800 ms duration) evoked rapid‐onset vasodilation (ROV) and blood flow responses that were blunted by ~50% and up to 81%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of ROV was up to 2‐fold greater at distal arterioles (3A and 4A) vs. proximal arterioles (2A) in CTRL; however, in PD, ROV of only 4A was greater than 2A (P < 0.05). Rhythmic contraction (2 and 8 Hz, 30 s) evoked vasodilatory and blood flow responses that were also attenuated by ~50% and up to 71%, respectively, in PD vs. CTRL (P < 0.05). The magnitude of vasodilatory responses to rhythmic contraction was also up to 2.5‐fold greater at 4A vs. 2A in CTRL; however spatial differences in vasodilation across arteriolar branch orders was disrupted in PD.

Conclusions

Arteriolar dysregulation in pre‐diabetes causes deficits in contraction‐evoked dilation and blood flow, where greatest deficits occur at distal arterioles.
Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia
Authors: Henriksen Louise T. , Nersting Jacob , Raja Raheel A. , Frandsen Thomas L. , Rosthøj Steen , Schrøder Henrik , Albertsen Birgitte K. ,   the Nordic Society of Paediatric Haematology and Oncology (NOPHO) group
Published: April 2014

L‐asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS‐directed anti‐leukaemia therapy. The objective of this study was to describe CSF asparagine depletion during 30 weeks of pegylated asparaginase therapy, 1000 iu/m2 i.m. every second week, and to correlate CSF asparagine concentration with serum L‐asparaginase enzyme activity. Danish children (1–17 years) with ALL, treated according to the Nordic Society of Paediatric Haematology and Oncology ALL2008 protocol, standard and intermediate risk, were included. CSF samples were obtained throughout L‐asparaginase treatment at every scheduled lumbar puncture. A total of 128 samples from 31 patients were available for analysis. Median CSF asparagine concentration decreased from a pre‐treatment level of 5·3 μmol/l to median levels ≤1·5 μmol/l. However, only 4/31 patients (five samples) had CSF asparagine concentrations below the limit of detection (0·1 μmol/l). In 11 patients, 24 paired same day serum and CSF samples were obtained. A decrease in CSF asparagine corresponded to serum enzyme activities above 50 iu/l. Higher serum enzyme activities were not followed by more extensive depletion. In conclusion, pegylated asparaginase 1000 iu/m2 i.m. every second week effectively reduced CSF asparagine levels.
Risk factors and management of severe life‐threatening anaphylaxis in patients with clonal mast cell disorders
Authors: Valent P.
Published: April 2014

Several different risk factors and conditions may predispose to severe life‐threatening anaphylaxis. Systemic mastocytosis (SM) is one such condition. Although many SM patients are suffering from mild or even no mediator‐related symptoms, others have recurrent episodes of severe anaphylaxis, with clear signs of a mast cell activation syndrome (MCAS) despite prophylactic therapy with anti‐mediator‐type drugs. In several of these patients, an IgE‐dependent allergy is diagnosed. The severity and frequency of MCAS reactions neither correlate with the burden of neoplastic mast cells nor with the levels of specific IgE or the basal tryptase level. However, there is a relationship between severe anaphylaxis in SM and the type of allergen. Notably, many of these patients suffer from hymenoptera venom allergy. Currently recommended therapies include the prophylactic use of anti‐mediator‐type drugs, long‐term immunotherapy for hymenoptera venom allergic patients, and epinephrine‐self‐injector treatment for emergency situations. In patients who present with an excess burden of mast cells, such as smouldering SM, cytoreductive therapy with cladribine (2CdA) may reduce the frequency of severe events. For the future, additional treatment options, such as IgE‐depletion or the use of tyrosine kinase inhibitors blocking IgE‐dependent mediator secretion as well as KIT activation, may be useful alternatives.
Posterior alveolar ridge resorption in bar‐retained mandibular overdentures: 10‐year results of a prospective clinical trial
Authors: Raedel Michael , Lazarek‐Scholz Kristina , Marré Birgit , Boening Klaus W. , Walter Michael H.
Published: April 2014

Objectives

Data on posterior alveolar ridge resorption (PARR) in patients with two implant supported mandibular overdentures is very heterogeneous. The aim of this prospective study was to observe the PARR after ten years for a study population treated with a titanium bar retained overdenture on two IMZ‐implants.

Material and methods

The data pool consisted of digital and digitized conventional panoramic radiographs taken prior to implant placement and at follow up appointments. Digital measurements were carried out following an established procedure (“Tuebingen method” by Gomez‐Roman). For each patient a linear regression was calculated resulting in a relative area related PARR‐value per year. A simplified geometrical scenario was used for the estimation of absolute bone height losses.

Results

Data of 23 patients was available. The mean observation period was 9.4 years (±2.4 years). An average area related PARR‐rate of 1.02% per year was observed with high individual differences ranging from 0.15% and 2.63% per year. The estimated average ten year vertical bone loss in the chewing center was 1.5 mm.

Conclusions

Posterior bone resorption was found to be in the range previously reported for different implant restorations and therefore does not represent a particular problem of two implant bar retained overdentures. The results strengthen the two implant concept.
Fifteen‐year trends and predictors of preparation for pregnancy in women with pre‐conception Type 1 and Type 2 diabetes: a population‐based cohort study
Authors: Glinianaia S. V. , Tennant P. W. G. , Crowder D. , Nayar R. , Bell R.
Published: April 2014

Aims

To investigate trends in indicators of preparation for pregnancy in women with Type 1 and Type 2 diabetes and explore their predictors.

Methods

Data on 2293 pregnancies delivered during 1996–2010 by women with Type 1 (n = 1753) and Type 2 (n = 540) diabetes were obtained from the Northern Diabetes in Pregnancy Survey. Multiple logistic regression was used to analyse the relationship between potential predictors and three indicators of inadequate pregnancy preparation: non‐attendance for pre‐conception care; no pre‐conception folate consumption; and peri‐conception HbA1c ≥ 53 mmol/mol (≥ 7%).

Results

Overall, 40.3% of women with diabetes attended pre‐conception care, 37.4% reported pre‐conception folate consumption, and 28.2% had adequate peri‐conception HbA1c. For all patients, pre‐conception folate consumption improved over time, while peri‐conception glucose control did not. Attendance for pre‐conception care for women with Type 1 diabetes significantly declined. Residence in deprived areas, smoking and younger maternal age (for women aged < 35 years) were independently associated with all three indicators of inadequate preparation for pregnancy. Additional predictors of inadequate peri‐conception HbA1c were: Type 1 diabetes (adjusted odds ratio 5.51, 95% CI 2.71–11.22), longer diabetes history (adjusted odds ratio 1.16, 95% CI 1.09–1.23 per year increase for those with < 15 years' diabetes duration), non‐white ethnicity (adjusted odds ratio 3.13, 95% CI 1.23–7.97) and higher BMI (adjusted odds ratio 1.05, 95% CI 1.01–1.09 per 1‐kg/m2 increase). Non‐attendance for pre‐conception care was additionally associated with Type 2 diabetes (P = 0.003) and multiparity (P < 0.0001).

Conclusions

There are socio‐demographic inequalities in preparation for pregnancy among women with diabetes. Women with Type 2 diabetes were less likely to attend pre‐conception care. Pre‐conception services need to be designed to maximize uptake in all groups.
Reductions in resistance exercise‐induced hyperglycaemic episodes are associated with circulating interleukin‐6 in Type 1 diabetes
Authors: Turner D. , Luzio S. , Kilduff L. P. , Gray B. J. , Dunseath G. , Bain S. C. , Campbell M. D. , West D. J. , Bracken R. M.
Published: April 2014

Aims

To determine the influence of different volumes of resistance exercise on circulating interleukin‐6 (IL‐6) and to explore the relationships between IL‐6 and glycaemia.

Methods

Eight participants with complication‐free Type 1 diabetes, whose mean ± sem age was 38 (6) years, mean ± sem HbA1c concentration was 71 ±11 mmol/mol (8.7 ±1.0%) and mean ± sem Type 1 diabetes duration was 15 ±13 years, attended the research facility after an overnight fast on four separate occasions, having administered their basal insulin the night before (glargine 27.5±3.1U, n=8), but omitted morning rapid‐acting insulin. Participants completed either a one‐set (14‐min), two‐set (28‐min), or three‐set (42‐min) resistance exercise trial (eight exercises × 10 repetitions) at 67±3% one‐repetition maximum followed by a 60‐min recovery, or a resting control trial. Venous blood samples were taken before and after exercise. Data were analysed using repeated‐measures anova (P≤0.05).

Results

Whereas IL‐6 levels remained similar to baseline levels after one set of resistance exercises (30 min, P=0.287; 60 min, P=0.318), IL‐6 levels were > baseline levels at 60 min post‐exercise after a two‐set exercise trial (2.94 ± 0.94 pg/ml, P=0.002) and doubled at both 30 min (4.01 ± 1.00 pg/ml, P=0.048) and 60 min (4.28 ± 1.25 pg/ml, P=0.084) post‐exercise after the three‐set resistance exercise trial. Post‐exercise blood glucose area under the curve (mmol/l/60 min) was greater after both the one‐set (P=0.025) and two‐set trials (P=0.008), than after the control trial, but similar between the three‐set trial and the control trial (P=0.240). The rise in IL‐6 from baseline to peak concentration significantly correlated inversely with blood glucose area under the curve (r=‐0.65, P=0.041).

Conclusions

Circulating IL‐6 is increased by resistance exercise in a volume‐dependent manner, and resistance exercise‐induced increases in IL‐6 correlated with reductions in post‐exercise hyperglycaemia in Type 1 diabetes, suggesting a role for IL‐6 in improving post‐resistance exercise glycaemic disturbances in Type 1 diabetes.

(Clinical Trials Registry No: ISRCTN60407046)
An Unusual Cause of Bioprosthetic Mitral Valve Obstruction: Calcified Septum of Cor Triatriatum Sinister
Authors: Kalcik Macit , Ozan Gursoy M. , Toprak Cüneyt , Yesin Mahmut , Karakoyun Suleyman , Tuncer M. Altuğ , Ozkan Mehmet
Published: April 2014

Mini‐Abstract

Cor triatriatum sinister is a rare congenital cardiac anomaly in which the left atrium is divided into 2 chambers by a fibromuscular septum. Although the disease is generally diagnosed in early childhood, some patients remain asymptomatic until adulthood. Here, we present an unusual presentation of cor triatriatum sinister as a unique cause of mitral bioprosthetic valve obstruction. The calcified septum of the cor triatriatum sinister was delineated with the utility of two‐dimensional and real time three‐dimensional transesophageal echocardiography.
Identification of Prolapsing Mitral Valve Scallops by a Three‐Dimensional Multiplanar Reconstruction Method
Authors: Akhter Nausheen , Zhao Qiong , Andrei Adin‐Cristian , Kane Bonnie , McCarthy Patrick , Rigolin Vera H.
Published: April 2014

Background

The objectives of this study were twofold: to assess the diagnostic utility of three‐dimensional (3D) multiplanar reconstruction (MPR) in identifying prolapsing mitral valve (MV) scallops, and (2) to compare two‐dimensional (2D) transthoracic echocardiography (TTE) and 3DMPRto (2D) transesophageal echocardiography (TEE) approaches among patients with mitral valve prolapse (MVP).

Methods

Fifty‐five patients withMVPwho underwent MV repair or replacement were retrospectively analyzed using 3 types of echocardiographic studies (2DTEE, 2DTTE, 3DMPR). The operative (OR) findings were considered the gold standard.

Results

When 3DMPRwas combined with 2DTTE, the agreement with theORfindings was moderately strong for the A2 scallop (P < 0.001) and strong for the A3 scallop (P = 0.001), entire anterior leaflet (P < 0.001), P2 scallop (P < 0.001) and the entire posterior leaflet (P < 0.001). In comparison to theORfindings, 2DTEEdemonstrated moderately strong agreement for the A2 scallop (P = 0.010) and the entire anterior leaflet (P < 0.001), and strong agreement for the P2 scallop (P < 0.001) and entire posterior leaflet (P < 0.001).

Conclusions

Three‐dimensionalMPRshould be added to the armamentarium of complementary echo techniques in the evaluation ofMVP. There is increased benefit in combining 3DMPRwith 2DTTEfindings as part of the preoperative evaluation of patients withMVP.
Blood Flow Imaging in Transesophageal Echocardiography during Atrial Septal Defect Closure: A Comparison with the Current References
Authors: Nyrnes Siri Ann , Løvstakken Lasse , Døhlen Gaute , Skogvoll Eirik , Torp Hans , Skjærpe Terje , Norgård Gunnar , Samstad Stein , Graven Torbjørn , Haugen Bjørn Olav
Published: April 2014

Background

Flow visualization before transcatheter atrial septal defect (ASD) closure is essential to identify the number and size of ASDs and to map the pulmonary veins (PV). Previous reports have shown improved visualization of ASD and PV using blood flow imaging (BFI), which supplements color Doppler imaging (CDI) with angle‐independent information of flow direction. In this study, we compared transesophageal BFI with the current references in ASD sizing (balloon stretched diameter, BSD) and PV imaging (pulmonary angiography).

Methods

In this prospective study, 28 children were examined with transesophageal echocardiography (TEE) including BFI of the secundum ASD and the PV before interventional ASD closure. The maximum ASD diameter measured with BFI by 4 observers was compared to the corresponding BSD and CDI measurements. The repeatability of the BFI measurements was calculated as the residual standard deviation. BFI of the PV was compared to PV angiography.

Results

The mean maximum diameter measured by BFI was 12.1 mm (±SD 2.4 mm). The corresponding BSD and CDI measurements were 15.9 mm (±SD 3.0 mm) and 11.8 mm (±SD 2.5 mm), respectively. The residual standard deviation was 1.2 mm. Compared to PV angiography, the sensitivity of BFI in detecting the correct entry of the PV was 0.96 (95% CI: 0.82–1.0).

Conclusion

Transesohageal echocardiography with BFI of the PV agreed well with pulmonary angiography. BFI had lower estimates for ASD size than BSD, but with acceptable 95% limits of agreement. The repeatability of the BFI measurements was close to the inherent ultrasound measurement error.
Isolated Supravalvular Pulmonary Stenosis: A Rare Echocardiographic Finding
Authors: Maffè Stefano , Dellavesa Pierfranco , Paffoni Paola , Zenone Franco , Cucchi Lorenzo , Paino Anna Maria , Bergamasco Luca , Baduena Lara , Franchetti Pardo Nicolò , Zanetta Marco , Parravicini Umberto
Published: April 2014

Isolated supravalvular pulmonary stenosis is a rare finding, usually evidenced in the pediatric age. Here, we report a case of a 76‐year‐old patient with isolated, severely obstructive, pulmonary supravalvular stenosis. The peculiarity of the present case is the paucity of symptoms and lack of changes in right heart sections, despite of the importance of stenosis. The report confirms the utility of transthoracic two‐ and three‐dimensional echocardiography and transesophageal echocardiography in the detection and quantification of this rare anomaly.
Impact of therapy and disease‐related symptoms on health‐related quality of life in patients with follicular lymphoma: results of the population‐based PHAROS‐registry
Authors: Oerlemans Simone , Issa Djamila E. , van den Broek Esther C. , Nijziel Marten R. , Coebergh Jan Willem W. , Mols Floortje , van de Poll‐Franse Lonneke V.
Published: April 2014

Objectives

The increasing number of longer living patients with follicular lymphoma (FL) and serious side effects of treatment urged us to study the health‐related quality of life (HRQoL) and persistent (treatment‐related) symptoms in unselected patients after different treatment modalities and compare HRQoL of patients with a normative population.

Methods

The population‐based Eindhoven Cancer Registry was used to select patients diagnosed with FL during 2004–2010. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ‐C30) was completed twice, with a 1‐yr interval. This questionnaire was also completed by an age‐ and sex‐matched normative population (N = 580). Detailed data on treatment were extracted from the cancer registry and Population‐based HAematological Registry for Observational Studies (PHAROS).

Results

Of the 181 patients who were invited, 148 responded (82%, T1). Patients treated with immunochemotherapy reported clinically relevant higher mean fatigue scores than those who underwent radiotherapy (P = 0.02). No differences were observed on the other HRQoL scales between treatment groups. Mean HRQoL scores were worse for FL patients treated with immunochemotherapy compared with a normative population (P < 0.01). A quarter to 50% of patients persistently reported to be slowed down, lethargic, or persistently worried about future health or was limited in social activities. Subsequently, patients reporting these symptoms/worries had a lower global health status/HRQoL.

Conclusion

Alertness for persistent symptoms that occur during and after treatment of FL patients is needed and may help to avoid lasting negative influence on their HRQoL.
Prognostic impact of minimal residual disease analysis by flow cytometry in patients with acute myeloid leukemia before and after allogeneic hemopoietic stem cell transplantation
Authors: Bastos‐Oreiro Mariana , Perez‐Corral Ana , Martínez‐Laperche Carolina , Bento Leyre , Pascual Cristina , Kwon Mi , Balsalobre Pascual , Muñoz Cristina , Buces Elena , Serrano David , Gayoso Jorge , Buño Ismael , Anguita Javier , Diéz‐Martín José Luís
Published: April 2014

Allogeneic stem cell transplantation (allo‐SCT) has become the treatment of choice in patients with intermediate‐risk and high‐risk acute myeloid leukemia (AML). The quality of response to treatment, assessed in terms of detection of minimal residual disease (MRD), has been consistently associated with prognosis and clinical outcome in patients with AML. The aim of the present study was to evaluate the prognostic impact of analyzing MRD in bone marrow using 4‐color multiparametric flow cytometry (MFC) in 29 patients with AML before and after allo‐SCT. Eighteen patients who were shown to be MRD‐negative [≤0.1% leukemia‐associated immunophenotypes (LAIPs)] by MFC at transplantation and underwent allo‐SCT had lower rates of relapse (15% vs. 66%, P = 0.045), better overall 1‐yr survival (83% vs. 52%, P = 0.021) and a lower cumulative incidence of relapse (P = 0.032) than patients who were MRD‐positive (>0.1%). All post‐transplant MRD‐positive patients underwent a therapeutic intervention after transplant (tapering of immunosuppression, donor lymphocyte infusion, or re‐transplant) with the intention of preventing relapse. Disease was controlled and MRD disappeared in five of these patients. Disease recurred in the other seven patients. We can conclude that follow‐up with MFC for the detection of MRD in AML before and after SCT is useful for predicting relapse. In the post‐transplant setting, monitoring of MRD by MFC could be a key preemptive intervention.
Neural changes accompanying tinnitus following unilateral acoustic trauma in the guinea pig
Authors: Coomber Ben , Berger Joel I. , Kowalkowski Victoria L. , Shackleton Trevor M. , Palmer Alan R. , Wallace Mark N.
Published: April 2014

Animal models of tinnitus allow us to study the relationship between changes in neural activity and the tinnitus percept. Here, guinea pigs were subjected to unilateral noise trauma and tested behaviourally for tinnitus 8 weeks later. By comparing animals with tinnitus with those without, all of which were noise‐exposed, we were able to identify changes unique to the tinnitus group. Three physiological markers known to change following noise exposure were examined: spontaneous firing rates (SFRs) and burst firing in the inferior colliculus (IC), evoked auditory brainstem responses (ABRs), and the number of neurons in the cochlear nucleus containing nitric oxide synthase (NOS). We obtained behavioural evidence of tinnitus in 12 of 16 (75%) animals. Both SFRs and incidences of burst firing were elevated in the IC of all noise‐exposed animals, but there were no differences between tinnitus and no‐tinnitus animals. There were significant decreases in ipsilateral ABR latencies in tinnitus animals, contrary to what might be expected with a small hearing loss. Furthermore, there was an ipsilateral–contralateral asymmetry in NOS staining in the ventral cochlear nucleus (VCN) that was only apparent in tinnitus animals. Tinnitus animals had a significantly greater number of NOS‐containing neurons on the noise‐exposed side, whereas no‐tinnitus animals did not. These data suggest that measuring NOS in the VCN and recording ABRs supplement behavioural methods for confirming tinnitus in animals, and that nitric oxide is involved in plastic neural changes associated with tinnitus.
Clinical features, diagnostic imaging findings and concurrent injuries in 71 sports horses with suspensory branch injuries
Authors: Marneris D. , Dyson S. J.
Published: April 2014

There are limited data concerning suspensory ligament branch (SLB) injuries in sports horses. This retrospective study aimed to describe the limb and mediolateral distribution of SLB injuries, the case history of injured horses, clinical signs, response to diagnostic analgesia, presence of other injuries, ultrasonographic features, radiological abnormalities and outcome. Case records of sports horses with ultrasonographic evidence of SLB injury (1998–2012) were reviewed. Ultrasonographic images were assessed subjectively and objectively. Descriptive statistics were used to describe horse data and injury distribution. Pearson's Chi‐square tests were used to test sidedness, forelimbs and hindlimbs, and medial and lateral branches. Pearson's Chi‐square tests were used to test for the ability to detect SLB enlargement by palpation and ultrasonography. Seventy‐one horses had injuries in 88 limbs, 42 forelimbs and 46 hindlimbs; 39/71 (54.9%) horses with only one branch injured, 18 (25.3%) with 2, 3 (4.2%) with 3, and 11 (15.5%) with 4. There was no significant difference in the proportion of injured medial and lateral branches, forelimbs or hindlimbs, left fore vs. right fore, or left hind vs. right hind. Forelimb injuries were overrepresented in event horses (76.2%) and hindlimb injuries in dressage horses (87.1%). Twenty‐eight horses had primary SLB injuries; 43 had other concurrent injuries in the same limb, 23 involving the suspensory apparatus. There was a significant difference (P = 0.011 in the ability to detect palpable enlargement of an SLB (60/171, 35.1%), compared with enlargement detected ultrasonographically (111/171, 64.9%). Periligamentous fibrosis was present in 78.7% of injured hindlimb SLBs and in 35.8% of forelimbs. Of horses with primary SLB injuries, 43.5% returned to full athletic function at their previous level for at least one year and up to 5 years. Periligamentous fibrosis or hyperextension of the fetlock adversely influenced outcome.