bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline Assessment of Inpatient Burn Care at Tenwek Hospital, Bomet, Kenya
Authors: Otteni Craig R. , Saruni Seno Ivan , Duron Vincent P. , Hedges Jeremy P. , White Russell E.
Published: April 2013

Background

Burn injuries are a significant source of both death and disability in developing countries. The objective of this project was to create a database of baseline inpatient burn care data to facilitate improvement of preventive measures and clinical outcomes at Tenwek Hospital, Bomet, Kenya.

Methods

Both demographic and clinical data were obtained through a retrospective chart review conducted on inpatient burn patients admitted to Tenwek Hospital between January 1, 2006 and May 31, 2010.

Results

Of the 269 patients studied, 53 % were male and 47 % were female. More than half (59 %) of the burns occurred in children younger than age 5 years. All‐cause mortality rate of inpatient burn patients was 12 %. Cardiac arrest, sepsis, and respiratory failure/pneumonia caused 81 % of the deaths. Scalds caused 55 % of the burns. Thirteen percent of the burns were seizure‐related. Second degree burns accounted for 76 % of the burns. Forty‐three percent of patients received at least one surgical debridement during their hospital stay. Thirty‐seven percent of patients received at least one split‐thickness skin graft. Antibiotic treatment was administered to 55 % of patients. Fifty‐three percent of patients presented to Tenwek Hospital 1 day or more from the time of injury.

Conclusions

We propose that prevention efforts focus on minimizing children’s exposure to boiling liquids and open flames in homes, providing appropriate and consistent treatment to epileptics to prevent seizure‐related burns, and stressing the importance of early presentation for treatment. A more selective approach to antibiotic use should be encouraged to decrease costs to the patient and hospital and lessen the risk of antibiotic resistance.
Insights into congenital stationary night blindness based on the structure of G90D rhodopsin
Authors: Singhal Ankita , Ostermaier Martin K , Vishnivetskiy Sergey A , Panneels Valérie , Homan Kristoff T , Tesmer John J G , Veprintsev Dmitry , Deupi Xavier , Gurevich Vsevolod V , Schertler Gebhard F X , Standfuss Joerg
Published: April 2013

We present active‐state structures of the G protein‐coupled receptor (GPCRs) rhodopsin carrying the disease‐causing mutation G90D. Mutations of G90 cause either retinitis pigmentosa (RP) or congenital stationary night blindness (CSNB), a milder, non‐progressive form of RP. Our analysis shows that the CSNB‐causing G90D mutation introduces a salt bridge with K296. The mutant thus interferes with the E113Q‐K296 activation switch and the covalent binding of the inverse agonist 11‐cis‐retinal, two interactions that are crucial for the deactivation of rhodopsin. Other mutations, including G90V causing RP, cannot promote similar interactions. We discuss our findings in context of a model in which CSNB is caused by constitutive activation of the visual signalling cascade.
Ergodic and outage capacities of relaying channels in spectrum‐sharing constrained systems
Authors: Ben Fredj Kaïs , Aïssa Sonia , Musavian Leila
Published: April 2013

This study investigates the capacity of multiple relay channels in different fading and shadowing environments under spectrum‐sharing constraints. The authors consider that a secondary user (SU) is allowed to share the spectrum band with a primary user (PU) provided that the SU's transmit power remains below an interference power threshold set by the PU. Considering a scenario where the SU's transmitter and receiver cannot communicate directly, a relay node, chosen among a set of K terminals, helps transmitting data from the SU's transmitter to the destination. The SU's transmitter and chosen relay node adapt their corresponding transmission parameters so as to satisfy the interference‐power constraint at the PU's receiver. The authors derive closed‐form expressions for the ergodic capacity of the SU's channel in Rayleigh fading, Nakagami‐m fading and lognormal shadowing environments. They further obtain the outage capacity assuming the aforementioned environments and the above‐mentioned spectrum‐sharing limitations. Numerical results are provided to reinforce our theoretical derivations.
Attracting and repelling Lagrangian coherent structures from a single computation
Authors: Farazmand Mohammad , Haller George
Published: April 2013

Hyperbolic Lagrangian Coherent Structures (LCSs) are locally most repelling or most attracting material surfaces in a finite-time dynamical system. To identify both types of hyperbolic LCSs at the same time instance, the standard practice has been to compute repelling LCSs from future data and attracting LCSs from past data. This approach tacitly assumes that coherent structures in the flow are fundamentally recurrent, and hence gives inconsistent results for temporally aperiodic systems. Here, we resolve this inconsistency by showing how both repelling and attracting LCSs are computable at the same time instance from a single forward or a single backward run. These LCSs are obtained as surfaces normal to the weakest and strongest eigenvectors of the Cauchy-Green strain tensor.
World raspberry production and marketing: industry changes and trends from 1960 to 2010.
Authors: Kempler C. , Hall H. K.
Published: April 2013

Data on world raspberry production since the 1960s are analysed by region: Europe, North America, other Pacific Rim countries, and other southern hemisphere countries. The drivers for raspberry marketing are then discussed.
Sniffing on Microbes: Diverse Roles of Microbial Volatile Organic Compounds in Plant Health
Authors: Bitas Vasileios , Kim Hye-Seon , Bennett Joan W. , Kang Seogchan
Published: April 2013

Secreted proteins and metabolites play diverse and critical roles in organismal and organism–environment interactions. Volatile organic compounds (VOC) can travel far from the point of production through the atmosphere, porous soils, and liquid, making them ideal info-chemicals for mediating both short- and long-distance intercellular and organismal interactions. Critical ecological roles for animal- and plant-derived VOC in directing animal behaviors and for VOC as a language for plant-to-plant communication and regulators of various physiological processes have been well documented. Similarly, microbial VOC appear to be involved in antagonism, mutualism, intra- and interspecies regulation of cellular and developmental processes, and modification of their surrounding environments. However, the available knowledge of how microbial VOC affect other organisms is very limited. Evidence supporting diverse roles of microbial VOC with the focus on their impact on plant health is reviewed here. Given the vast diversity of microbes in nature and the critical importance of microbial communities associated with plants for their ecology and fitness, systematic exploration of microbial VOC and characterization of their biological functions and ecological roles will likely uncover novel mechanisms for controlling diverse biological processes critical to plant health and will also offer tangible practical benefits in addressing agricultural and environmental problems.
First Report of Soybean vein necrosis virus on Soybeans in Michigan
Authors: Jacobs J. L. , Chilvers M. I.
Published: April 2013

Soybean vein necrosis virus (SVNV) is associated with an emerging disease in soybean producing regions of the United States. Soybean leaves with necrotic vein symptoms were initially noted in 2008 or 2009 in fields across Arkansas, Kansas, Missouri, Illinois, Mississippi, Tennessee, and Kentucky and SVNV was determined to be the causal agent (2). In 2012, widespread reports of SVNV were made across most soybean (Glycine max) producing states including the recent confirmation of SVNV in Iowa and Wisconsin (1). Foliar symptoms similar to those reported for SVNV were observed at approximately 1 to 10% incidence in soybean fields across Michigan in late August and September of 2012, including fields located in Cass, Ingham, Midland, Saginaw, and Van Buren counties. Symptoms included chlorosis and necrosis which initiated on the veins with subsequent spread across the leaf. An initial sample collected from the East Lansing Agricultural Research Station was confirmed to have SVNV with a polyclonal antibody using double antibody sandwich (DAS)-ELISA at AC Diagnostics, Inc. (Fayetteville, AR) and with reverse transcription PCR by Ioannis Tzanetakis, University of Arkansas, Fayetteville. Additional samples from five fields were subsequently collected from Cass, Ingham, and Van Buren counties. Duplicate leaf tissue samples were tested with DAS-ELISA using the SVNV test kit (AC Diagnostics). All symptomatic leaf samples exhibited a strong positive reaction based on the optical density reading at 405 nm. Absorbance reading that exceeded the healthy soybean tissue by a standard deviation of +3× were considered positive. Total RNA was also extracted from each sample using the RNeasy Plant Mini Kit (Qiagen, Germantown, MD). Complementary DNA (cDNA) was generated using virus-specific LdetR and SdetR primers (2) with the High Capacity RT cDNA kit (Life Technologies; Carlsbad, CA). The cDNA was used as template for PCR with the SVNV-specific primers that amplify regions of the L (LdetF/LdetR) and the S (SdetF/SdetR) RNAs (1). Amplification products of the expected 297 and 861 bp size, respectively, were detected in all symptomatic samples while no amplification products were generated from healthy soybean plant tissues grown under greenhouse conditions. Significantly, this is the first documentation and confirmation of the widespread prevalence of SVNV across the state of Michigan in 2012.

References: (1) D. L. Smith et al. Plant Dis. http://dx.doi.org/10.1094/PDIS-11-12-1096-PDN . (2) J. Zhou et al. Virus Genes 43:289, 2011.
Neuraxial Anesthesia in Parturients with Intracranial Pathology
Authors: Leffert Lisa R. , Schwamm Lee H.
Published: April 2013

Parturients with intracranial lesions are often assumed to have increased intracranial pressure, even in the absence of clinical and radiographic signs. The risk of herniation after an inadvertent dural puncture is frequently cited as a contraindication to neuraxial anesthesia. This article reviews the relevant literature on the use of neuraxial anesthesia in parturients with known intracranial pathology, and proposes a framework and recommendations for assessing risk of neurologic deterioration, with epidural analgesia or anesthesia, or planned or inadvertent dural puncture. The authors illustrate these concepts with numerous case examples and provide guidance for the practicing anesthesiologist in determining the safety of neuraxial anesthesia.
Hepatitis C virus core+1/ARF protein decreases hepcidin transcription through an AP1 binding site
Authors: Kotta-Loizou Ioly , Vassilaki Niki , Pissas George , Kakkanas Athanassios , Bakiri Latifa , Bartenschlager Ralf , Mavromara Penelope
Published: April 2013

Chronic viral hepatitis C is characterized by iron accumulation in the liver, and hepcidin regulates iron absorption. Hepatitis C virus (HCV) core+1/ARFP is a novel protein produced by a second functional ORF within the core gene. Here, using reporter assays and HCV bicistronic replicons, we show that, similarly to core, core+1/ARFP decreases hepcidin expression in hepatoma cells. The activator protein 1 (AP1) binding site of the human hepcidin promoter, shown here to be relevant to basal promoter activity and to the repression by core, is essential for the downregulation by core+1/ARFP while the previously described C/EBP (CCAAT/enhancer binding protein) and STAT (signal transducer and activator of transcription) sites are not. Consistently, expression of the AP1 components c-jun and c-fos obliterated the repressive effect of core and core+1/ARFP. In conclusion, we provide evidence that core+1/ARFP downregulates AP1-mediated transcription, providing new insights into the biological role of core+1/ARFP, as well as the transcriptional modulation of hepcidin, the main regulator of iron metabolism.
AUXIN RESPONSE FACTOR17 Is Essential for Pollen Wall Pattern Formation in Arabidopsis
Authors: Yang Jun , Tian Lei , Sun Ming-Xi , Huang Xue-Yong , Zhu Jun , Guan Yue-Feng , Jia Qi-Shi , Yang Zhong-Nan
Published: April 2013

In angiosperms, pollen wall pattern formation is determined by primexine deposition on the microspores. Here, we show that AUXIN RESPONSE FACTOR17 (ARF17) is essential for primexine formation and pollen development in Arabidopsis (Arabidopsis thaliana). The arf17 mutant exhibited a male-sterile phenotype with normal vegetative growth. ARF17 was expressed in microsporocytes and microgametophytes from meiosis to the bicellular microspore stage. Transmission electron microscopy analysis showed that primexine was absent in the arf17 mutant, which leads to pollen wall-patterning defects and pollen degradation. Callose deposition was also significantly reduced in the arf17 mutant, and the expression of CALLOSE SYNTHASE5 (CalS5), the major gene for callose biosynthesis, was approximately 10% that of the wild type. Chromatin immunoprecipitation and electrophoretic mobility shift assays showed that ARF17 can directly bind to the CalS5 promoter. As indicated by the expression of DR5-driven green fluorescent protein, which is an synthetic auxin response reporter, auxin signaling appeared to be specifically impaired in arf17 anthers. Taken together, our results suggest that ARF17 is essential for pollen wall patterning in Arabidopsis by modulating primexine formation at least partially through direct regulation of CalS5 gene expression.
Proton-transfer compounds with 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (sulfamethazine): the structures and hydrogen bonding in the salts with 5-nitrosalicylic acid and picric acid
Authors: Smith Graham , Wermuth Urs D.
Published: April 2013

The structures of the anhydrous proton-transfer compounds of the sulfa drug sulfamethazine with 5-nitrosalicylic acid and picric acid, namely 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2-hydroxy-5-nitrobenzoate, C12H15N4O2S+·C7H4NO4−, (I), and 2-(4-aminobenzenesulfonamido)-4,6-dimethylpyrimidinium 2,4,6-trinitrophenolate, C12H15N4O2S+·C6H2N3O7−, (II), respectively, have been determined. In the asymmetric unit of (I), there are two independent but conformationally similar cation–anion heterodimer pairs which are formed through duplex intermolecular N+—H...Ocarboxylateand N—H...Ocarboxylatehydrogen-bond pairs, giving a cyclic motif [graph setR22(8)]. These heterodimers form separate and different non-associated substructures through aniline N—H...O hydrogen bonds, one one-dimensional, involving carboxylate O-atom acceptors, the other two-dimensional, involving both carboxylate and hydroxy O-atom acceptors. The overall two-dimensional structure is stabilized by π–π interactions between the pyrimidinium ring and the 5-nitrosalicylate ring in both heterodimers [minimum ring-centroid separation = 3.4580 (8) Å]. For picrate (II), the cation–anion interaction involves a slightly asymmetric chelating N—H...OR21(6) hydrogen-bonding association with the phenolate O atom, together with peripheral conjointR12(6) interactions between the same N—H groups and O atoms of theortho-related nitro groups. An inter-unit amine N—H...Osulfonehydrogen bond gives one-dimensional chains which extend alongaand inter-associate through π–π interactions between the pyrimidinium rings [centroid–centroid separation = 3.4752 (9) Å]. The two structures reported here now bring to a total of four the crystallographically characterized examples of proton-transfer salts of sulfamethazine with strong organic acids.
Advances in understanding the pathogenesis of HLH
Authors: Usmani G. Naheed , Woda Bruce A. , Newburger Peter E.
Published: April 2013

Haemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder resulting from immune dysfunction reflecting either primary immune deficiency or acquired failure of normal immune homeostasis. Familial HLH includes autosomal recessive and X‐linked disorders characterized by uncontrolled activation of T cells and macrophages and overproduction of inflammatory cytokines, secondary to defects in genes encoding proteins involved in granule‐dependent cytolytic pathways. In older children and adults, HLH is associated more often with infections, malignancies, autoimmune diseases, and acquired immune deficiencies. HLH, macrophage activation syndrome, sepsis, and systemic inflammatory response syndrome are different clinical entities that probably represent a common immunopathological state, termed cytokine storm. These conditions may be clinically indistinguishable; all include massive inflammatory response, elevated serum cytokine levels, multi‐organ involvement, haemophagocytic macrophages, and often death. Tissues of haematopoietic and lymphoid function are directly involved; other organs are secondarily damaged by circulating cytokines and chemokines. Haemophagocytic disorders are now increasingly diagnosed in the context of severe inflammatory reactions to viruses, malignancies and systemic connective tissue diseases. Many of these cases may reflect underlying genetic predispositions to HLH. The detection of gene defects has contributed considerably to our understanding of HLH, but the mechanisms leading to acquired HLH have yet to be fully determined.
Efficacy and safety of long‐acting intramuscular testosterone undecanoate in aging men: a randomised controlled study
Authors: Tan Wei Shen , Low Wah Yun , Ng Chirk Jenn , Tan Wei Keith , Tong Seng Fah , Ho Christopher , Khoo Ee Ming , Lee George , Lee Boon Cheok , Lee Verna , Tan Hui Meng
Published: April 2013

Objective

To evaluate the efficacy and safety of long‐acting i.m. testosterone undecanoate (TU) in Malaysian men with testosterone deficiency (TD).

Patients and Methods

A total of 120 men, aged 40–70 years, with TD (serum total testosterone [TT] ≤ 12 nmol/L) were randomised to receive either i.m. TU (1000 mg) or placebo.

In all, 58 and 56 men in the placebo and treatment arm, respectively, completed the study.

Participants were seen six times in the 48‐week period and the following data were collected: physical examination results, haemoglobin, haematocrit, TT, lipid profile, fasting blood glucose, sex hormone‐binding globulin, liver function test, prostate‐ specific antigen (PSA) and adverse events.

Results

The mean (sd) age of the participants was 53.4 (7.6) years.

A significant increase in serum TT (P < 0.001), PSA (P = 0.010), haematocrit (P < 0.001), haemoglobin (P < 0.001) and total bilirubin (P = 0.001) were seen in the treatment arm over the 48‐week period.

Two men in the placebo arm and one man in the treatment arm developed myocardial infarction.

Common adverse events observed in the treatment arm included itching/swelling/pain at the site of injection, flushing and acne.

Overall, TU injections were well tolerated.

Conclusions

TU significantly increases serum testosterone in men with TD.

PSA, haemoglobin and haematocrit were significantly elevated but were within clinically safe limits.

There was no significant adverse reaction that led to the cessation of treatment.
Penetratin and Derivatives Acting as Antibacterial Agents
Authors: Garro Adriana D. , Olivella Mónica S. , Bombasaro José A. , Lima Beatriz , Tapia Alejandro , Feresin Gabriela , Perczel Andras , Somlai Csaba , Penke Botond , López Cascales Javier , Rodríguez Ana M. , Enriz Ricardo D.
Published: April 2013

The synthesis, in vitro evaluation and conformational study of penetratin and structurally related derivatives acting as antibacterial agents are reported. Among the compounds evaluated here, two methionine sulphoxide derivatives (RQIKIWFQNRRM[O]KWKK‐NH2 and RQIKIFFQNRRM[O]KFKK‐NH2) exhibited the strongest antibacterial effect in this series. In order to better understand the antimicrobial activity obtained for these peptides, we performed an exhaustive conformational analysis using different approaches. Molecular dynamics simulations were performed using two different media (water and trifluoroethanol/water). The results of these theoretical calculations were corroborated using experimental CD measurements. The electronic study for these peptides was carried out using molecular electrostatic potentials obtained from RHF/6‐31G(d) calculations. In addition, the non‐apeptide RQIRRWWQR‐NH2 showed strong inhibitory action against the Gram‐negative and Gram‐positive bacteria tested in this study.
Fluctuating water levels control water chemistry and metabolism of a charophyte‐dominated pond
Authors: Christensen Jesper P. A. , Sand‐Jensen Kaj , Staehr Peter A.
Published: April 2013

To investigate seasonal variability and importance of environmental drivers of ecosystem metabolism in a shallow pond characterised by low and fluctuating water depth, clear water and shortage of nutrients, we measured primary production and respiration during May–September and examined their relationships to environmental parameters (light, temperature and pH).

Using a combination of free water measurements of O2, pH, temperature and conductivity, in situ mesocosm and laboratory bottle experiments, we documented extreme daily variations in environmental variables (e.g. 0–700 mmol O2 m−3, pH 7.5–9.5, 18–32 °C) and high and variable areal rates of gross primary production (GPP, 30–316 mmol O2 m−2 day−1) and community respiration (R, 26–318 mmol O2 m−2 day−1). These rates of benthic charophytes under oligotrophic conditions are comparable to those obtained by pelagic phytoplankton communities under highly eutrophic conditions. By using sediment resources, benthic charophytes can achieve high biomasses and high metabolic rates.

Pond metabolism reflected the physiology of the dominant charophyte, with light‐saturated photosynthesis occurring during 55% of the light hours. Experiments and photosynthetic models showed inorganic carbon limitation of GPP at pHs above 9.5 during mid‐summer periods of low water levels, while R was strongly influenced by temperature.

According to open water measurements of O2, the pond was net autotrophic (mean NEP = 12 ± 13 (SD) mmol O2 m−2 day−1) but net heterotrophic when based on dissolved inorganic carbon (DIC) dynamics (10 ± 29 mmol CO2 m−2 day−1), suggesting that the significant input of DIC in inflowing water from the surrounding limestone soils mimics elevated respiration.
Fatigue, anxiety and depression levels, activities of daily living of patients with chronic obstructive pulmonary disease
Authors: Karakurt Papatya , Ünsal Ayla
Published: April 2013

The aim of this cross‐sectional study was to determine the fatigue, anxiety and depression levels, activities of daily living of patients with chronic obstructive pulmonary disease (n = 255). It was found that there was significant difference between Visual Analogue Scale for Fatigue (VAS‐F) point averages and gender, education levels, marital status and economical status of patient with chronic obstructive pulmonary disease. Among the participants in this study, 36.5% had an anxiety disorder whereas 69.0% exhibited depression. In the study, it was determined that 85.5% of those were independent in their Katz's Index of Activities of Daily Living (ADLs) and 49.4% of those were independent in their Lawton and Brody's Index of Instrumental Activities of Daily Living (IADLs). This study has shown that VAS‐F, the Hospital Anxiety and Depression Scale, ADL and IADL instruments that measure the various aspects of health‐related quality of living can contribute considerably to a more diversified understanding of the patients' situation with chronic obstructive pulmonary disease.
US and European severe asthma cohorts: what can they teach us about severe asthma?
Authors: Kupczyk M. , Wenzel S.
Published: April 2013

Abstract. Kupczyk M, Wenzel S (Medical University of Lodz, Lodz, Poland; University of Pittsburgh Pittsburgh, PA, USA; Karolinska Institutet, Stockholm, Sweden). US and European severe asthma cohorts: what can they teach us about severe asthma? (Review). J Intern Med 2012; 272: 121–132.

Asthma is a global health problem affecting around 300 million patients of all ages and ethnic groups in all countries around the world. In the majority of subjects with persistent, mild‐to‐moderate asthma (MA), the disease can be relatively well controlled by the use of currently available medications; however, five to ten per cent of patients suffer from a particularly severe disease that is poorly controlled clinically and often refractory to usual treatment. Improved care of severe asthma (SA) is a major unmet medical need and several international consortia aim at improving our understanding of mechanisms in SA. To manage SA better, standardized definitions and concepts of asthma severity, risk and level of control are critical. In the following sections, we present several guidelines approaches and definitions followed by an overview of US (SARP) and European (ENFUMOSA, BIOAIR, U‐BIOPRED) SA networks. Key findings regarding SA phenotypes, risk factors and pathophysiology are discussed. International cooperation in the area of respiratory diseases, including SA, across the Atlantic Ocean, will lead to a better understanding of asthma pathology, especially of those severe, not well controlled or difficult‐to‐treat cases.
Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study
Authors: Collste O. , Sörensson P. , Frick M. , Agewall S. , Daniel M. , Henareh L. , Ekenbäck C. , Eurenius L. , Guiron C. , Jernberg T. , Hofman‐Bang C. , Malmqvist K. , Nagy E. , Arheden H. , Tornvall P.
Published: April 2013

Objectives

Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients.

Design

The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study.

Setting

Coronary care units in the Stockholm metropolitan area.

Subjects

Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded.

Results

In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 6–28) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified.

Conclusion

In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.
Glycated haemoglobin and the risk of cardiovascular disease, diabetes and all‐cause mortality in the Copenhagen City Heart Study
Authors: Eskesen K. , Jensen M. T. , Galatius S. , Vestergaard H. , Hildebrandt P. , Marott J. L. , Jensen J. S.
Published: April 2013

Objective

Individuals with diabetes mellitus (DM) have a considerably elevated risk of developing serious health problems including cardiovascular disease (CVD). Long‐term elevated levels of blood glucose in nondiabetic individuals may also be associated with increased risk of CVD. The aim of this study was to investigate the relationships between glycated haemoglobin A1c (HbA1c) and CVD, DM and all‐cause mortality.

Subjects and design

The Copenhagen City Heart Study is a prospective study of individuals from the Danish general population. The cohort was followed for 10 years via national registers with respect to incident CVD, DM and all‐cause mortality. Follow‐up was 100% complete.

Results

A total of 5127 subjects were included, of whom 597 had DM. In the nondiabetic population, HbA1c was significantly associated with incident CVD events in both univariate [hazard ratio (HR) 1.38, 95% CI 1.11–1.71] and multivariate analyses (HR 1.31, 95% CI 1.05–1.64). In the nondiabetic population, increased levels of HbA1c were correlated with developing DM. There was a threefold increase in risk of incident DM per unit increase in HbA1c with a univariate HR of 3.83 (95% CI 1.96–7.51). This relationship was essentially unchanged after multivariate adjustments (HR 4.19, 95% CI 2.01–8.71). Furthermore, we found that net reclassification improvement for diagnosed DM and CVD was significantly improved with the addition of HbA1c in the analyses. Although not statistically significant, we found a strong trend towards an association between HbA1c and all‐cause mortality (HR 1.21, 95% CI 0.99–1.47). We did not find the same associations amongst the population with DM.

Conclusion

In the Danish general population, HbA1c was strongly associated with CVD in individuals without DM.
The Experience of Carers in Supporting People with Intellectual Disabilities through the Process of Bereavement: An Interpretative Phenomenological Analysis
Authors: Handley Emily , Hutchinson Nick
Published: April 2013

Background

This study explored the personal experiences of family carers and residential care staff in supporting adults with intellectual disabilities through the process of bereavement.

Method

A semi‐structured interview was used to interview 11 carers on their experience of supporting adults with intellectual disabilities through the process of bereavement. The transcripts were analysed using interpretative phenomenological analysis (IPA).

Results

A total of five superordinate themes were identified: (i) Factors making the experience difficult for carers, (ii) Factors that helped carers, (iii) Carers' perspectives on the responses of people with intellectual disabilities, (iv) Approaches to supporting people with intellectual disabilities and (v) Carers' perspectives on support.

Conclusions

Supporting people with intellectual disabilities through bereavement is an emotionally demanding task for carers. The support needs of carers need to be acknowledged and addressed in order to ensure that adequate support is available to people with intellectual disabilities following bereavement.
Food models for portion size estimation of Asian foods
Authors: Lanerolle P. , Thoradeniya T. , de Silva A.
Published: April 2013

Background

Novel portion size estimation aids relevant to the cognitive potential of children are necessary for an improved accuracy in dietary recall. We developed graduated realistic food models for Asian foods and tested their accuracy and precision in children.

Methods

Food models were constructed for nine commonly consumed food items using a range of low cost materials. These were tested among a random sample of 80 school children (aged 10–16 years). A total of 719 estimations were made.

Results

A high percentage (68%) of correct estimations and high correlation (r > 0.95, P < 0.001) for estimated versus actual weight were observed. Bland–Altman analysis indicated 91% of estimations within the limits of agreement. Accuracy and precision was high for both amorphous and non‐amorphous foods.

Conclusions

Portion size estimation using realistic food models is found to be accurate and precise and is suitable for use in children.
Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study
Authors: Penno G. , Solini A. , Bonora E. , Fondelli C. , Orsi E. , Zerbini G. , Trevisan R. , Vedovato M. , Gruden G. , Laviola L. , Nicolucci A. , Pugliese G. ,   the Renal Insufficiency And Cardiovascular Events (RIACE) study, group
Published: April 2013

Objectives

Poorer control of risk factors for cardiovascular disease (CVD) has been reported in diabetic women, as compared with diabetic men. It has been proposed that this finding is due to gender disparities in treatment intensity. We investigated this hypothesis in a large contemporary cohort of subjects with type 2 diabetes.

Design

Observational, cross‐sectional study.

Subjects and setting

Consecutive patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study (n = 15 773), attending 19 hospital‐based diabetes clinics in 2007–2008.

Main outcome measures

Traditional CVD risk factors, macro‐ and microvascular complications and current glucose‐, lipid‐ and blood pressure (BP)‐lowering treatments were assessed.

Results

Although CVD was more prevalent in men, women showed a less favourable CVD risk profile and worse performance in achieving treatment targets for haemoglobin A1c, LDL, HDL and non‐HDL cholesterol, systolic blood pressure (BP) and in particular obesity [body mass index (BMI) and waist circumference], but not for triglycerides and diastolic BP. However, women were more frequently receiving pharmacological treatment for hypertension and to a lesser extent hyperglycaemia and dyslipidaemia than men, and female gender remained an independent predictor of unmet therapeutic targets after adjustment for confounders such as treatments, BMI, duration of diabetes and, except for the systolic BP goal, age.

Conclusions

In women with type 2 diabetes from the RIACE cohort, a more adverse CVD risk profile and a higher likelihood of failing treatment targets, compared with men, were not associated with treatment differences. This suggests that factors other than gender disparities in treatment intensity are responsible.
Bariatric surgery for obese children and adolescents: a systematic review and meta‐analysis
Authors: Black J. A. , White B. , Viner R. M. , Simmons R. K.
Published: April 2013

The number of obese young people continues to rise, with a corresponding increase in extreme obesity and paediatric‐adolescent bariatric surgery. We aimed to (i) systematically review the literature on bariatric surgery in children and adolescents; (ii) meta‐analyse change in body mass index (BMI) 1‐year post‐surgery and (iii) report complications, co‐morbidity resolution and health‐related quality of life (HRQoL).

A systematic literature search (1955–2013) was performed to examine adjustable gastric band, sleeve gastrectomy, Roux‐en‐Y gastric bypass or biliopancreatic diversions operations among obese children and adolescents. Change in BMI a year after surgery was meta‐analysed using a random effects model.

In total, 637 patients from 23 studies were included in the meta‐analysis. There were significant decreases in BMI at 1 year (average weighted mean BMI difference: −13.5 kg m−2; 95% confidence interval [CI] −14.1 to −11.9). Complications were inconsistently reported. There was some evidence of co‐morbidity resolution and improvements in HRQol post‐surgery.

Bariatric surgery leads to significant short‐term weight loss in obese children and adolescents. However, the risks of complications are not well defined in the literature. Long‐term, prospectively designed studies, with clear reporting of complications and co‐morbidity resolution, alongside measures of HRQol, are needed to firmly establish the harms and benefits of bariatric surgery in children and adolescents.
Is there an association between microbial exposure and food allergy? A systematic review
Authors: Marrs Tom , Bruce Kenneth D. , Logan Kirsty , Rivett Damian W. , Perkin Michael R. , Lack Gideon , Flohr Carsten
Published: April 2013

The environmental factors driving the recent increase in the prevalence of food allergy (FA) are unclear. Since associations have been demonstrated between microbial exposure and the likelihood of eczema and respiratory allergies, we reviewed the evidence for FA. Medline was systematically searched from inception to the end of July 2012 for studies investigating links between FA and environmental exposures, likely to influence microbial exposure, such as Caesarean delivery, family size, day‐care attendance, childhood infections, immunizations and antibiotic use. We selected studies reporting food challenge data, reported doctor‐diagnosed (RDD) FA and food sensitization. Methodological differences and study heterogeneity precluded meta‐analysis. A total of 46 studies were identified, of which 28 (60.9%) were prospective and 13 (28.3%) used food challenges to diagnose FA. Caesarean delivery was investigated in 13 studies, of which three infant cohorts demonstrated an increase in challenge‐proven FA (one cohort) and food sensitization (two cohorts), and one cross‐sectional study reported increased RDDFA. Four studies investigated the effect of having siblings, with one infant cohort demonstrating less challenge‐proven FA and a cross‐sectional study showing a decrease in RDDFA. Attending childcare before 6 months was associated with less challenge‐proven FA in one cohort. A cross‐sectional survey identified an inverse relationship between hepatitis A serology and peanut sensitization. One of eleven trials investigating probiotics demonstrated a quicker acquisition of milk tolerance amongst allergic infants. Factors influencing microbial exposure may be partly responsible for rising FA burden, but further prospective studies using double‐blind placebo controlled food challenges as an outcome are required.
Relationship between breast milk sCD14, TGF‐β1 and total IgA in the first month and development of eczema during infancy
Authors: Ismail Intan H. , Licciardi Paul V. , Oppedisano Frances , Boyle Robert J. , Tang Mimi L. K.
Published: April 2013

Introduction

The overall beneficial effects of breastfeeding for infants have been well documented, but its role in allergy prevention is controversial.

Objective

We investigated the relationship between breast milk immunomodulatory factors and subsequent development of eczema and atopic sensitization in the first year of life.

Methods

Day 7 and 28 breast milk samples were collected from mothers carrying infants at high risk of allergic disease. Aqueous‐phase breast milk samples were assayed for TGF‐β1, sCD14 and total IgA. Infants were assessed for the presence of eczema and atopic sensitization at 12 months of age. The levels of breast milk TGF‐β1, sCD14 and total IgA were compared in infants who subsequently developed eczema and sensitization in the first year and those who did not.

Results

The levels of breast milk sCD14, total IgA, and TGF‐β1 at either day 7 or 28 were not associated with subsequent development of eczema or atopic sensitization during the first year of life.

Conclusion

Levels of breast milk immune parameters were not associated with eczema outcomes or sensitization in infants at 12 months. This suggests that apparent immunological effects on breast milk immunomodulatory factors may not necessarily lead to clinical benefits, and these immune markers may not be critical determinants of allergic disease in infancy.
Self-Assembling Cages from Coiled-Coil Peptide Modules
Authors: Fletcher Jordan M. , Harniman Robert L. , Barnes Frederick R. H. , Boyle Aimee L. , Collins Andrew , Mantell Judith , Sharp Thomas H. , Antognozzi Massimo , Booth Paula J. , Linden Noah , Miles Mervyn J. , Sessions Richard B. , Verkade Paul , Woolfson Derek N.
Published: April 2013

From Coils to Cages

Self-assembly strategies that mimic protein assembly, such as the formation of viral coats, often begin with simpler peptide assemblies.

Fletcher
et al.

(p.
595
, published online 11 April; see the Perspective by

Ardejani and Orner

) designed two coiled-coil peptide motifs, a heterodimer, and a homotrimer. Both peptides contained cysteine residues and could link through disulfide bonds, so that the trimer could form the vertices of a hexagonal network and the dimer its edges. However, these components are flexible and, rather than form extended sheets, they closed to form particles ∼100 nanometers in diameter.
Ribosomal Protein SA Haploinsufficiency in Humans with Isolated Congenital Asplenia
Authors: Bolze Alexandre , Mahlaoui Nizar , Byun Minji , Turner Bridget , Trede Nikolaus , Ellis Steven R. , Abhyankar Avinash , Itan Yuval , Patin Etienne , Brebner Samuel , Sackstein Paul , Puel Anne , Picard Capucine , Abel Laurent , Quintana-Murci Lluis , Faust Saul N. , Williams Anthony P. , Baretto Richard , Duddridge Michael , Kini Usha , Pollard Andrew J. , Gaud Catherine , Frange Pierre , Orbach Daniel , Emile Jean-Francois , Stephan Jean-Louis , Sorensen Ricardo , Plebani Alessandro , Hammarstrom Lennart , Conley Mary Ellen , Selleri Licia , Casanova Jean-Laurent
Published: April 2013

Spleen Knockout Explained

Isolated congenital asplenia (ICA) is a rare disorder where patients are born without a spleen and are at increased risk of bacterial infection but have no other developmental abnormalities. Through sequence analysis of familial and sporadic cases,

Bolze
et al.

(p.
976
, published online 11 April) found that ICA patients carry mutations in the gene encoding ribosomal protein SA and as a result express about half the normal amount of this protein. The mechanism by which reduced expression of a housekeeping protein causes an organ-specific defect remains unclear.
Clinical implications of scapular dyskinesis in shoulder injury: the 2013 consensus statement from the ‘scapular summit’
Authors: Kibler W Ben , Ludewig Paula M , McClure Phil W , Michener Lori A , Bak Klaus , Sciascia Aaron D
Published: April 2013

The second international consensus conference on the scapula was held in Lexington Kentucky. The purpose of the conference was to update, present and discuss the accumulated knowledge regarding scapular involvement in various shoulder injuries and highlight the clinical implications for the evaluation and treatment of shoulder injuries. The areas covered included the scapula and shoulder injury, the scapula and sports participation, clinical evaluation and interventions and known outcomes. Major conclusions were (1) scapular dyskinesis is present in a high percentage of most shoulder injuries; (2) the exact role of the dyskinesis in creating or exacerbating shoulder dysfunction is not clearly defined; (3) shoulder impingement symptoms are particularly affected by scapular dyskinesis; (4) scapular dyskinesis is most aptly viewed as a potential impairment to shoulder function; (5) treatment strategies for shoulder injury can be more effectively implemented by evaluation of the dyskinesis; (6) a reliable observational clinical evaluation method for dyskinesis is available and (7) rehabilitation programmes to restore scapular position and motion can be effective within a more comprehensive shoulder rehabilitation programme.
ACTIVE CONTROL OF BUILDINGS WITH BILINEAR HYSTERESIS AND TIME DELAY
Authors: LIU KUN , CHEN LONG-XIANG , CAI GUO-PING
Published: April 2013

In this paper, an active controller for buildings with bilinear hysteresis and time delay is studied. The bilinear hysteretic model is treated as a stiffness restoring force. By using specific transformation and augmentation of state parameters, the equation of motion of the system with an explicit time delay is transformed into a standard state space where there is no explicit time delay. A linear quadratic Gaussian control method is proposed for the controller design with time delay. The method is verified with numerical simulations of three-story and 20-story buildings. Comparison study of simulation results indicates that the control performance will deteriorate if the time delay is not taken into account in the control design. The proposed time-delay controller not only effectively compensate the time delay for better control effectiveness, but it also works well with both small and large time-delay problems.
Rhythmic Control of the ARF-MDM2 Pathway by ATF4 Underlies Circadian Accumulation of p53 in Malignant Cells
Authors: Horiguchi Michiko , Koyanagi Satoru , Hamdan Ahmed M. , Kakimoto Keisuke , Matsunaga Naoya , Yamashita Chikamasa , Ohdo Shigehiro
Published: April 2013

The sensitivity of cancer cells to chemotherapeutic agents varies according to circadian time. Most chemotherapeutic agents ultimately cause cell death through cell-intrinsic pathways as an indirect consequence of DNA damage. The p53 tumor suppressor gene (TRP53) configures the cell deaths induced by chemotherapeutic agents. In this study, we show that the transcription factor ATF4, a component of the mammalian circadian clock, functions in circadian accumulation of p53 protein in tumor cells. In murine fibroblast tumor cells, ATF4 induced the circadian expression of p19ARF (Cdkn2a). Oscillation of p19ARF interacted in a time-dependent manner with MDM2, a specific ubiquitin ligase of p53, resulting in a rhythmic prevention of its degradation by MDM2. Consequently, the half-life of p53 protein varied in a circadian time-dependent manner without variation in mRNA levels. The p53 protein accumulated during those times when the p19ARF–MDM2 interaction was facilitated. Notably, the ability of the p53 degradation inhibitor nutlin-3 to kill murine fibroblast tumor cells was enhanced when the drug was administered at those times of day during which p53 had accumulated. Taken together, these results suggested that ATF4-mediated regulation of the p19ARF–MDM2 pathway underlies the circadian accumulation of p53 protein in malignant cells. Furthermore, they suggest an explanation for how the sensitivity of cancer cells to chemotherapeutic agents is enhanced at those times of day when p53 protein has accumulated, as a result of circadian processes controlled by ATF4. Cancer Res; 73(8); 2639–49. ©2013 AACR.
Menin Epigenetically Represses Hedgehog Signaling in MEN1 Tumor Syndrome
Authors: Gurung Buddha , Feng Zijie , Iwamoto Daniel V. , Thiel Austin , Jin Guanghui , Fan Chen-Min , Ng Jessica M.Y. , Curran Tom , Hua Xianxin
Published: April 2013

Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumor syndrome that includes susceptibility to pancreatic islet tumors. This syndrome results from mutations in the MEN1 gene, encoding menin. Although menin acts as an oncogenic cofactor for mixed lineage leukemia (MLL) fusion protein–mediated histone H3 lysine 4 methylation, the precise basis for how menin suppresses gene expression and proliferation of pancreatic beta cells remains poorly understood. Here, we show that menin ablation enhances Hedgehog signaling, a proproliferative and oncogenic pathway, in murine pancreatic islets. Menin directly interacts with protein arginine methyltransferase 5 (PRMT5), a negative regulator of gene transcription. Menin recruits PRMT5 to the promoter of the Gas1 gene, a crucial factor for binding of Sonic Hedgehog (Shh) ligand to its receptor PTCH1 and subsequent activation of the Hedgehog signaling pathway, increases repressive histone arginine symmetric dimethylation (H4R3m2s), and suppresses Gas1 expression. Notably, MEN1 disease-related menin mutants have reduced binding to PRMT5, and fail to impart the repressive H4R3m2s mark at the Gas1 promoter, resulting in its elevated expression. Pharmacologic inhibition of Hedgehog signaling significantly reduces proliferation of insulinoma cells, and expression of Hedgehog signaling targets including Ptch1, in MEN1 tumors of mice. These findings uncover a novel link between menin and Hedgehog signaling whereby menin/PRMT5 epigenetically suppresses Hedgehog signaling, revealing it as a target for treating MEN1 tumors. Cancer Res; 73(8); 2650–8. ©2013 AACR.