bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunoproteomics of processed beef proteins reveal novel galactose‐α‐1,3‐galactose‐containing allergens
Authors: Apostolovic D. , Tran T. A. T. , Hamsten C. , Starkhammar M. , Cirkovic Velickovic T. , van Hage M.
Published: June 2014

Background

Red meat allergy presents a novel form of food allergy with severe delayed allergic reactions where IgE antibodies are directed against the carbohydrate α‐Gal epitope. Food preparation and processing can influence the allergenicity of proteins. The aim of this study was to characterize the proteomic profile of different beef preparations and to investigate their α‐Gal reactivity and potential allergenicity.

Methods

Extracts from raw, boiled, fried, and medium rare prepared beef were assessed by 2D PAGE for the comparison of protein profiles. IgE‐binding proteins were identified using immunoblot‐coupled proteomic analysis using sera from red meat‐allergic patients. Presence of the α‐Gal epitope was verified using anti‐α‐Gal antibody and IgE inhibition immunoblot with α‐Gal.

Results

Multiple IgE‐binding proteins were detected in the different beef preparations, many of which were also recognized by the anti‐α‐Gal antibody. Protein spots reacting with IgE in patient sera were analyzed by MS/MS, resulting in identification of 18 proteins with high identification scores. Seven of the 18 beef allergens identified using meat‐allergic patient sera were also recognized by the anti‐α‐Gal monoclonal antibody, and four of them were stabile to thermal treatment. Furthermore, a dose‐dependent inhibition of red meat‐allergic patients’ IgE to beef by α‐Gal was demonstrated.

Conclusions

We show that the α‐Gal epitope is commonly present in IgE‐reactive beef proteins recognized by meat‐allergic patients. Seven novel α‐Gal‐containing IgE‐binding proteins were identified, of which four were stable to heat treatment. Thus, the allergenicity of red meat proteins is preserved even upon different thermal cooking.
Long‐term ongoing pregnancy rate and mode of conception after a positive and negative post‐coital test
Authors: Hessel Marloes , Brandes Monique , de Bruin Jan Peter , Bots Rob S.G.M. , Kremer Jan A.M. , Nelen Willianne L.D.M. , Hamilton Carl J.C.M.
Published: June 2014

Objective

Many fertility clinics have decided to abolish the post‐coital test. Yet, it is a significant factor in prognostic models that predict the spontaneous pregnancy rate within one year. The aim of this study was to evaluate (1) the long‐term outcome of infertile couples with a positive or a negative post‐coital test during their fertility work‐up and (2) the contribution of the different modes of conception.

Design

Retrospective cohort study.

Setting

Three fertility clinics in the Netherlands, of which two are secondary care training hospitals and is a one tertiary care academic training hospital.

Population

2476 newly referred infertile couples, where a post‐coital test was performed in 1624 couples.

Methods

After basic fertility work‐up, couples were treated according to the national treatment protocols.

Main outcome measures

Spontaneous and overall ongoing pregnancy rate.

Results

The spontaneous and overall ongoing pregnancy rates after three years were 37.7 and 77.5% after a positive post‐coital test compared with 26.9 and 68.8% after a negative test (p < 0.001). Even in couples with severe male factor infertility (total motile sperm count <3) (p = 0.005) and mild male factor infertility (total motile sperm count 3–20) (p < 0.001), there was a significantly higher spontaneous ongoing pregnancy rate, justifying expectant management.

Conclusion

After a follow‐up of three years a positive post‐coital test is still associated with a higher spontaneous and a higher overall ongoing pregnancy rate, even in couples with severe male factor infertility.
Guidelines for the diagnosis and treatment of cobalamin and folate disorders
Authors: Devalia Vinod , Hamilton Malcolm S. , Molloy Anne M. ,   the British Committee for Standards in Haematology
Published: June 2014

Summary of key recommendations

The clinical picture is the most important factor in assessing the significance of test results assessing cobalamin status because there is no ‘gold standard’ test to define deficiency.

Serum cobalamin currently remains the first‐line test, with additional second‐line plasma methylmalonic acid to help clarify uncertainties of underlying biochemical/functional deficiencies. Serum holotranscobalamin has the potential as a first‐line test, but an indeterminate ‘grey area’ may still exist. Plasma homocysteine may be helpful as a second‐line test, but is less specific than methylmalonic acid. The availability of these second‐line tests is currently limited.

Definitive cut‐off points to define clinical and subclinical deficiency states are not possible, given the variety of methodologies used and technical issues, and local reference ranges should be established.

In the presence of discordance between the test result and strong clinical features of deficiency, treatment should not be delayed to avoid neurological impairment.

Treatment of cobalamin deficiency is recommended in line with the British National Formulary. Oral therapy may be suitable and acceptable provided appropriate doses are taken and compliance is not an issue.

Serum folate offers equivalent diagnostic capability to red cell folate and is the first‐line test of choice to assess folate status.
Prenatal and post‐natal exposure to antibiotics and risk of asthma in childhood
Authors: Metsälä J. , Lundqvist A. , Virta L. J. , Kaila M. , Gissler M. , Virtanen S. M.
Published: June 2014

Background

Evidence on the association between post‐natal exposure to antibiotics and the development of asthma is extensive, but inconsistent and even less is known about prenatal exposure.

Objective

The aim of this study was to examine the associations between prenatal and post‐natal exposure to different antibiotics and the risk of childhood asthma in a population‐ and register‐based nested case–control study.

Methods

All children who were born in 1996–2004 in Finland and diagnosed with asthma by 2006 were identified from a national health register. For each case, one matched control was selected. Information on asthma diagnoses, purchased anti‐asthmatic drugs and antibiotics as well as putative confounders was obtained from national health registries. The associations were analysed using conditional logistic regression for children diagnosed at the age of 3 years or later (n = 6 690 case–control pairs).

Results

Maternal use of any antibiotics during pregnancy was associated with an increased risk of asthma in the offspring [adjusted odds ratio (OR) = 1.31 (95% confidence interval (CI): 1.21–1.42)]. Several maternal specific antibiotics were associated with the risk of asthma, and the strongest association was observed for cephalosporins [OR = 1.46 (95% CI 1.30–1.64)]. Child's use of antibiotics during the first year of life was associated with an increased risk of asthma [OR = 1.60 (95% CI 1.48–1.73)]. Child's use of cephalosporins [OR = 1.79 (95% CI 1.59–2.01)], sulphonamides and trimethoprim [OR = 1.65 (95% CI 1.34–2.02)], macrolides [OR = 1.61 (95% CI 1.46–1.78)] and amoxicillin [OR = 1.46 (95% CI 1.35–1.58)] was associated with an increased risk of asthma.

Conclusions and Clinical Relevance

Both prenatal and post‐natal exposure to antibiotics was associated with an increased risk of asthma. The potential role of adverse effects of antibiotics on the gut microbiota and the development of asthma should be further explored.
Intense imagery movements: a common and distinct paediatric subgroup of motor stereotypies
Authors: Robinson Sally , Woods Martin , Cardona Francesco , Baglioni Valentina , Hedderly Tammy
Published: June 2014

Aim

The aim of this article is to describe a subgroup of children who presented with stereotyped movements in the context of episodes of intense imagery. This is of relevance to current discussions regarding the clinical usefulness of diagnosing motor stereotypies during development.

Method

The sample consisted of 10 children (nine males, one female; mean age 8y 6mo [SD 2y 5mo], range 6–15y). Referrals were from acute paediatricians, neurologists, and tertiary epilepsy services. Children were assessed by multidisciplinary teams with expertise in paediatric movement disorders.

Results

Stereotypies presented as paroxysmal complex movements involving upper and lower limbs. Imagery themes typically included computer games (60%), cartoons/films (40%), and fantasy scenes (30%). Comorbid developmental difficulties were reported for 80% of children. Brain imaging and electrophysiological investigations had been conducted for 50% of the children before referral to the clinic.

Interpretation

The descriptive term ‘intense imagery movements’ (IIM) was applied if (after interview) the children reported engaging in acts of imagery while performing stereotyped movements. We believe these children may form a common and discrete stereotypy subgroup, with the concept of IIM being clinically useful to ensure the accurate diagnosis and clinical management of this paediatric movement disorder.
Clofarabine/cyclophosphamide for debulking before stem cell transplantation
Authors: Rabitsch Werner , Böhm Alexandra , Bojic Marija , Schellongowski Peter , Wöhrer Stefan , Sliwa Thamer , Keil Felix , Worel Nina , Greinix Hildegard , Hauswirth Alexander , Kalhs Peter , Jaeger Ulrich , Valent Peter , Sperr Wolfgang R.
Published: June 2014

Background

Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative rescue therapy for patients (pts) with chemotherapy‐refractory acute leukaemia. Disease control prior to HSCT is essential for long‐term disease‐free survival after HSCT.

Patients and Methods

We have retrospectively analysed the outcome of 20 pts aged 21–64 years with refractory leukaemia (acute myeloid leukaemia, n = 16; acute lymphatic leukaemia, n = 4) who received debulking therapy with clofarabine (10 mg/m², days 1–4) and cyclophosphamide (200 mg/m², days 1–4; ClofCy) prior to HSCT.

Results

Clofarabine/cyclophosphamide (1–4 cycles) was well tolerated and resulted in a substantial reduction of leukaemic cells in all pts. HSCT was performed in 15 of 20 pts. After HSCT (myeloablative, n = 9; dose‐reduced, n = 6), all pts showed engraftment and full donor chimerism (related donors, n = 4 or unrelated donors, n = 11) and all pts achieved complete haematologic remission (CR). The median survival after HSCT is 531 days (range: 48–1462 days), and six pts are still alive after a median of 1245 days. Seven pts died after they had relapsed between days +152 and +1496. One patient died from acute graft‐versus‐host disease (day +48) and one from systemic fungal infection (day +87).

Conclusion

Clofarabine/cyclophosphamide is a novel effective treatment approach for pts with chemotherapy‐refractory acute leukaemia prior to HSCT. Whether this novel debulking protocol leads to improved long‐term outcome in pts with refractory leukaemias remains to be determined in forthcoming clinical studies.
Role of 9p21 and 2q36 variants and arterial stiffness in the prediction of coronary artery disease
Authors: Vakalis Konstantinos , Bechlioulis Aris , Naka Katerina K. , Chatzikyriakidou Anthoula , Gartzonika Konstantina , Vezyraki Patra , Kolios Georgios , Pappas Konstantinos , Katsouras Christos S. , Georgiou Ioannis , Michalis Lampros K.
Published: June 2014

Background

Genetic polymorphisms and arterial stiffness indices have been associated with cardiovascular prognosis and the presence and extent of angiographic coronary artery disease (CAD). We aimed to investigate whether arterial stiffness indices and 9p21 and 2q36 variants may improve prediction of CAD presence and extent when added to classical cardiovascular risk factors in patients at high risk for CAD.

Materials and methods

In this cross‐sectional study, we enrolled 183 consecutive patients with suspected stable CAD (age 61 ± 9 years, 134 males) referred for diagnostic coronary angiography. Framingham risk score (FRS) was calculated. Arterial stiffness was assessed by carotid–femoral pulse wave velocity (PWV) and central augmentation index (AIx) using applanation tonometry. Genetic polymorphisms of 9p21 (rs1333049) and 2q36 (rs2943634) loci were also analysed.

Results

Higher FRS and PWV and the presence of rs2943634 risk allele were independent predictors of CAD (Nagelkerke R2 0·252, P < 0·001), while higher FRS and the presence of rs1333049 risk allele were independent predictors of multivessel CAD (Nagelkerke R2 0·190, P < 0·001). Genetic polymorphisms and vascular indices did not improve the predictive accuracy of FRS‐based models (P > 0·1 for all) for CAD presence or extent.

Conclusions

In these high‐risk patients, 9p21 and 2q36 variants and PWV were independently associated with CAD presence and extent, but the addition of both genetic data and arterial stiffness indices to FRS did not improve the prediction of CAD compared with FRS alone. Further studies are needed to clarify the prognostic role of genetic and vascular indices in the prediction of angiographic CAD.
FGF‐23 dysregulates calcium homeostasis and electrophysiological properties in HL‐1 atrial cells
Authors: Kao Yu‐Hsun , Chen Yao‐Chang , Lin Yung‐Kuo , Shiu Rong‐Jie , Chao Tze‐Fan , Chen Shih‐Ann , Chen Yi‐Jen
Published: June 2014

Background

Fibroblast growth factor (FGF)‐23 is a key regulator of phosphate homeostasis. Higher FGF‐23 levels are correlated with poor outcomes in cardiovascular diseases. FGF‐23 can produce cardiac hypertrophy and increase intracellular calcium, which can change cardiac electrical activity. However, it is not clear whether FGF‐23 possesses arrhythmogenic potential through calcium dysregulation. Therefore, the purposes of this study were to evaluate the electrophysiological effects of FGF‐23 and identify the underlying mechanisms.

Methods

Patch clamp, confocal microscope with Fluo‐4 fluorescence, and Western blot analyses were used to evaluate the electrophysiological characteristics, calcium homeostasis and calcium regulatory proteins in HL‐1 atrial myocytes with and without FGF‐23 (10 and 25 ng/mL) incubation for 24 h.

Results

FGF‐23 (25 ng/mL) increased L‐type calcium currents, calcium transient and sarcoplasmic reticulum Ca2+ contents in HL‐1 cells. FGF‐23 (25 ng/mL)‐treated cells (n = 14) had greater incidences (57%, 17% and 15%, P < 0·05) of delayed afterdepolarizations than control (n = 12) and FGF‐23 (10 ng/mL)‐treated cells (n = 13). Compared with control cells, FGF‐23 (25 ng/mL)‐treated cells (n = 14) exhibited increased phosphorylation of calcium/calmodulin‐dependent protein kinase IIδ and phospholamban (PLB) at threonine 17 but had similar phosphorylation extents of PLB at serine 16, total PLB and sarcoplasmic reticulum Ca2+‐ATPase protein. Moreover, the FGF receptor inhibitor (PD173074, 10 nM), calmodulin inhibitor (W7, 5 μM) and phospholipase C inhibitor (U73122, 1 μM) attenuated the effects of FGF‐23 on calcium/calmodulin‐dependent protein kinase II phosphorylation.

Conclusions

FGF‐23 increases HL‐1 cells arrhythmogenesis with calcium dysregulation through modulating calcium‐handling proteins.
Melanocortin 4 receptor activation inhibits presynaptic N‐type calcium channels in amygdaloid complex neurons
Authors: Agosti Francina , López Soto Eduardo J. , Cabral Agustina , Castrogiovanni Daniel , Schioth Helgi B. , Perelló Mario , Raingo Jesica
Published: June 2014

The melanocortin 4 receptor (MC4R) is a G protein‐coupled receptor involved in food intake and energy expenditure regulation. MC4R activation modifies neuronal activity but the molecular mechanisms by which this regulation occurs remain unclear. Here, we tested the hypothesis that MC4R activation regulates the activity of voltage‐gated calcium channels and, as a consequence, synaptic activity. We also tested whether the proposed effect occurs in the amygdala, a brain area known to mediate the anorexigenic actions of MC4R signaling. Using the patch‐clamp technique, we found that the activation of MC4R with its agonist melanotan II specifically inhibited 34.5 ± 1.5% of N‐type calcium currents in transiently transfected HEK293 cells. This inhibition was concentration‐dependent, voltage‐independent and occluded by the Gαs pathway inhibitor cholera toxin. Moreover, we found that melanotan II specifically inhibited 25.9 ± 2.0% of native N‐type calcium currents and 55.4 ± 14.4% of evoked inhibitory postsynaptic currents in mouse cultured amygdala neurons. In vivo, we found that the MC4R agonist RO27‐3225 increased the marker of cellular activity c‐Fos in several components of the amygdala, whereas the N‐type channel blocker ω conotoxin GVIA increased c‐Fos expression exclusively in the central subdivision of the amygdala. Thus, MC4R specifically inhibited the presynaptic N‐type channel subtype, and this inhibition may be important for the effects of melanocortin in the central subdivision of the amygdala.
Relative Cost/Benefit Trade‐Off Between Cover‐Seeking and Escape Behaviour in an Ancestral Fish: The Importance of Structural Habitat Heterogeneity
Authors: Wishingrad Van , Chivers Douglas P. , Ferrari Maud C. O.
Published: June 2014

Fleeing from predators and moving into protective habitats are two common antipredator behaviours in the animal kingdom. Surprisingly, the relative cost/benefit trade‐off of each behavioural option has rarely been examined empirically. Here, we investigate the interplay between decisions surrounding escape behaviour and rocky microhabitat occupancy in lake sturgeon, Acipenser fulvescens. In high‐risk clear‐water environments, sturgeon responded to danger by evoking an escape response and by seeking cover in rocky microhabitats. However, in low‐risk turbid environments, we found that sturgeon responded to danger by seeking cover in rocky microhabitats, but not fleeing to a significant degree. Cover‐seeking behaviour may therefore be a relatively low‐cost/high‐benefit antipredator strategy. These findings highlight the importance of structural habitat heterogeneity for prey animals in predator‐dominated landscapes.
Why mammalian wound‐healing researchers may wish to turn to Drosophila as a model
Authors: Muñoz‐Soriano Verónica , López‐Domenech Sandra , Paricio Nuria
Published: June 2014

Wound healing is an essential and complex biological process that allows tissue continuity and functioning to be restored after injury. Understanding the molecular and cellular mechanisms underlying wound repair is essential to develop new therapies that could be useful not only to accelerate the normal healing process but also to treat healing pathologies that appear as a consequence of improper wound resolution. Numerous models have been developed to study wound healing both in vitro and in vivo. In vitro models have been useful to study some steps of epithelial repair. However, the development of effective treatments for wound healing is still required, and this could mainly be achieved using animal models. Although rodent models are currently preferred to study this process, they also have some limitations. Currently, the fruit fly Drosophila is a well‐established model to study processes relevant to human health and is becoming one of the favourite model organisms in biomedical research. The reason for this success is that it can be effectively used in target discovery and drug screens. In such a scenario, we would like to provide a defense for using Drosophila as an in vivo model of wound healing, assuming that many mammalian researchers may not be initially convinced with the idea. In this paper, we discuss the benefits and limitations of using Drosophila in wound‐healing research, especially presenting this organism as a promising tool for the identification of new therapeutic targets and drugs in this context.
When is enough … enough? Developing consensus of definition of failure of immune tolerance induction in patients with haemophilia and inhibitors
Authors: Barnes C. , Brown S. A. , Curtin J. , Dunkley S.
Published: June 2014

Immune tolerance induction (ITI) is the preferred management of haemophilia A patients who develop high titre inhibitors against factor VIII. However, the optimal ITI regimen, predictors of ITI outcome and definitions of successful and unsuccessful ITI remain unclear. The aim of this project was to develop a consensus on the definition of ITI treatment failure for Australian clinical practice using a modified Delphi approach. Three consecutive surveys were distributed to the directors of 17 haemophilia treatment centres in Australia. Participants were asked to rate their agreement with definitions of ITI treatment failure generated from a literature review. Thirty‐five statements regarding ITI achieved consensus (majority agree or strongly agree) during the three survey rounds. After round 3, four statements achieved majority disagreement, and for two statements no consensus was reached. Our study demonstrates that clinicians in Australia necessitate an arbitrary time to assess ITI failure, but that clinical outcomes of ITI are important in assessing response. Assessment over any 3‐ to 6‐month period without a 20% reduction in inhibitor titre is suggestive of failure, but a reduction in bleeding phenotype alone may be sufficient to continue ITI. Overall, a period of 3 or 5 years of ITI may be required to determine response to ITI. Documentation of improvement in clinical measures, supported by the laboratory features of factor VIII inhibitor levels and pharmacokinetics, is essential in assessing the success of failure of ITI in these patients.
‘All illness is personal to that individual’: a qualitative study of patients’ perspectives on treatment adherence in bronchiectasis
Authors: McCullough Amanda R. , Tunney Michael M. , Elborn J. Stuart , Bradley Judy M. , Hughes Carmel M.
Published: June 2014

Background

Adherence to treatment is low in bronchiectasis and is associated with poorer health outcomes. Factors affecting adherence decisions have not been explored in patients with bronchiectasis.

Objective

We aimed to explore patients’ perspectives on adherence, factors affecting adherence decision making and to develop a conceptual model explaining this decision‐making process in adults with bronchiectasis.

Methods

Adults with bronchiectasis participated in one‐to‐one semi‐structured interviews. Interviews were audio‐recorded, transcribed verbatim and analysed independently by two researchers using thematic analysis. Data from core themes were extracted, categorized into factors affecting adherence decision making and used to develop the conceptual model.

Results

Participants’ beliefs about treatment, the practical aspects of managing treatment, their trust in health‐care professionals and acceptance of disease and treatment were important aspects of treatment adherence. The conceptual model demonstrated that adherence decisions were influenced by participants’ individual balance of barriers and motivating factors (treatment‐related, disease‐related, health‐care‐related, personal and social factors).

Conclusion

Adherence decision‐making in bronchiectasis is complex, but there is the potential to enhance adherence by understanding patients’ specific barriers and motivators to adherence and using this to tailor adherence strategies to individual patients and treatments.
MicroRNA‐100‐5p indirectly modulates the expression of Il6, Ptgs1/2 and Tlr4 mRNA in the mouse follicular dendritic cell‐like cell line, FL‐Y
Authors: Aungier Susan R. , Ohmori Hitoshi , Clinton Michael , Mabbott Neil A.
Published: June 2014

Follicular dendritic cells (FDC) are important stromal cells within the B‐cell follicles and germinal centres (GC) of secondary lymphoid tissues. FDC trap and retain native antigens on their surfaces in the form of immune complexes that they display to B cells, in order to select those cells with the highest antigen affinity. MicroRNAs are short, non‐coding RNAs that are approximately 18–25 nucleotides in length that regulate gene expression at the post‐transcriptional level by repressing the translation of target genes. In the current study, in vivo and in vitro systems were used to identify microRNAs that were potentially expressed by FDC. Constitutive lymphotoxin‐β receptor (LTβR) stimulation is required to maintain FDC in their differentiated state. We show that the rapid de‐differentiation of spleen FDC that accompanied LTβR‐blockade, coincided with a significant decrease in the expression of mmu‐miR‐100‐5p, mmu‐miR‐138‐5p and mmu‐miR‐2137. These microRNAs were shown to be expressed in the FDC‐like cell line, FL‐YB, and specific inhibition of mmu‐miR‐100‐5p significantly enhanced expression of Il6, Ptgs1/2 and Tlr4 mRNA in this cell line. The expression of Il6, Ptgs1/2 and Tlr4 by FDC play important roles in regulating GC size and promoting high‐affinity antibody responses, so it is plausible that mmu‐miR‐100‐5p may help to regulate the expression of these genes during GC reactions.
Prefabricated Composite Resin Veneers – A Clinical Review
Authors: Gomes George , Perdigão Jorge
Published: June 2014

Objective

This clinical technique article is focused on the use of prefabricated veneers to enhance the esthetic appearance of the anterior dentition in patients who needed an alternative esthetic solution more affordable than traditional porcelain veneers.

Clinical considerations

Because prefabricated composite veneer systems have been recently introduced, they are not widely used. TheComponeer system (Coltene,Altstätten,Switzerland) contains thin pre‐polymerized hybrid composite shells, several shades of a direct hybrid composite resin, an etch‐and‐rinse adhesive system, and restorative accessories including finishing points and disks. The prefabricated restorations can be customized in the mouth for color and shape. The technique described in this article can be used to restore function and esthetics in one office visit.

Conclusions

The prefabricated composite veneer technique has some of the advantages of direct composite restorations, as only one session is required without the need to take impressions to send to the dental laboratory. This new treatment option may open new opportunities for dental professionals and their patients. However, it is paramount to carry out controlled clinical studies with this restorative technique prior to recommending it without restrictions in general practice.

Clinical Significance

The clinical technique described in this paper has the potential for being used routinely to lengthen anterior teeth, to correct malpositioned teeth, to mask discolorations, and to close diastemas. The technique can also be used to restore extensive caries lesions and tooth fractures, and to refurbish large old anterior restorations, especially when other treatment options are out of reach for the patient for financial reasons.
Medical, psychological and social features in a large cohort of adults with Prader–Willi syndrome: experience from a dedicated centre in France
Authors: Laurier V. , Lapeyrade A. , Copet P. , Demeer G. , Silvie M. , Bieth E. , Coupaye M. , Poitou C. , Lorenzini F. , Labrousse F. , Molinas C. , Tauber M. , Thuilleaux D. , Jauregi J.
Published: June 2014

Background

Prader–Willi syndrome (PWS) is a developmental genetic disorder characterised by a variable expression of medical, cognitive and behavioural symptoms. In adulthood, the prevalence and severity of these symptoms determine the quality of life of the affected persons. Because of their rare disease condition, data on health and social problems in adults with PWS are scarce. In this research, we present medical, psychological and social features of a large cohort of adults admitted to a specialised PWS centre in France and analyse the differences according to genotype, gender and age.

Methods

Data from154 patients (68 men/86 women), with a median age of 27 years (range 16–54), were collected during their stay in our centre. Clinical histories were completed using information from parents or main caregivers, and the same medical team performed the diagnosis of different clinical conditions. Statistical analyses were performed to determine the influence of factors such as genotype, age or gender.

Results

Paternal deletion genotype was the most frequent (65%) at all ages. Most patients had mild or moderate intellectual disability (87%). Only 30% had studied beyond primary school and 70% were in some special educational or working programme. Most of them lived in the family home (57%). The most prevalent somatic comorbidities were scoliosis (78%), respiratory problems (75%), dermatological lesions (50%), hyperlipidaemia (35%), hypothyroidism (26%), Type 2 diabetes mellitus (25%) and lymph oedema (22%). Some form of psychotropic treatment was prescribed in 58% of subjects, and sex hormones in 43%. Patients with deletion had a higher body mass index (44 vs. 38.9 kg/m2) and displayed higher frequency of sleep apnoeas. Non‐deletion patients received insulin treatment (19% vs. 4%) and antipsychotic treatment (54.8% vs. 32.7%) more frequently. No difference was observed in the prevalence of Type 2 diabetes between the two genotype groups. Patients >27 years of age had a higher rate of comorbidities (Type 2 diabetes, hypertension, respiratory problems and lymph oedema). Gender differences were minor.

Conclusions

Adult patients with PWS showed high prevalence of comorbid health problems that need to be monitored for early treatment. Some of them are influenced by genotype and age. Another salient problem concerns the lack of adapted structures for better social integration. Further data about the real life and health conditions of adults with PWS are necessary to further our knowledge of the natural history of the disease and to design appropriate care strategies.
Diagnostic and Prognostic Impact of pc‐ASPECTS Applied to Perfusion CT in the Basilar Artery International Cooperation Study
Authors: Pallesen Lars‐Peder , Gerber Johannes , Dzialowski Imanuel , van der Hoeven Erik J.R.J. , Michel Patrik , Pfefferkorn Thomas , Ozdoba Christoph , Kappelle L. Jaap , Wiedemann Baerbel , Khomenko Andrei , Algra Ale , Hill Michael D. , von Kummer Ruediger , Demchuk Andrew M. , Schonewille Wouter J. , Puetz Volker ,   On behalf of the BASICS Study Group
Published: June 2014

BACKGROUND AND PURPOSE

The posterior circulation Acute Stroke Prognosis Early CT Score (pc‐APECTS) applied to CT angiography source images (CTA‐SI) predicts the functional outcome of patients in the Basilar Artery International Cooperation Study (BASICS). We assessed the diagnostic and prognostic impact of pc‐ASPECTS applied to perfusion CT (CTP) in the BASICS registry population.

METHODS

We applied pc‐ASPECTS to CTA‐SI and cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) parameter maps of BASICS patients with CTA and CTP studies performed. Hypoattenuation on CTA‐SI, relative reduction in CBV or CBF, or relative increase in MTT were rated as abnormal.

RESULTS

CTA and CTP were available in 27/592 BASICS patients (4.6%). The proportion of patients with any perfusion abnormality was highest for MTT (93%; 95% confidence interval [CI], 76%‐99%), compared with 78% (58%‐91%) for CTA‐SI and CBF, and 46% (27%‐67%) for CBV (P < .001). All 3 patients with a CBV pc‐ASPECTS < 8 compared to 6/23 patients with a CBV pc‐ASPECTS ≥ 8 had died at 1 month (RR 3.8; 95% CI, 1.9‐7.6).

CONCLUSION

CTP was performed in a minority of the BASICS registry population. Perfusion disturbances in the posterior circulation were most pronounced on MTT parameter maps. CBV pc‐ASPECTS < 8 may indicate patients with high case fatality.
Natural history of snoring in Hong Kong adolescents
Authors: Ng Daniel K , Chan Chung‐hong , Ng Eugene P
Published: June 2014

Aim

To determine the natural history of snoring in children when they reached adolescence and the underlying risk factors for persistence of habitual snoring.

Methods

A follow‐up telephone survey was conducted to determine the natural history of snoring in children who reached adolescence. The targeted interviewees of the follow‐up survey were parents of 3047 children. Adolescents who were snoring ≥6 nights a week were defined as habitual snorers. Potential risk factors for persistent and incident habitual snoring were studied, including age, gender, allergic rhinitis, asthma, body mass index (BMI), sleep duration and daytime sleepiness.

Results

Of the 3047 subjects, 2005 (65.8%) were successfully interviewed by phone. The prevalence of habitual snorers was 12.7%. Ninety‐one adolescents were persistent habitual snorers. Allergic rhinitis, male gender and higher BMI at follow‐up were identified as significant risk factors for persistent habitual snoring. A further 163 children were identified as incident habitual snorers. The risk factors for incident habitual snoring included male gender, asthma, higher BMI at follow‐up and younger age at the first survey. In the current study, the mean sleep duration was 7.6 ± 1.0 h. Overall, 90% of the current cohort slept less than the lower limit of international recommendations for sleep duration.

Conclusions

Around 40.6% of habitually snoring children continued to snore habitually as adolescents in the current study, while 9.2% of the initial non‐habitual snorers became habitual snorers. Male gender and higher BMI were significant risk factors for both persistent and incident habitual snoring.
Vitamin D insufficiency among hospitalised children in the Northern Territory
Authors: Binks Michael J , Smith‐Vaughan Heidi C , Bar‐Zeev Naor , Chang Anne B , Andrews Ross M
Published: June 2014

Aim

Acute lower respiratory infections (ALRIs) are the most common reason for hospitalisation of young children in the Northern Territory of Australia. International studies have linked vitamin D deficiency with increased risk of ALRI in paediatric populations, but this has not been explored in tropical regions such as the Top End of the Northern Territory. The aim of this study is to determine the prevalence of vitamin D insufficiency among children hospitalised with ALRI in the Northern Territory.

Methods

Vitamin D serum metabolite (25OHD3) levels were retrospectively measured using liquid chromatography–mass spectrometry in 74 children (64% male; 57% Indigenous) aged less than 3 years admitted to Royal Darwin Hospital in the Northern Territory of Australia between May 2008 and May 2010.

Results

There were 44 (59%) ALRI‐classified hospitalisations and 30 (41%) non‐ALRI‐classified hospitalisations. The most common ALRI diagnoses were bronchiolitis (n = 22, 30%) and pneumonia (n = 21, 28%), whereas the most common non‐ALRI diagnosis was gastroenteritis (n = 20, 27%). Overall, 24/74 (32%) children had 25OHD3 levels <75 nmol/L (insufficiency). For children hospitalised with ALRI, 23% (10/44) had vitamin D insufficiency compared with 47% (14/30) among children hospitalised for other reasons (odds ratio 0.34, 95% confidence interval 0.11–1.03; P = 0.043). Twelve of the 20 (60%) children hospitalised for gastroenteritis had vitamin D insufficiency.

Conclusions

Vitamin D insufficiency was observed in almost one‐third of these hospitalised children. Children hospitalised with an ALRI were less likely to have vitamin D insufficiency compared with children hospitalised for other conditions (predominantly gastroenteritis).
Primary ciliary dyskinesia: Overlooked and undertreated in children
Authors: Hosie Patrick , Fitzgerald Dominic A , Jaffe Adam , Birman Catherine S , Morgan Lucy
Published: June 2014

Primary ciliary dyskinesia (PCD) is a multi‐organ disorder associated with chronic oto‐sino‐pulmonary disease, neonatal respiratory distress, situs abnormalities and reduced fertility. Repeated respiratory tract infections leads to the almost universal development of bronchiectasis. These clinical manifestations are a consequence of poorly functioning motile cilia. However, confirming the diagnosis is quite difficult and is often delayed, so the true incidence of PCD may be significantly higher than current estimates. Nasal nitric oxide has been earmarked as a useful screening tool for identifying patients, but its use is limited in pre‐school‐aged children. Due to the rarity of PCD, the evidence base for management is somewhat limited, and treatment regimens are extrapolated from other suppurative lung disorders, like cystic fibrosis.
Oral vitamin B12 treatment is effective for children with nutritional vitamin B12 deficiency
Authors: Bahadir Aysenur , Reis Pınar Gökçe , Erduran Erol
Published: June 2014

Aim

Despite being one of common preventable deficiency disorders, vitamin B12 (vit‐B12) deficiency can lead to serious health problems both in children and adult. The familiar treatment through parenteral route for vit‐B12 deficiency frequently leads to poor adherence, and adequate response to treatment has lead to interest in oral supplementation. This study investigates the efficacy of oral vit‐B12 treatment in children with nutritional vit‐B12 deficiency.

Methods

Forty‐seven children (from 1 month to 17 years) with vit‐B12 levels below 200 pg/mL were allocated either of two study groups: Group 1 (1–20 months) and Group 2 (6–17 years) which were subdivided according to the duration of treatment (Group 1A&2A: 4 months; Group 1B&2B: 8 months of 1000 μg oral vit‐B12, every day for a week, every other day for 2 weeks, 2 days a week for 2 weeks, then once a week).

Results

Vit‐B12 levels among all groups were significantly restored following high oral vit‐B12 doses (P = 0.013, P = 0.001), the regimen being more effective in Group1A and Group1B. Correlation analysis of serum vit‐B12 levels and age at the end of treatment revealed a decreasing trend with the increasing patient age (corelation respectively −65.2%, P = 0.08; −35.4%; P = 0.25).

Conclusion

Data from this study indicate that oral vit‐B12 (1000 μg) for 4 months is effective, giving clinicians more choice, for treatment of children with nutritional vit‐B12 deficiency. However, despite this high dose, lower levels were achieved in older children indicating the necessity of dosage adjustment in accordance with body weight.
Melatonin promotes the acquisition of neural identity through extracellular‐signal‐regulated kinases 1/2 activation
Authors: Chen Xueran , Li Xian , Du Zhaoxia , Shi Wei , Yao Yao , Wang Chen , He Kun , Hao Aijun
Published: June 2014

Melatonin, a major pineal secretory product, exerts a range of physiological and neuroprotective effects. However, the functional significance of melatonin in determining neural identity, and the mechanisms by which this may occur, is unknown. In this study, P19 cells were used as a model system and cell behavior was monitored. Our data show that melatonin plays an important role in determining cell fate during neural commitment and promoting the differentiation of pluripotent P19 cells (Oct4+Sox2+) into neural stem cells (Oct4−Sox2+). This promotion appears to coincide with the activation of the MT1 receptor and phosphorylation of extracellular‐signal‐regulated kinases 1/2 (ERK1/2). Furthermore, our results show that melatonin regulates neural fate specification of P19 cells through two distinct mechanisms: the promotion of nuclear localization of ERK1/2 and upregulation of Sox2 transcription, and suppression of Smad1‐induced expression of mesodermal‐specific genes, such as Bra.
Effects of supplemental nanoparticle trivalent chromium on the nutrient utilization, growth performance and serum traits of broilers
Authors: Lin Y. C. , Huang J. T. , Li M. Z. , Cheng C. Y. , Lien T. F.
Published: June 2014

The aim of this study was to investigate the effect of dietary supplementation of nanoparticle trivalent chromium on nutrient utilization, growth performance and serum traits of broilers. This study included two trials. In trial 1, 32 three‐week‐old broilers were divided into four groups: the control, chromium chloride (CrCl3), chromium picolinate (CrPic) and nanoparticle chromium picolinate (NanoCrPic). Chromium was added at a 1200 μg/kg level to evaluate the nutrient and chromium utilization. In trial 2, 160 one‐day‐old broilers were randomly divided into four groups as in trial 1, with four replicates. The results of trial 1 indicated that the chromium utilization is as follows: NanoCrPic > CrPic > CrCl3 and control groups, with significant differences between groups (p < 0.05). Crude fat utilization in CrCl3 group was lower than in that the control group (p < 0.05). The results of trial 2 indicated that feed intake of 4–5 weeks showed better result in the CrCl3 group than that in the CrPic group (p < 0.05). The results of serum traits indicated that the LDL‐cholesterol in the NanoCrPic groups was lower than that in the CrPic group (p < 0.05). The NanoCrpic and CrPic groups showed significantly increased serum chromium concentration when compared with the control and CrCl3 groups; the triglyceride level in the CrCl3 group was lower than that in the CrPic group (p < 0.05). This study concluded that compared with CrPic, NanoCrpic supplementation could increase chromium utilization and lower the serum LDL‐cholesterol of broilers.
Effects of the proteasome inhibitor, bortezomib, on cytodifferentiation and mineralization of periodontal ligament cells
Authors: Kitagaki J. , Miyauchi S. , Xie C. J , Yamashita M. , Yamada S. , Kitamura M. , Murakami S.
Published: June 2014

Background and Objective

The proteasome inhibitor, bortezomib, is known to induce osteoblastic differentiation in a number of cell lines, such as mesenchymal stem cells and osteoblastic precursor cells. As periodontal ligament (PDL) cells are multipotent, we examined whether bortezomib may induce the differentiation of PDL cells into hard‐tissue‐forming cells.

Material and Methods

A mouse PDL clone cell line, MPDL22 cells, was cultured in mineralization medium in the presence or absence of bortezomib. Expression of calcification‐related genes and calcified‐nodule formation were evaluated by real‐time PCR and Alizarin Red staining, respectively.

Results

Bortezomib increased the expression of calcification‐related mRNAs, such as tissue nonspecific alkaline phosphatase isoenzyme (ALPase), bone sialoprotein (Bsp), runt‐related transcription factor 2 (Runx2) and osteopontin, and calcified‐nodule formation in MPDL22 cells. These effects were induced, in part, by increasing the cytosolic accumulation and nuclear translocation of β‐catenin, leading to an increase in expression of bone morphogenetic protein (Bmp)‐2, ‐4 and ‐6 mRNAs. In addition, bortezomib enhanced BMP‐2‐induced expression of Bsp and osteopontin mRNAs and increased calcified‐nodule formation in MPDL22 cells.

Conclusion

Bortezomib induced cytodifferentiation and mineralization of PDL cells by enhancing the accumulation of β‐catenin within the cytosol and the nucleus and increasing the expression of Bmp‐2, ‐4 and ‐6 mRNAs. Moreover, bortezomib enhanced the BMP‐2‐induced cytodifferentiation and mineralization of PDL cells, suggesting that bortezomib may be efficacious for use in periodontal regeneration therapy.
Supply Chain Drivers of Organizational Flexibility—A Study of U.S. Manufacturing Industries
Authors: Cheng Liang‐Chieh (Victor) , Cantor David E. , Grimm Curtis M. , Dresner Martin E.
Published: June 2014

In this article, we investigate supply chain–related drivers that contribute to organizational flexibility (i.e., the ability of top management to be responsive to a firm's internal and external needs). Organizational flexibility occurs when a firm outsources manufacturing and operates with a more flexible structure. Drawing upon the supply network perspective, this study develops hypotheses relating attributes of the supplier, customer, and focal industries to the use of a flexible organizational strategy. Using an industry‐level data set to test the hypotheses, we show that heterogeneity of supply sources and scale economies (in the focal and downstream industries) are positively associated with a greater degree of organizational flexibility, in terms of contract manufacturing in the focal industry. However, industry concentration levels in the focal and downstream industries are negatively associated with organizational flexibility.
Mutation of praR in Rhizobium leguminosarum enhances root biofilms, improving nodulation competitiveness by increased expression of attachment proteins
Authors: Frederix Marijke , Edwards Anne , Swiderska Anna , Stanger Andrew , Karunakaran Ramakrishnan , Williams Alan , Abbruscato Pamela , Sanchez‐Contreras Maria , Poole Philip S. , Downie J. Allan
Published: June 2014

In Rhizobium leguminosarum bv. viciae, quorum‐sensing is regulated by CinR, which induces the cinIS operon. CinI synthesizes an AHL, whereas CinS inactivates PraR, a repressor. Mutation of praR enhanced biofilms in vitro. We developed a light (lux)‐dependent assay of rhizobial attachment to roots and demonstrated that mutation of praR increased biofilms on pea roots. The praR mutant out‐competed wild‐type for infection of pea nodules in mixed inoculations. Analysis of gene expression by microarrays and promoter fusions revealed that PraR represses its own transcription and mutation of praR increased expression of several genes including those encoding secreted proteins (the adhesins RapA2, RapB and RapC, two cadherins and the glycanase PlyB), the polysaccharide regulator RosR, and another protein similar to PraR. PraR bound to the promoters of several of these genes indicating direct repression. Mutations in rapA2, rapB, rapC, plyB, the cadherins or rosR did not affect the enhanced root attachment or nodule competitiveness of the praR mutant. However combinations of mutations in rapA, rapB and rapC abolished the enhanced attachment and nodule competitiveness. We conclude that relief of PraR‐mediated repression determines a lifestyle switch allowing the expression of genes that are important for biofilm formation on roots and the subsequent initiation of infection of legume roots.
Leaf out times of temperate woody plants are related to phylogeny, deciduousness, growth habit and wood anatomy
Authors: Panchen Zoe A. , Primack Richard B. , Nordt Birgit , Ellwood Elizabeth R. , Stevens Albert‐Dieter , Renner Susanne S. , Willis Charles G. , Fahey Robert , Whittemore Alan , Du Yanjun , Davis Charles C.
Published: June 2014

Leaf out phenology affects a wide variety of ecosystem processes and ecological interactions and will take on added significance as leaf out times increasingly shift in response to warming temperatures associated with climate change. There is, however, relatively little information available on the factors affecting species differences in leaf out phenology.

An international team of researchers from eight Northern Hemisphere temperate botanical gardens recorded leaf out dates of c. 1600 woody species in 2011 and 2012.

Leaf out dates in woody species differed by as much as 3 months at a single site and exhibited strong phylogenetic and anatomical relationships. On average, angiosperms leafed out earlier than gymnosperms, deciduous species earlier than evergreen species, shrubs earlier than trees, diffuse and semi‐ring porous species earlier than ring porous species, and species with smaller diameter xylem vessels earlier than species with larger diameter vessels. The order of species leaf out was generally consistent between years and among sites.

As species distribution and abundance shift due to climate change, interspecific differences in leaf out phenology may affect ecosystem processes such as carbon, water, and nutrient cycling. Our open access leaf out data provide a critical framework for monitoring and modelling such changes going forward.