bluuebunny/crossref_metadata_2025 huggingface dataset:
Intolerance of uncertainty, appraisals, coping, and anxiety: The case of the 2009 H1N1 pandemic
Authors: Taha Sheena , Matheson Kim , Cronin Tracey , Anisman Hymie
Published: July 2013

Objectives

Although ambiguous and uncertain situations, such as those dealing with the threat of widespread viral illness, may have pronounced psychological ramifications, there have been few studies that examined the factors that contributed to such outcomes. The purpose of the present investigation was to examine emotional reactions to a health threat.

Design

A structural equation model examined the interplay between anxiety and intolerance of uncertainty, as sequentially mediated by appraisals and coping strategies.

Methods

Adult participants over the age of 18 (N = 1,027) completed online self‐report measures during the H1N1 pandemic in 2009.

Results

Greater intolerance of uncertainty was related to lower appraisals of self‐ and other control, which predicted low levels of problem‐focused coping and greater reports of H1N1‐related anxiety. Additionally, individuals with a high intolerance of uncertainty were more likely to perceive the pandemic as threatening and also were more apt to use emotion‐focused coping strategies, and both of these factors predicted elevated levels of anxiety.

Conclusions

Together, these data indicate that threats, such as those related to a potential pandemic, not only have implications for physical health, but also for psychological distress, and that such outcomes vary with a constellation of appraisal and coping factors.

Statement of contribution

What is already known on this subject? It has been established that the public is often confused by the threat that a potential pandemic virus poses and that they are unsure of what information related to the disease they can trust. Government health agencies often walk the line of minimizing the threat to prevent panic, but simultaneously emphasize the importance of action (vaccination) to prevent a worldwide pandemic.

What does this study add?

Beyond the physical threat of a pandemic, a significant psychological toll may occur for certain individuals.

Anxiety regarding H1N1 is heightened amongst those who cannot tolerate uncertainty.

Appraisals of threat, control, and the use of emotion‐focused coping mediate the above relationship.
Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis‐like phenotypes
Authors: Ramos M.D. , Trujillano D. , Olivar R. , Sotillo F. , Ossowski S. , Manzanares J. , Costa J. , Gartner S. , Oliva C. , Quintana E. , Gonzalez M.I. , Vazquez C. , Estivill X. , Casals T.
Published: July 2013

The term cystic fibrosis (CF)‐like disease is used to describe patients with a borderline sweat test and suggestive CF clinical features but without two CFTR(cystic fibrosis transmembrane conductance regulator) mutations. We have performed the extensive molecular analysis of four candidate genes (SCNN1A, SCNN1B, SCNN1G and SERPINA1) in a cohort of 10 uncharacterized patients with CF and CF‐like disease. We have used whole‐exome sequencing to characterize mutations in the CFTR gene and these four candidate genes. CFTR molecular analysis allowed a complete characterization of three of four CF patients. Candidate variants in SCNN1A, SCNN1B, SCNN1G and SERPINA1 in six patients with CF‐like phenotypes were confirmed by Sanger sequencing and were further supported by in silico predictive analysis, pedigree studies, sweat test in other family members, and analysis in CF patients and healthy subjects. Our results suggest that CF‐like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors.
Postural asymmetries in young adults with cerebral palsy
Authors: Rodby‐Bousquet Elisabet , Czuba Tomasz , Hägglund Gunnar , Westbom Lena
Published: July 2013

Aim

The purpose was to describe posture, ability to change position, and association between posture and contractures, hip dislocation, scoliosis, and pain in young adults with cerebral palsy (CP).

Methods

Cross‐sectional data of 102 people (63 males, 39 females; age range 19–23y, median 21y) out of a total population with CP was analysed in relation to Gross Motor Function Classification System (GMFCS) levels I (n=38), II (n=21), III (n=13), IV (n=10), and V (n=20). The CP subtypes were unilateral spastic (n=26), bilateral spastic (n=45), ataxic (n=12), and dyskinetic CP (n=19). The Postural Ability Scale was used to assess posture. The relationship between posture and joint range of motion, hip dislocation, scoliosis, and pain was analysed using logistic regression and Spearman's correlation.

Results

At GMFCS levels I to II, head and trunk asymmetries were most common; at GMFCS levels III to V postural asymmetries varied with position. The odds ratios (OR) for severe postural asymmetries were significantly higher for those with scoliosis (OR=33 sitting), limited hip extension (OR=39 supine), or limited knee extension (OR=37 standing). Postural asymmetries correlated to hip dislocations: supine (rs=0.48), sitting (rs=0.40), standing (rs=0.41), and inability to change position: supine (rs=0.60), sitting (rs=0.73), and standing (rs=0.64).

Conclusions

Postural asymmetries were associated with scoliosis, hip dislocations, hip and knee contractures, and inability to change position.
Perinatal brain lesions and cognitive outcome
Authors: Mercuri Eugenio , Ricci Daniela
Published: July 2013

This commentary is on the original article by van Buuren et al. on pages 934–940 of this issue.
Sustainable Procurement: Integrating Classroom Learning with University Sustainability Programs
Authors: Goldschmidt Kyle , Harrison Terry , Holtry Matthew , Reeh Jeremy
Published: July 2013

Organizations are facing increased pressure from various stakeholders to address issues of sustainability, resulting in a growing demand for sustainability education and training. Procurement groups remain the key drivers of many sustainability‐related strategies, placing pressure on universities to integrate sustainability concepts into the business curriculum. This article describes a replicable educational model that allows students to learn about sustainable procurement while concurrently promoting sustainability within the university community.
Longitudinal Strain in Friedreich Ataxia: A Potential Marker for Early Left Ventricular Dysfunction
Authors: St John Sutton Martin , Ky Bonnie , Regner Sean R. , Schadt Kim , Plappert Ted , He Jiwei , D'Souza Benjamin , Lynch David R.
Published: July 2013

Background

Friedreich's ataxia (FRDA) is a neurodegenerative disorder resulting from deficiency of frataxin, characterized by cardiac hypertrophy associated with heart failure and sudden cardiac death. However, the relationship between remodeling and novel measures of cardiac function such as strain, and the time‐dependent changes in these measures are poorly defined.

Methods and Results

We compared echocardiographic parameters of cardiac size, hypertrophy, and function in 50 FRDA patients with 50 normal controls and quantified the following measures of cardiac remodeling and function: left ventricular (LV) volumes, mass, relative wall thickness (RWT), ejection fraction (EF), and myocardial strain. Linear regression analysis was used to identify significant differences in echocardiographic parameters in FRDA compared with normal subjects. In analyses adjusted for age, sex, and body surface area, significant differences were observed between parameters of remodeling (LV mass, RWT, and volumes) and function in FRDA patients compared with controls. In particular, longitudinal strain was significantly decreased in FRDA patients compared with controls (−12.4% vs. −16.0%, P < 0.001), despite similar and normal left ventricular ejection fraction (LVEF). Over 3 years of follow‐up, there was no change in strain, LV size, LV mass, or LVEF among FRDA patients.

Conclusion

Longitudinal strain is reduced in FRDA despite normal LVEF, indicative of subclinical cardiac dysfunction. Given late declines in LVEF in FRDA, longitudinal strain may provide an earlier index of myocardial dysfunction in FRDA.
Effect on disability and safety of Tafamidis in late onset of Met30 transthyretin familial amyloid polyneuropathy
Authors: Lozeron P. , Théaudin M. , Mincheva Z. , Ducot B. , Lacroix C. , Adams D. ,   French Network for FAP (CORNAMYL)
Published: July 2013

Background and purpose

The aim of this study was to assess the effect of Tafamidis, which slows the progression of early stages of Met30 transthyretin (TTR) familial amyloidosis polyneuropathy (FAP) in more advanced cases.

Methods

The study was a prospective, non‐randomized controlled trial carried out at the French national reference centre for FAP with follow‐up at 1 year. Thirty‐seven consecutive Met30‐TTR‐FAP patients were enrolled between December 2009 and July 2011, with NIS‐LL (Neuropathy Impairment Score‐lower limbs) > 10 and Karnofsky score > 60. Their mean (SD) age was 56.4  (19) years. Seventy‐seven per cent of patients had a walking disability. Seven patients (19%) were withdrawn for adverse effects. The primary study outcome measurements, planned before data collection began, were NIS‐LL and NIS‐UL (upper limbs) scores and disability scores.

Results

Of the 37 patients entered into the study, 29 were evaluated at 6 months and 13 at 12 months. During the first 6 months of treatment, the mean progression of NIS‐LL score was 4.8 and was similar to that during the period before treatment. Among the 45% of patients without NIS‐LL progression, the NIS‐UL score worsened in 55%. During the first year, 55% deteriorated with respect to disability and 38% with respect to NIS only; only two patients (7%) remained stable. Four (out of 20; 20%) patients who were previously stage 1 reached stage 2 (walking with aid) after this period. Two out of nine patients who were initially normotensive developed orthostatic hypotension. There were a total of 19 adverse events, including four febrile urinary tract infections and three severe diarrhoeas, with faecal incontinence in two.

Conclusion

In most patients with advanced Met30 TTR‐FAP, Tafamidis is not able to stop disease progression, in respect of both NIS‐LL and disability. Other anti‐amyloid medicines should be assessed in this context.
A randomized phase III trial of adjunctive zonisamide in pediatric patients with partial epilepsy
Authors: Guerrini Renzo , Rosati Anna , Segieth Joanna , Pellacani Simona , Bradshaw Kate , Giorgi Luigi
Published: July 2013

Purpose

To assess the efficacy and safety/tolerability of adjunctive zonisamide treatment in pediatric patients with partial epilepsy.

Methods

In this phase III, double‐blind, randomized, placebo‐controlled, multicenter trial, 207 patients (age 6–17 years) with partial epilepsy, receiving one or two antiepileptic drugs, were randomized to receive adjunctive zonisamide or placebo. Zonisamide was initiated at 1 mg/kg/day, titrated to a target dose of 8 mg/kg/day over 8 weeks (one down‐titration permitted), and maintained for 12 weeks. The primary efficacy end point was the proportion of responders (≥50% seizure frequency reduction from baseline) during the 12‐week maintenance period. Safety/tolerability assessments included the incidence of treatment‐emergent adverse events (TEAEs).

Key Findings

In total, 93 (86.9%) of 107 patients randomized to zonisamide and 90 (90.0%) of 100 patients randomized to placebo completed the trial. Responder rates were 50% for zonisamide versus 31% for placebo (p = 0.0044; intention‐to‐treat population, last observation carried forward). The overall incidence of TEAEs was similar for zonisamide (55.1%) versus placebo (50.0%), with low rates of serious TEAEs with zonisamide and placebo (3.7% vs. 2.0%) and TEAEs leading to withdrawal (0.9% vs. 3.0%). TEAEs reported more frequently with zonisamide versus placebo were decreased appetite (6.5% vs. 4.0%), decreased weight (4.7% vs. 3.0%), somnolence (4.7% vs. 2.0%), vomiting (3.7% vs. 2.0%), and diarrhea (3.7% vs. 1.0%).

Significance

Adjunctive zonisamide treatment was shown to be effective and well tolerated in pediatric patients with partial epilepsy. No new or unexpected safety findings emerged.
Extended treatment with selective phosphatidylinositol 3‐kinase and mTOR inhibitors has effects on metabolism, growth, behaviour and bone strength
Authors: Smith Greg C. , Ong Wee‐Kiat , Costa Jessica L. , Watson Maureen , Cornish Jillian , Grey Andrew , Gamble Greg D. , Dickinson Michelle , Leung Sophie , Rewcastle Gordon W. , Han Weiping , Shepherd Peter R.
Published: July 2013

The class I phosphatidylinositol 3‐kinases (PtdIns3Ks) mediate the effects of many hormones and growth factors on a wide range of cellular processes, and activating mutations or gene amplifications of class I PtdIns3K isoforms are known to contribute to oncogenic processes in a range of tumours. Consequently, a number of small‐molecule PtdIns3K inhibitors are under development and in clinical trial. The central signalling role of PtdIns3K in many cellular processes suggests there will be on‐target side effects associated with the use of these agents. To gain insights into what these might be we investigated the effect of extended daily dosing of eight small‐molecule inhibitors of class Ia PtdIns3Ks. Animals were characterized in metabolic cages to analyse food intake, oxygen consumption and movement. Insulin tolerance and body composition were analysed at the end of the experiment, the latter using EchoMRI. Bone volume and strength was assessed by micro‐CT and three‐point bending, respectively. Surprisingly, after sustained dosing with pan‐PtdIns3K inhibitors and selective inhibitors of the p110α isoform there was a resolution of the impairments in insulin tolerance observed in drug‐naïve animals treated with the same drugs. However, pan‐PtdIns3K inhibitors and selective inhibitors of the p110α have deleterious effects on animal growth, animal behaviour and bone volume and strength. Together, these findings identify a range of on target effects of PtdIns3K inhibitors and suggest use of these drugs in humans may have important adverse effects on metabolism, body composition, behaviour and skeletal health.
Expression of micro‐RNAs in peripheral blood mononuclear cells from primary biliary cirrhosis patients
Authors: Katsushima Fumiko , Takahashi Atsushi , Sakamoto Natsumi , Kanno Yukiko , Abe Kazumichi , Ohira Hiromasa
Published: July 2013

Aim

The aim of this study was to clarify the relationship between the expression of micro‐RNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) and clinical presentation in patients with primary biliary cirrhosis (PBC).

Methods

This study involved 58 patients with PBC, patients with control diseases including 25 patients with autoimmune hepatitis (AIH), six patients with PBC‐AIH overlap syndrome, 23 patients with systemic lupus erythematosus (SLE), and 30 healthy controls. After miRNA was extracted from PBMCs, the expressions of miR‐26a, miR‐328, miR‐299‐5p, miR‐146a, miR‐155, miR‐16, miR‐132 and let7a were quantified by real‐time PCR. The relationships between all miRNA expressions and clinical test parameters were also examined.

Results

In PBC, the expressions of miR‐155 and miR‐146a were significantly increased compared to those in healthy controls. For miR‐26a, miR‐299‐5p, miR‐328 and let‐7a, although no significant difference was observed in expression between patients and healthy controls, expressions were significantly increased in PBC compared to those in AIH. Expressions of miR‐299‐5p were significantly increased in PBC patients resistant to treatment with ursodeoxycholic acid (n = 18) compared to those in healthy controls. In the evaluation of the relationship between miRNA expression and clinical test parameters, significant and positive correlations were found for miR‐299‐5p with alkaline phosphatase, gamma‐glutamyl transpeptidase, total bilirubin and immunoglobulin M levels.

Conclusion

The preset results suggest the existence of miRNAs that exhibit disease‐specific increases in expression and miRNAs closely correlated with clinical test values in PBC. Further analyses of these miRNAs may contribute to the elucidation of the pathology of PBC.
The Determinants of Dementia after Stroke (DEDEMAS) Study: Protocol and Pilot Data
Authors: Wollenweber Frank A. , Zietemann Vera , Rominger Axel , Opherk Christian , Bayer-Karpinska Anna , Gschwendtner Andreas , Andrews Lisa Coloma , Bürger Katharina , Duering Marco , Dichgans Martin
Published: July 2013

Rationale

About 20% of stroke patients develop dementia within a few months after their event, but the determinants and mechanisms of poststroke dementia are insufficiently understood.

Aims

To identify and characterize the determinants of cognitive impairment poststroke.

Design

Observational prospective study in patients with acute stroke and no prior dementia. Six hundred subjects will be characterized by detailed interview, standardized clinical examinations, biometric measures (intima-media thickness, waist-hip ratio, and ankle-brachial index), multimodal imaging (magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography (FDG-PET), amyloid-positron emission tomography (amyloid-PET), and retinal imaging), analysis of biomarkers derived from blood and cerebrospinal fluid, and detailed cognitive testing at repeat time points. Patients will be followed for five-years with a total of five personal visits and three telephone interviews.

Study Outcomes

Primary end-point is the occurrence of post-stroke dementia. Secondary end-points include poststroke cognitive impairment–no dementia, stroke recurrence, and death. Predictive factors for poststroke dementia will be identified by multiple Cox proportional-hazards model.

Results

Baseline characteristics of the first 71 patients (study inclusion between May 2011 and August 2012) are as follows: median age, 70 years (interquartile range, 65–75); female gender, 25 (35%); median National Institutes of Health Stroke Scale at admission, 2 ( 1 – 4 ); and etiological stroke subtypes according to TOAST classification, 15% large artery disease, 18% small vessel disease, 35% cardioembolic, and 32% undetermined or multiple competing etiologies.

Discussion

This study will provide insights into the mechanisms of poststroke dementia and hold the potential to identify novel diagnostic markers and targets for preventive therapies. The study is registered at http://www.clinicaltrials.gov (NCT01334749) and will be extended as a multicenter study starting 2013.
Topical negative pressure coupled with split‐thickness skin grafting for the treatment of hidradenitis suppurativa: a case report
Authors: Jianbing Tang , Biao Cheng , Qin Li , Yanhong Wu
Published: July 2013

Hidradenitis suppurativa is a cutaneous, chronic, recurrent inflammatory disease. Here, we report the case of a 66‐year‐old man who had hidradenitis suppurativa in the buttocks. He suffered from diabetes mellitus. In the past, he had perianal abscesses. Because of improper treatment of furuncle infections in the buttocks, skin ulcers formed, which worsened and resulted in multiple fistulas. The skin lesion surface was large and the infection was severe. After wound debridement treatment, topical negative pressure and nutritional support were given. After one and a half months, the wound healed with split‐thickness skin grafting. In a 2‐year follow‐up, there was no evidence of hidradenitis suppurativa recurrence.
Severe hidradenitis suppurativa treatment using platelet‐rich plasma gel and Hyalomatrix
Authors: Nicoli Fabio , Balzani Alberto , Lazzeri Davide , Gentile Pietro , Chilgar Ram M , Di Pasquali Camilla , Nicoli Marzia , Bocchini Ilaria , Agovino Annarita , Cervelli Valerio
Published: July 2013

Hidradenitis suppurativa (HS) can be a debilitating chronic disease. The underlying cause of the disease is still not clear. HS may be managed through numerous different medical or surgical procedures. Surgical treatment may consist of local excisions and reconstruction using a variety of methods: perforator flaps, skin grafts, local flaps, primary closure or secondary wound healing with vacuum and other devices. This report describes our experience with surgical excision and closure using platelet‐rich plasma (PRP) gel and Hyalomatrix PA (HPA) in a patient with severe HS involving most of the body surface. We treated the patient with resection of severe HS of the nuchae and closure with PRP gel prepared with the RegenKit® to promote neovascularisation and HPA, a delivery system for hyaluronic acid, to induce a neodermis at the wound bed and to stimulate regeneration in a humid and protected environment. Complete wound healing was achieved after 2 months. The obtained result proved the efficacy of this treatment without complications. No recurrence was observed during the 1 year after the surgical procedure. Severe HS can be safely and effectively managed with wide excision, PRP gel and Hyalomatrix to achieve a successful outcome.
Effective management of patients with diabetes foot ulcers: outcomes of an Interprofessional Diabetes Foot Ulcer Team
Authors: Ogrin Rajna , Houghton Pamela E , Thompson G William
Published: July 2013

A longitudinal observational study on a convenience sample was conducted between 4 January and 31 December of 2010 to evaluate clinical outcomes that occur when a new Interprofessional Diabetes Foot Ulcer Team (IPDFUT) helps in the management of diabetes‐related foot ulcers (DFUs) in patients living in a small urban community in Ontario, Canada. Eighty‐three patients presented to the IPDFUT with 114 DFUs of average duration of 19·5 ± 2·7 weeks. Patients were 58·4 ± 1·4 years of age and 90% had type 2 diabetes, HbA1c of 8·3 ± 2·0%, with an average diabetes duration of 22·3 ± 3·4 years; in 69% of patients, 78 DFUs healed in an average duration of 7·4 ± 0·7 weeks, requiring an average of 3·8 clinic visits. Amputation of a toe led to healing in three patients (4%) and one patient required a below‐knee amputation. Six patients died and three withdrew. Adding a skilled IPDFUT that is trained to work together resulted in improved healing outcomes. The rate of healing, proportion of wounds closed and complication rate were similar if not better than the results published previously in Canada and around the world. The IPDFUT appears to be a successful model of care and could be used as a template to provide effective community care to the patients with DFU in Ontario, Canada.
Effect of blended learning environment on transfer of learning: an experimental study
Authors: Demirer V. , Sahin I.
Published: July 2013

The main purpose of the study is to investigate the effect of the blended learning and face‐to‐face learning on students' academic achievements and transfer of learning. The first aim of the study is to analyse the students' academic achievements to determine the change of theoretical knowledge in terms of the instructional method applied in this study. However, students' performances during the learning process are not always a good indicator. Therefore, the second aim of the study is to examine transferring students' theoretical knowledge to their educational multimedia projects. For this purpose, 14 weeks of pre‐ and post‐test experimental study is designed. The study is administered through an educational technology course in which students learn how to develop educational multimedia materials. The participants are undergraduate pre‐service teachers; they are assigned randomly to the experimental and control group. While the experimental group has both online and classroom sessions, the control group has only face‐to‐face classroom sessions. Although there is no significant difference between the groups in terms of academic achievement, the students in the blended group are more successful in transferring their knowledge to their projects than the ones in the face‐to‐face group. In conclusion, the results show that the blended learning approach has a positive effect on the transfer of learning.
Biased sex‐ratio and sex‐biased heterozygote disadvantage affect the maintenance of a genetic polymorphism and the properties of hybrid zones
Authors: Nouvellet P. , Gourbière S.
Published: July 2013

The evolution of biodiversity is a major issue of modern biology, and it is becoming increasingly topical as the ongoing erosion of diversity puts serious threats on human well‐being. An elementary mechanism that allows maintaining diversity is the interplay between dispersal and heterozygote selective disadvantage, which can lead to self‐sustainable spatial genetic structures and is central to the stability of hybrid zones. Theoretical studies supporting the importance of this mechanism assume a balanced sex‐ratio and a heterozygote disadvantage equally affecting both sexes, despite the multiplicity of empirical evidence that (i) adult sex‐ratio is usually biased towards either male or female and that (ii) heterozygote disadvantage often affects a single sex. We expanded the existing theory by weighting the strength of selection against heterozygote according to the biased in sex‐ratio and in heterozygote disadvantage. The range of conditions allowing for the maintenance of polymorphism can then either double or vanish. We discuss the implications of such finding for birds, mammals and insects diversity. Finally, we provide simple analytical predictions about the effect of those biased on the width and speed of hybrid zones and on the time for the spread of beneficial mutations through such zones.
Bioecology of some key cashew insect pests and diseases in diverse habitats and landscapes in Tanzania
Authors: Agboton B. V. , Salifu D. , Seguni Z. , Sijaona M. E. , Shomari S. , Ekesi S. , Maniania N. K.
Published: July 2013

Cashew (Anacardium occidentale) is an economically important cash crop for many rural households in Tanzania. However, its production is constrained by some insect pests and diseases. As a prerequisite for the development of a more sustainable integrated insect pest and disease management strategy for cashew, information on the biology and ecology of the key insect pests and diseases in a changing environment, and on influencing biotic and abiotic factors, is needed. Surveys were conducted in the major cashew nut‐producing areas of Tanzania for two seasons: August to December, 2009, and August to December, 2010. Data on number of infested and infected shoots by key insect pests and diseases, natural enemies and associated farmer practices, namely synthetic pesticide use and intercropping systems, were collected from different subzones within agroecological zones. Our data showed that abundance and diversity of key cashew insect pests and diseases were influenced by agroecological zones and subzones. Intercropping was more commonly practised in the northern than in the southern zone. Agrochemicals were most frequently used in the southern agroecological zone and affected the occurrence of natural enemies, notably the weaver ant that was more abundant in the northern zone. Furthermore, our findings revealed that Helopeltis sp. and the powdery mildew remained the major constraints to cashew nut production in Tanzania.
Localization, morphology and transcriptional profile of Aspergillus flavus during seed colonization
Authors: Dolezal Andrea L. , Obrian Gregory R. , Nielsen Dahlia M. , Woloshuk Charles P. , Boston Rebecca S. , Payne Gary A.
Published: July 2013

Aspergillus flavus is an opportunistic fungal pathogen that infects maize kernels pre‐harvest, creating major human health concerns and causing substantial agricultural losses. Improved control strategies are needed, yet progress is hampered by the limited understanding of the mechanisms of infection. A series of studies were designed to investigate the localization, morphology and transcriptional profile of A. flavus during internal seed colonization. Results from these studies indicate that A. flavus is capable of infecting all tissues of the immature kernel by 96 h after infection. Mycelia were observed in and around the point of inoculation in the endosperm and were found growing down to the germ. At the endosperm–germ interface, hyphae appeared to differentiate and form a biofilm‐like structure that surrounded the germ. The exact nature of this structure remains unclear, but is discussed. A custom‐designed A. flavus Affymetrix GeneChip® microarray was used to monitor genome‐wide transcription during pathogenicity. A total of 5061 genes were designated as being differentially expressed. Genes encoding secreted enzymes, transcription factors and secondary metabolite gene clusters were up‐regulated and considered to be potential effector molecules responsible for disease in the kernel. Information gained from this study will aid in the development of strategies aimed at preventing or slowing down A. flavus colonization of the maize kernel.
Production of Oocytes of Nile Tilapia (Oreochromis niloticus) for In Vitro Fertilization via Hormonal Treatments
Authors: Fernandes AFA , Alvarenga ÉR , Oliveira DAA , Aleixo CG , Prado SA , Luz RK , Sarmento NLAF , Teixeira EA , Luz MR , Turra EM
Published: July 2013

Contents

Only a few studies have described hormonal treatments for induction of synchronicity and gamete collection in Nile tilapia (Oreochromis niloticus), both important for assortative matings in breeding programmes and essential for polyploidy technologies. In this study, we compared the effectiveness of carp pituitary extract (CPE), Nile tilapia pituitary extract (TPE), human chorionic gonadotropin (hCG) and gonadotropin‐releasing hormone (GnRH) protocols on the induction of spawning and egg production in Nile tilapia. Among the hormonal treatments analysed, only hCG was effective for producing viable gametes for in vitro fertilization. To verify the viability of this hormonal treatment, hCG was tested using different doses (1000, 2000, 3000, 4000 and 5000 IU/kg) in a large number of females (208 animals) from two Nile tilapia lines. The results indicated that hCG doses between 1000 and 5000 IU/kg could be used to induce final oocyte maturation in Nile tilapia with collection of stripped oocytes. This is the first study to report differential reproductive responses to hormonal treatment between tilapia lines: line 1 was more efficient at producing eggs and post‐hatching larvae after hCG induction than line 2. In conclusion, we demonstrated that the hCG protocol may be applied on a large scale to induce final oocyte maturation in Nile tilapia. The development of a protocol for in vitro fertilization in Nile tilapia may aid in breeding programmes and biotechnological assays for the development of genetically modified lines of Nile tilapia.
Frequent Hemodialysis: A Critical Review
Authors: Diaz‐Buxo Jose A. , White Sarah A. , Himmele Rainer
Published: July 2013

Conventional, thrice‐weekly hemodialysis (CHD) is the most commonly prescribed dialysis regimen. Despite widespread acceptance of CHD, long‐term analyses of registry data have revealed an increased risk for mortality during the long 2‐day interdialytic interval of thrice‐weekly therapies. High mortality rates during this period suggest that there may be a role for more frequent HD in improving patient outcomes and survival through elimination of the long interdialytic period. Several regimens have been investigated including: short, daily HD, frequent nocturnal HD, and alternate‐day HD. In this review, we provide an in‐depth summary of current data comparing the effects of frequent and CHD modalities on survival, hospitalizations, vascular access complications, burden of therapy, quality of life, residual renal function, cardiovascular parameters, bone mineral metabolism, and anemia. Limitations of the data as well as the role of frequent dialysis in clinical practice are also discussed.
Combined inhalation of beta2‐agonists improves swim ergometer sprint performance but not high‐intensity swim performance
Authors: Kalsen A. , Hostrup M. , Bangsbo J. , Backer V.
Published: July 2013

There is a high prevalence of asthma and airway hyperresponsiveness (AHR) in elite athletes, which leads to a major use of beta2‐agonists. In a randomized double‐blinded crossover study, we investigated the effects of combined inhalation of beta2‐agonists (salbutamol, formoterol, and salmeterol), in permitted doses within the World Anti‐Doping Agency 2013 prohibited list, in elite swimmers with (AHR, n = 13) or without (non‐AHR, n = 17) AHR. Maximal voluntary isometric contraction of m. quadriceps (MVC), sprint performance on a swim ergometer and performance in an exhaustive swim test at 110% of VO2max were determined. Venous plasma interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) were measured post‐exercise. No improvement was observed in the exhaustive swim test, but swim ergometer sprint time was improved (P < 0.05) in both groups from 57 ± 1.7 to 56 ± 1.8 s in AHR and 58.3 ± 1 to 57.4 ± 1 s in non‐AHR. MVC and post‐exercise plasma IL‐6 increased (P < 0.05) with beta2‐agonists in both groups, whereas IL‐8 only increased in AHR. In summary, inhalation of beta2‐agonists, in permitted doses, did not improve swim performance in elite swimmers. However, swim ergometer sprint performance and MVC were increased, which should be considered when making future anti‐doping regulations.
Health of mobile pastoralists in theSahel – assessment of 15 years of research and development
Authors: Montavon A. , Jean‐Richard V. , Bechir M. , Daugla D. M. , Abdoulaye M. , Bongo Naré R. N. , Diguimbaye‐Djaibé C. , Alfarouk I. O. , Schelling E. , Wyss K. , Tanner M. , Zinsstag J.
Published: July 2013

In theSahel, betweenMauritania and Somalia includingNorthernKenya, about 20–30 million people live as mobile pastoralists. The rhythm of their migration follows the seasons and the availability of resources such as water, pasture and salt. Despite their high exposure to zoonoses and problems caused by extreme climatic conditions, mobile pastoralists are virtually excluded from health services because the provision of social services adapted to their way of life is challenging. In cooperation with various partners in the region, theSwissTropical andPublicHealthInstitute has been active in research and development in theSahel for 15 years. Based on the perceived needs of mobile pastoralists and the necessities of development, interdisciplinary research has considerably contributed to better understanding of their situation and their problems. Close contact between humans and livestock necessitates close cooperation between human and animal health specialists. Such useful approaches should be continued and extended.
A galactosyltransferase acting on arabinogalactan protein glycans is essential for embryo development in Arabidopsis
Authors: Geshi Naomi , Johansen Jorunn N. , Dilokpimol Adiphol , Rolland Aurélia , Belcram Katia , Verger Stéphane , Kotake Toshihisa , Tsumuraya Yoichi , Kaneko Satoshi , Tryfona Theodora , Dupree Paul , Scheller Henrik V. , Höfte Herman , Mouille Gregory
Published: July 2013

Arabinogalactan proteins (AGPs) are a complex family of cell‐wall proteoglycans that are thought to play major roles in plant growth and development. Genetic approaches to studying AGP function have met limited success so far, presumably due to redundancy within the large gene families encoding AGP backbones. Here we used an alternative approach for genetic dissection of the role of AGPs in development by modifying their glycan side chains. We have identified an Arabidopsis glycosyltransferase of CAZY family GT31 (AtGALT31A) that galactosylates AGP side chains. A mutation in the AtGALT31A gene caused the arrest of embryo development at the globular stage. The presence of the transcript in the suspensor of globular‐stage embryos is consistent with a role for AtGALT31A in progression of embryo development beyond the globular stage. The first observable defect in the mutant is perturbation of the formative asymmetric division of the hypophysis, indicating an essential role for AGP proteoglycans in either specification of the hypophysis or orientation of the asymmetric division plane.
Reference intervals for common coagulation tests of preterm infants (CME)
Authors: Christensen Robert D. , Baer Vickie L. , Lambert Diane K. , Henry Erick , Ilstrup Sarah J. , Bennett Sterling T.
Published: July 2013

Background:

Fresh‐frozen plasma (FFP) is sometimes administered to nonbleeding preterm neonates who are judged to be at risk for bleeding because they have abnormal coagulation tests. The benefits/risks of this practice are not well defined. One limitation to progress is lack of reference intervals for the common coagulation tests, thus limiting precision about whether coagulation tests are indeed abnormal.

Study Design and Methods:

In a sequential observational study, fetal blood was drawn at preterm birth (≤34 weeks) from the umbilical vein near the placenta. Fibrinogen, prothrombin time, activated partial thromboplastin time, D‐dimer, platelet (PLT) count, and mean PLT volume were measured. Reference intervals were constructed using 5th and 95th percentile values. Associations were then sought between abnormal coagulation values at birth and bleeding problems identified during the first week.

Results:

Coagulation tests were drawn at 175 preterm deliveries and the results were organized into reference intervals by gestational age. No abnormal coagulation value, either alone or in combination, predicted hemorrhage (intraventricular, gastrointestinal, or pulmonary) during the first week. However, fibrinogen exceeding the 95th percentile was associated with evidence of in utero infection/inflammation (correlations with elevated C‐reactive protein, p < 0.01, and elevated immature to total neutrophil ratio, p < 0.001).

Conclusions:

Abnormal coagulation values at preterm birth do not predict bleeding during the first week. This suggests to us that bleeding in the days after preterm birth is not generally the result of in utero coagulopathy. These findings bring into question the value of coagulation screening of nonbleeding preterm infants and prophylactic FFP administration to those with abnormal values.
The mechanism underlying maintenance of the endocochlear potential by the K+ transport system in fibrocytes of the inner ear
Authors: Adachi Naoko , Yoshida Takamasa , Nin Fumiaki , Ogata Genki , Yamaguchi Soichiro , Suzuki Toshihiro , Komune Sizuo , Hisa Yasuo , Hibino Hiroshi , Kurachi Yoshihisa
Published: July 2013

Key points

The endocochlear potential (EP) of +80 mV in cochlear endolymph is essential for audition and controlled by K+ transport across the lateral cochlear wall composed of two epithelial barrier layers, the syncytium containing the fibrocytes and the marginal cells.

The EP depends upon the diffusion potential elicited by a large K+ gradient across the apical surface of the syncytium.

We examined by electrophysiological approaches an involvement of Na+,K+‐ATPase, which occurs at the syncytium's basolateral surface comprising the fibrocytes’ membranes and would mediate K+ transport across the lateral wall, in maintenance of the EP.

We show that the Na+,K+‐ATPase sustains the syncytium's high [K+] that is crucial for the K+ gradient across the apical surface of the syncytium.

The results help us better understand the mechanism underlying the establishment of the EP as well as the pathophysiological process for deafness induced by dysfunction of the ion transport apparatus.

Abstract  The endocochlear potential (EP) of +80 mV in the scala media, which is indispensable for audition, is controlled by K+ transport across the lateral cochlear wall. This wall includes two epithelial barriers, the syncytium and the marginal cells. The former contains multiple cell types, such as fibrocytes, which are exposed to perilymph on their basolateral surfaces. The apical surfaces of the marginal cells face endolymph. Between the two barriers lies the intrastrial space (IS), an extracellular space with a low K+ concentration ([K+]) and a potential similar to the EP. This intrastrial potential (ISP) dominates the EP and represents the sum of the diffusion potential elicited by a large K+ gradient across the apical surface of the syncytium and the syncytium's potential, which is slightly positive relative to perilymph. Although a K+ transport system in fibrocytes seems to contribute to the EP, the mechanism remains uncertain. We examined the electrochemical properties of the lateral wall of guinea pigs with electrodes sensitive to potential and K+ while perfusing into the perilymph of the scala tympani blockers of Na+,K+‐ATPase, the K+ pump thought to be essential to the system. Inhibiting Na+,K+‐ATPase barely affected [K+] in the IS but greatly decreased [K+] within the syncytium, reducing the K+ gradient across its apical surface. The treatment hyperpolarized the syncytium only moderately. Consequently, both the ISP and the EP declined. Fibrocytes evidently use the Na+,K+‐ATPase to achieve local K+ transport, maintaining the syncytium's high [K+] that is crucial for the K+ diffusion underlying the positive ISP.
Oscillation in Electric Power Steering Test Torque Due to Universal Joint Angle and Control Strategy
Authors: Yang Zhong-Xing
Published: July 2013

To perform torque load test on an active EPS (electric power steering) system, the EPS column is required to make a user-defined angular displacement under a user-defined test load applied at the end of the pinion shaft. As universal joints are used in the EPS system for spatial arrangement, the angular velocity and torque on the driven shaft vary twice from those on the driving shaft in one rotation circle. This introduces a fluctuation in the velocity and torque on the driven shaft at a frequency twice that of the shaft rotation. The angular acceleration of the pinion shaft exerts on the coupling an inertia load which prevents the required load from precise transmission. To eliminate the oscillatory deviation in the test load applied at a target position in a multibody rotation system while not changing the shafts axes angle arrangement, a control strategy based on a proportional integral derivative controller (PID) with compensation using rotary acceleration feedback, newly developed for torque control, is discussed in this paper. The load control at a target point is achieved by modifying the torque input with a compensation signal to cancel out the oscillatory deviation in the test load.
Uncertainty Quantification of a Nonlinear Aeroelastic System Using Polynomial Chaos Expansion With Constant Phase Interpolation
Authors: Desai Ajit , Witteveen Jeroen A. S. , Sarkar Sunetra
Published: July 2013

The present study focuses on the uncertainty quantification of an aeroelastic instability system. This is a classical dynamical system often used to model the flow induced oscillation of flexible structures such as turbine blades. It is relevant as a preliminary fluid-structure interaction model, successfully demonstrating the oscillation modes in blade rotor structures in attached flow conditions. The potential flow model used here is also significant because the modern turbine rotors are, in general, regulated in stall and pitch in order to avoid dynamic stall induced vibrations. Geometric nonlinearities are added to this model in order to consider the possibilities of large twisting of the blades. The resulting system shows Hopf and period-doubling bifurcations. Parametric uncertainties have been taken into account in order to consider modeling and measurement inaccuracies. A quadrature based spectral uncertainty tool called polynomial chaos expansion is used to quantify the propagation of uncertainty through the dynamical system of concern. The method is able to capture the bifurcations in the stochastic system with multiple uncertainties quite successfully. However, the periodic response realizations are prone to time degeneracy due to an increasing phase shifting between the realizations. In order to tackle the issue of degeneracy, a corrective algorithm using constant phase interpolation, which was developed earlier by one of the authors, is applied to the present aeroelastic problem. An interpolation of the oscillatory response is done at constant phases instead of constant time and that results in time independent accuracy levels.
Drug Targeting
Authors: Vinson Valda K.
Published: July 2013

A method to monitor drug binding to proteins in cells may help in target validation and drug optimization.
Mutagenesis Mapping of the Protein-Protein Interaction Underlying FusB-Type Fusidic Acid Resistance
Authors: Cox Georgina , Edwards Thomas A. , O'Neill Alex J.
Published: July 2013

FusB-type proteins represent the predominant mechanism of resistance to fusidic acid in staphylococci and act by binding to and modulating the function of the drug target (elongation factor G [EF-G]). To gain further insight into this antibiotic resistance mechanism, we sought to identify residues important for the interaction of FusB with EF-G and thereby delineate the binding interface within the FusB–EF-G complex. Replacement with alanine of any one of four conserved residues within the C-terminal domain of FusB (F
156
, K
184
, Y
187
, and F
208
) abrogated the ability of the protein to confer resistance to fusidic acid; the purified mutant proteins also lost the ability to bind
S. aureus
EF-G
in vitro. E. coli
EF-G, which is not ordinarily able to bind FusB-type proteins, was rendered competent for binding to FusB following deletion of a 3-residue tract (
529
SNP
531
) from domain IV of the protein. This study has identified key regions of both FusB and EF-G that are important for the interaction between the proteins, findings which corroborate our previous
in silico
prediction for the architecture of the complex formed between the resistance protein and the drug target (G. Cox, G. S. Thompson, H. T. Jenkins, F. Peske, A. Savelsbergh, M. V. Rodnina, W. Wintermeyer, S. W. Homans, T. A. Edwards, and A. J. O'Neill, Proc. Natl. Acad. Sci. U. S. A. 109:2102-2107, 2012).
In Vivo
Studies Suggest that Induction of VanS-Dependent Vancomycin Resistance Requires Binding of the Drug to
d
-Ala-
d
-Ala Termini in the Peptidoglycan Cell Wall
Authors: Kwun Min Jung , Novotna Gabriela , Hesketh Andrew R. , Hill Lionel , Hong Hee-Jeon
Published: July 2013

VanRS two-component regulatory systems are key elements required for the transcriptional activation of inducible vancomycin resistance genes in bacteria, but the precise nature of the ligand signal that activates these systems has remained undefined. Using the resistance system in
Streptomyces coelicolor
as a model, we have undertaken a series of
in vivo
studies which indicate that the VanS sensor kinase in VanB-type resistance systems is activated by vancomycin in complex with the
d
-alanyl-
d
-alanine (
d
-Ala-
d
-Ala) termini of cell wall peptidoglycan (PG) precursors. Complementation of an essential
d
-Ala-
d
-Ala ligase activity by constitutive expression of
vanA
encoding a bifunctional
d
-Ala-
d
-Ala and
d
-alanyl-
d
-lactate (
d
-Ala-
d
-Lac) ligase activity allowed construction of strains that synthesized variable amounts of PG precursors containing
d
-Ala-
d
-Ala. Assays quantifying the expression of genes under VanRS control showed that the response to vancomycin in these strains correlated with the abundance of
d
-Ala-
d
-Ala-containing PG precursors; strains producing a lower proportion of PG precursors terminating in
d
-Ala-
d
-Ala consistently exhibited a lower response to vancomycin. Pretreatment of wild-type cells with vancomycin or teicoplanin to saturate and mask the
d
-Ala-
d
-Ala binding sites in nascent PG also blocked the transcriptional response to subsequent vancomycin exposure, and desleucyl vancomycin, a vancomycin analogue incapable of interacting with
d
-Ala-
d
-Ala residues, failed to induce
van
gene expression. Activation of resistance by a vancomycin–
d
-Ala-
d
-Ala PG complex predicts a limit to the proportion of PG that can be derived from precursors terminating in
d
-Ala-
d
-Lac, a restriction also enforced by the bifunctional activity of the VanA ligase.