bluuebunny/crossref_metadata_2025 huggingface dataset:
Age at puberty and risk of testicular cancer: a meta‐analysis
Authors: Maule M. , Malavassi J. L. , Richiardi L.
Published: June 2012

Testicular cancer is one of the most rapidly increasing tumour types but its aetiology is still largely unexplained. Cryptorchidism and familial testicular cancer, established risk factors, explain less than 10% of all cases. Among investigated post‐natal factors, early puberty was suggested as a potential risk factor but the topic has been poorly investigated. We undertook a meta‐analysis of the effect of age at puberty on testicular cancer risk, attempting at enhancing the homogeneity in the definition of the exposure among studies to obtain valid pooled estimates. Search strategies were conducted in PubMed on December 2011. All markers of puberty onset (age at voice change, age when started shaving and reported age at onset) were considered. We re‐categorized age at puberty from all studies into a common three‐level variable: younger than peers, same age as peers, older than peers. A total of 391 references were retrieved, of which 12 met the inclusion criteria. Later puberty appeared to be protective. In particular late vs. same age at start shaving gave an OR of 0.84 (95% CI: 0.75–0.95, five studies); late vs. same age at voice change gave an OR of 0.87 (95% CI: 0.75–1.01, five studies); and later age than peers at reported onset of puberty gave an OR of 0.81 (95% CI: 0.73–0.89, eight studies). Early puberty showed no effect on testicular cancer risk. This meta‐analysis has found consistent evidence of a decreased risk of testicular cancer in association with later puberty, suggesting that post‐natal factors may contribute to testicular cancer risk.
Are nurses prepared to respond to a bioterrorist attack: a narrative synthesis
Authors: Smith Claire , Hewison Alistair
Published: June 2012

Aim.  To report a review and narrative synthesis conducted to analyse and evaluate nurses’ preparedness to respond to a bioterrorist event.

Background.  The anthrax attack on the USA in 2001 resulted in the development of global response strategies for future bioterrorist events. However, despite these actions, it remains unclear whether nurses are prepared to respond to such events.

Data sources.  A search for relevant research articles was conducted using the MEDLINE, CINAHL, BNI, and EMBASE databases to locate articles published in the period 1996–March 2010.

Design.  Narrative Synthesis

Review methods.  A narrative synthesis of qualitative and quantitative studies was undertaken and the articles reviewed using Greenhalgh’s critical appraisal criteria. The review was conducted with inclusion and exclusion criteria applied to ensure the studies examined focussed on the hospital nurse’s role in responding to a bioterrorist event.

Results.  Seven original research studies were included in the review. Four themes were identified as affecting nurses’ preparedness for a bioterrorist attack. These were perceptions of bioterrorism, the role of formal knowledge, the role of institutional plans and policies, and personal factors. The overarching theme centred on nurses’ willingness to respond to a bioterrorist event. It was clear that, although nurses were willing to respond to a bioterrorist attack, they felt unprepared to do so.

Conclusions.  Existing nurse education in areas such as infection control can incorporate bioterrorism training to improve preparedness, yet nurses must also prepare themselves personally for a bioterrorist attack.
Novel insights about the mechanism of visceral hypersensitivity in maternally separated rats
Authors: Bian Z. X.
Published: June 2012

Visceral hypersensitivity (VHS) is one of the most important characteristics of functional gastrointestinal disorders, including irritable bowel syndrome (IBS). Stress, whether physical or psychological, is known to be a crucial factor for inducing and maintaining visceral sensitivity in humans and rodents, but how stress induces VHS is not fully understood. In a recent study published in Neurogastroenterology and Motility, Wouters et al. demonstrate, for the first time, that maternal separation induces activation of periaqueductal gray (PAG), the hippocampus and the somatosensory cortex concomitantly with increased deactivation of the pre‐frontal cortex. The findings provide insight on the role of maternal separation in inducing regional cerebral blood flow changes and cerebral plasticity. These novel insights on the role of central activation in the modulation of stress‐induced VHS add to our growing understanding of the mechanisms that underlie VHS and suggest potential new drug development targets in stress‐related diseases, including IBS.
Patient advocacy and patient centredness in participant recruitment to randomized‐controlled trials: implications for informed consent
Authors: Tomlin Zelda , deSalis Isabel , Toerien Merran , Donovan Jenny L.
Published: June 2012

Context  With the routinization of evidence‐based medicine and of the randomized‐controlled trial (RCT), more patients are becoming ‘sites of evidence production’ yet, little is known about how they are recruited as participants; there is some evidence that ‘substantively valid consent’ is difficult to achieve.

Objective  To explore the views and experiences of nurses recruiting patients to randomized‐controlled trials and to examine the extent to which their recruitment practices were patient‐centred and patient empowering.

Design  Semi‐structured in‐depth interviews; audio recording of recruitment appointments; thematic interactional analysis (drawing on discourse and conversation analysis).

Setting and participants  Nurses recruiting patients to five publicly funded RCTs and patients consenting to the recording of their recruitment sessions.

Main outcome measures  The views of recruiting nurses about their recruitment role; the extent to which nurse–patient interactions were patient‐centred; the nature of the nurses’ interactional strategies and the nature and extent of patient participation in the discussion.

Results  The nurses had a keen sense of themselves as clinicians and patient advocates and their perceptions of the trial and its interventions were inextricably linked to those of the patients. However, many of their recruitment practices made it difficult for patients to play an active and informed part in the discussion about trial participation, raising questions over the quality of consent decisions.

Conclusion  Nurses working in patient recruitment to RCTs need to reconcile two different worlds with different demands and ethics. Evidence production, a central task in evidence‐based medicine, poses a challenge to patient‐centred practice and more research and relevant training are needed.
Evaluation of Genetic Traits for Improving Productivity and Adaptation of Groundnut to Climate Change in India
Authors: Singh P. , Boote K. J. , Kumar U. , Srinivas K. , Nigam S. N. , Jones J. W.
Published: June 2012

Anticipated climate change will alter the temperature and rainfall characteristics of crop growing seasons. This will require genetic improvement of crops for adapting to future climates for higher yields. The CROPGRO model for groundnut was used to evaluate genetic traits of Virginia and Spanish types of groundnut for various climate scenarios of India. The analysis revealed that productivity of groundnut can be increased in current and future climates by adjusting the duration of various life‐cycle phases, especially the seed‐filling to physiological maturity (SD‐PM). Increased maximum leaf photosynthesis rate (AMAX), increased partitioning to reproductive organs (XFRT) and increased individual seed‐fill duration (SFDUR) all contributed to the increase in pod yield in all climates. More determinate pod set (shorter PODUR) was beneficial only in the water deficit environments. The positive effect of increasing specific leaf area (SLA) and leaf size (SIZLF) on pod yield was greater in environments more favourable for plant growth. Increasing reproductive tolerance to high temperature by 2 °C increased pod yield of groundnut in warmer environments, especially where the crop often suffers from drought. Increased adaptive partitioning to roots (ATOP) increased drought resistance of groundnut on high water‐holding capacity soils. Combination of traits had additive effects and pod yield increased substantially. These results indicate that the CROPGRO model can be used to assess the potential of individual or combination of plant traits for guiding breeding of improved groundnut varieties for current and future climates.
Trabeculectomy: the limitations for registrar training
Authors: Sun Lisa L , Lee Graham A
Published: June 2012

Abstract

Background:  Trainee exposure to glaucoma surgery was analysed and outcomes compared with those of consultant cases.

Design:  Retrospective review was carried out at Princess Alexandra Hospital and Royal Brisbane and Women's Hospital, two major tertiary teaching hospitals in Brisbane, Queensland, Australia.

Participants:  Two hundred and forty‐eight consecutive public patients undergoing primary trabeculectomy surgery between 2003 and 2010.

Methods:  The rate of trabeculectomy performed by trainees, the success and complication rates were examined and compared with those of consultant ophthalmologists.

Main Outcome Measures:  Intraocular pressure was divided into two groups of ≤21 mmHg and ≤15 mmHg and visual field progression.

Results:  Two hundred and forty‐eight primary trabeculectomy cases were performed between 2003 and 2010. Trainees carried out 145 cases (59%), making the rate of trabeculectomy operations 1.1 per trainee per year (16–17 trainees) as compared with 1.6 per trainee per year from 1996 to 2002 at the same institutions. Complications rates in the first postoperative week were similar between consultants and trainees, the most common being wound leak and hyphaema. An intraocular pressure of ≤15 mmHg without the use of topical medications was achieved in 25 out of 50 (50%) glaucoma‐interest consultant, 24 out of 53 (45.3%) general consultant and 68 out of 145 (46.9%) trainee cases (P = 0.951). The rate of visual field progression was also statistically similar between trainees and consultants (19.5% and 21.3%), respectively.

Conclusion:  With increasing trainee numbers, the rate of trabeculectomy surgery is declining compared with previous years, with less trainee exposure to trabeculectomy surgery and inability to achieve surgical competency levels.
Hyaluronidase toxicity: a possible cause of postoperative periorbital inflammation
Authors: Zamora‐Alejo Katherine , Moore Sacha , Leatherbarrow Brian , Norris Jonathan H , Lake Damien B , Malhotra Raman , Selva Dinesh , Goggin Michael
Published: June 2012

Abstract

Background:  Periorbital inflammation following regional anaesthesia is commonly attributed to hyaluronidase allergy. This case series suggests an alternative explanation in some patients.

Design:  Retrospective case series.

Participants:  Seven patients presenting with postoperative non‐infectious periorbital inflammation following peribulbar or sub‐tenons anaesthesia, presenting at four different institutions, are described.

Methods:  Data on patient demographics, operative data, clinical presentation, treatment and allergy testing were collected among the four institutions.

Main Outcome Measures:  Response to treatment and allergy testing were noted among the patients included in this study.

Results:  Seven patients (five female) underwent uneventful phacoemulsification under a peribulbar or sub‐tenon's block, all including hyaluronidase with concentrations ranging 50–250 IU/mL. The onset of inflammatory symptoms and signs varied from 12 h to 3 days after the surgery. The most common form of presentation was lid swelling and chemosis. Patients were treated with oral corticosteroids, with good clinical response. Four patients underwent skin prick and intradermal testing to the local anaesthetic used, and to the suspect and a control hyaluronidase batch. The results were all negative, excluding allergy as the aetiology of this toxic periorbital syndrome, in at least these four patients.

Conclusion:  Hyaluronidase toxicity, potentially related to concentration of hyaluronidase, may be a cause of postoperative periorbital inflammation after cataract surgery, rather than hypersensitivity.
No histological evidence of orbicularis oculi muscle hypertrophy in congenital epiblepharon
Authors: Kakizaki Hirohiko , Takahashi Yasuhiro , Kang Hyera , Ikeda Hiroshi , Iwaki Masayoshi , Selva Dinesh , Leibovitch Igal
Published: June 2012

Abstract

Background:  To analyse the microscopic anatomy of the orbicularis oculi muscle in patients with congenital epiblepharon and to determine whether hypertrophy of the orbicularis oculi muscle, which is considered as a possible cause of this eyelid malposition, exists.

Methods:  Sixty‐seven eyelids with congenital epiblepharon of 41 Japanese patients, as well as 30 control eyelids of 24 Japanese patients with other eyelid pathologies (upper eyelid: fourteen blepharoptosis, one trichiasis and two retractions; lower eyelid: five involutional entropions, one trichiasis and seven retractions) were analysed. These controls contained no orbicularis pathology such as cicatrization or orbitopathy. The muscle specimens were obtained from the central part of the pretarsal orbicularis oculi muscle during surgery. The specimens were stained with haematoxylin & eosin. Only specimens with cross‐sectional areas that included large muscle fibres were selected. In each section, 10 muscle fibres were measured across their smallest diameter, thereby avoiding inaccurate measurements of muscle kinking occurring during the processing or by any obliquity of the plane of section. Measurements of the muscle fibre diameter were made with a digital measure.

Results:  There were no significant differences in the average diameter of the muscle fibres between the patients with congenital epiblepharon and the control group.

Conclusions:  There was no evidence of orbicularis oculi muscle hypertrophy in congenital epiblepharon.
Intravitreal ranibizumab as an adjunct for Ahmed valve surgery in open‐angle glaucoma: a pilot study
Authors: Desai Rajen U , Singh Kuldev , Lin Shan C
Published: June 2012

Abstract

Background:  To determine the safety and efficacy of intravitreal ranibizumab therapy before and after Ahmed tube insertion for open‐angle glaucoma as a means of optimizing postoperative intraocular pressure control.

Design:  Randomized, controlled trial.

Participants:  Open‐angle glaucoma patients scheduled for Ahmed tube insertion, randomized to ranibizumab or control groups.

Methods:  Ranibizumab (0.5 mg in 0.05 mL) was administered intravitreally at three time points: 9 days prior to surgery, 1 month post‐surgery and 2 months post‐surgery. Control patients underwent the same procedure without ranibizumab.

Main Outcome Measure:  Success at 6 months postoperatively was defined as intraocular pressure <18 mmHg with no adjunctive medications or intraocular pressure <15 mmHg with one adjunctive medication.

Results:  The study and control arms included six and five subjects, respectively, with four in each arm undergoing combined cataract surgery. In the ranibizumab arm, the preoperative and postoperative intraocular pressure/medication usage was 21.0 ± 6.7 mmHg on 3.2 ± 1.5 medications and 14.7 ± 1.9 mmHg on 0.5 ± 0.8 medications, respectively. In the control arm, preoperative and postoperative intraocular pressure/medication usage was 18.8 ± 3.8 mmHg on 2.8 ± 1.3 medications and 16.2 ± 3.6 mmHg with 1.8 ± 1.6 medications, respectively. Success was achieved in 83% of subjects in the ranibizumab group compared with 40% in the control group (two‐tailed Fisher's exact test, P = 0.24).

Conclusion:  The findings from this small pilot comparative study suggest that intravitreal ranibizumab use may be a safe and potentially effective adjunctive treatment modality in improving success after Ahmed tube placement.
Indigenous access to cataract surgery: an assessment of the barriers and solutions within the Australian health system
Authors: Boudville Andrea I , Anjou Mitchell D , Taylor Hugh R
Published: June 2012

Abstract

Background:  To identify barriers in the health systems that limit access to cataract surgery for Indigenous Australians and present strategies to overcome these barriers.

Design:  Interview and focus group‐based qualitative study.

Participants:  Five hundred thirty participants were consulted in semi‐structured interviews, focus group discussions and stakeholder workshops.

Methods:  Semi‐structured interviews with a cross‐section of health‐care professionals, eye care practitioners, primary health‐care workers, hospital staff and health department staff were conducted in 21 site locations. Focus group discussions with clients from seven Aboriginal Health Services in Victoria were conducted. Stakeholder workshops included Aboriginal Community Controlled Health sector, eye care sector, government departments and non‐government organizations. A total of 279 semi‐structured interviews were conducted in the Northern Territory, New South Wales, Queensland, South Australia, Victoria and Western Australia. Three stakeholder workshops were held.

Main Outcome Measures:  Barriers and solutions to increase access to cataract surgery for Indigenous Australians.

Results:  Analysis of the participant responses identified health system barriers at primary care, specialist care and hospital levels. These included: long waiting times, cost of surgery, complexity of the steps involved in treatment, lack of surgical capacity and low awareness of regional eye health needs. Strategies to overcome these barriers involve a system‐wide approach to increase provision and utilization of services.

Conclusion:  The need for surgery is real and services need to expand beyond current levels. The solutions for overcoming barriers to cataract surgery could be used as a model for other health interventions which rely on close interaction between primary and specialist care services.
Improving bioregional frameworks for conservation by including mammal distributions
Authors: BINO GILAD , RAMP DANIEL , KINGSFORD RICHARD T.
Published: June 2012

Large identifiable landscape units, such as ecoregions, are used to prioritize global and continental conservation efforts, particularly where biodiversity knowledge is inadequate. Setting biodiversity representation targets using coarse large‐scale biogeographic boundaries, can be inefficient and under‐representative. Even when using fine‐scale biodiversity data, representation deficiencies can occur through misalignment of target distributions with such prioritization frameworks. While this pattern has been recognized, quantitative approaches highlighting misalignments have been lacking, particularly for assemblages of mammal species. We tested the efficacy of Australia's bioregions as a spatial prioritization framework for representing mammal species, within protected areas, in New South Wales. We produced an approach based on mammal assemblages and assessed its performance in representing mammal distributions. Substantial spatial misalignment between New South Wales's bioregions and mammal assemblages was revealed, reflecting deficiencies in the representation of more than half of identified mammal assemblages. Using a systematic approach driven by fine‐scale mammalian data, we compared the efficacy of these two frameworks in securing mammalian representation within protected areas. Of the 61 species, 38 were better represented by the mammalian framework, with remaining species only marginally better represented when guided by bioregions. Overall, the rate at which mammal species were incorporated into the protected area network was higher (5.1% ± 0.6 sd) when guided by mammal assemblages. Guided by bioregions, systematic conservation planning of protected areas may be constrained in realizing its full potential in securing representation for all of Australia's biodiversity. Adapting the boundaries of prioritization frameworks by incorporating amassed information from a broad range of taxa should be of conservation significance.
RNA‐binding proteins involved in RNA localization and their implications in neuronal diseases
Authors: Tolino Marco , Köhrmann Martin , Kiebler Michael A.
Published: June 2012

Very often, developmental abnormalities or subtle disturbances of neuronal function may yield brain diseases even if they become obvious only late in life. It is therefore our intention to highlight fundamental mechanisms of neuronal cell biology with a special emphasis on dendritic mRNA localization including local protein synthesis at the activated synapse. Furthermore, we would like to point out possible links to neuronal or synaptic dysfunction. In particular, we will focus on a series of well‐known RNA‐binding proteins that are involved in these processes and outline how their dysfunction might yield neurodevelopmental, neurodegenerative or neuropsychiatric disorders. We are convinced that increasing our understanding of RNA biology in general and the mechanisms underlying mRNA transport and subsequent translation at the synapse will ultimately generate important novel RNA‐based tools in the near future that will allow us to hopefully treat some of these devastating diseases.
Urologists and oncologists: adapting to a new treatment paradigm in castration‐resistant prostate cancer (CRPC)
Authors: Sartor A. Oliver , Fitzpatrick John M.
Published: June 2012

What's known on the subject? and What does the study add?

The interplay between urologists and oncologists in the treatment of prostate cancer has been long standing. Recent paradigm shifts in treatment are reviewed with an emphasis on how these treatments may eventually alter the dynamic equilibrium between urology and oncology specialists.

The treatment landscape for men with castration‐resistant prostate cancer (CRPC) is undergoing significant changes; a redefinition of the respective roles of oncologists and urologists will probably occur. In addition, the advent of the multidisciplinary team or coordinated‐care approach, which has been gathering momentum over the last decade, will become not simply a preference but a clear necessity. In the present review, we explore the current wave of new treatments and describe the possibility of more complex approaches to combined therapy. New treatment options include abiraterone acetate, cabazitaxel, MDV3100 (in development), radium‐223 (in development) and sipuleucel‐T. We also present the traditional roles of the urologist and oncologist in caring for patients with CRPC and discuss how these may change. Compounding the new potential for treatment success, as well as the complexity of therapeutic strategies, is the emergence of novel biomarkers to evaluate treatment efficacy and to assist in patient prognosis. The prospects for successful treatment of patients with CRPC have developed considerably so that these patients may soon have a reasonable expectation of therapeutic efficacy and meaningful extension of their lives.
Expression of epithelial–mesenchymal transition markers in renal cell carcinoma: impact on prognostic outcomes in patients undergoing radical nephrectomy
Authors: Harada Ken‐ichi , Miyake Hideaki , Kusuda Yuji , Fujisawa Masato
Published: June 2012

What's known on the subject? and What does the study add?

There have been few studies evaluating the prognostic value of epithelial‐mesenchymal transition markers in renal cell carcinoma (RCC); therefore, the significance of these markers in the prognosis of patients with RCC, particularly that in those with localized disease, remains largely unknown.

Consideration of the expression levels of potential epithelial‐mesenchymal transition markers, particularly clusterin and Twist in addition to conventional prognostic parameters, would contribute to the prediction of disease recurrence after radical nephrectomy for localized renal cell carcinoma.

OBJECTIVE

To evaluate the expression of multiple molecular markers involved in the process of epithelial–mesenchymal transition (EMT) in renal cell carcinoma (RCC) with the aim of clarifying the prognostic significance of these markers in patients undergoing radical nephrectomy.

PATIENTS AND METHODS

The expression levels of 11 EMT markers, including E‐cadherin, N‐cadherin, β‐catenin, γ‐catenin, clusterin, Slug, Snail, Twist, vimentin, ZEB1 and ZEB2, in radical nephrectomy specimens from 122 patients with clinically localized RCC were measured by immunohistochemical staining.

RESULTS

In this series, disease recurrence occurred in 39 (32.0%) patients, with a 5‐year recurrence‐free survival rate of 64.4%.

Univariate analysis identified expression levels of E‐cadherin, clusterin, Twist and vimentin, in addition to C‐reactive protein (CRP) level, pathological stage and microvascular invasion, as significant predictors for disease recurrence.

Of these, expression levels of clusterin and Twist, CRP levels and microvascular invasion appeared to be independently related to disease recurrence on multivariate analysis.

There were significant differences in recurrence‐free survival according to positive numbers of these four independent factors: disease recurrence occurred in two of 26 patients negative for any risk factor (7.7%), 23 of 73 pateints positive for one or two risk factors (31.5%) and 14 of 23 patients positive for three or four risk factors (60.9%).

CONCLUSION

Consideration of the expression levels of potential EMT markers, particularly clusterin and Twist, in RCC specimens, in addition to conventional prognostic parameters, contributes to the accurate prediction of disease recurrence after radical nephrectomy for localized RCC.
Cumulative impacts of fisheries in the California Current
Authors: Kaplan Isaac C , Gray Iris A , Levin Phillip S.
Published: June 2012

Ecosystem‐based fisheries management calls for the consideration of the indirect and cumulative effects of fishing, in addition to estimating direct fishing mortality. Here, we quantify such effects of fishing fleets, and their interactions, using a spatially explicit Atlantis simulation model of the food web and fisheries in the California Current. Simulations testing the effects of single fleets suggested that bottom trawl, fixed gear, and hake (Merluccius productus) trawl primarily have direct impacts on their target and bycatch species. Few indirect effects from these three fleets extended through predator–prey links to other parts of the food web. In contrast, effects of the purse seine fleet extended beyond the three groups it harvested, strongly altering the abundance of predators, planktonic prey, and benthos. In terms of nine ecosystem attributes, our experiments involving single fleets identified six fleets that caused the bulk of negative impacts. Specific fleets impacted different aspects of the ecosystem, for instance with groundfish gears causing reductions in piscivore abundance, and hake trawl and purse seine increasing krill through reducing abundance of planktivores. In terms of interactions among fleets' effects, the vast majority of effects were simply additive – the combined effect of two fleets was simply the sum of the individual fleets' effects. The analyses offer one way to sharpen the focus of ecosystem‐based fisheries management in the California Current, emphasizing impacts and interactions of particular stressors.
Child Trafficking: ‘Worst Form’ of Child Labour, or Worst Approach to Young Migrants?
Authors: Huijsmans Roy , Baker Simon
Published: June 2012

This article presents a critique to the human trafficking discourse in relation to child migration, based on data obtained from the anti‐trafficking community in the Greater Mekong Sub‐region combined with an analysis of secondary material. It also presents a set of qualitative accounts of migration at a young age from Lao PDR and Thailand. On this basis a more theorized, grounded and nuanced perspective on child labour migration is developed. This situates child labour migration historically, embeds it within overarching processes of rural transformation and accounts for young migrants’ agency in the social process of migration, the latter shedding light on the social production of exploitation in relation to young migrants.
Immunomagnetic exclusion of E‐cadherin‐positive hepatoblasts in fetal mouse liver cell cultures impairs morphogenesis and gene expression of sinusoidal endothelial cells
Authors: Takabe Yurie , Yagi Shinomi , Koike Toru , Shiojiri Nobuyoshi
Published: June 2012

Previous studies have shown that various cell–cell interactions between hepatoblasts and nonparenchymal cells, including sinusoidal endothelial cells and stellate cells, are indispensable for the development of fetal murine hepatic architecture. The present study was undertaken to determine the effects of hepatoblasts on the sinusoidal structural formation using a culture system of fetal mouse livers. Primitive sinusoidal structures extensively developed in fetal livers, and were composed of LYVE‐1‐ and PECAM‐1‐positive endothelial cells, desmin‐positive stellate cells and F4/80‐positive macrophages. When fetal liver cells at 12.5 days of gestation were cultured in vitro, hepatoblasts spread on glass slides and gave rise to hepatocytes on day 5. Desmin‐positive stellate cells also spread on the glass slides. PECAM‐1‐positive endothelial cells became slender and developed into anastomosing capillary networks. When fetal liver cells were cultured without hepatoblasts, which were excluded by an immunomagnetic method using anti‐E‐cadherin antibodies, endothelial cells had impaired growth and capillary formation. These results demonstrated that capillary formation of endothelial cells was induced by the presence of hepatoblasts. VEGF and the conditioned medium containing humoral factors produced by hepatoblasts/hepatocytes did not induce capillary formation of endothelial cells in cultures of nonparenchymal cells, although they significantly increased the number of endothelial cells on the glass slides. The presence of hepatoblasts also significantly stimulated expression of CD32b mRNA, which is a sinusoidal endothelial marker. Hepatoblasts may work as a positive stimulator of sinusoid morphogenesis and maturation in liver development, in which a signal other than VEGF may play a decisive role, together with VEGF.
Neuro‐ophthalmological disorders in cerebral palsy: ophthalmological, oculomotor, and visual aspects
Authors: FAZZI ELISA , SIGNORINI SABRINA G , LA PIANA ROBERTA , BERTONE CHIARA , MISEFARI WALTER , GALLI JESSICA , BALOTTIN UMBERTO , BIANCHI PAOLO EMILIO
Published: June 2012

Aim  Cerebral visual impairment (CVI) is a disorder caused by damage to the retrogeniculate visual pathways. Cerebral palsy (CP) and CVI share a common origin: 60 to 70% of children with CP also have CVI. We set out to describe visual dysfunction in children with CP. A further aim was to establish whether different types of CP are associated with different patterns of visual involvement.

Methods  A total of 129 patients (54 females, 75 males; mean age 4y 6mo, SD 3y 5mo; range 3mo–15y) with CP (51 with diplegia, 61 with tetraplegia, and 17 with hemiplegia; 62 [48%] of participants were able to walk) and CVI enrolled at the Centre of Child Neuro‐ophthalmology (at the Department of Child Neurology and Psychiatry, IRCCS ‘C. Mondino Institute of Neurology’, University of Pavia) underwent an assessment protocol including neurological examination, developmental and/or cognitive assessment, neuro‐ophthalmological evaluation including ophthalmological assessment, evaluation of visual acuity, contrast sensitivity, optokinetic nystagmus, visual field and stereopsis, and neuroradiological investigations.

Results  Visual dysfunction in diplegia was characterized mainly by refractive errors (75% of patients), strabismus (90%), abnormal saccadic movements (86%), and reduced visual acuity (82%). The participants with hemiplegia showed strabismus (71%) and refractive errors (88%); oculomotor involvement was less frequent (59%). This group had the largest percentage of patients with altered visual field (64%). Children with tetraplegia showed a severe neuro‐ophthalmological profile, characterized by ocular abnormalities (98%), oculomotor dysfunction (100%), and reduced visual acuity (98%).

Interpretation  Neuro‐ophthalmological disorders are one of the main symptoms in CP. Each clinical type of CP is associated with a distinct neuro‐ophthalmological profile. Early and careful neuro‐ophthalmological assessment of children with CP is essential for an accurate diagnosis and for personalized rehabilitation.
Outcome of children with hyperventilation‐induced high‐amplitude rhythmic slow activity with altered awareness
Authors: BARKER ALEXANDER , NG JOANNE , RITTEY CHRISTOPHER D C , KANDLER ROSALIND H , MORDEKAR SANTOSH R
Published: June 2012

Hyperventilation‐induced high‐amplitude rhythmic slow activity with altered awareness (HIHARS) is increasingly being identified in children and is thought to be an age‐related non‐epileptic electrographic phenomenon. We retrospectively investigated the clinical outcome in 15 children (six males, nine females) with HIHARS (mean age 7y, SD 1y 11mo; range 4y 6mo–11y). The presenting feature in 11 cases was blank spells – two of these children also had generalized tonic–clonic seizures (GTCS) – and in one individual the main concern was deteriorating school performance. Three children had symptoms suggestive of focal motor seizures. Of the nine children presenting solely with blank spells, further follow‐up (mean duration 18mo, SD 21mo) revealed full resolution of symptoms in six, but three had persistent symptoms. In our study, the symptoms of children with HIHARS presenting with blank spells in isolation appeared to resolve spontaneously and did not evolve into convulsive seizures or other paroxysmal events considered to be clearly epileptic. Children (with HIHARS) who presented with clinical features suggestive of GTCS or focal motor seizures (with or without blank spells) and/or had epileptiform discharges on interictal electroencephalography were subsequently diagnosed with epilepsy.
Ontogeny of the Upper Cambrian (Furongian) Olenid trilobite Protopeltura aciculate (Angelin, 1854) from Skåne and Västergötland, Sweden
Authors: MÅNSSON KRISTINA , CLARKSON EUAN N. K.
Published: June 2012

Abstract:  The ontogeny of the trilobite Protopeltura aciculata (Angelin, 1854) is described on the basis of material from the upper Cambrian (Furongian) of Andrarum (Skåne) and Hjelmsäter (Västergötland), Sweden. P. aciculata is present in the Parabolina brevispina and Parabolina spinulosa zones. Protopeltura aciculata is represented by all stages of growth, from early protaspides to holaspides, although most of the specimens are disarticulated and precise degrees are unknown. The cranidia have therefore been allocated to five morphological groups. Cuticular sculpture of the cranidia changes throughout ontogeny. Large tubercles are present in earlier stages, disappear gradually in middle meraspid stages and are replaced with a very faint granulation. The transitory pygidium, relatively large and shield‐shaped with upwardly and backwardly directed marginal spines in early meraspides, later becomes very small, triangular‐shaped and lacking spines as a late meraspid and holaspid. The development of hypostomes and librigenae is also described. Protopeltura aciculata shows major intraspecific variations throughout development, especially regarding the pygidium where variation is much less constrained than in many other olenids. This high developmental plasticity may be a survival strategy for a trilobite living in a stressed environment. Protopeltura inhabited a dysoxic environment, possibly unusually prone to localised spreading of anoxic or toxic water. Some morphs may have been less vulnerable than others to such stresses, surviving by chance and thus enabling the species to continue.
Molecular requirements for inhibition of the chemokine receptor CCR8 – probe‐dependent allosteric interactions
Authors: Rummel PC , Arfelt KN , Baumann L , Jenkins TJ , Thiele S , Lüttichau HR , Johnsen A , Pease J , Ghosh S , Kolbeck R , Rosenkilde MM
Published: June 2012

BACKGROUND AND PURPOSE Here we present a novel series of CCR8 antagonists based on a naphthalene‐sulfonamide structure. This structure differs from the predominant pharmacophore for most small‐molecule CC‐chemokine receptor antagonists, which in fact activate CCR8, suggesting that CCR8 inhibition requires alternative structural probes.

EXPERIMENTAL APPROACH The compounds were tested as inverse agonists and as antagonists against CCL1‐induced activity in Gαi signalling and chemotaxis. Furthermore, they were assessed by heterologous competition binding against two radiolabelled receptor ligands: the endogenous agonist CCL1 and the virus‐encoded antagonist MC148.

KEY RESULTS All compounds were highly potent inverse agonists with EC50 values from 1.7 to 23 nM. Their potencies as antagonists were more widely spread (EC50 values from 5.9 to 1572 nM). Some compounds were balanced antagonists/inverse agonists whereas others were predominantly inverse agonists with >100‐fold lower potency as antagonists. A correspondingly broad range of affinities, which followed the antagonist potencies, was disclosed by competition with [125I]‐CCL1 (Ki 3.4–842 nM), whereas the affinities measured against [125I]‐MC148 were less widely spread (Ki 0.37–27 nM), and matched the inverse agonist potencies.

CONCLUSION AND IMPLICATIONS Despite highly potent and direct effects as inverse agonists, competition‐binding experiments against radiolabelled agonist and tests for antagonism revealed a probe‐dependent allosteric effect of these compounds. Thus, minor chemical changes affected the ability to modify chemokine binding and action, and divided the compounds into two groups: predominantly inverse agonists and balanced antagonists/inverse agonists. These studies have important implications for the design of new inverse agonists with or without antagonist properties.
Pseudotyped adeno‐associated viral vector tropism and transduction efficiencies in murine wound healing
Authors: Keswani Sundeep G. , Balaji Swathi , Le Louis , Leung Alice , Lim Foong‐Yen , Habli Mounira , Jones Helen N. , Wilson James M. , Crombleholme Timothy M.
Published: June 2012

Cell specific gene transfer and sustained transgene expression are goals of cutaneous gene therapy for tissue repair and regeneration. Adeno‐associated virus serotype 2 (AAV2/2) mediated gene transfer to the skin results in stable transgene expression in the muscle fascicles of the panniculus carnosus in mice, with minimal gene transfer to the dermal or epidermal elements. We hypothesized that pseudotyped AAV vectors may have a unique and characteristic tropism and transduction efficiency profile for specific cells in the cutaneous wounds. We compared transduction efficiencies of cells in the epidermis, cells in the dermis, and the fascicles of the panniculus carnosus by AAV2/2 and three pseudotyped AAV vectors, AAV2/5, AAV2/7, and AAV2/8 in a murine excisional wound model. AAV2/5 and AAV2/8 result in significantly enhanced transduction of cells both in the epidermis and the dermis compared to AAV2/2. AAV2/5 transduces both the basilar and supra‐basilar keratinocytes. In contrast, AAV2/8 transduces mainly supra‐basilar keratinocytes. Both AAV2/7 and AAV2/8 result in more efficient gene transfer to the muscular panniculus carnosus compared to AAV2/2. The capsid of the different pseudotyped AAV vectors produces distinct tropism and efficiency profiles in the murine wound healing model. Both AAV2/5 and AAV2/8 administration result in significantly enhanced gene transfer. To further characterize cell specific transduction and tropism profiles of the AAV pseudotyped vectors, we performed in vitro experiments using human and mouse primary dermal fibroblasts. Our data demonstrate that pseudotyping strategy confers a differential transduction of dermal fibroblasts, with higher transduction of both human and murine cells by AAV2/5 and AAV2/8 at early and later time points. At later time points, AAV2/2 demonstrates increased transduction. Interestingly, AAV2/8 appears to be more efficacious in transducing human cells as compared to AAV2/5. The pseudotype‐specific pattern of transduction and tropism observed both in vivo and in vitro suggests that choice of AAV vectors should be based on the desired target cell and the timing of transgene expression in wound healing for gene transfer therapy in dermal wounds.
Epsilon Aminocaproic Acid for the Prevention of Delayed Postoperative Bleeding in Retired Racing Greyhounds Undergoing Gonadectomy
Authors: Marín Liliana M. , Iazbik M Cristina , Zaldivar‐Lopez Sara , Guillaumin Julien , McLoughlin Mary A. , Couto C Guillermo
Published: June 2012

Objective

To evaluate the effects of epsilon aminocaproic acid (EACA) on the prevalence of postoperative bleeding in retired racing Greyhounds (RRG), and to assess its effects on selected thrombelastography (TEG) and fibrinolysis variables.

Study Design

Double‐blinded, prospective, randomized study.

Methods

100 RRG had elective ovariohysterectomy or orchiectomy and were administeredEACAor placebo for 3 days after surgery.TEGvariables were analyzed preoperatively and 24, 48, and 72 hours after surgery.

Results

Thirty percent (15/50) ofRRGin the placebo group had delayed postoperative bleeding starting 36–48 hours after surgery compared with 10% (5/50) in theEACAgroup (P= .012). On theTEGvariables, the slopes forRandKtime were significantly different between treatment groups (P<.05); theRandKtime decreased over time in the EACA group after surgery whereas they increased in the placebo group. The angle, maximal amplitude (MA), andGslopes were also significantly different between treatment groups (P= .001, .001, and .006, respectively). The angle,MA, andGincreased postoperatively over time in theEACAgroup and decreased in the placebo group. All these changes are supportive of hypercoagulability associated withEACAadministration.

Conclusion

Postoperative administration ofEACAsignificantly decreased the prevalence of postoperative bleeding inRRGundergoing surgery by increasing the clot strength.
Ectomesenchymal chondromyxoid tumor: histopathologic and immunohistochemical study of two cases without a chondroid component
Authors: Palma Guzmán José Mario , de Andrade Bruno Augusto Benevenuto , Rizo Victor Hugo Toral , Romañach Mário José , León Jorge Esquiche , de Almeida Oslei Paes
Published: June 2012

Ectomesenchymal chondromyxoid tumor (ECT) is a rare benign neoplasm usually affecting the anterior dorsum of the tongue. Histopathologically, it is formed by spindle, round and/or polygonal cells embedded in a chondromyxoid matrix. Immunohistochemical positivity for vimentin, S‐100 protein, glial fibrillary acid protein and neuron‐specific enolase are helpful to confirm the diagnosis. There are 42 cases of ECT of the tongue reported in the English language literature, three of them showing no chondroid matrix. We describe two additional cases of ECT lacking the chondroid component, exhibiting areas of reticulated myxoid and cellular pattern. Considering the microscopical features, ECT can be classified in classic and ‘chondroid‐free’ variants, the latter including the reticulated myxoid and cellular patterns. It is important to consider that the cellular ECT usually exhibits predominance of an infiltrative atypical cellular component that may mimic a malignant tumor.

Palma Guzmán JM, de Andrade BAB, Rizo VHT, Romañach MJ, León JE, de Almeida OP. Ectomesenchymal chondromyxoid tumor: histopathologic and immunohistochemical study of two cases without a chondroid component.
N‐acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin‐induced diabetic rats
Authors: Toker H. , Ozdemir H. , Balcı H. , Ozer H.
Published: June 2012

Toker H, Ozdemir H, Balcı H, Ozer H. N‐acetylcysteine decreases alveolar bone loss on experimental periodontitis in streptozotocin‐induced diabetic rats. J Periodont Res 2012; 47: 793–799. © 2012 John Wiley & Sons A/S

Background and Objective:  The purpose of this study was to evaluate the morphometric and histopathological changes associated with experimental periodontitis in diabetic rats in response to systemic administration of N‐acetylcysteine (NAC), a sulfhydryl‐containing thiol antioxidant.

Material and methods:  Sixty Wistar rats were divided into six experimental groups: nonligated (NL) group; ligature‐only (L) group; streptozotocin‐only (STZ) group; STZ and ligature (STZ + L) group; and systemic administration of NAC and ligature (70 and 100 mg/kg body weight per day, respectively) (NAC70 and NAC100 groups). Diabetes mellitus was induced by 60 mg/kg of streptozotocin. Silk ligatures were placed at the gingival margin of the lower first molars of the mandibular quadrant. The study duration was 30 d and the animals were killed at the end of this period. Changes in alveolar bone levels were clinically measured and tissues were histopathologically examined to assess the differences among the study groups.

Results:  At the end of the 30‐d study period, alveolar bone loss was significantly higher in the STZ + L group compared with the other groups (p < 0.05). Also, alveolar bone loss in all the NAC groups was significantly lower than in the STZ + L and L groups (p < 0.05). The osteoblastic activity in the NAC100 group was significantly higher than in the other groups (p < 0.05).

Conclusion:  Within the limits of this study, it can be suggested that NAC, when administered systemically, prevents alveolar bone loss in the diabetic rat model.
An online survey of knowledge of the weaning guidelines, advice from health visitors and other factors that influence weaning timing in UK mothers
Authors: Moore Amanda P. , Milligan Peter , Goff Louise M.
Published: June 2012

The UK weaning guidelines recommend the introduction of solid food at or around 6 months. The evidence suggests that knowledge of the guidelines is high, although only a small minority of parents wait until 6 months to wean. The aim of this study was to assess understanding of the UK weaning guidelines in a sample of UK parents and investigate the associations of this understanding with weaning timing, and in comparison to other influencing factors. This study conducted an online survey of UK parents. Eligible participants had weaned a child since the introduction of the current guidelines. Of 3607 participants, 86% accurately understood the guidelines. Eighty‐seven per cent of health visitors were reported to have advised weaning at or around 6 months. Knowledge of the guidelines was associated with later weaning (independently of demographic factors) (P < 0.001) but did not ensure compliance: 80% of mothers who weaned before 24 weeks and 65% who weaned before 17 weeks were aware of the guidelines. Younger mothers (P < 0.001), those receiving benefits (P < 0.001), those educated only to 16 (P < 0.001) and minority ethnic groups (P < 0.001) had lower levels of awareness. Poor understanding of the guidelines was the most reliable predictor of early weaning (P = 0.021) together with young maternal age (P = 0.014). Following the baby‐led weaning approach was the most reliable predictor of those weaning at 26 weeks, together with the Internet being the most influential source of advice. Understanding of the current weaning guidelines is high and is a key independent predictor of weaning age in this population.