bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic risk factors for the development of allergic disease identified by genome‐wide association
Authors: Portelli M. A. , Hodge E. , Sayers I.
Published: April 2014

An increasing proportion of the worldwide population is affected by allergic diseases such as allergic rhinitis (AR), atopic dermatitis (AD) and allergic asthma and improved treatment options are needed particularly for severe, refractory disease. Allergic diseases are complex and development involves both environmental and genetic factors. Although the existence of a genetic component for allergy was first described almost 100 years ago, progress in gene identification has been hindered by lack of high throughput technologies to investigate genetic variation in large numbers of subjects. The development of Genome‐Wide Association Studies (GWAS), a hypothesis‐free method of interrogating large numbers of common variants spanning the entire genome in disease and non‐disease subjects has revolutionised our understanding of the genetics of allergic disease. Susceptibility genes for asthma, AR and AD have now been identified with confidence, suggesting there are common and distinct genetic loci associated with these diseases, providing novel insights into potential disease pathways and mechanisms. Genes involved in both adaptive and innate immune mechanisms have been identified, notably including multiple genes involved in epithelial function/secretion, suggesting that the airway epithelium may be particularly important in asthma. Interestingly, concordance/discordance between the genetic factors driving allergic traits such as IgE levels and disease states such as asthma have further supported the accumulating evidence for heterogeneity in these diseases. While GWAS have been useful and continue to identify novel genes for allergic diseases through increased sample sizes and phenotype refinement, future approaches will integrate analyses of rare variants, epigenetic mechanisms and eQTL approaches, leading to greater insight into the genetic basis of these diseases. Gene identification will improve our understanding of disease mechanisms and generate potential therapeutic opportunities.
A comparative analysis of symptom and medication scoring methods used in clinical trials of sublingual immunotherapy for seasonal allergic rhinitis
Authors: Calderon M. A. , Bernstein D. I. , Blaiss M. , Andersen J. S. , Nolte H.
Published: April 2014

Symptom and medication use are the key outcomes for assessing the efficacy of subcutaneous (SCIT) and sublingual allergen immunotherapy (SLIT). Our objective was to explore the similarities and differences between existing scoring mechanisms used in clinical trials of SLIT for seasonal allergens and characterize the impact that such differences may have on efficacy reporting. Randomized, double‐blind, placebo‐controlled clinical trials investigating the efficacy of SLIT for seasonal allergic rhinitis (2009–2013) were selected for review. Simulated and published data were used to demonstrate differences in scoring methods. Symptom and medication scoring methods across trials, although all designed to achieve the same objective, included important differences. The maximum daily symptom score (DSS) can vary widely depending on the number of symptoms assessed, and terminology of symptoms is not consistent. Similarly, daily medication scoring (DMS) methods differ greatly among studies and are dependent on medications allowed and weighting of scores assigned to each medication. When published DSS and DMS scores were used to calculate simulated daily combined scores (DCSs) based on various published methods, changes from placebo ranged from 19% to 29% when assuming all variables other than the DSS and DMS methods were equal. Variations in trial design, analysis, and seasonal characteristics also have effects on symptom and medication scoring outcomes. We identified multiple differences in trial scoring methods and design that make comparison among trials difficult. Symptom, medication, or combined scores cannot be indirectly compared among trials without taking the methods of scoring and other trial differences into account.
Defining and managing risk in asthma
Authors: Blakey J. D. , Zaidi S. , Shaw D. E.
Published: April 2014

Asthma attacks are a major global source of morbidity and cost. The incidence and impact of asthma attacks have not improved despite widespread adoption of effective universal treatment guidelines. Consequently, there is increasing interest in managing asthma based on specific assessments of both current symptoms and future risk. In this review, we consider ‘risk’ in asthma, and how it might be assessed from the patient's history and objective measurements. We also discuss the potential for encouraging shared decision‐making and improving medical consensus through explicit communication of risk and highlight the potential opportunities and challenges in risk assessment to improve asthma management through individualised treatment strategies.
ATP4A autoimmunity and Helicobacter pylori infection in children with type 1 diabetes
Authors: Chobot A , Wenzlau J , Bak-Drabik K , Kwiecien J , Polanska J , Rewers M
Published: April 2014

Persistent presence of ATP4A autoantibodies (ATP4AA) directed towards parietal cells is typical for atrophic body gastritis (ABG), an autoimmune disease associated with type 1 diabetes. We assessed whether Helicobacter pylori (Hp) infection might be associated with positivity for ATP4AA in children with type 1 diabetes. Sera were collected from 70 (38♀) type 1 diabetes children [aged 13·2 ± 4·5 years, age at diagnosis 8·8 ± 4·3 years, diabetes duration 4·5 ± 3·8 years, mean HbA1c 7·8 ± 1·6% (62 ± 17·5 mmol/mol)] seen at the regional diabetes clinic in Katowice, Poland. Patients were tested concurrently for Hp infection by means of a 13C urea breath test. ATP4AA were measured using a novel radioimmunoprecipitation assay developed at the Barbara Davies Center for Childhood Diabetes, University of Colorado. ATP4AA were present in 21 [30%, 95% confidence interval (CI) = 19–41%] and Hp infection was detected in 23 (33%, 95% CI = 22–44%) children. There was no statistically significant association between ATP4AA presence and Hp status. ATP4AA presence was not associated with current age, age at type 1 diabetes diagnosis, diabetes duration or current HbA1c. ATP4AA were more prevalent in females [42% (26–58%)] than males [16% (3–28%)], P = 0·016. ATP4A are found in nearly one-third of children with type 1 diabetes and more common among females. In this cross-sectional analysis, Hp infection was not associated with autoimmunity against parietal cells.
Critical size defects for bone regeneration experiments in rabbit calvariae: systematic review and quality evaluation using ARRIVE guidelines
Authors: Delgado‐Ruiz Rafael Arcesio , Calvo‐Guirado José Luis , Romanos Georgios E.
Published: April 2014

Objectives

To perform a systematic review of studies that report the healing of critical size defects (CSDs) in rabbit calvaria and to determine the quality of the studies according to ARRIVE guidelines.

Materials and methods

An Internet search was made in duplicate between December 2011 and August 2013 using MEDLINE, PubMed and Google Scholar (without restrictions on date of publication) for rabbit studies reporting the healing of CSD in the calvaria. Animal Research Reporting in Vivo Experiment (ARRIVE) guidelines (a list of 20 aspects to score and to ensure comparison between different experimental studies in animals) were used to evaluate the quality of the selected works.

Results

Twenty‐five manuscripts were evaluated. Case–control studies predominated (92.59%). Animal age was not stated in 70.37% of the studies; weight was not reported in 29.62%; most animals weighed 3.5 kg (26.31%). A CSD dimension of 15 mm was common (51.61%), generally located centrally (51.85%), followed by bilateral locations (48.14%). Circular (66.66%), rectangular (14.81%), square (14.81%) and ovoid (1.48%) geometries were used. Histomorphometric data showed incomplete healing in all CSDs and higher percentages of healing in smaller defects (<10 mm). The longer the healing time allowed, the more bone healing took place, for both smaller and larger defects (>15 mm). Minimum quality grades were assigned to ARRIVE items study design (6), experimental animals (8), housing and husbandry (9), sample size (10), allocation (11), statistics (13), results‐baseline data (14), numbers analyzed (15), adverse events (17) and funding (20).

Conclusions

Data on CSDs in rabbit calvariae lack homogeneity. Smaller defects can be considered critical depending on the time of sacrifice. When new diagnostic technologies are used in addition to histomorphometry, these should be applied with caution to facilitate future comparison with other research. The ARRIVE guidelines should be followed in any animal research protocol to improve the homogeneity, comparison and reproducibility between studies.
Does the addition of targeted biological agents to first‐line chemotherapy for advanced colorectal cancer increase complete response? A systematic review and meta‐analysis
Authors: Qi W.‐X. , Shen Z. , Tang L.‐N. , Yao Y.
Published: April 2014

Aim

The study assessed whether the addition of monoclonal antibodies (MoAbs) to first‐line chemotherapy for advanced colorectal cancer (CRC) increases the complete response (CR) compared with controls.

Method

PubMed was reviewed for randomized clinical trials (RCTs) with approved MoAbs (bevacizumab, cetuximab and panitumumab) vs non‐MoAbs as first‐line therapy for patients with advanced CRC. The incidence and ratio of CR events were calculated in patients assigned to MoAbs compared with controls.

Results

A total of 3790 patients from nine RCTs were included for analysis. The overall incidence of CR in patients treated with MoAbs was 2.4% (95% CI: 1.7–3.3%) compared with 1.3% (95% CI: 0.8–2.2%) in controls. Comparison of the different types of MoAbs showed that the incidence of CR was higher for bevacizumab (3.1%, 95% CI: 2.1–4.3%) than for cetuximab (0.8%, 95% CI: 0.4–1.8%). The addition of MoAbs to chemotherapy significantly increased the OR of obtaining a CR compared with controls (OR = 1.96; 95% CI: 1.12–3.46; P = 0.02). No significant differences in the OR were observed in any of the subgroups.

Conclusion

The CR is a rare event in advanced CRC; however, the addition of MoAbs to first‐line chemotherapy significantly increases the curative rate of metastatic disease compared with controls.
No increase in colorectal cancer in patients under 50 years of age: a Victorian experience from the last decade
Authors: Sia C. S. , Paul E. , Wale R. J. , Lynch A. C. , Heriot A. G. , Warrier S. K.
Published: April 2014

Aim

The study aimed to assess whether there has been an increase in the incidence of colorectal cancer (CRC) among young patients in Victoria and whether such cancers are more advanced at presentation.

Method

The Victorian Cancer registry database was searched for patients, 18–50 years of age, diagnosed with CRC [young colorectal cancer (YCRC)] between 2000 and 2010. Average annual percentage changes and incidence rate ratios (IRRs) were calculated to characterize trends in CRC rates over time and to make comparisons with patients over 50 years of age with CRC [late colorectal cancer (LCRC)].

Results

Of 37432 CRCs registered during the study period, 2635 (7%) were in YCRC patients (annual increase in incidence = 1.7%; 95% CI: 0.5–2.9), compared with 34797 (93%) in LCRC patients (annual increase in incidence = 1.3%; 95% CI: 0.9–1.6). A small, nonsignificant increase in the incidence of YCRC over time was observed [IRR = 1.004 (95% CI: 0.992–1.016) for YCRC vs 0.989 (95% CI: 0.986–0.992) for LCRC]. Rectal cancer was more common in YCRC patients than in LCRC patients (42% vs 34%, respectively; P < 0.0001). The cancer would have been seen on flexible sigmoidoscopy in 63% of YCRC patients compared with 53.6% of LCRC patients (P < 0.0001). YCRC patients were more likely to have node‐positive disease (49.3% YCRC patients vs 40% LCRC patients; P < 0.0001), especially those with colonic cancer (52.7% YCRC patients vs 41.2% LCRC patients; P < 0.0001).

Conclusion

There has been an increase in incident cases of YCRC. A small, nonsignificant increase in the incidence of YCRC over time was observed. Young patients are more likely to have rectal cancer and to be node positive.
Intestinal obstruction in von Recklinghausen's disease
Authors: Trilling B. , Faucheron J.‐L.
Published: April 2014

Aim

Gastrointestinal manifestations occur in up to 25% of patients with neurofibromatosis type 1. This review reports all published cases of acute intestinal obstruction due to neurofibromatosis type 1 and identifies mechanisms of obstruction, the nature of the tumour and the outcome.

Method

A systematic review of the literature on acute intestinal obstruction due to neurofibromatosis type 1 was performed by searching the major electronic databases. All relevant references were reviewed for possible inclusion. All the references of the relevant articles were screened for any further articles that were missed in the initial search.

Results

We identified 25 articles from 1972 to 2013 reporting 25 patients with von Recklinghausen's disease who underwent laparotomy for acute intestinal obstruction. Three further patients were operated on in our institution. The mean age of the patients was 44.2 years and the male/female ratio 15/13. The mechanisms of obstruction were intrinsic obstruction (16), extrinsic obstruction (8) and intussusception (4). Histology was reported to show neurofibroma (19), gastrointestinal stromal tumour (5) and adenocarcinoma (4). Among patients whose outcome was mentioned (17), 10 were asymptomatic after a mean follow‐up of 1.5 years.

Conclusion

Acute bowel obstruction is a rare manifestation of neurofibromatosis type 1. Surgery is often necessary to treat the complication and to determine the exact nature of the tumour and the prognosis.
Engaging Community Health Centers (CHCs) in Research Partnerships: The Role of Prior Research Experience on Perceived Needs and Challenges
Authors: Beeson Tishra , Jester Michelle , Proser Michelle , Shin Peter
Published: April 2014

Despite community health centers’ substantial role in local communities and in the broader safety‐net healthcare system, very limited research has been conducted on community health center research experience, infrastructure, or needs from a national perspective. A national survey of 386 community health centers was conducted in 2011 and 2012 to assess research engagement among community health centers and their perceived needs, barriers, challenges, and facilitators with respect to their involvement in public health and health services research. This paper analyzes the differences between health centers that currently conduct or participate in research and health centers that have no prior research experience to determine whether prior research experience is indicative of different perceived challenges and research needs in community health center settings.
Children's learning of number words in an indigenous farming‐foraging group
Authors: Piantadosi Steven T. , Jara‐Ettinger Julian , Gibson Edward
Published: April 2014

We show that children in the Tsimane', a farming‐foraging group in the Bolivian rain‐forest, learn number words along a similar developmental trajectory to children from industrialized countries. Tsimane' children successively acquire the first three or four number words before fully learning how counting works. However, their learning is substantially delayed relative to children from the United States, Russia, and Japan. The presence of a similar developmental trajectory likely indicates that the incremental stages of numerical knowledge – but not their timing — reflect a fundamental property of number concept acquisition which is relatively independent of language, culture, age, and early education.
The influence of visual and tactile perception on hand control in children with Duchenne muscular dystrophy
Authors: Troise Denise , Yoneyama Simone , Resende Maria Bernadette , Reed Umbertina , Xavier Gilberto Fernando , Hasue Renata
Published: April 2014

Aim

To investigate tactile perception and manual dexterity, with or without visual feedback, in males with Duchenne muscular dystrophy (DMD).

Method

Forty males with DMD (mean age 9y 8mo, SD 2y 3mo; range 5–14y), recruited from the teaching hospital of the School of Medicine of the University of São Paulo, with disease severity graded as ‘1’ to ‘6’ on the Vignos Scale and ‘1’ on Brooke's Scale, and 49 healthy males (mean age 8y 2mo; range 5–11y; SD 1y 11mo), recruited from a local education center, participated in the study. We assessed tactile perception using two‐point discrimination and stereognosis tests, and manual dexterity using the Pick‐Up test with the eyes either open or closed. Analysis of variance was used to compare groups; a p value of less than 0.05 was considered statistically significant.

Results

Males with DMD exhibited no impairment in tactile perception, as measured by the two‐point discrimination test and the number of objects correctly named in the stereognosis test. Manipulation during stereognosis was statistically slower with both hands (p<0.001), and manual dexterity was much worse in males with DMD when there was no visual feedback (p<0.001).

Interpretation

Males with DMD exhibited disturbances in manipulation during stereognosis and dexterity tests. Hand control was highly dependent on visual information rather than on tactile perception. Motor dysfunction in males with DMD, therefore, might be related to altered neural control.
Mastery motivation as a predictor of occupational performance following upper limb intervention for school‐aged children with congenital hemiplegia
Authors: Miller Laura , Ziviani Jenny , Ware Robert S , Boyd Roslyn N
Published: April 2014

Aim

To determine the extent to which children's mastery motivation predicts occupational performance outcomes following upper limb intervention (ULI).

Method

In this cohort study, participants received 45 hours of ULI, either in an intensive group‐based or distributed individualized model. The Dimensions of Mastery Questionnaire (DMQ) measured mastery motivation at baseline. Occupational performance outcomes were assessed at baseline and 13 weeks’ post‐intervention using the Canadian Occupational Performance Measure (COPM). Multivariable models determined the contribution of mastery motivation to COPM outcome irrespective of group membership.

Results

Forty‐two children with congenital hemiplegia (29 males, 13 females; mean age 7y 8mo [SD 2y 2mo]; range 5y 1mo–12y 8mo; Manual Ability Classification System [MACS] I=20 and II=22; predominant motor type unilateral spastic n=41) participated in the study. Significant gains were seen in COPM performance and satisfaction scores (p<0.001) post‐intervention with no between group differences. Children who had greater persistence with object‐oriented tasks (p=0.02) and better manual ability (p=0.03) achieved higher COPM performance scores at 13 weeks. Children's persistence on object‐oriented tasks was the strongest predictor of COPM satisfaction (p=0.01).

Interpretation

Children's persistence with object‐oriented tasks as well as manual abilities needs to be considered when undertaking ULI. Predetermining children's motivational predispositions can assist clinicians to tailor therapy sessions individually based on children's strengths, contributing to effective engagement in ULI.
Diabetes‐specific emotional distress in people with Type 2 diabetes: a comparison between primary and secondary care
Authors: Stoop C. H. , Nefs G. , Pop V. J. , Wijnands‐van Gent C. J. M. , Tack C. J. , Geelhoed‐Duijvestijn P. H. L. M. , Diamant M. , Snoek F. J. , Pouwer F.
Published: April 2014

Aims

To compare levels of diabetes distress in people with Type 2 diabetes treated in primary and secondary care and to examine demographic and clinical correlates that may explain potential differences in levels of distress between care settings.

Methods

People with Type 2 diabetes from 24 primary care practices (n = 774) and three secondary care clinics (n = 526) completed the Problem Areas In Diabetes questionnaire. Data on HbA1c levels and diabetes complications were derived from medical charts. Hierarchical ordinal regression analysis was used to investigate which correlates could explain the potential differences in level of diabetes distress between care settings.

Results

Diabetes distress levels and the prevalence of elevated diabetes distress were considerably lower in the participants treated in primary care (mean (sd) total diabetes distress score 8 (11); 4% of participants with a Problem Areas In Diabetes score ≥ 40) than in secondary care (mean (sd) total diabetes distress score 23 (21); 19% of participants with a Problem Areas In Diabetes score ≥ 40, P < 0.001). In addition to care setting, the following variables were also independently related to diabetes distress: younger age, ethnic minority status, using insulin, having a higher HbA1c level, having a higher BMI and the presence of neuropathy. Other diabetes complications were not independently associated with diabetes distress.

Conclusions

In primary care, lower levels of diabetes distress were reported than in secondary care. The difference in diabetes distress between care settings can be largely, but not fully, explained by specific demographic and clinical characteristics. These results need to be interpreted with caution as they are based on two separate studies, but do call into question the need to screen for diabetes distress in people with Type 2 diabetes in primary care.
The psychosocial impact associated with diabetes‐related amputation
Authors: McDonald S. , Sharpe L. , Blaszczynski A.
Published: April 2014

Aims

Research has suggested that the additional impact of a diabetes‐related amputation is associated with poorer physical functioning, poorer psychosocial outcome and greater body image disturbance. However, no study to date has compared patients with diabetes with and without amputation and adequately controlled for additional medical morbidity often found among individuals with an amputation. The aim of this study was to statistically control for any group differences on medical and demographic variables to examine the isolated psychosocial impact of diabetes‐related amputation.

Methods

Individuals with diabetes with an amputation (n = 50) were compared to a control sample (individuals with diabetes without an amputation; n = 240). All participants completed a demographic and medical questionnaire, as well as measures of psychological distress, quality of life and body image.

Results

The results indicated that, in univariate analyses, depression, physical quality of life and body image disturbance were all poorer in the amputee group. These differences remained for body image disturbance (P = 0.005), but were no longer significant for depression or physical quality of life in multivariate analyses controlling for important demographic and medical variables.

Conclusions

The present study found that the impact of diabetes‐related amputation was significant for body image disturbance. However, it appears that other psychosocial outcomes are better accounted for by medical co‐morbidities common in this group rather than the amputation itself. This research certainly highlights that clinicians must assess for and address all potential medical contributors to psychosocial outcomes, rather than assuming that people will experience poorer outcomes following amputation.
Effectiveness of a group diabetes education programme in under‐served communities in South Africa: a pragmatic cluster randomized controlled trial
Authors: Mash R. J. , Rhode H. , Zwarenstein M. , Rollnick S. , Lombard C. , Steyn K. , Levitt N.
Published: April 2014

Aim

To evaluate the effectiveness of group education, led by health promoters using a guiding style, for people with Type 2 diabetes in public sector community health centres in Cape Town.

Methods

This was a pragmatic clustered randomized controlled trial with 17 randomly selected intervention and 17 control sites. A total of 860 patients with Type 2 diabetes, regardless of therapy used, were recruited from the control sites and 710 were recruited from the intervention sites. The control sites offered usual care, while the intervention sites offered a total of four monthly sessions of group diabetes education led by a health promoter. Participants were measured at baseline and 12 months later. Primary outcomes were diabetes self‐care activities, 5% weight loss and a 1% reduction in HbA1c levels. Secondary outcomes were self‐efficacy, locus of control, mean blood pressure, mean weight loss, mean waist circumference, mean HbA1c and mean total cholesterol levels and quality of life.

Results

A total of 422 (59.4%) participants in the intervention group did not attend any education sessions. No significant improvement was found in any of the primary or secondary outcomes, apart from a significant reduction in mean systolic (‐4.65 mmHg, 95% CI 9.18 to ‐0.12; P = 0.04) and diastolic blood pressure (‐3.30 mmHg, 95% CI ‐5.35 to ‐1.26; P = 0.002). Process evaluation suggested that there were problems with finding suitable space for group education in these under‐resourced settings, with patient attendance and with full adoption of a guiding style by the health promoters.

Conclusion

The reported effectiveness of group diabetes education offered by more highly trained professionals, in well‐resourced settings, was not replicated in the present study, although the reduction in participants' mean blood pressure is likely to be of clinical significance.
Oesophageal function assessed by high‐resolution manometry in patients with diabetes and inadequate glycaemic control
Authors: Roman S. , Marjoux S. , Thivolet C. , Mion F.
Published: April 2014

Aims

To describe oesophageal function in people with diabetes and poor glycaemic control using oesophageal high‐resolution manometry and to compare the result between control subjects and patients with gastro‐oesophageal reflux disease.

Methods

The results of oesophageal high‐resolution manometry and a gastric emptying test were reviewed in 20 patients with diabetes. The high‐resolution manometry protocol consisted of 5‐ml swallows of water and multiple swallows of water. Oesophageal motility disorders were classified according to the Chicago classification system. The occurence of multiphasic contractions and intragastric and intrabolus pressures were measured. High‐resolution manometry results were compared between 10 control subjects and 20 patients with gastro‐oesophageal reflux disease. Data were expressed as medians and compared using Mann–Whitney and chi‐squared tests.

Results

Oesophageal motility disorders were similarly distributed between the groups. Multiphasic contractions occurred more frequently in patients with diabetes than in those with gastro‐oesophageal reflux disease (60 vs 20% per patient; P<0.01) and were not observed in control subjects. Gastric emptying was delayed in six patients with diabetes and did not correlate with symptoms or oesophageal motility disorders. Intrabolus pressure was higher in patients with diabetes and gastroparesis than in those without (17 vs 10 mmHg; P=0.02) and correlated with intragastric pressure (r=0.46, P<0.01). During multiple swallows of water, oesophageal contractile activity was incompletely inhibited in 83% of patients with diabetes and gastroparesis vs 9% without (P<0.01). Oesophageal function and gastric emptying were not influenced by fasting glycaemia.

Conclusions

Patients with gastroparesis might present with impaired inhibition of contractile activity during multiple swallows of water. Increased intrabolus pressure is suggestive of delayed oesophageal clearance as a consequence of gastroparesis.
Nomads no more: early juvenile coho salmon migrants contribute to the adult return
Authors: Bennett Todd R. , Roni Phil , Denton Keith , McHenry Michael , Moses Raymond
Published: April 2014

The downstream movement of coho salmon fry and parr in the fall, as distinct from the spring migration of smolts, has been well documented across the range of the species. In many cases, these fish overwinter in freshwater, but they sometimes enter marine waters. It has long been assumed that these latter fish did not survive to return as adults and were ‘surplus’ to the stream's carrying capacity. From 2004 to 2010, we passive integrated transponder tagged 25,981 juvenile coho salmon in three streams in Washington State to determine their movement, survival and the contribution of various juvenile life histories to the adult escapement. We detected 86 returning adults, of which 32 originated from fall/winter migrants. Half of these fall/winter migrants spent ~1 year in the marine environment, while the other half spent ~2 years. In addition, the median return date for fall/winter migrants was 16 days later than spring migrants. Our results indicated that traditional methods of spring‐only smolt enumeration may underestimate juvenile survival and total smolt production, and also overestimate spring smolt‐to‐adult return (SAR). These are important considerations for coho salmon life cycle models that assume juvenile coho salmon have a fixed life history or use traditional parr‐to‐smolt and SAR rates.
Lineage‐dependent skewing of loss of heterozygosity (LOH) of KRAS gene in a case of juvenile myelomonocytic leukemia
Authors: Tokuda Kiriko , Eguchi‐Ishimae Minenori , Iwabuki Hidehiko , Kawakami Sanae , Tauchi Hisamichi , Ishii Eiichi , Eguchi Mariko
Published: April 2014

Juvenile myelomonocytic leukemia (JMML) is a clonal disease arising from abnormal hematopoietic stem cells, although the involvement of lymphoid lineage differs among reported cases. Here, we present a case of JMML with a KRAS G13D mutation. The mutation was detected in various hematopoietic lineages, including T and B lymphocytes and also in lineage− CD34+CD38− hematopoietic stem cells, showing a different percentage of affected cells in each lineage. Single cell‐based analysis of hematopoietic cells revealed the loss of wild‐type KRAS in a significant proportion of G13D‐harboring cells. The percentage of loss of heterozygosity (LOH)/non‐LOH cells showed lineage‐dependent skewing in hematopoietic cells. The loss of the wild‐type KRAS allele may be a common secondary genetic change in KRAS‐related JMML and may affect the differentiation behavior of early JMML progenitors.
Innovative approach for improved rFVIII concentrate
Authors: Morfini Massimo
Published: April 2014

The development of a new recombinant factor VIII was designed and implemented to answer a number of unmet needs of patients affected by hemophilia A. Turoctocog alfa is bioengineered in a specific Chinese hamster ovary clone to present translational and posttranslational characteristics (sulphation, glycosylation) biosimilar to natural circulating forms of FVIII, with the aim to devoid any minimal change which may impact immunogenicity and antigenicity of recombinant protein. Both producer cell line and media are maintained free of any animal or human plasma derivative. Downstream processes of purification are performed by five steps (immunoaffinity chromatography, ion‐exchange chromatography, virus inactivation by means of solvent‐detergent treatment and nanofiltration, and to end with gel filtration), to provide the best possible margin of safety from known and unknown infectious agents. Large clinical trials seem to confirm the expectations placed in Turoctocog alfa in terms of high quality and safety of recombinant FVIII toward the goal of overcoming actual and future challenges of hemophilia therapy.
Anaplastic lymphoma kinase‐positive anaplastic large cell lymphoma: current and future perspectives in adult and paediatric disease
Authors: Eyre Toby A. , Khan Dalia , Hall Georgina W. , Collins Graham P.
Published: April 2014

Anaplastic large cell lymphoma (ALCL) is a rare T‐cell lymphoma seen in both adults and children. ALCL is associated with a characteristic chromosomal translocation, t(2;5)(p23;35) which fuses the anaplastic lymphoma kinase (ALK) gene on chromosome 2 with the nucleophosmin (NPM) gene on chromosome 5, resulting in a NPM‐ALK fusion protein, ALK over‐expression and constitutive tyrosine kinase activity. This aggressive lymphoma is more prevalent in males and can present with extranodal involvement (lung, skin and marrow infiltration) and haemophagocytic lymphohistocytosis. The long‐term overall survival is approximately 70–90% in children and over 70% in adults. Staging systems and prognostic risk factors are different in both childhood and adult ALCL. Treatment in adults is typically anthracycline‐based, with autologous stem cell transplantation (ASCT) salvaging patients in relapsed disease. There is evidence for ALL‐like therapy or intensive, pulsed anthracycline‐based induction in children. ASCT, allogeneic SCT and vinblastine maintenance are all considered reasonable options in relapsed childhood disease. The anti‐CD30 immunoconjugate Brentuximab Vedotin and the specific ALK inhibitor Crizotinib are changing the treatment paradigm in ALCL (ALK‐positive or negative) and ALK‐positive ALCL respectively. Both agents have shown encouraging responses in relapsed ALCL. It remains to be seen how these novel agents are used, but it is very possible that they may improve overall responses and survival in both children and adults. This review highlights the presentation, histopathological features, prognostic factors, and evidence‐based treatment approaches in the first line and relapsed setting in ALK‐positive ALCL. The review concludes by discussing the novel approaches using Brentuximab and Crizotinib which are being tested in clinical trials.
Role of paraventricular nucleus‐projecting norepinephrine/epinephrine neurons in acute and chronic stress
Authors: Flak Jonathan N. , Myers Brent , Solomon Matia B. , McKlveen Jessica M. , Krause Eric G. , Herman James P.
Published: April 2014

Chronic variable stress (CVS) exposure modifies the paraventricular nucleus of the hypothalamus (PVN) in a manner consistent with enhanced central drive of the hypothalamo‐pituitary‐adrenocortical (HPA) axis. As previous reports suggest that post‐stress enhancement of norepinephrine (NE) action contributes to chronic stress regulation at the level of the PVN, we hypothesised that PVN‐projecting NE neurons were necessary for the stress facilitatory effects of CVS. Following intra‐PVN injection of saporin toxin conjugated to a dopamine beta‐hydroxylase (DBH) antibody (DSAP), in rats PVN DBH immunoreactivity was almost completely eliminated, but immunoreactive afferents to other key regions involved in stress integration were spared (e.g. DBH fiber densities were unaffected in the central nucleus of the amygdala). Reductions in DBH‐positive fiber density were associated with reduced numbers of DBH‐immunoreactive neurons in the nucleus of the solitary tract and locus coeruleus. Following 2 weeks of CVS, DSAP injection did not alter stress‐induced adrenal hypertrophy or attenuation of body weight gain, indicating that PVN‐projecting NE [and epinephrine (E)] neurons are not essential for these physiological effects of chronic stress. In response to acute restraint stress, PVN‐targeted DSAP injection attenuated peak adrenocorticotrophic hormone (ACTH) and corticosterone in controls, but only attenuated peak ACTH in CVS animals, suggesting that enhanced adrenal sensitivity compensated for reduced excitatory drive of the PVN. Our data suggest that PVN‐projecting NE/E neurons contribute to the generation of acute stress responses, and are required for HPA axis drive (ACTH release) during chronic stress. However, loss of NE/E drive at the PVN appears to be buffered by compensation at the level of the adrenal.
Cellular prion protein is present in dopaminergic neurons and modulates the dopaminergic system
Authors: Rial Daniel , Pamplona Fabrício A. , Moreira Eduardo L. G. , Moreira Karin M. , Hipolide Débora , Rodrigues Diana I. , Dombrowski Patrícia A. , Da Cunha Claudio , Agostinho Paula , Takahashi Reinaldo N. , Walz Roger , Cunha Rodrigo A. , Prediger Rui D.
Published: April 2014

Cellular prion protein (PrPC) is widely expressed in the brain. Although the precise role of PrPC remains uncertain, it has been proposed to be a pivotal modulator of neuroplasticity events by regulating the glutamatergic and serotonergic systems. Here we report the existence of neurochemical and functional interactions between PrPC and the dopaminergic system. PrPC was found to co‐localize with dopaminergic neurons and in dopaminergic synapses in the striatum. Furthermore, the genetic deletion of PrPC down‐regulated dopamine D1 receptors and DARPP‐32 density in the striatum and decreased dopamine levels in the prefrontal cortex of mice. This indicates that PrPC affects the homeostasis of the dopaminergic system by interfering differently in different brain areas with dopamine synthesis, content, receptor density and signaling pathways. This interaction between PrPC and the dopaminergic system prompts the hypotheses that the dopaminergic system may be implicated in some pathological features of prion‐related diseases and, conversely, that PrPC may play a role in dopamine‐associated brain disorders.
Region‐ and domain‐dependent action of nomifensine
Authors: Shu Zhan , Taylor I. Mitch , Walters Seth H. , Michael Adrian C.
Published: April 2014

The dopamine (DA) terminal fields in the rat dorsal striatum (DS) and nucleus accumbens core (NAcc) are organized as patchworks of domains that exhibit distinct kinetics of DA release and clearance. The present study used fast‐scan cyclic voltammetry recordings of electrically evoked DA overflow to test the hypothesis that nomifensine might exhibit domain‐dependent actions within the NAcc, as we previously found to be the case within the DS. Within the NAcc, nomifensine preferentially enhanced evoked DA overflow in the slow domains compared with the fast domains. To seek a kinetic explanation for nomifensine's selective actions, we quantified the apparent KM of DA clearance by numerically evaluating the derivative of the descending phase of the DA signal after the end of the stimulus. For comparison, we likewise quantified the apparent KM in the domains of the DS. As expected, because it is a competitive inhibitor, nomifensine significantly increased the apparent KM in both the fast and slow domains of both the NAcc and DS. However, our analysis also led to the novel finding that nomifensine preferentially increases the apparent KM in the NAcc compared with the DS; the apparent KM increased by ~500% in the NAcc and by ~200% in the DS.
The potential impact of a single amino‐acid substitution on the efficacy of equine influenza vaccines
Authors: Yamanaka T. , Cullinane A. , Gildea S. , Bannai H. , Nemoto M. , Tsujimura K. , Kondo T. , Matsumura T.
Published: April 2014

Reasons for performing study

The protection induced by an equine influenza (EI) vaccine strain depends on its antigenic relatedness to the challenge virus. Although the World Organisation for Animal Health (OIE) recommend that both Florida sublineage clade 1 (Fc1) and clade 2 (Fc2) viruses should be included in EI vaccines, Japanese EI vaccines have not, thus far, been updated to include a Fc2 virus.

Objectives

To evaluate the efficacy of antibodies raised against Japanese EI vaccine strains in the neutralisation of recent Fc2 viruses.

Study design

Antigenic analysis.

Methods

Virus neutralisation tests were performed using antisera from experimentally infected horses and from horses that had received a primary course of the currently available vaccines.

Results

Antiserum raised against the Japanese EI vaccine strain, A/equine/La Plata/1993, exhibited poor cross‐neutralising activity against the Fc2 viruses isolated recently in Ireland and the UK, which have the substitution of alanine to valine at position 144 in antigenic site A of the haemagglutinin gene. In contrast, the antiserum exhibited good cross‐neutralising activity against the Fc2 viruses without the substitution. This finding was supported in experiments with antisera collected from vaccinated horses.

Conclusions

This suggests that the efficacy of the Japanese EI vaccine for some of the recent Fc2 viruses is suboptimal and that vaccines should be updated in accordance with the OIE recommendations.
A synthesis of methane emissions from 71 northern, temperate, and subtropical wetlands
Authors: Turetsky Merritt R. , Kotowska Agnieszka , Bubier Jill , Dise Nancy B. , Crill Patrick , Hornibrook Ed R. C. , Minkkinen Kari , Moore Tim R. , Myers‐Smith Isla H. , Nykänen Hannu , Olefeldt David , Rinne Janne , Saarnio Sanna , Shurpali Narasinha , Tuittila Eeva‐Stiina , Waddington J. Michael , White Jeffrey R. , Wickland Kimberly P. , Wilmking Martin
Published: April 2014

Wetlands are the largest natural source of atmospheric methane. Here, we assess controls on methane flux using a database of approximately 19 000 instantaneous measurements from 71 wetland sites located across subtropical, temperate, and northern high latitude regions. Our analyses confirm general controls on wetland methane emissions from soil temperature, water table, and vegetation, but also show that these relationships are modified depending on wetland type (bog, fen, or swamp), region (subarctic to temperate), and disturbance. Fen methane flux was more sensitive to vegetation and less sensitive to temperature than bog or swamp fluxes. The optimal water table for methane flux was consistently below the peat surface in bogs, close to the peat surface in poor fens, and above the peat surface in rich fens. However, the largest flux in bogs occurred when dry 30‐day averaged antecedent conditions were followed by wet conditions, while in fens and swamps, the largest flux occurred when both 30‐day averaged antecedent and current conditions were wet. Drained wetlands exhibited distinct characteristics, e.g. the absence of large flux following wet and warm conditions, suggesting that the same functional relationships between methane flux and environmental conditions cannot be used across pristine and disturbed wetlands. Together, our results suggest that water table and temperature are dominant controls on methane flux in pristine bogs and swamps, while other processes, such as vascular transport in pristine fens, have the potential to partially override the effect of these controls in other wetland types. Because wetland types vary in methane emissions and have distinct controls, these ecosystems need to be considered separately to yield reliable estimates of global wetland methane release.
Survival and other clinical outcomes of maintenance hemodialysis patients in Taiwan: A 5‐year multicenter follow‐up study
Authors: Chen Huan‐Sheng , Cheng Chun‐Ting , Hou Chun‐Cheng , Liou Hung‐Hsiang , Lim Paik‐Seong
Published: April 2014

The increasing aging and diabetes mellitus (DM) patients in dialysis population make the quality maintenance of dialysis an imperative issue. Recently, an increasing number of dialysis centers were run by private dialysis providers, many of which apply quality assurance programs and performance management systems to dialysis care. We studied patients in dialysis facilities in Taiwan run by a private chain to see clinical outcomes of centers operating under these systemic strategies. Hemodialysis patients from January 1, 2008 to December 31, 2012 in 25 dialysis facilities in Taiwan, which received the management and consultation from a dialysis service provider, NephroCare (NC), were included. Data pivotal to quality of dialysis were analyzed. During a 5‐year interval, 5161 hemodialysis patients were included. For volume control, the proportion of patients with weight gain ≥4.5% decreases from 41.7% to 30.2%. Mean Kt/V is 1.74 ± 0.28. Mean albumin level is 3.92 ± 0.38 g/dL. Patients with phosphate <5.5 mg/dL is up to 71.8%. The mean hemoglobin level is 10.70 ± 1.40 g/dL. More than 80% of patients have adequate iron status. Further, 73% of patients use native arteriovenous fistula. Hospitalization‐free survival rate was 56% at the fifth year. Patient survival rate at the fifth year was 66.4%. Overall clinical performances were maintained very stable in NC facilities from this temporal data analysis. The hospitalization and survival rate also compare favorably with those reported internationally. These results warrant further studies to justify the application of this kind of quality assurance programs and performance management systems in dialysis care.
Physical examination of arteriovenous fistula: The influence of professional experience in the detection of complications
Authors: Sousa Clemente Neves , Teles Paulo , Dias Vanessa Filipa Ferreira , Apóstolo João Luís Alves , Figueiredo Maria Henriqueta Jesus Silva , Martins Maria Manuela
Published: April 2014

Vascular access is one of the leading causes of mobilization of financial resources in health systems for people with chronic kidney disease on hemodialysis. Physical examination of the arteriovenous fistula (AVF) has demonstrated its effectiveness in identifying complications. We decided to evaluate the influence of nurses' professional experience in the detection of complications of the AVF (venous stenosis and steal syndrome). The study took place in eight hemodialysis centers between May and September of 2011 in the north of Portugal. Sample was constituted by registered nurses. The nurses involved in the experiment were divided in two groups: those who had more than 5 years of experience and those who had less than 5 years of experience. Ninety‐two nurses participated in the study: 34 nurses had less than 5 years of professional experience and 58 had more than 5 years of professional experience. In the practices considered by nurses in the detection of venous stenosis, there were no differences observed between the groups (P > 0.05). In steal syndrome, there were no differences observed between the groups in the practices of the nurses in the detection of this complication of the AVF (P > 0.05). We concluded that professional experience does not influence the detection of venous stenosis and steal syndrome.
Gonadoblastoma: an immunohistochemical study and comparison to Sertoli cell nodule with intratubular germ cell neoplasia, with pathogenetic implications
Authors: Kao Chia‐Sui , Ulbright Thomas M , Idrees Muhammad T
Published: April 2014

Aims

To investigate the immunohistochemical properties of the sex cord cells of gonadoblastoma and Sertoli cell nodule with intratubular germ cell neoplasia unclassified (IGCNU) as a means of objective distinction and to provide insight into the pathogenesis.

Methods and results

Immunohistochemical stains for SOX9, FoxL2 and SF‐1 were performed on 10 gonadoblastomas (all phenotypical females) and 14 Sertoli cell nodules with IGCNU in normal phenotypical males with coexisting germ cell tumours. The sex cord cells of gonadoblastomas showed strong, diffuse FoxL2 and SF‐1 positivity and focal weak to moderate SOX9 reactivity, whereas those of Sertoli cell nodules with IGCNU were uniformly, strongly positive for SOX9 and SF‐1, while negative for FoxL2.

Conclusions

Coexpression of SOX9 and FoxL2 in the sex cord cells of gonadoblastomas provides evidence that these morphologically ambiguous sex cord cells are incompletely differentiated. The strong, diffuse SOX9 and SF‐1 positivity and absence of FoxL2 reactivity in the Sertoli cell nodules with IGNCU support full Sertoli cell differentiation of the sex cord cells and distinguish them from gonadoblastomas. Deficient SOX9 expression in gonadoblastoma supports a current model of pathogenesis where immature germ cells, in the absence of well‐formed Sertoli cells, retain a fetal phenotype and susceptibility to malignant transformation.