bluuebunny/crossref_metadata_2025 huggingface dataset:
Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema attacks: a pilot study
Authors: Reshef A. , Moldovan D. , Obtulowicz K. , Leibovich I. , Mihaly E. , Visscher S. , Relan A.
Published: November 2012

Background

Hereditary angioedema (HAE) is a disease characterized by recurrent tissue swelling affecting various body locations. Recent literature shows that patients with frequent attacks may benefit from long‐term prophylaxis. This study evaluated the safety and prophylactic effect of weekly administrations of recombinant C1INH (rhC1INH).

Methods

Patients with a history of HAE attacks occurring ≥every 2 weeks received a once weekly administration of 50 U/kg rhC1INH. Hereditary angioedema attack history was collected at screening. Breakthrough attacks during the study were recorded at each visit. Following a 2‐week run‐in period, HAE patients received 8 weekly rhC1INH administrations and were followed‐up for an additional 6 weeks. Efficacy was evaluated by comparing the HAE attack incidence during the treatment period to the historical attacks over the previous 2 years. Safety evaluation was based on clinical laboratory and adverse events (AEs) reports.

Results

The 25 participants reported a mean of 0.9 attacks/week over the past 2 years. The mean breakthrough attack rate during the treatment period was 0.4 attacks/week (95% CI 0.28–0.56). A total of 30 treatment‐emergent‐AEs were reported in 13 patients, all mild to moderate. One patient died from a laryngeal attack 25 days after last study drug administration. The only possible drug related AEs reported were dry mouth, dizziness and anxiety in one patient and hypotension in another. There were no allergic AEs and no neutralizing antibodies observed.

Conclusions

Weekly administrations of 50 U/kg rhC1INH appeared to reduce the frequency of HAE attacks and were generally safe and well tolerated.
Peripartum outcomes and anaesthetic management of parturients with moderate to complex congenital heart disease or pulmonary hypertension*
Authors: Maxwell B. G. , El‐Sayed Y. Y. , Riley E. T. , Carvalho B.
Published: November 2012

We performed a retrospective cohort analysis of pregnancies among women with moderate to complex congenital heart disease or pulmonary hypertension over a 12‐year period, resulting in a cohort of 107 cases in 65 women. Neuraxial analgesia or anaesthesia was provided in 84%, 89% and 95% of spontaneous vaginal, operative vaginal and caesarean deliveries, respectively. The caesarean delivery rate was 43% compared to our institution average of 27% over the same period (p = 0.02), and 38% had operative vaginal deliveries compared to a 10.5% institution rate (p < 0.01). Invasive monitoring was used in 28% of all deliveries. There were one maternal and two neonatal deaths. This study provides detailed anaesthetic and peripartum management of women with congenital heart disease, a patient population in whom evidence‐based practice and data are largely lacking. We observed a predominance of neuraxial anaesthetic techniques, increased caesarean and operative delivery rates, and favourable maternal and neonatal outcomes. Multicentre studies and registries to compare anaesthetic and obstetric management strategies further and delineate risk factors for adverse outcomes are required.
The association of pre‐operative physical fitness and physical activity with outcome after scheduled major abdominal surgery
Authors: Dronkers J. J. , Chorus A. M. J. , van Meeteren N. L. U. , Hopman‐Rock M.
Published: November 2012

We studied whether reported physical activity and measurements of fitness (hand, leg and inspiration) were associated with postoperative in‐hospital mortality, length of stay and discharge destination in 169 patients after major oncological abdominal surgery. In multivariate analysis, adequate activity level (OR 5.5, 95% CI 1.4–21.9) and inspiratory muscle endurance (OR 5.2, 95% CI 1.4–19.1) were independently associated with short‐term mortality, whereas conventional factors, such as age and heart disease, were not. Adequate activity level (OR 6.7, 95% CI 1.4–3.0) was also independently associated with discharge destination. The factors that were independently associated with a shorter length of hospital stay were as follows: absence of chronic obstructive pulmonary disease (HR 0.6, 95% CI 0.3–1.1); adequate activity level (HR 0.6, 95% CI 0.4–0.8); and inspiratory muscle strength (HR 0.6, 95% CI 0.5–0.9). For all postoperative outcomes physical activity and fitness significantly improved the predictive value compared with known risk factors, such as age and comorbidities. We conclude that pre‐operative questionnaires of physical activity and measurements of fitness contribute to the prediction of postoperative outcomes.
A review of enhanced recovery for thoracic anaesthesia and surgery
Authors: Jones N. L. , Edmonds L. , Ghosh S. , Klein A. A.
Published: November 2012

During the past decade, there has been a dramatic increase in the number of thoracic surgical procedures carried out in the UK. The current financial climate dictates that more efficient use of resources is necessary to meet escalating demands on healthcare. One potential means to achieve this is through the introduction of enhanced recovery protocols, designed to produce productivity savings by driving reduction in length of stay. These have been promoted by government bodies in a number of surgical specialties, including colorectal, gynaecological and orthopaedic surgery. This review focuses on aspects of peri‐operative care that might be incorporated into such a programme for thoracic anaesthesia, for which an enhanced recovery programme has not yet been introduced in the UK, and a review of the literature specific to this area of practice has not been published before. We performed a comprehensive search for published work relating to the peri‐operative management and optimisation of patients undergoing thoracic surgery, and divided these into appropriate areas of practice. We have reviewed the specific interventions that may be included in an enhanced recovery programme, including: pre‐optimisation; minimising fasting time; thrombo‐embolic prophylaxis; choice of anaesthetic and analgesic technique and surgical approach; postoperative rehabilitation; and chest drain management. Using the currently available evidence, the design and implementation of an enhanced recovery programme based on this review in selected patients as a package of care may reduce morbidity and length of hospital stay, thus maximising utilisation of available resources.
Arrhythmogenic risk of pulmonary artery catheterisation in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation
Authors: Bergmann L. , Großwendt T. , Kahlert P. , Konorza T. , Wendt D. , Thielmann M. , Heusch G. , Peters J. , Kottenberg E.
Published: November 2012

Many clinicians consider severe aortic stenosis to be a contraindication to pulmonary artery catheterisation, except during open heart surgery with cardiopulmonary bypass. This is due to the perceived high risk of arrhythmia, although the true incidence of ventricular tachycardia and fibrillation remains unclear. We conducted a retrospective study to estimate the incidence of severe arrhythmias during pulmonary artery catheterisation in 380 patients with severe aortic stenosis scheduled for transcatheter aortic valve implantation. Ventricular fibrillation was seen in only one patient (0.26%), and this was successfully terminated by external defibrillation. No episodes of ventricular tachycardia were recorded and there were also no arrhythmias during removal of the catheter. We have therefore concluded that pulmonary artery catheterisation in patients with severe aortic stenosis is not associated with a high incidence of ventricular fibrillation or tachycardia, allowing pulmonary artery pressure monitoring to be performed relatively safely in such patients.
Dedicated emergency theatres improve service delivery and surgeons' job satisfaction
Authors: Stupart Douglas A. , Watters David A. , Guest Glenn D. , Cuthbert Vanessa , Ryan Shannon
Published: November 2012

Background

There are well‐described benefits to separating emergency and elective surgery. Geelong Hospital lacked the resources to implement a separate acute surgical unit, but instituted daily dedicated emergency general surgery operating sessions, managed by an on‐site consultant. This study aims to assess the impact of this on service delivery and surgeons' job satisfaction.

Methods

From 1 February 2011, daily half‐day operating lists were allocated for general surgical emergencies. Patients treated on these lists were studied prospectively until 31 December 2011. Theatre waiting times and hospital stay were compared with the previous year. A quality‐of‐life questionnaire was administered to participating surgeons before the project commenced and after 6 months.

Results

A total of 966 patients underwent surgery during an emergency general surgery admission in the control period, and 984 underwent surgery during the study period. The median time from arrival in the emergency department (ED) to surgery was reduced from 19 (18–21) h in the control group to 18 (17–19) h in the study group (P = 0.033). The time from booking surgery to operation was reduced from 4.8 (4.3–5.4) h to 3.9 (3.5–4.3) h (P < 0.0001). For patients undergoing emergency laparotomy, the time from booking to surgery was reduced from 3.1 (2.2–4.1) to 2.4 (1.8–2.9) h, and hospital stay was reduced from 13 (11–15) to 10 (9–12) days (P = 0.0089). The surgeons' responses to the questionnaires showed improvement in job satisfaction (P < 0.0001).

Conclusion

This intervention has improved service delivery for emergency surgery patients, and improved the participating surgeons' job satisfaction.
Review article: a comparison of glucagon‐like peptides 1 and 2
Authors: Janssen P. , Rotondo A. , Mulé F. , Tack J.
Published: November 2012

Background

Recent advancements in understanding the roles and functions of glucagon‐like peptide 1 (GLP‐1) and 2 (GLP‐2) have provided a basis for targeting these peptides in therapeutic strategies.

Aim

To summarise the preclinical and clinical research supporting the discovery of new therapeutic molecules targeting GLP‐1 and GLP‐2.

Methods

This review is based on a comprehensive PubMed search, representing literature published during the past 30 years related to GLP‐1 and GLP‐2.

Results

Although produced and secreted together primarily from L cells of the intestine in response to ingestion of nutrients, GLP‐1 and GLP‐2 exhibit distinctive biological functions that are governed by the expression of their respective receptors, GLP‐1R and GLP‐2R. Through widespread expression in the pancreas, intestine, nervous tissue, et cetera, GLP‐1Rs facilitates an incretin effect along with effects on appetite and satiety. GLP‐1 analogues resistant to degradation by dipeptidyl peptidase‐IV and inhibitors of dipeptidyl peptidase‐IV have been developed to aid treatment of diabetes and obesity. The GLP‐2R is expressed almost exclusively in the stomach and bowel. The most apparent role for GLP‐2 is its promotion of growth and function of intestinal mucosa, which has been targeted for therapies that promote repair and adaptive growth. These are used as treatments for intestinal failure and related conditions.

Conclusions

Our growing understanding of the biology and function of GLP‐1, GLP‐2 and corresponding receptors has fostered further discovery of fundamental biological function as well as new categories of potent therapeutic medicines.
Insulin resistance predicts sustained virological response to treatment of chronic hepatitis C independently of the IL28b rs12979860 polymorphism
Authors: del Campo J. A. , Ampuero J. , Rojas L. , Conde M. , Rojas Á. , Maraver M. , Millán R. , García‐Valdecasas M. , García‐Lozano J. R. , González‐Escribano M. F. , Romero‐Gómez M.
Published: November 2012

Background

Insulin resistance has been strongly associated with the attainment of sustained viral response (SVR) in hepatitis C patients.

Aim

To determine, in a cohort of Spanish patients with chronic hepatitis C treated with peginterferon plus ribavirin (P+R), whether insulin resistance predicts SVR independently of interleukin‐28B rs12979860 polymorphism.

Methods

Insulin resistance was measured as [HOMA‐IR = Insulin (IU/mL)*glucose (mmol/L)/22.5]. Genotype, viral load and histological fibrosis using Scheuer score were also measured. Binary logistic regression analysis was used for statistical purposes.

Results

In a cohort of 240 patients [78% genotype 1, 24% showing advanced fibrosis, 71% high viral load (≥800 000 IU/mL), 31% IL28b genotype CC and 50% with HOMA >2] treated with P+R, 126 (53%) reached SVR. HOMA‐IR index (HOMA <2: 63% vs. HOMA >2: 42%; P = 0.001 and IL28b (genotype CC: 68% vs. genotype CT/TT: 45%; P = 0.002) were significantly associated with SVR. In multivariable logistic regression analysis in the overall cohort, variables independently associated were: viral genotype OR: 0.29 (95% CI: 0.11–0.78), P = 0.01; fibrosis OR: 1.62 (95% CI: 1.22–2.16), P = 0.001; HOMA‐IR OR: 1.22 (95% CI: 1.02–1.47), P = 0.03; and IL28B genotype OR: 2.43 (95% CI: 1.45–4.07), P = 0.001. The analyses also showed that degree of steatosis, HOMA‐IR >2, mild fibrosis and IL28B CC genotype were significantly related to SVR in patients infected with HCV genotypes 1&4, but not in those with genotypes 2&3. No differences were seen in glucose, insulin level or HOMA‐IR index segregated according to IL28B genotypes.

Conclusion

Our results suggest that insulin resistance, fibrosis stage and IL28B polymorphisms were independent variables associated with sustained viral response.
Short‐term efficacy of tacrolimus in steroid‐refractory ulcerative colitis – experience in 130 patients
Authors: Schmidt K. J. , Herrlinger K. R. , Emmrich J. , Barthel D. , Koc H. , Lehnert H. , Stange E. F. , Fellermann K. , Büning J.
Published: November 2012

Background

Steroid‐refractory ulcerative colitis (UC) remains a challenging condition warranting surgery upon failure of pharmacological treatment. Calcineurin inhibitors or infliximab are alternatives in this situation. Data on the efficacy and safety of tacrolimus in this setting are limited.

Aim

To study the short‐term efficacy and safety of tacrolimus in moderate‐to‐severe steroid‐refractory UC. The role of thiopurines in this situation and predictors of colectomy were evaluated.

Methods

In three centers, all charts from tacrolimus‐treated patients with steroid‐refractory UC were reviewed. Efficacy was assessed by colectomy‐free survival and clinical remission at 3 months.

Results

We identified 130 patients with pancolitis in 75 (59%), left‐sided disease in 35 (27%) and proctitis in 18 patients (14%) (disease localisation not obtainable in two patients). The median age was 40 (range: 18–81). Clinical activity according to the median Lichtiger score decreased from 13 (range: 4–17) at baseline to 3 (0–14) at week 12. Eighteen patients underwent colectomy within the first 3 months of treatment with tacrolimus (14%). Clinical remission was achieved in 94 patients (72%) in this period. Thiopurines given in parallel to tacrolimus tended to limit colectomy and significantly increased remission (P = 0.002) in the short‐term. No other predictors of colectomy or remission were identified. Side effects were noticed in 53% of patients and no severe events occurred.

Conclusion

This large survey confirms the efficacy and safety of tacrolimus in patients with steroid‐refractory ulcerative colitis.
The natural history of eosinophilic oesophagitis in the transition from childhood to adulthood
Authors: Menard‐Katcher P. , Marks K. L. , Liacouras C. A. , Spergel J. M. , Yang Y.‐X. , Falk G. W.
Published: November 2012

Background

Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition affecting both children and adults. Little is known about the natural history of EoE in the transition from childhood into adulthood.

Aim

To determine the prevalence of EoE symptoms and impact of EoE on quality of life among adults diagnosed with EoE during childhood.

Methods

This is a cross‐sectional study of EoE patients from the Children's Hospital of Philadelphia EoE registry. Patients ≥18 years diagnosed with EoE during childhood were administered validated dysphagia [Mayo Dysphagia Questionnaire (MDQ)‐30] and Quality of Life (PAGI‐QOL) questionnaires. Ongoing EoE treatments were ascertained.

Results

A total of 140 EoE patients ≥18 years were identified; 53 completed all questions. Only 6 (11%) subjects had positive (n = 2) or indeterminate (n = 4) dysphagia scores. However, of 47 patients with negative scores, 18 (37%) reported ongoing difficulty swallowing. The mean PAGI‐QOL score was 4.58/5. The dietary dimension score was 3.73/5. Current pharmacological EoE treatments were topical steroids (3/53) and interleukin‐5 antagonists (3/53). Additionally, 26/53 (49%) were on PPI therapy and 40/53 (76%) were following allergy directed diets.

Conclusions

The majority of young adults diagnosed with EoE during childhood continue to require pharmacological treatment and/or dietary modification for EoE. A substantial proportion of this population experiences ongoing swallowing difficulties that a standard dysphagia questionnaire fails to capture. Dietary quality of life, but not total quality of life, appears to be adversely affected. These data suggest that EoE diagnosed during childhood remains a significant medical issue during early adulthood, and that better EoE symptom measurement instruments are needed.
Human stem cell‐derived astrocytes and their application to studying Nrf2‐mediated neuroprotective pathways and therapeutics in neurodegeneration
Authors: Gupta Kunal , Chandran Siddharthan , Hardingham Giles E.
Published: November 2012

Glia, including astrocytes, are increasingly at the forefront of neurodegenerative research for their role in the modulation of neuronal function and survival. Improved understanding of underlying disease mechanisms, including the role of the cellular environment in neurodegeneration, is central to therapeutic development for these currently untreatable diseases. In these endeavours, experimental models that more closely reproduce the human condition have the potential to facilitate the transition between experimental studies in model organisms and patient trials. In this review we discuss the growing role of astrocytes in neurodegenerative diseases, and how astrocytes generated from human pluripotent stem cells represent a useful tool for analyzing astrocytic signalling and influence on neuronal function.
The Politics of Home Birth in the United States
Authors: Declercq Eugene
Published: November 2012

Home birth has emerged as a political issue in several states in the United States, and this essay examines two aspects of home births politics. First, legislative battles over home birth policy do not conform to our typical models of partisan (i.e., Democratic vs Republican) politics, and attempts at advocacy cannot rely on classical strategies of alignment with a dominant party in a state. Second, the debates over home birth have increasingly begun to parallel current partisan battles in their emotion and intensity with the related gridlock and reluctance to consider compromises that are often necessary to achieve policy goals. This essay calls for a greater willingness for all sides to approach home birth less as an ideological mission and more as a health policy challenge to support consumers interested in an integrated system of care. (BIRTH 39:4 December 2012)
Evidence‐Based Medicine and Perinatal Care: From Dawn to Dusk
Authors: Keirse Marc J. N. C.
Published: November 2012

Since the concept of “evidence‐based medicine” was first launched 20 years ago as a new method of teaching the practice of medicine, it has had an enormous impact on practice in many fields of health care. From the very start, professionals in pregnancy and perinatal care were at the forefront of attempts to collect good evidence systematically on the benefits and harms of health care interventions during pregnancy and in and around childbirth. Perinatal practice has largely benefitted from that endeavor. However, it has also suffered from the ill‐effects of the narrow view that evidence, to be good evidence, needs to be randomized evidence. Twenty years on, it may be time to reflect on what is meant by evidence and how to use it, not as a doctrine or dogma, but as a valuable tool and a tremendous asset to improve outcomes for mothers and babies. (BIRTH 39:4 December 2012)
Breastfeeding Triumphs
Authors: Lawrence Ruth A.
Published: November 2012

The Renaissance of breastfeeding is at hand. With the energy of an epidemic and the passion of a crusade, breastfeeding has become the norm for infant feeding. The World Health Organization (WHO) and the Centers for Disease Control and Prevention have affirmed breastfeeding's value to public health. Strong organizations such as the American Academy of Pediatrics, American College of Obstetricians and Gynecologists, American Association of Family Practice, and the Academy of Breastfeeding Medicine have confirmed the value of human milk. The discussion is over. Leading the charge is an eclectic group of health professionals and women, but the cause cannot rest. Efforts to change hospital behavior are key, but the support for mother‐baby couples at home for the weeks and months that follow has just begun. Duration is the challenge. Employment and employers comprise one arm of the campaign. The other arms of the effort are under construction. Now is a time to move ahead, not rest on past achievement. (BIRTH 39:4 December 2012)
Ethics and “Normal Birth”
Authors: Lyerly Anne Drapkin
Published: November 2012

The concept of “normal birth” has been promoted as ideal by several international organizations, although debate about its meaning is ongoing. In this article, I examine the concept of normalcy to explore its ethical implications and raise a trio of concerns. First, in its emphasis on nonuse of technology as a goal, the concept of normalcy may marginalize women for whom medical intervention is necessary or beneficial. Second, in its emphasis on birth as a socially meaningful event, the mantra of normalcy may unintentionally avert attention to meaning in medically complicated births. Third, the emphasis on birth as a normal and healthy event may be a contributor to the long‐standing tolerance for the dearth of evidence guiding the treatment of illness during pregnancy and the failure to responsibly and productively engage pregnant women in health research. Given these concerns, it is worth debating not just what “normal birth” means, but whether the term as an ideal earns its keep. (BIRTH 39:4 December 2012)
Dispositional emotion coping styles and physiological responses to expressive writing
Authors: Tamagawa Rie , Moss‐Morris Rona , Martin Alexandra , Robinson Elizabeth , Booth Roger J.
Published: November 2012

Objectives

The purpose of these two studies was to assess how repressors and defensive, high‐anxious individuals exhibit their psychological and health characteristics subjectively through self‐reports and objectively through physiological markers and ratings of emotional expression.

Design

Cross‐sectional descriptive design (study one) and randomized controlled design (study two).

Methods

In the first descriptive study, repressors, defensive, high‐anxious individuals and low‐anxious individuals were identified from a pool of 748 undergraduates. Participants were asked to complete questionnaires assessing psychological and health characteristics. In the second experimental study, the three groups were randomized into either emotional or non‐emotional writing conditions. Participants were asked to write three essays on either an emotional or a non‐emotional topic in a single day.

Results

In the first study, defensive, high‐anxious individuals reported significantly more distress, symptoms, sickness behaviours and difficulty expressing anger relative to repressors. In the second study, there was a significant difference in salivary cortisol concentrations between the two writing conditions regardless of the emotional coping grouping. Analysis of the writing showed no significant differences among repressors, defensive, high‐anxious and low‐anxious individuals in their cognitive and affective expression.

Conclusions

Whereas self‐reports of health outcomes and psychological traits clearly distinguish repressors and defensive, high‐anxious individuals, more objective indices of emotional expressiveness and physiology do not appear to do so. The results also indicate that expressive writing may be helpful to reduce physiological arousal towards emotionally charged memories.

Statement of contribution

What is already known on this subject? Emotion inhibition and Health: Emotional inhibition is associated with aversive health. Little previous work has differentiated emotional inhibition due to repression or suppression. Emotion expression and Health: Expressing emotions through expressive writing may be salutary. Little is known about the physiological basis to explain all the health‐relevant changes following expressive writing. A moderating role of dispositional emotional expressiveness in the context of expressive writing is inconclusive.

What does this study add? Unlike repression, suppression (defensive, high‐anxious) was associated with poor self‐reported health. There was a greater reduction of cortisol response while writing emotionally compared with writing non‐emotionally. Repressors and suppressive (defensive, high‐anxious) individuals were distinctive on self‐reported health, but were similar in objective endocrine responses to expressive writing.
A qualitative exploration of the identities of parents with a learning disability
Authors: Shewan Laura , McKenzie Karen , Quayle Ethel , Crawley Rowan
Published: November 2012

Accessible summary

The number of parents with a learning disability in the United Kingdom (UK) is growing.

Parents with a learning disability do have some difficulties.

Parents with a learning disability see that their learning disability is separate to being a mum or dad.

Becoming a parent is important to people with a learning disability.

There are an increasing number of parents with a learning disability in the UK. Existing research in the area suggests that this group of parents face a number of issues including social isolation and over‐representation in child protection systems. This study explored what parents understood about their learning disability and how they perceived this to impact on them in their parenting role. This exploratory study adopted a qualitative approach, involving semi‐structured interviews with eight parents (three mothers, five fathers). The study suggested that as a result of having a learning disability parents experience some difficulties, however, these tend to be related to specific tasks only. In their parenting role, three separate identities were conveyed: as a person with a learning disability; as a mother or father, and as an individual (outside of their identity with learning disability or parenthood). The findings presented here are drawn from a larger qualitative study.
Career counselling at school for placement in sheltered workshops?
Authors: Fasching Helga
Published: November 2012

Accessible summary

This study is about transition from school to work in Austria.

In Austria, students with intellectual disabilities leave school earlier than other students.

Many students with intellectual disabilities join sheltered workshops.

This means that students with intellectual disabilities in Austria do not have the same choices as other people.

This leads to disadvantages in the lives of the students with intellectual disabilities.

Learning helps people to take decisions independently.

The right to learn is very important, also for people with disabilities.

This article explores how career counselling at school contributes to supporting inclusive transition processes from school to regular vocational training and occupation for school‐leavers with an intellectual disability. In a first step, a quantitative parent survey analyses how the type of school influences the recommendations of career counselling at school. Subsequently, the quantitative results are subjected to a more profound analysis by means of a qualitative teacher survey. The results show that career counselling at school functions as a ‘gatekeeper’ during the transition process from school to working life. In this context, the recommendations of career counselling at school are closely linked to the type of school attended. The majority of special school students are recommended occupational therapy, while the majority of students with special educational needs in general schools are recommended qualifying measures/vocational training. These results suggest that the recommendation of occupational therapy by career counsellors at school is closely linked to a negative attitude of teachers towards the cognitive abilities of students with intellectual disabilities. Segregated structures in the system also add to negative attitudes.
Ca2+ sparks promote myogenic tone in retinal arterioles
Authors: Kur J , Bankhead P , Scholfield CN , Curtis TM , McGeown JG
Published: November 2012

Background and Purpose

Ca2+ imaging reveals subcellular Ca2+ sparks and global Ca2+ waves/oscillations in vascular smooth muscle. It is well established that Ca2+ sparks can relax arteries, but we have previously reported that sparks can summate to generate Ca2+ waves/oscillations in unpressurized retinal arterioles, leading to constriction. We have extended these studies to test the functional significance of Ca2+ sparks in the generation of myogenic tone in pressurized arterioles.

Experimental Approach

Isolated retinal arterioles (25–40 μm external diameter) were pressurized to 70 mmHg, leading to active constriction. Ca2+ signals were imaged from arteriolar smooth muscle in the same vessels using Fluo4 and confocal laser microscopy.

Key Results

Tone development was associated with an increased frequency of Ca2+ sparks and oscillations. Vasomotion was observed in 40% of arterioles and was associated with synchronization of Ca2+ oscillations, quantifiable as an increased cross‐correlation coefficient. Inhibition of Ca2+ sparks with ryanodine, tetracaine, cyclopiazonic acid or nimodipine, or following removal of extracellular Ca2+, resulted in arteriolar relaxation. Cyclopiazonic acid‐induced dilatation was associated with decreased Ca2+ sparks and oscillations but with a sustained rise in the mean global cytoplasmic [Ca2+] ([Ca2+]c), as measured using Fura2 and microfluorimetry.

Conclusions and Implications

This study provides direct evidence that Ca2+ sparks can play an excitatory role in pressurized arterioles, promoting myogenic tone. This contrasts with the generally accepted model in which sparks promote relaxation of vascular smooth muscle. Changes in vessel tone in the presence of cyclopiazonic acid correlated more closely with changes in spark and oscillation frequency than global [Ca2+]c, underlining the importance of frequency‐modulated signalling in vascular smooth muscle.
Planning for the Future in Times of Social Change
Authors: Schoon Ingrid
Published: November 2012

This article examines the interlinkages between macro‐ and microcontextual change, using evidence on changing education expectations among teenagers in three U.K. age cohorts born in 58, 1970, and 1989/1990 and related international studies. It discusses the multiple and interlinked factors and processes shaping educational expectations of young people, focusing on interactions with a changing sociohistorical context, institutional filters, family processes, social structures, and gender. It is argued that career choice and individual life planning have to be understood as an interactive and dialectical process linking individuals and the wider sociohistorical context. Changing opportunities set the stage for individual choice and behavior, which then aggregate to form a new historical context for subsequent cohorts. The effects of social change do not merely “trickle down”; individual and collective decisions and actions can “push up” as well, changing the social context, which in turn influences them. There are, however, variations in experience by social structure and gender, associated with the marginalization of the most disadvantaged. Thus, a key consideration in the study of individual life planning is the situated nature of decision making and the reciprocal and dynamic interactions between individual and context.
Non‐allergic, mastocytosis‐associated rhinitis
Authors: Dollner R. , Taraldsrud E. , Iversen K. , Osnes T. , Kristensen B. , Kramer M. F.
Published: November 2012

Background

Systemic mastocytosis (SM) is a clonal proliferative disorder of mast cells (MC) that causes pathological accumulation of mast cells in various tissues, which results in clinical symptoms (e.g. diarrhoea, urticaria) due to MC mediator release. Previous studies have shown that up to fifty percent of rhinitis symptoms in SM patients are non‐allergic and it has been assumed that these nasal complaints in SM patients are due an increased nasal mast cell burden. Nevertheless, to date there are no data supporting this hypothesis.

Objective

The study aims to investigate if the presence of allergy‐suggesting nasal complaints in non‐allergic SM patients is correlated with objective measure of nasal mast cell burden.

Patients and methods

Eleven adult patients with systemic mastocytosis underwent a comprehensive rhinologic work‐up. All patients fulfilled the clinical ARIA criteria for rhinitis. The allergologic work‐up included serological allergy testing, determination of tryptase levels (serum and nasal secretion), skin prick testing, and nasal provocation testing.

Results

Ten out of eleven SM patients with clinical persistent allergic rhinitis were found to be non‐allergic. In these patients, the most predominant symptoms were rhinorrhea, sneezing, and itching. All three symptoms were strongly correlated with the nasal tryptase level but not to the level of serum tryptase.

Conclusion and Clinical relevance

Non‐allergic persistent nasal complaints in systemic mastocytosis were significantly correlated with elevated nasal tryptase level as a measure of local MC burden. Furthermore, elevated nasal tryptase correlated with persistent rhinorrhea, sneezing, and itching as predominant symptoms, which seems to characterize a non‐allergic mastocytosis‐associated rhinitis (NAMAR) in systemic mastocytosis.
Major lineages of Nolidae (Lepidoptera, Noctuoidea) elucidated by molecular phylogenetics
Authors: Zahiri Reza , Lafontaine J. Donald , Holloway Jeremy D. , Kitching Ian J. , Schmidt B. Christian , Kaila Lauri , Wahlberg Niklas
Published: November 2012

To elucidate the evolutionary relationships of the major lineages within the moth family Nolidae, we analysed a molecular dataset comprising eight independent gene regions (6.4 kbp), cytochrome c oxidase subunit I (COI) from the mitochondrial genome, and elongation factor‐1α (EF‐1α), ribosomal protein S5 (RpS5), carbamoylphosphate synthase domain protein (CAD), cytosolic malate dehydrogenase (MDH), glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH), isocitrate dehydrogenase (IDH) and wingless genes from the nuclear genome, using parsimony and model‐based evolutionary methods (maximum likelihood and Bayesian inference). Our analyses revealed a well‐resolved phylogenetic hypothesis, again recovering the six previously recognized families within Noctuoidea (i.e. Oenosandridae, Notodontidae, Euteliidae, Erebidae, Nolidae and Noctuidae), and monophyly of the quadrifid Noctuoidea (i.e. Euteliidae, Erebidae, Nolidae and Noctuidae). The family Nolidae is diagnosed and characterized by two synapomorphies from morphology: construction of a ridged boat‐shaped cocoon that bears a vertical exit slit at one end; and two other morphological character states: elongation of the forewing retinaculum into a bar‐like or digitate condition and possession of a postpiracular counter‐tympanal hood. We present a new phylogenetic hypothesis for Nolidae consisting of eight strongly supported subfamilies, two of which are erected here: Diphtherinae, Risobinae, Collomeninae subfam. nov., Beaninae subfam. nov., Eligminae, Westermanniinae, Nolinae and Chloephorinae. Where we are able, each monophyletic lineage is diagnosed by morphological autapomorphies and within each subfamily, monophyletic tribes and subtribes are circumscribed, most of which are also diagnosable by morphological apomorphies. We also describe two new taxa: Gelastocerini trib. nov. and Etannina subtrib. nov. The Neotropical subfamily Diphtherinae, here newly circumscribed, is considered to be the plesiomorphic sister lineage to the rest of Nolidae. Diphtherinae are characterized by loss of the proximal pair of metatibial spurs in males and by the presence of a frontal tubercle, which is presumably associated with a derived strategy of emergence from the cocoon.
iMinerva: A Mathematical Model of Distributional Statistical Learning
Authors: Thiessen Erik D. , Pavlik Philip I.
Published: November 2012

Statistical learning refers to the ability to identify structure in the input based on its statistical properties. For many linguistic structures, the relevant statistical features are distributional: They are related to the frequency and variability of exemplars in the input. These distributional regularities have been suggested to play a role in many different aspects of language learning, including phonetic categories, using phonemic distinctions in word learning, and discovering non‐adjacent relations. On the surface, these different aspects share few commonalities. Despite this, we demonstrate that the same computational framework can account for learning in all of these tasks. These results support two conclusions. The first is that much, and perhaps all, of distributional statistical learning can be explained by the same underlying set of processes. The second is that some aspects of language can be learned due to domain‐general characteristics of memory.
Sodium and calcium mechanisms of rhythmic bursting in excitatory neural networks of the pre‐Bötzinger complex: a computational modelling study
Authors: Jasinski Patrick E. , Molkov Yaroslav I. , Shevtsova Natalia A. , Smith Jeffrey C. , Rybak Ilya A.
Published: November 2012

The neural mechanisms generating rhythmic bursting activity in the mammalian brainstem, particularly in the pre‐Bötzinger complex (pre‐BötC), which is involved in respiratory rhythm generation, and in the spinal cord (e.g. locomotor rhythmic activity) that persist after blockade of synaptic inhibition remain poorly understood. Experimental studies in rodent medullary slices containing the pre‐BötC identified two mechanisms that could potentially contribute to the generation of rhythmic bursting: one based on the persistent Na+ current (INaP), and the other involving the voltage‐gated Ca2+ current (ICa) and the Ca2+‐activated nonspecific cation current (ICAN), activated by intracellular Ca2+ accumulated from extracellular and intracellular sources. However, the involvement and relative roles of these mechanisms in rhythmic bursting are still under debate. In this theoretical/modelling study, we investigated Na+‐dependent and Ca2+‐dependent bursting generated in single cells and heterogeneous populations of synaptically interconnected excitatory neurons with INaP and ICa randomly distributed within populations. We analysed the possible roles of network connections, ionotropic and metabotropic synaptic mechanisms, intracellular Ca2+ release, and the Na+/K+ pump in rhythmic bursting generated under different conditions. We show that a heterogeneous population of excitatory neurons can operate in different oscillatory regimes with bursting dependent on INaP and/or ICAN, or independent of both. We demonstrate that the operating bursting mechanism may depend on neuronal excitation, synaptic interactions within the network, and the relative expression of particular ionic currents. The existence of multiple oscillatory regimes and their state dependence demonstrated in our models may explain different rhythmic activities observed in the pre‐BötC and other brainstem/spinal cord circuits under different experimental conditions.
Predictors of newly diagnosed atrial fibrillation in cryptogenic stroke: a cohort study
Authors: Bugnicourt J.‐M. , Flament M. , Guillaumont M.‐P. , Chillon J.‐M. , Leclercq C. , Canaple S. , Lamy C. , Godefroy O.
Published: November 2012

Background and purpose

A significant proportion of cryptogenic ischaemic strokes are due to paroxysmal atrial fibrillation (AF). As paroxysmal AF appears to inexorably progress to persistent or permanent AF, this study with long‐term follow‐up was designed to establish the profile of patients who developed AF after hospital discharge.

Methods

All patients with cryptogenic ischaemic stroke over a 1‐year period were included (n = 164). Patients were prospectively followed up at the outpatient clinic. Information on long‐term outcome included the presence of newly diagnosed AF (NDAF). A specific NDAF assessment was performed at least 2 years after the index stroke using a structured telephone interview. Baseline clinical, laboratory, and echocardiographic data of these patients were retrospectively recorded. Independent predictive factors were then used to produce a predictive grading score for NDAF, derived by logistic regression analysis.

Results

With a median follow‐up of 854 days, 22 cases of NDAF (13%) were observed. On multivariate analysis, factors associated with NDAF were age ≥72 years (two points), history of coronary artery disease (one point) or stroke (one point), and left atrial area ≥16 cm2 (two points) (total score ranging from 0 to 6). Patients with a score ≤1 point did not have NDAF during follow‐up.

Conclusions

In cryptogenic ischaemic stroke, the NDAF score can be used to target patients at high risk of developing AF after hospital discharge, as a score of 0–1 was highly predictive of the absence of NDAF during follow‐up. These results need to be confirmed in prospective studies.
Deep subcortical infarct burden in relation to apolipoprotein B/AI ratio in patients with intracranial atherosclerotic stenosis
Authors: Park J.‐H. , Hong K.‐S. , Lee J. , Kim Y.‐J. , Song P.
Published: November 2012

Background and purpose

Pre‐existing brain infarct (PBI), frequently seen on magnetic resonance imaging and usually silent, is recognized as a risk factor for future stroke. Increased apolipoprotein B (apoB)/apoAI ratio is known to be a risk predictor of ischaemic stroke and is associated with intracranial atherosclerotic stenosis (ICAS). However, little is known about the association of apoB/apoAI ratio with PBI.

Methods

A total of 522 statin‐/fibrate‐naïve Korean patients, who experienced acute ischaemic stroke, were categorized into three groups: ICAS (n = 254), extracranial (n = 51), and no cerebral atherosclerotic stenosis (n = 217). We explored the association between apoB/apoAI ratio and PBI lesions according to atherosclerosis type (ICAS, ECAS, and NCAS), PBI location (deep subcortical [ds‐PBI] versus hemispheric [h‐PBI]), and symptomatic PBI (s‐PBI) which was relevant to a prior clinical stroke event.

Results

Pre‐existing brain infarct(+) patients showed a higher apoB/apoAI ratio than PBI(−) patients (0.81 ± 0.28 vs. 0.72 ± 0.23, P < 0.001). In ICAS group, patients with higher apoB/apoAI ratio quartiles had more PBIs, ds‐PBIs, and s‐PBIs (P = 0.020, P = 0.025, and P = 0.001, respectively). With multivariable analyses, the highest apoB/apoAI ratio quartile was associated with PBI (OR, 2.56; 95% CI, 1.39–4.73), ds‐PBI (2.48; 1.33–4.62), and advanced (≥3) ds‐PBIs (2.68; 1.27–5.63) in ICAS group, but not with h‐PBI. s‐PBI had a dose–response relationship with apoB/apoAI ratio quartiles (6.18; 1.31–29.13 for the second; 5.34; 1.06–26.83 for the third; and 12.17; 2.50–59.19 for the fourth quartile), when referenced to the first quartile.

Conclusion

ApoB/apoAI ratio is associated with asymptomatic deep subcortical ischaemic burden as well as with symptomatic lesion in patients with ICAS.
Pharmacological blockade of TRPV1 receptors modulates the effects of 6‐OHDA on motor and cognitive functions in a rat model of Parkinson's disease
Authors: Razavinasab Moazamehosadat , Shamsizadeh Ali , Shabani Mohammad , Nazeri Masoud , Allahtavakoli Mohammad , Asadi‐Shekaari Majid , Esmaeli‐Mahani Saeed , Sheibani Vahid
Published: November 2012

TRPV1 receptors and cannabinoid system are considered as important modulators of basal ganglia functions, and their pharmacologic manipulation represents a promising therapy to alleviate Parkinson‐induced hypokinesia. Recent evidence suggests that the blockade of cannabinoid receptors might be beneficial to alleviate motor deficits observed in Parkinson's disease. In the present study, we have evaluated the effects of AMG9810, a selective antagonist of TRPV1 receptors, on the motor and cognitive functions in a rat model of Parkinson's disease generated by an intracerebroventricular injection of 6‐ hydroxydopamine (6‐OHDA) (200 μg per animal). The injection of 10 nmol of AMG9810 for a single dose (AMG1) and for 2 weeks (AMG14) partially attenuated the hypokinesia shown by these animals in motor function evaluation tests, whereas chronic administration of AMG had destructive effects on learning and memory in 6‐OHDA‐treated rats. Animals in the AMG 1 and AMG 14 groups showed an increased latency to fall in rotarod and grasping tests in each trials compared with 6‐OHDA‐treated rats (P < 0.01) and DMSO 1 and 14 groups (P < 0.05). Our data indicate that pharmacological blockade of TRPV1 receptors by AMG 9810 attenuates the hypokinetic effects of 6‐OHDA and that TRPV1 receptors play an important role in 6‐OHDA‐induced hypokinesia, athough elucidation of the neurochemical substrate involved in this process remains a major challenge for the future.
Trade‐off of dynamic fragility but not of robustness in metabolic pathways in silico
Authors: Quinton‐Tulloch Mark J. , Bruggeman Frank J. , Snoep Jacky L. , Westerhoff Hans V.
Published: November 2012

Selective robustness is a key feature of biochemical networks. It confers a fitness benefit to organisms living in dynamic environments. The (in‐)sensitivity of a network to external perturbations results from the interplay between network dynamics, structure and enzyme kinetics. In this work, we focus on the subtle interplay between robustness and control (fragility). We describe a quantitative method for defining the fragility and robustness of system fluxes to perturbations. We find that for many mathematical models of metabolic pathways, the robustness of fluxes vis‐à‐vis perturbations of all the enzyme activities is captured by a broad distribution of the robustness coefficients. We find that in cases where a metabolic pathway flux is made less robust with respect to the perturbation of a particular network step, the average robustness may still be increased. We then show that fragility is conserved upon a perturbation of network processes and equate fragility with control as defined in metabolic control analysis. This highlights the non‐intuitive nature of the interplay between fragility and robustness and the need for a dynamic network understanding.