bluuebunny/crossref_metadata_2025 huggingface dataset:
Follow‐up study of 2‐year‐olds born at very low gestational age in Estonia
Authors: Toome Liis , Varendi Heili , Männamaa Mairi , Vals Mari‐Anne , Tänavsuu Triinu , Kolk Anneli
Published: November 2012

Aim

To study very low gestational age (VLGA, <32 weeks) infants at 2 years of age and to identify the predictors of adverse outcomes.

Methods

A population‐based cohort of 155 surviving VLGA infants born in Estonia in 2007 was followed up and compared with a matched full‐term (FT) control group. A logistic regression model was used to test associations between risk factors and adverse outcomes.

Results

No impairment was found in 60% of the VLGA infants. Neurodevelopmental impairment was noted in 12% of VLGA infants, with 8% of the infants affected by cerebral palsy without independent walking, 5% with cognitive delay, 10% with language delay and 1% with hearing impairment. The differences between preterm and FT infants in terms of the mean Cognitive, Language, and Motor Composite Scores assessed using the Bayley‐III scales were in excess of 0.5 SD. Somatic growth delay was a significant problem among preterm infants. The existence of severe neonatal cerebral lesions was the most significant predictor of adverse outcomes.

Conclusion

In all domains studied, adverse conditions were more prevalent among VLGA infants than among the FT control group. Efforts to reduce neonatal morbidity in preterm infants should be a key priority for health care in Estonia.
Self‐perceived health status and mental health outcomes in young adults born with less than 1000 g
Authors: Natalucci G , Becker J , Becher K , Bickle GM , Landolt MA , Bucher HU
Published: November 2012

Aim

To assess self‐perceived health status and mental health outcomes of former extremely low‐birth‐weight (ELBW) infants at young adulthood compared with community norms and to analyse predictors of poor outcome.

Methods

Fifty‐five ELBW adults, 18 men (33%), with median (range) gestational age of 28.7 (25.0–34.0) weeks and birth weight of 930 (680–990) grams, born in Switzerland, were included. They self‐rated their health status and mental health at a mean (range) age of 23.3 (21.8–25.9) years. Health status was measured by the Medical Outcomes Study Short Form‐36 questionnaire and mental health by the Brief Symptom Inventory.

Results

The mean scores for both outcome measures were in the normal range. However, the study group self‐rated significantly higher physical health status and lower mental health status compared with the community norms, and scores for self‐perceived mental health tended to be worse in the former. ELBW adults reported more problems in socio‐emotional role functioning compared with the community norms. Female sex was associated with poorer and bronchopulmonary dysplasia with better mental health status.

Conclusion

Health status and mental health of former ELBW adults were overall satisfying. However, the comparison with the community norms revealed differences, which may be important for parental and patient counselling and developing support strategies.
A non‐fatal case of invasive zygomycete (Lichtheimia corymbifera) infection in an allogeneic haematopoietic cell transplant recipient
Authors: Eickhardt Steffen , Braendstrup Peter , Clasen‐Linde Erik , Jensen Karl E. , Alhede Morten , Bjarnsholt Thomas , Høiby Niels , Vindeløv Lars , Moser Claus
Published: November 2012

Post‐transplant infections in allogeneic haematopoietic cell transplant (allo‐HCT) recipients often have severe consequences. This is especially the case when dealing with zygomycete infections where the result is often fatal. A major problem when dealing with zygomycete infections is the need for an accurate and fast diagnosis as the phylum is highly resistant towards the conventional antifungals. We herein describe a non‐fatal case of Lichtheimia corymbifera infection in an allo‐HCT recipient.
Rumination variations: aetiology and classification of abnormal behavioural responses to digestive symptoms based on high‐resolution manometry studies
Authors: Tucker E. , Knowles K. , Wright J. , Fox M. R.
Published: November 2012

Background

Rumination is the voluntary, albeit subconscious return of gastric contents to the mouth. Currently, rumination syndrome and repetitive belching disorders are considered separate diagnoses, as defined by Rome III criteria and high‐resolution oesophageal manometry (HRM).

Aim

To test the hypothesis that these conditions represent a common behavioural response to aversive digestive stimuli and that successful treatment can be directed at both the stimulus and the response.

Methods

Case‐note review of consecutive patients with a final diagnosis of behavioural digestive disorders between August 2009 and October 2011.

Results

Thirty‐five of 46 (76%) patients exhibited ‘classical’ rumination with abdomino‐gastric strain (R‐waves) driving gastric contents across the lower oesophageal sphincter; 5 (11%) had ‘reflux‐related’ rumination with R‐waves seen during gastro‐oesophageal common cavity (reflux) events and 6 had (13%) supra‐gastric belching. All received at least one biofeedback session at the time of diagnosis with a good response reported by 20/46 (43%) of the patients, which included 3 with supra‐gastric belching. Additionally, rumination ceased in cases in which definitive treatment relieved the symptoms that triggered abnormal behaviour (e.g. fundoplication in ‘reflux‐rumination’).

Conclusions

Rumination and many of its variations, excluding only some cases of supra‐gastric belching, are associated with abdomino‐gastric strain, a generic abnormal behavioural response to a variety of aversive digestive stimuli. All types of rumination can respond to biofeedback. High‐resolution oesophageal
manometry identifies subgroups with distinct mechanisms of disease that respond to specific management targeted at the symptoms that trigger the abnormal behaviour.
Soluble epoxide hydrolase inhibitor, TUPS, protects against isoprenaline‐induced cardiac hypertrophy
Authors: Althurwi Hassan N , Tse Mandy MY , Abdelhamid Ghada , Zordoky Beshay NM , Hammock Bruce D , El‐Kadi Ayman OS
Published: November 2012

Background and Purpose

We have previously shown that isoprenaline‐induced cardiac hypertrophy causes significant changes in the expression of cytochromes P450 (CYP) and soluble epoxide hydrolase (sEH) genes. Therefore, it is important to examine whether the inhibition of sEH by 1‐(1‐methanesulfonyl‐piperidin‐4‐yl)‐3‐(4‐trifluoromethoxy‐phenyl)‐urea (TUPS) will protect against isoprenaline‐induced cardiac hypertrophy.

Experimental Approach

Male Sprague–Dawley rats were treated with TUPS (0.65 mg kg−1 day−1, p.o.), isoprenaline (5 mg kg−1 day−1, i.p.) or the combination of both. In vitro H9c2 cells were treated with isoprenaline (100 μM) in the presence and absence of either TUPS (1 μM) or 11,12 EET (1 μM). The expression of hypertrophic, fibrotic markers and different CYP genes were determined by real‐time PCR.

Key Results

Isoprenaline significantly induced the hypertrophic, fibrotic markers as well as the heart to body weight ratio, which was significantly reversed by TUPS. Isoprenaline also caused an induction of CYP1A1, CYP1B1, CYP2B1, CYP2B2, CYP4A3 and CYP4F4 gene expression and TUPS significantly inhibited this isoprenaline‐mediated effect. Moreover, isoprenaline significantly reduced 5,6‐, 8,9‐, 11,12‐ and 14,15‐EET and increased their corresponding 8,9‐, 11,12‐ and 14,15‐dihydroxyeicosatrienoic acid (DHET) and the 20‐HETE metabolites. TUPS abolished these isoprenaline‐mediated changes in arachidonic acid (AA) metabolites. In H9c2 cells, isoprenaline caused a significant induction of ANP, BNP and EPHX2 mRNA levels. Both TUPS and 11,12‐EET significantly decreased this isoprenaline‐mediated induction of ANP, BNP and EPHX2.

Conclusions and Implications

TUPS partially protects against isoprenaline‐induced cardiac hypertrophy, which confirms the role of sEH and CYP enzymes in the development of cardiac hypertrophy.
Bacillus Calmette–Guerin (BCG) immunotherapy for bladder cancer: Current understanding and perspectives on engineered BCG vaccine
Authors: Kawai Koji , Miyazaki Jun , Joraku Akira , Nishiyama Hiroyuki , Akaza Hideyuki
Published: November 2012

Since the first report in 1976, accumulated clinical evidence has supported intravesical Bacillus Calmette–Guerin (BCG) therapy as one of the standard methods of management of intermediate‐ and high‐risk non‐muscle invasive bladder cancer. Despite its efficacy, intravesical BCG therapy is associated with a variety of adverse events (AEs), most of which are tolerable or controllable with supportive care. However, some patients receiving intravesical BCG therapy may experience uncommon but severe AEs, leading to cessation of BCG therapy. Not all, but most severe AEs result from either local or systemic infection with live BCG. Intravesical instillation of BCG elicits multiple immune reactions, although the precise immunological mechanism of BCG therapy is not clear. It is convenient to separate the complex reactions into the following three categories: infection of urothelial cells or bladder cancer cells, induction of immune reactions, and induction of antitumor effects. Recently, our knowledge about each category has increased. Based on this understanding, predictors of the efficacy of intravesical BCG therapy, such as urinary cytokine measurement and cytokine gene polymorphism, have been investigated. Recently, preclinical studies using a novel engineered mycobacterium vaccine have been conducted to overcome the limitations of BCG therapy. One approach is Th1 cytokine‐expressing recombinant forms of BCG; another approach is development of non‐live bacterial agents to avoid AEs due to live BCG infection. We also briefly describe our approach using an octaarginine‐modified liposome‐incorporating BCG cell wall component to develop future substitutes for live BCG. (Cancer Sci 2013; 104: 22–27)
T cell activation status determines the cytokine pattern induced by zymosan and bacterial DNA both in thymocytes and splenocytes
Authors: Zimmermann C , Weber A , Mausberg A K , Kieseier B C , Hartung H P , Hofstetter H H
Published: November 2012

Proinflammatory cytokines are essential mediators of the immunopathology associated with microbial sepsis. The fungal cell wall component zymosan and bacterial DNA are well-studied experimental tools for investigating these processes, simulating the presence of fungal or bacterial infection. Cells of the immune periphery, but also immune cells in the thymus, are affected essentially by the presence of microbes or their immune stimuli in sepsis. For this reason, we investigated the cytokine pattern present in the spleen (containing mature immune cells) and the thymus (containing immature immune cells) upon exposure to zymosan and Escherichia coli DNA. To study the role of T cell activation status, we investigated ex-vivo cultures with and without αCD3 stimulation for changes in their cytokine secretion pattern as measured by cytokine enzyme-linked immunospot (ELISPOT) and flow cytometry analysis. We found that both substances strongly co-stimulate αCD3-induced interferon (IFN)-γ and interleukin (IL)-6 secretion in the thymus and in the spleen, but stimulate IL-17 production only moderately. Moreover, zymosan increases PLP peptide (PLPp)-specific IFN-γ and IL-6 production in experimental autoimmune encephalomyelitis (EAE) induced in Swiss Jim Lambert (SJL)/J mice, confirming that T cell activation status is crucial for the cytokines secreted by an immune cell population encountering a microbial pathogen or immunostimulating parts of it.
Cytotoxic T lymphocyte antigen 4-immunoglobulin G is a potent adjuvant for experimental allergen immunotherapy
Authors: Maazi H , Shirinbak S , den Boef L E , Fallarino F , Volpi C , Nawijn M C , van Oosterhout A J M
Published: November 2012

Allergen-specific immunotherapy (SIT) is the only treatment for allergic diseases that targets allergen-specific T helper type 2 (Th2) cells, which are the cause of the disease. There is an unmet requirement for adjuvants that increase the clinical efficacy of SIT allowing application of lower doses of the allergen, thereby reducing the risk of anaphylactic reactions. Cytotoxic T lymphocyte antigen 4–immunoglobulin (CTLA-4–Ig) has been shown to induce immunological tolerance in autoimmunity and allograft transplantation by blocking T cell co-stimulation and induction of the immunoregulatory enzyme indoleamine 2,3 dioxygenase (IDO). Previously, we showed that CTLA-4–Ig treatment at the time of allergen inhalation induced tolerance to subsequent allergen exposure in a mouse model of asthma. In this study, we test the hypothesis that CTLA-4–Ig acts as an adjuvant for experimental SIT. We evaluated the adjuvant effects of CTLA-4–Ig on SIT in a mouse model of ovalbumin-driven asthma. We used both wild-type and IDO-deficient mice to assess the role of IDO in the adjuvant effects of CTLA-4–Ig. Co-administration of CTLA-4–Ig strongly increased SIT-induced suppression of airway hyperreactivity (AHR), specific IgE in serum, airway eosinophilia and Th2 cytokine levels. Moreover, we found that CTLA-4–Ig, as an adjuvant for SIT, is equally effective in IDO-deficient and wild-type mice, demonstrating that the effect of CTLA-4–Ig is independent of IDO expression. We show that CTLA-4–Ig acts as a potent adjuvant to augment the therapeutic effects of SIT. As the adjuvant activity of CTLA-4–Ig is independent of IDO, we conclude that it acts by blocking CD28-mediated T cell co-stimulation.
Assessment of anodized titanium implants bioactivity
Authors: El‐wassefy Noha A. , Hammouda Ibrahim M. , Habib Ahmed Nour El‐deen A. , El‐awady Ghada Y. , Marzook Hamdy A.
Published: November 2012

Objectives

This study was conducted to create nanostructured surface titanium implants by anodic oxidation process aiming to bring out bioactivity and to assess the resultant bioactivity both in vitro and in vivo.

Materials and Methods

An economic protocol was used to apply anodic spark discharge and create surface nanoporosities on grade II commercially pure titanium (cpTi). The in vitro investigation included morphology, surface chemical analysis, roughness and crystalline structure of titanium oxide (TiO2) film prepared. Assessment of the bioactivity was carried out by immersing the specimens in simulate body fluid (SBF) and investigating the surface‐deposited layer. The in vivo investigation was conducted by surgically placing the anodized implants into rabbits tibia for different healing periods. Then biomechanical evaluation was performed to verify the effect of treatments on the interface resistance to shear force. Routine histological analysis was performed to evaluate the bone tissue reactions to anodized implants.

Results

Anodization of titanium implants produced morphological changes, raised the percentage of oxygen in the TiO2 layer, increased surface area and roughness of implants remarkably, and modified the crystallinity of the film. The in vitro assessments of bioactivity showed that a layer of calcium phosphate was precipitated on the titanium surfaces 7 days after soaking into SBF. The implant–bone interface resistance to shear force was enhanced at 2‐week healing period. This was confirmed by histological findings.

Conclusion

Nanostructured surface titanium implants could be prepared by anodic oxidation with resultant accelerated bioactivity that may be recommended for early loading.
Boards of Directors and Financial Risk during the Credit Crisis
Authors: McNulty Terry , Florackis Chris , Ormrod Phillip
Published: November 2012

Research Question/Issue

This research examines the relationship between board processes and corporate financial risk. Using a unique questionnaire survey about board behavior, several measures related to board processes are developed and used to explain certain aspects of financial risk during the recent crisis.

Research Findings/Insights

In a sample of 141 companies with complete data collected from company chairs on both board structure and process, board process is found to be an important determinant of financial risk during the crisis of 2008–2009. In particular, financial risk is lower where non‐executive directors have high effort norms and where board decision processes are characterized by a degree of cognitive conflict. The impact of cognitive conflict is, however, found to be less pronounced in boards with high levels of cohesiveness.

Theoretical/Academic Implications

The study provides theoretical and empirical advancement of the governance literature towards an understanding of group process‐oriented views of boards' work and effectiveness. This study identifies the significance of board processes and their impact on financial risk supported by quantitative empirics. Findings of a strong relationship between board process and financial risk augment existing theories to suggest that the effects of boards work through group processes that bring executives and non‐executives together in relations laced with control and collaboration.

Practitioner/Policy Implications

Regulators, acting post the financial crisis have produced governance codes that emphasize risk management as a key responsibility of boards. The link between board process and financial risk established in this paper provides evidence for company chairs and other directors on the possibilities and potential effectiveness of boards in discharging this responsibility.
Glycaemic responses to glucose and rice in people of Chinese and European ethnicity
Authors: Kataoka M. , Venn B. J. , Williams S. M. , Te Morenga L. A. , Heemels I. M. , Mann J. I.
Published: November 2012

Aims

Diabetes rates are especially high in China. Risk of Type 2 diabetes increases with high intakes of white rice, a staple food of Chinese people. Ethnic differences in postprandial glycaemia have been reported. We compared glycaemic responses to glucose and five rice varieties in people of European and Chinese ethnicity and examined possible determinants of ethnic differences in postprandial glycaemia.

Methods

Self‐identified Chinese (n = 32) and European (n = 31) healthy volunteers attended on eight occasions for studies following ingestion of glucose and jasmine, basmati, brown, Doongara® and parboiled rice. In addition to measuring glycaemic response, we investigated physical activity levels, extent of chewing of rice and salivary α‐amylase activity to determine whether these measures explained any differences in postprandial glycaemia.

Results

Glycaemic response, measured by incremental area under the glucose curve, was over 60% greater for the five rice varieties (P < 0.001) and 39% greater for glucose (P < 0.004) amongst Chinese compared with Europeans. The calculated glycaemic index was approximately 20% greater for rice varieties other than basmati (P = 0.01 to 0.05). Ethnicity [adjusted risk ratio 1.4 (1.2–1.8) P < 0.001] and rice variety were the only important determinants of incremental area under the glucose curve.

Conclusions

Glycaemic responses following ingestion of glucose and several rice varieties are appreciably greater in Chinese compared with Europeans, suggesting the need to review recommendations regarding dietary carbohydrate amongst rice‐eating populations at high risk of diabetes.
Iron homeostasis in the Metabolic Syndrome
Authors: Datz Christian , Felder Thomas K. , Niederseer David , Aigner Elmar
Published: November 2012

The metabolic syndrome (MetS) affects iron homeostasis in a many‐faceted fashion. On the one side, hyperferritinaemia with normal or mildly elevated transferrin saturation is observed in approximately one‐third of patients with non‐alcoholic fatty liver disease (NAFLD) or the MetS. This constellation has been named the ‘dysmetabolic iron overload syndrome (DIOS)’. Current evidence suggests that elevated body iron stores exert a detrimental effect on the clinical course of obesity‐related conditions and that iron removal improves insulin sensitivity and delays the onset of T2DM. On the other side, iron deficiency is a frequent finding in more progressed stages of obesity. The mechanisms underlying the DIOS and obesity‐related iron deficiency appear strikingly similar as elevated hepcidin concentrations, low expression of duodenal ferroportin (FPN) and impaired iron absorption are found in both conditions. This review summarizes the current knowledge about the dysregulation of iron homeostasis in the MetS and particularly in its hepatic manifestation NAFLD.
Primary tooth resorption and its role in the normal tooth eruption process
Authors: Frazier‐Bowers Sylvia A. , Rhoads Stephanie G.
Published: November 2012

The objective of this article is to review the process of permanent tooth eruption and primary tooth resorption in the context of the major theories of tooth eruption. This review will also focus on diagnostic criteria including radiographic, clinical, and genetic analysis to help distinguish between eruption anomalies such as isolated ankylosis of primary or permanent teeth versus eruption failure. Our studies of eruption failure have revealed that a much greater number of cases than previously suspected account for a hereditary form of eruption failure versus an isolated ankylosis. The importance of distinguishing eruption failure from isolated ankylosis (in primary and especially permanent teeth) is that the resultant management and prognosis differs greatly between the two. Management of isolated ankylosis is definitively treated by extraction of the offending tooth while eruption failure from a genetic defect may result in no treatment at all or multiple single tooth osteotomies. A complete understanding of the clinical presentation and biological mechanisms underlying eruption and eruption disorders will facilitate the best diagnosis and patient management of difficult clinical cases.
The relationship between body composition, training and race performance in a group ofThoroughbred flat racehorses
Authors: Fonseca R. G. , Kenny D. A. , Hill E. W. , Katz L. M.
Published: November 2012

Reasons for performing study

Few noninvasive measures associated with performance assessment are available for racehorse trainers. Evaluation of body composition of superior human sprinters has revealed a lower fat mass (FM), percentage (%) fat and greater fat‐free mass (FFM), but to date there have been few studies evaluating this in racehorses.

Objectives

To determine the effects of age, gender and training on body composition and the relationship between body composition, physiological measurements and performance in Thoroughbred racehorses.

Methods

At 2, 5 and 8 months of training, rump fat thickness (RFT) was ultrasonographically measured in 1‐, 2‐ and 3‐year‐old Thoroughbreds (n = 148), with FM, % fat and FFM calculated. Speed, heart rate, plasma lactate and serum creatine kinase concentrations were recorded during each fast work session. Training duration (number of training days) and intensity (number of fast work sessions) were collated for each training period. Retrospective racing performance was used to categorise horses as elite or nonelite.

Results

FFMwas greater in males (P = 0.006) at all training stages. There were no interactions between training duration, intensity, gender and age (P>0.05); all effects were linear. Training duration had a negative effect onRFT(P = 0.0002),FM(P<0.0001) and % fat (P<0.0001) and a positive effect onFFM(P = 0.01). Training intensity had a negative effect onRFT(P = 0.009),FM(P<0.0001), % fat (P<0.0001) andFFM(P<0.0001).FFMwas greater for elite vs. nonelite horses at all training stages (P = 0.003), for males (P = 0.05) and females (P = 0.04) and for 2‐ (P = 0.002) and 3‐year‐olds (P = 0.02).

Conclusions

While age and training affect body composition,FFMis associated with performance.

Potential relevance

Body composition assessment may assist fitness and performance evaluation.
Discontinuous thoracic venous cardiomyocytes and heart exhibit synchronized developmental switch of troponin isoforms
Authors: Kracklauer Martin P. , Feng Han‐Zhong , Jiang Wenrui , Lin Jenny L.‐C. , Lin Jim J.‐C. , Jin Jian‐Ping
Published: November 2012

Cardiomyocyte‐like cells have been reported in thoracic veins of rodents and other mammals, but their differentiation state and relationship to the muscle mass in the heart remain to be characterized. Here we investigated the distribution, ultrastructure, expression and developmental regulation of myofilament proteins of mouse and rat pulmonary and azygos venous cardiomyocytes. Tracing cardiomyocytes in transgenic mouse tissues using a lacZ reporter gene driven by a cloned rat cardiac troponin T promoter demonstrated scattered distribution of cardiomyocytes discontinuous from the atrial sleeves. The longitudinal axis of venous cardiomyocytes is perpendicular to that of the vessel. These cells contain typical sarcomere structures and intercalated discs as shown in electron microscopic images, and express cardiac isoforms of troponin T, troponin I and myosin. The expression of troponin I isoform genes and the alternative splicing of cardiac troponin T in thoracic venous cardiomyocytes are regulated during postnatal development in precise synchrony with that in the heart. However, the patterns of cardiac troponin T splicing in adult rat thoracic venous cardiomyocytes are slightly but clearly distinct from those in the atrial and ventricular muscles. The data indicate that mouse and rat thoracic venous cardiomyocytes residing in extra‐cardiac tissue possess a physiologically differentiated state and an intrinsically pre‐set developmental clock, which are apparently independent of the very different hemodynamic environments and functional features of the vessels and heart.
Synergistic impacts of sediment contamination and dam presence on river functioning
Authors: COLAS FANNY , BAUDOIN JEAN‐MARC , DANGER MICHAEL , USSEGLIO‐POLATERA PHILIPPE , WAGNER PHILIPPE , DEVIN SIMON
Published: November 2012

1. Dam presence is commonly associated with strong accumulation of polluted sediments. In spite of this context of multiple stressors, physical effects are often solely considered in the ecological assessment of the dam impacts.

2. We studied four ‘reservoir/downstream reach’ systems differing in levels of sediment contamination in reservoirs. Using assemblages and biotrait (i.e. ecological or biological attribute) responses of macroinvertebrate communities and leaf litter breakdown, we examined the individual effects and potential interactions between sediment contamination and dam presence along the gradient of ecotoxic pressure.

3. Leaf breakdown rates ranged from 0.0044° per day in the most contaminated reservoir to 0.0120° per day in the reference reservoir. Comparisons of community trait profiles among reservoirs highlighted a gradient of trait responses to sediment contamination.

4. In the absence of toxic contamination, the dam‐induced modifications in biotraits of invertebrate assemblages were not related to a reduction of leaf litter breakdown. Conversely, contaminated sediment in reservoir induced strong functional disturbances (i.e. bioecological shifts and reduction of leaf litter breakdown) downstream of dams.

5. Key biotrait categories positively related to leaf litter breakdown rate have been identified. They corresponded mainly to shredders and/or small‐sized (<0.5 cm) insects, using aquatic (e.g. crawlers) or aerial (e.g. fliers) active dispersal strategies. In addition, trait categories positively correlated to contamination level have been considered as ‘response’ traits. They corresponded to large‐sized (>4 cm) species, having several generations per year (polyvoltin), using asexual reproduction and/or disseminating by drift (aquatic, passive).

6. In the current context of ecological continuity restoration, this study has identified the risks associated with the presence of historical contamination in the run‐of‐river reservoirs for downstream ecosystem health.
Factor VIII Bypassing Activity (FEIBA) assays: standardization and development of the 1st NIBSC Working Standard for FEIBA – results from a collaborative study
Authors: Raut S. , Daniels S. , Gärtner P. , Hunfeld A. , Leitner M. , Hockley J. , Heath A.
Published: November 2012

Factor‐Eight‐Inhibitor‐Bypassing‐Activity (FEIBA) is a bypassing‐agent used to control spontaneous bleeding or cover surgical interventions in Haemophiliacs who develop neutralizing antibodies against FVIII/FIX. The market lot‐release of FEIBA is dependent on specific clot‐based assays, carried out by both the manufacturer and regulatory authorities, relative to manufacturer's in‐house standards, which are produced on a small‐scale and are replaced frequently. We sought to standardize the FEIBA assay by developing a FEIBA primary standard which would be internationally available in sufficiently large quantities, with a predicted lifetime of many years. A collaborative study involving the manufacturer and three regulatory authorities, was carried out in which a candidate material, sample B (06/172), was calibrated by assays relative to the manufacturer's in‐house FEIBA standards (C and D). All laboratories used their routine validated methods (16 APTT‐assays, 8 ACTIN‐FS‐assays and 27 DAPTTIN‐assays). Intra‐laboratory geometric coefficients of variation (GCVs) for candidate B ranged from 3% to 29% (GCVs <9% from majority of labs). Assessment of inter‐laboratory variability gave overall GCV values of 6.9% and 4.4% relative to standards C and D, respectively, for all methods. There was good agreement in potency estimation between laboratories using each of the three methods, with the overall potencies by the three methods differing by less than 10% of the overall mean, giving an overall combined potency of 28.0 units per ampoule. All participants agreed that candidate B (06/172) be established as the 1st NIBSC Working Standard for FEIBA with an assigned potency of 28.0 units per ampoule, based on combined results for both methods, relative to either standard C or D.
Increasing trend of HIV/AIDS among Arab and Jewish male persons in Israel, 1986–2010
Authors: Mor Z , Grayeb E , Beany A , Grotto I
Published: November 2012

Objectives

The aim of the study was to compare the HIV/AIDS burdens in Jewish and Arab Israeli males, as HIV/AIDS affects different population groups disproportionally.

Methods

The National HIV/AIDS Registry (NHAR) was used as the source of HIV/AIDS infection records, while the Israeli Central Bureau of Statistics was used to determine group‐specific disease rates.

Results

Between 1986 and 2010, 3499 HIV/AIDS‐infected male Israelis were reported to the NHAR: 3369 (96.3%) Jews and 130 (3.7%) Arabs, with an average annual incidence of 5.5 and 0.8 per 100 000 of the population, respectively (P = 0.05). Of the Jews, 1018 (29.9%) were born in Ethiopia, while 2389 were Jews who were not Ethiopian‐born (JNE). Most of the Arabs (n = 99; 74.8%) were Muslims, followed by Christians (21; 16.2%) and Druze (13; 10%). AIDS rather than HIV infection at the time of reporting was diagnosed in 568 (23.8%) of the JNE and 31 (23.8%) of the Arabs (p = 1). The most affected age group was those aged 25–34 years among the JNE and those aged 20–24 years among the Arabs, and the respective cumulative death rates were 24.9% (n = 594) and 32.5% (n = 40) (P = 0.1). The point prevalences in 2010 were 58.4 and 11.4 per 100 000 for JNE and Arabs, and in adults aged 15–59 years they were 71.5 and 26.3 per 100 000, respectively. In Muslims, Christians and Druze, the point prevalences were 4.2, 11.2 and 7.1 per 100 000, and in adults aged 15–59 years they were 22.6, 42.9 and 29.4, respectively. The most common risk group among JNE was men who have sex with men (MSM; n = 1223; 51.2%), followed by injecting drug users (n = 661; 27.7%), while among Arabs it was MSM (n = 63; 48.1%), followed by heterosexuals (n = 36; 27.3%).

Conclusions

The HIV/AIDS burden in Israeli Arab males was significantly lower than that in Jews, and in both populations the most common risk group was MSM, with the proportion of MSM increasing with time.
Utility of new mature erythrocyte and reticulocyte indices in screening for iron‐deficiency anemia in a pediatric population
Authors: Osta V. , Caldirola M. S. , Fernandez M. , Marcone M. I. , Tissera G. , Pennesi S. , Ayuso C.
Published: November 2012

Introduction

Iron‐deficient erythropoiesis attributable to nutritional deficiency is the most common cause of anemia in early childhood. Beckman Coulter has proposed new parameters: red blood cell size factor (RSf) and low hemoglobin density (LHD%).urn:x-wiley:17515521:media:ijlh12030:ijlh12030-math-0001

The aims of the present communication were to establish reference ranges (RR) for RSf and LHD% in a healthy pediatric population; to evaluate clinical utility of these parameters in the diagnosis of iron‐deficiency anemia (IDA); and to compare RSf and LHD% with RET‐He.

Methods

Two hundred healthy infants and 51 with IDA were analyzed on Coulter LH750 and Sysmex XT2000i analyzers.

Results

RR for RSf in children aged 0.5–6 years, 82.2–102.0 and 83.7–103.1 fl in the group aged 6‐18 years. RR for LHD% was 1.1–9.0%. ROC analysis for RSf and LHD% in the diagnosis of IDA showed an AUC 0.8460 and 0.8654, respectively. The best RSf value to detect a restricted erythropoiesis was 89fl, sensitivity 92%, specificity 81%. LHD% optimal cutoff point was 6.0%, sensitivity 80%, and specificity 88%. Good correlation was observed between these parameters with Ret‐He, r = 0.888 and r = −0.790, respectively.

Conclusion

RSf and LHD% could be useful tools in the screening of IDA. These parameters can be obtained in the course of routine blood counts, with no additional cost or need for more blood sampling.
Terlipressin therapy for moderate‐to‐severe hyponatraemia in patients with liver failure
Authors: Prakoso E. , Jones C. , Koorey D. J. , Strasser S. I. , Bowen D. , McCaughan G. W. , Shackel N. A.
Published: November 2012

Background

Hyponatraemia in liver failure is associated with increased morbidity and mortality. Improving serum sodium in liver failure has been observed in patients receiving terlipressin.

Methods

We assessed the response of hyponatraemia in patients with liver failure to terlipressin using comparative retrospective analysis.

Results

Twenty‐three patients received terlipressin for hyponatraemia after failed conservative management (median age 52 years (27–67), model for end‐stage liver disease score 28 (16–38)). The median therapy was 7 days (1–27), with an average total dose of 25 mg (4–90) and a mean follow up of 51 days (5–1248). These patients were compared with 11 hyponatraemic patients managed conservatively during the same period with comparable age, baseline serum sodium and follow up. After 1 week of terlipressin therapy, serum sodium increased from a median of 120 (115–128) to 129 mmol/L (121–144) (P < 0.001), and at the end of terlipressin therapy, the serum sodium had increased significantly to 131 mmol/L (120–148) (P < 0.001). In comparison, in the conservatively managed group, the serum sodium did not increase significantly from the baseline of 123 (117–127) mmol/L. Adverse events occurred in 26% of patients receiving terlipressin, which predominantly pulmonary oedema. Importantly, more hyponatraemic patients treated with terlipressin (48%) were alive compared with the conservative group (18%), despite the latter having a significantly lower baseline median MELD score of 21 (16–30) (P = 0.008). Moreover, the transplant‐free survival was higher in the terlipressin (30%) compared with the conservative group (0%).

Conclusions

Terlipressin is effective in treating hyponatraemia in liver failure. Importantly, terlipressin use results in better transplant‐free survival but also more adverse events.
Short‐ and long‐term outcomes for patients with variceal haemorrhage in a tertiary hospital
Authors: Halland M. , Ansley S. J. , Stokes B. J. , Fitzgerald M. N. , Inder K. J. , Duggan J. M. , Duggan A.
Published: November 2012

Background/Aim

To determine short‐ and long‐term outcomes among a cohort of patients with variceal haemorrhage at a tertiary referral centre, and to determine the predictive value of the model for end‐stage liver disease (MELD) score for mortality in these patients.

Methods

Prospective database hospital audit that captured patients who presented with or were transferred with variceal haemorrhage between 2004 and 2008, and a retrospective review of long‐term outcomes. Patients who presented to or were transferred to John Hunter Hospital, a tertiary referral hospital, with confirmed variceal bleeding were included. The main outcome measures were in‐hospital, 6 weeks and end‐of‐audit mortality. We also recorded cause, location and degree of planning surrounding the deaths in this patient group. We analysed the MELD score for patients with complete survival data.

Results

We recorded 93 episodes of variceal haemorrhage from 78 unique patients during the initial study period. The in‐hospital mortality, 6 weeks mortality and end‐of‐audit mortality were 2.6, 9.0 and 59, respectively, and median survival time was 3.2 years (95% confidence interval 0.0, 6.1). The most frequent cause of death was related to complications of end‐stage liver disease at 74%, followed by variceal bleeding (19%) and unknown (6%). A Cox proportional hazard model showed that the risk of mortality is increased by 1.06 (1.01–1.11) for each unit increase in MELD score.

Conclusions

Short‐term outcomes for patients with variceal bleeding continue to improve, but long‐term prognosis remains guarded and should prompt further emphasis on advanced care planning to optimise patient care.
Immunosuppressive properties of mesenchymal stromal cells derived from amnion, placenta, Wharton's jelly and umbilical cord
Authors: Manochantr S. , U‐pratya Y. , Kheolamai P. , Rojphisan S. , Chayosumrit M. , Tantrawatpan C. , Supokawej A. , Issaragrisil S.
Published: November 2012

Background

The role of bone marrow‐derived mesenchymal stromal cells (BM‐MSC) in preventing the incidence and ameliorating the severity of graft‐versus‐host disease (GvHD) has recently been reported. However, as the collection of BM‐MSC is an invasive procedure, more accessible sources of MSC are desirable.

Aim

This study aimed to explore the alternative sources of MSC from amnion, placenta, Wharton's jelly and umbilical cord, which are usually discarded.

Methods

MSC from those tissues were isolated using mechanical dissociation and enzymatic digestion. Their capacity for proliferation and differentiation, and ability to suppress alloreactive T‐lymphocytes were studied and compared with those of BM‐MSC.

Results

MSC derived from amnion, placenta, Wharton's jelly and umbilical cord were similar to BM‐MSC regarding the cell morphology, the immunophenotype as well as the differentiation ability. These MSC also elicited a similar degree of immunosuppression, as evidenced by the inhibition of alloreactive T‐lymphocytes in the mixed lymphocyte reaction, compared with that of BM‐MSC. MSC from umbilical cord and Wharton's jelly had a higher proliferative capacity, whereas those from amnion and placenta had a lower proliferative capacity compared with BM‐MSC.

Conclusion

The results obtained from this study suggest that MSC from amnion, placenta, Wharton's jelly and umbilical cord can therefore be potentially used for substituting BM‐MSC in several therapeutic applications, including the treatment of GvHD.
Retro‐fitting an older (S)TEM with two Cs aberration correctors for 80 kV and 60 kV operation
Authors: BÖRRNERT F. , BACHMATIUK A. , GORANTLA S. , WOLF D. , LUBK A. , BÜCHNER B. , RÜMMELI M.H.
Published: November 2012

For the characterization of light materials using transmission electron microscopy, a low electron acceleration voltage of 80 kV or even 60 kV is attractive due to reduced beam damage to the specimen. The concomitant reduction in resolving power of the microscope can be restored when using spherical aberration (Cs) correctors, which for the most part are only available in the latest and most expensive microscopes. Here, we show that upgrading of existing TEMs is an attractive and cost‐effective alternative. We report on the low‐voltage performance on graphitic material of a JEOL JEM‐2010F built in the early 1990s and retro‐fitted with a conventional imaging Cs corrector and a probe Cs corrector. The performance data show Cs retro‐fitted instruments can compete very favourably against more modern state‐of‐the‐art instruments in both conventional imaging (TEM) and scanning (STEM) modes.
Application of microscopical techniques in the study of autolysosome dynamics in PC12 neurites
Authors: YANG YI , FENG LIN QING , ZHENG XIAO XIANG , ZHANG LI HUI
Published: November 2012

Autophagy is a principal degradation pathway for the turnover of intracellular proteins or cytoplasmic organelles in response to starvation. During autophagic activation, autophagosomes fuse with lysosomes to form autolysosomes where incorporated materials are degraded. However, the dynamics of autolysosomes in neurites of live cells was still poorly known. In this study, various subsets of microscope were applied to analyse the autophagy induction and highly dynamic transport of autolysosomes in rat PC12 neurites. Beading formation was found in degenerating PC12 neurites under phase contrast light microscope after serum deprivation. The monomeric red fluorescence protein‐green fluorescence protein‐light chain 3–labelled autolysosomes accumulated throughout PC12 neurites after 18 h of serum deprivation as revealed by fluorescence microscope analysis. The single‐membrane autolysosomes were also visualized in PC12 cells under transmission electron microscope. Moreover, fluorescence recovery after photobleaching experiment, which was conducted by confocal laser scanning microscope, demonstrated that autolysosomes were motile vesicles and moved along PC12 neurites during starvation. The directional transport of monomeric red fluorescence protein ‐labelled autolysosomes in neurites was further monitored by a motorized video microscope. Both anterograde and retrograde transport of autolysosomes were observed. In addition, the autolysosomes were precisely mapped by using 2D Gaussian fitting and then their highly dynamic movement was robustly tracked by using multidimensional assignment. Collectively, by using different microscopical techniques, our results confirmed the dynamic transport of autolysosomes in starved PC12 neurites and may provide valuable insight into understanding the biophysical characteristics of autolysosomes in neurites under physiological and pathological conditions.
A role for the miR396/GRF network in specification of organ type during flower development, as supported by ectopic expression of Populus trichocarpa miR396c in transgenic tobacco
Authors: Baucher M. , Moussawi J. , Vandeputte O. M. , Monteyne D. , Mol A. , Pérez‐Morga D. , El Jaziri M.
Published: November 2012

The MIR396 family, composed of ath‐miR396a and ath‐miR396b in Arabidopsis, is conserved among plant species and is known to target the Growth‐Regulating Factor (GRF) gene family. ath‐miR396 overexpressors or grf mutants are characterised by small and narrow leaves and show embryogenic defects such as cotyledon fusion. Heterologous expression of ath‐miR396a has been reported in tobacco and resulted in reduction of the expression of three NtGRF genes. In this study, the precursor of the Populus trichocarpa ptc‐miR396c, with a mature sequence identical to ath‐miR396b, was expressed under control of the CaMV35S promoter in tobacco. Typical phenotypes of GRF down‐regulation were observed, including cotyledon fusion and lack of shoot apical meristem (SAM). At later stage of growth, transgenic plants had delayed development and altered specification of organ type during flower development. The third and fourth whorls of floral organs were modified into stigmatoid anthers and fasciated carpels, respectively. Several NtGRF genes containing a miR396 binding site were found to be down‐regulated, and the cleavage of their corresponding mRNA at the miR396 binding site was confirmed for two of them using RACE‐PCR analysis. The data obtained agree with the functional conservation of the miR396 family in plants and suggest a role for the miR396/GRF network in determination of floral organ specification.
Partisan Bias in Opinion Formation on Episodes of Political Controversy: Evidence from Great Britain
Authors: Wagner Markus , Tarlov Jessica , Vivyan Nick
Published: November 2012

Voters form judgements about political controversies through a process of motivated reasoning driven by two goals: the desire to reach an objectively accurate conclusion ( accuracy) and the desire to reach a conclusion congruent with pre-existing views ( direction). The impact of directional goals may depend on political sophistication. We test our hypotheses using data from a 2011 British survey that measured voters' opinions on three specific real-life political controversies. We use voters' underlying tolerance of political misconduct as an indicator of accuracy goals and party identification as a measure of directional goals. We find that partisan predispositions and tolerance of political misconduct are both important in shaping voter opinions and that partisanship has the strongest influence among the more knowledgeable and interested voters. These findings further our understanding of how voters react to political controversies and how they process new political information.
Modelling Local and Regional Economic Development in Turkey: A “Curate's Egg”
Authors: Ersoy Aksel , Taylor Michael
Published: November 2012

This paper explores and unpacks the nature of the processes shaping regional economic growth in Turkey using an econometric modelling strategy. Existing empirical research in this field has focussed on regions in economically advanced and technologically innovative economies. As a consequence, the broader picture of the dynamics of regional development in less developed countries, particularly its social and political origins and the overall changes in regional inequality, has remained elusive and less clear. In this study, a set of econometric models is developed to explore the validity of a range of theoretical propositions in explaining the trajectories of regional economic change in Turkey between 2004 and 2008. Growth is calibrated in terms of employment and changing rates of unemployment in the chosen time period in the 81 provinces of Turkey. The results of the study explain that implications of the current local and regional economic development theories are a “Curate's Egg”—good in parts—because these theories are only partially relevant in the Turkish context.