bluuebunny/crossref_metadata_2025 huggingface dataset:
Connecting fractional anisotropy from medical images with mechanical anisotropy of a hyperviscoelastic fibre-reinforced constitutive model for brain tissue
Authors: Giordano Chiara , Kleiven Svein
Published: November 2013

Brain tissue modelling has been an active area of research for years. Brain matter does not follow the constitutive relations for common materials and loads applied to the brain turn into stresses and strains depending on tissue local morphology. In this work, a hyperviscoelastic fibre-reinforced anisotropic law is used for computational brain injury prediction. Thanks to a fibre-reinforcement dispersion parameter, this formulation accounts for anisotropic features and heterogeneities of the tissue owing to different axon alignment. The novelty of the work is the correlation of the material mechanical anisotropy with fractional anisotropy (FA) from diffusion tensor images. Finite-element (FE) models are used to investigate the influence of the fibre distribution for different loading conditions. In the case of tensile–compressive loads, the comparison between experiments and simulations highlights the validity of the proposed FA–
k
correlation. Axon alignment affects the deformation predicted by FE models and, when the strain in the axonal direction is large with respect to the maximum principal strain, decreased maximum deformations are detected. It is concluded that the introduction of fibre dispersion information into the constitutive law of brain tissue affects the biofidelity of the simulations.
Global assessment of the status of coral reef herbivorous fishes: evidence for fishing effects
Authors: Edwards C. B. , Friedlander A. M. , Green A. G. , Hardt M. J. , Sala E. , Sweatman H. P. , Williams I. D. , Zgliczynski B. , Sandin S. A. , Smith J. E.
Published: November 2013

On coral reefs, herbivorous fishes consume benthic primary producers and regulate competition between fleshy algae and reef-building corals. Many of these species are also important fishery targets, yet little is known about their global status. Using a large-scale synthesis of peer-reviewed and unpublished data, we examine variability in abundance and biomass of herbivorous reef fishes and explore evidence for fishing impacts globally and within regions. We show that biomass is more than twice as high in locations not accessible to fisheries relative to fisheries-accessible locations. Although there are large biogeographic differences in total biomass, the effects of fishing are consistent in nearly all regions. We also show that exposure to fishing alters the structure of the herbivore community by disproportionately reducing biomass of large-bodied functional groups (scraper/excavators, browsers, grazer/detritivores), while increasing biomass and abundance of territorial algal-farming damselfishes (Pomacentridae). The browser functional group that consumes macroalgae and can help to prevent coral–macroalgal phase shifts appears to be most susceptible to fishing. This fishing down the herbivore guild probably alters the effectiveness of these fishes in regulating algal abundance on reefs. Finally, data from remote and unfished locations provide important baselines for setting management and conservation targets for this important group of fishes.
Populists in Parliament: Comparing Left-Wing and Right-Wing Populism in the Netherlands
Authors: Otjes Simon , Louwerse Tom
Published: November 2013

In parliament, populist parties express their positions almost every day through voting. There is great diversity among them, for instance between left-wing and right-wing populist parties. This gives rise to the question: is the parliamentary behaviour of populists motivated by their populism or by their position on the left/right spectrum? This article compares the parliamentary voting behaviour of the Dutch SP and PVV, the only left-wing and right-wing populist parties that have been in a Western European parliament for more than four years. We find that for their voting behaviour the left/right position of these populist parties is more important than their shared populism. Only on one core populist issue (opposition to supranational institutions) do we find strong similarity in their voting behaviour.
Loss of Functional NADPH Oxidase 2 Protects Against Alcohol‐Induced Bone Resorption in Female p47phox−/− Mice
Authors: Mercer Kelly E. , Sims Clark R. , Yang Carrie S. , Wynne Rebecca A. , Moutos Christopher , Hogue William R. , Lumpkin Charles K. , Suva Larry J. , Chen Jin‐Ran , Badger Thomas M. , Ronis Martin J. J.
Published: November 2013

Background

In bone, NADPH oxidase (NOX)‐derived reactive oxygen species (ROS) superoxide and/or hydrogen peroxide are an important stimulus for osteoclast differentiation and activity. Previously, we have demonstrated that chronic ethanol (EtOH) consumption generates excess NOX‐dependent ROS in osteoblasts, which functions to stimulate nuclear factor kappa‐β receptor ligand (RANKL)–RANK signaling, thus increasing osteoclastogenesis and activity. This activity can be blocked by co‐administration of EtOH with the pan‐NOX inhibitor diphenylene idonium (DPI).

Methods

To test whether EtOH‐induced bone loss is dependent on a functional NOX2 enzyme, 6‐week‐old female C57BL/6J‐Ncf1/p47phox−/− (p47phox KO) and wild‐type (WT) mice were pair‐fed EtOH diets for 40 days. Bone loss was assessed by 3‐point bending, micro‐computed tomography and static histomorphometric analysis. Additionally, ST2 cultured cells were co‐treated with EtOH and NOX inhibitors, DPI, gliotoxin, and plumbagin, after which changes in ROS production, and in RANKL and NOX mRNA expression were analyzed.

Results

In WT mice, EtOH treatment significantly reduced bone density and mechanical strength, and increased total osteoclast number and activity. In EtOH‐treated p47phox KO mice, bone density and mechanical strength were completely preserved. EtOH p47phox KO mice had no changes in osteoclast numbers or activity, and no elevations in serum CTX or RANKL gene expression (p < 0.05). In both WT and p47phox KO mice, EtOH feeding reduced biochemical markers of bone formation (p < 0.05). In vitro EtOH exposure of ST2 cells increased ROS, which was blocked by pretreating with DPI or the NOX2 inhibitor gliotoxin. EtOH‐induced RANKL and NOX2 gene expression were inhibited by the NOX4‐specific inhibitor plumbagin.

Conclusions

These data suggest that NOX2‐derived ROS is necessary for EtOH‐induced bone resorption. In osteoblasts, NOX2 and NOX4 appear to work in tandem to increase RANKL expression, whereas EtOH‐mediated inhibition of bone formation occurs via a NOX2‐independent mechanism.
Usefulness of indirect alcohol biomarkers for predicting recidivism of drunk‐driving among previously convicted drunk‐driving offenders: results from the Recidivism Of Alcohol‐impaired Driving (ROAD) study
Authors: Maenhout Thomas M. , Poll Anneleen , Vermassen Tijl , De Buyzere Marc L. , Delanghe Joris R. ,   the ROAD Study Group
Published: November 2013

Aim

In several European countries, drivers under the influence (DUI), suspected of chronic alcohol abuse are referred for medical and psychological examination. This study (the ROAD study, or Recidivism Of Alcohol‐impaired Driving) investigated the usefulness of indirect alcohol biomarkers for predicting drunk‐driving recidivism in previously convicted drunk‐driving offenders.

Design, setting, participants and measurements

The ROAD study is a prospective study (2009–13) that was performed on 517 randomly selected drivers in Belgium. They were convicted for drunk‐driving for which their licence was confiscated. The initial post‐arrest blood samples were collected and analysed for percentage carbohydrate‐deficient transferrin (%CDT), transaminsase activities [alanine amino transferase (ALT), aspartate amino transferase (AST)], gamma‐glutamyltransferase (γGT) and red cell mean corpuscular volume (MCV). The observation time for each driver was 3 years and dynamic.

Findings

A logistic regression analysis revealed that ln(%CDT) (P < 0.001), ln(γGT) (P < 0.01) and ln(ALT) (P < 0.05) were the best biochemical predictors of recidivism of drunk‐driving. The ROAD index (which includes ln(%CDT), ln(γGT), ‐ln(ALT) and the sex of the driver) was calculated and had a significantly higher area under the receiver operator characteristic curve (0.71) than the individual biomarkers for drunk‐driving recidivism. Drivers with a high risk of recidivating (ROAD index ≥ 25%; third tertile) could be distinguished from drivers with an intermediate risk (16% ≤ ROAD index < 25%; second tertile; P < 0.001) and a low recidivism risk (ROAD index < 16%; first tertile; P < 0.05).

Conclusions

Of all routinely used indirect alcohol markers, percentage of carbohydrate‐deficient transferrin is the major predictor of recidivism of drunk‐driving. The association with gamma‐glutamyltransferase, alanine amino transferase and the sex of the driver could have additional value for identifying drunk‐drivers at intermediate risk of recidivism. Non‐specific indirect alcohol markers, such as alanine amino transferase, gamma‐glutamyltransferase, aspartate amino transferase and red cell mean corpuscular volume have minimal added value to % carbohydrate‐deficient transferrin for distinguishing drunk drivers with a low or high risk of recidivism.
Interleukin‐31 does not induce immediate itch in atopic dermatitis patients and healthy controls after skin challenge
Authors: Hawro T. , Saluja R. , Weller K. , Altrichter S. , Metz M. , Maurer M.
Published: November 2013

Background

The most intriguing function attributed to interleukin‐31 (IL‐31) is its ability to induce pruritus in pathologic conditions, such as atopic dermatitis (AD). As of today, this feature of IL‐31 was tested in vivo only in animal models.

Methods

Ten patients with AD and 10 healthy controls were challenged with IL‐31 and NaCl (negative control) by skin prick testing. Twenty additional healthy controls were subjected to skin prick testing with histamine. Itch and local inflammatory responses of the skin were assessed for up to 72 h.

Results

All of the histamine‐challenged subjects developed immediate pruritus (i.e. within the first 5 min). In contrast, only one IL‐31‐ and two of the NaCl‐challenged subjects reported immediate itch at the provocation site (short lasting, for 2–6 min). Nine subjects (five patients with AD) reported late itch responses to IL‐31 challenges with a mean delay of 143 min. No subject reported late itch responses to histamine or NaCl testing. There was no significant difference in IL‐31‐induced itch start time, duration and intensity between patients with AD and healthy volunteers.

Conclusion

IL‐31 does not induce immediate itch responses in humans. The late onset of IL‐31‐induced itch supports the notion that IL‐31 exerts its pruritic effect indirectly via keratinocytes and secondary mediators, rather than through its receptors on cutaneous nerves.
Initial axillary surgery: results from the BreastSurgANZ Quality Audit
Authors: Chong Chilton , Walters David , de Silva Primali , Taylor Corey , Spillane Andrew , Kollias James , Pyke Chris , Campbell Ian , Maddern Guy
Published: November 2013

Background

The aim of this study was to establish the preference and reasons for initial axillary surgery performed on women with invasive breast cancer in Australia and New Zealand using data from the Breast Surgeon's Society of Australia and New Zealand Quality Audit (BQA) according to whether sentinel lymph node (SLN) biopsy, axillary lymph node dissection (ALND) or no axillary surgery was used.

Methods

Patient data from 1999 to 2011 were categorized according to primary tumour size (≤3 cm or >3 cm) and analysed by year of diagnosis, type of initial axillary surgery and frequency of second axillary surgery following SLN biopsy. Patient age at diagnosis, health insurance status, surgeon caseload and hospital location were also examined as factors affecting the likelihood of performing different types of axillary surgery.

Results

Seventy thousand six hundred and eighty‐eight episodes of early breast cancer with axillary surgery data were reported to the BQA in the study period. The proportion of patients undergoing SLN biopsy as the first operation increased over this period in both tumour size groups with a concomitant decline in the use of ALND as the first operation over the same interval. Elderly women (>70 years old) were four times less likely to undergo axillary surgery for their initial management when compared with women aged 41–70 years old (P < 0.001). Factors favouring ALND as the initial surgery over SLN biopsy included larger tumour size, elderly age, uninsured status and having surgery in a regional centre.

Conclusions

From 1999 to 2011, SLN biopsy as the initial axillary surgery has been widely adopted by surgeons reporting to the BQA. Future evaluation of the BQA data in the following 3–5 years will be performed to monitor this progression.
RIDGE ESTIMATORS FOR PROBIT REGRESSION: WITH AN APPLICATION TO LABOUR MARKET DATA
Authors: Locking Håkan , Månsson Kristofer , Shukur Ghazi
Published: November 2013

In this paper we propose ridge regression estimators for probit models since the commonly applied maximum likelihood (ML) method is sensitive to multicollinearity. An extensive Monte Carlo study is conducted where the performance of the ML method and the probit ridge regression (PRR) is investigated when the data are collinear. In the simulation study we evaluate a number of methods of estimating the ridge parameter k that have recently been developed for use in linear regression analysis. The results from the simulation study show that there is at least one group of the estimators of k that regularly has a lower mean squared error than the ML method for all different situations that have been evaluated. Finally, we show the benefit of the new method using the classical Dehejia and Wahba dataset which is based on a labour market experiment.
Cost‐effectiveness of tooth replacement strategies for partially dentate elderly: a randomized controlled clinical trial
Authors: McKenna Gerald , Allen Finbarr , Woods Noel , O'Mahony Denis , Cronin Michael , DaMata Cristiane , Normand Charles
Published: November 2013

Objective

To conduct a cost‐effectiveness analysis comparing two different tooth replacement strategies for partially dentate older patients, namely partial removable dental prostheses (RDP) and functionally orientated treatment based on the shortened dental arch concept (SDA).

Methods

Ninety‐two partially dentate older patients completed a randomized controlled clinical trial. Patients were randomly allocated to two treatment groups: the RDP group and the SDA group. Treatment effect was measured using impact on oral health–related quality of life (OHrQOL), and the costs involved in providing and maintaining care were recorded for all patients. Patients were followed for 12 months after treatment intervention. All treatment was provided by a single operator.

Results

The total cost of achieving the minimally important clinical difference (MID) in OHrQOL for an average patient in the RDP group was €464.64. For the SDA group, the cost of achieving the MID for an average patient was €252.00. The cost‐effectiveness ratio was therefore 1:1.84 in favour of SDA treatment.

Conclusion

With an increasingly ageing population, many patients will continue to benefit from removable prostheses to replace their missing natural teeth. From a purely economic standpoint, the results from this analysis suggest that the treatment of partially dentate older adults should be focused on functionally orientated treatment because it is simply more cost‐effective.
Role of c-Jun N-terminal kinase isoforms in the cellular activity of melanoma cell lines
Authors: Kogushi-Nishi H. , Jinnin M. , Kobayashi Y. , Muchemwa F. C. , Hirano A. , Makino T. , Fukushima S. , Masuguchi S. , Ishihara T. , Inoue Y. , Ihn H.
Published: November 2013

Background

The c-Jun N-terminal kinase (JNK) is thought to be involved in inflammation, proliferation and apoptosis.

Aim

To examine the role of JNK isoforms in metastasis, proliferation, migration and invasion of the malignant melanoma (MM) cell lines SK-MEL-28, SK-MEL-3 and WM164, using a kinase-specific inhibitor or isoform-specific small interfering (si)RNAs.

Results

SK-MEL-3, a cell line established from metastatic MM, showed slightly increased phosphorylation of both JNK1 and JNK2, whereas WM164, a cell line derived from primary MM, showed significant phosphorylation of JNK1. A JNK inhibitor, SP600125, inhibited cell proliferation of SK-MEL-3 but not SK-MEL-28 or WM164. Transfection of JNK1-specific siRNA reduced the migratory activity of WM164 cells, while silencing of either JNK1 or JNK2 strongly suppressed the invasive activity of SK-MEL-3.

Conclusions

Our study suggests that JNK isoforms have different roles in MM. Metastasis of MM may be regulated by JNK2, while invasion is regulated by both JNK1 and JNK2. JNK1 and JNK2 respectively mediate cell migration and cell proliferation. Further understanding of the specific roles of JNK isoforms in the pathogenesis of MM may lead to the development of therapies targeting specific isoforms.
Exercise practices in individuals at clinical high risk of developing psychosis
Authors: Deighton Stephanie , Addington Jean
Published: November 2013

Aim

Recent research suggests aerobic exercise has a positive impact on symptoms and cognition in psychosis. Because individuals with psychosis are at risk of weight gain and the resultant metabolic side‐effects, developing effective exercise programmes is of interest. Furthermore, this may be a useful intervention for those who are at risk of developing psychosis, that is, those at clinical high risk (CHR). The aim of this initial exploratory project was to examine the role of exercise in participants at CHR for psychosis.

Methods

A comprehensive questionnaire was developed to assess current physical activity involvement; exercise levels in terms of frequency, intensity and duration; and perceived fitness levels. Reported barriers to exercise and reasons for exercising were also considered. Eighty participants, 40 CHR and 40 healthy controls, were assessed with this questionnaire.

Results

Overall, both groups were involved in a wide range of physical activity. Healthy controls reported higher levels of participation in indoor/outdoor activities and strength and/or flexibility training. They also exercised more frequently, more intensely and reported higher perceived fitness levels than CHR participants. Levels of exercise were unrelated to clinical symptoms and functioning in CHR participants. CHR youth reported more barriers to exercise and less positive reasons for exercising that were related to self‐perception.

Conclusion

The results suggest that exercise should be investigated further in the CHR population as it may have treatment implications.
Consequences of inhibition of bumetanide metabolism in rodents on brain penetration and effects of bumetanide in chronic models of epilepsy
Authors: Töpfer Manuel , Töllner Kathrin , Brandt Claudia , Twele Friederike , Bröer Sonja , Löscher Wolfgang
Published: November 2013

The diuretic bumetanide, which acts by blocking the Na–K–Cl cotransporter (NKCC), is widely used to inhibit neuronal NKCC1, particularly when NKCC1 expression is abnormally increased in brain diseases such as epilepsy. However, bumetanide poorly penetrates into the brain and, in rodents, is rapidly eliminated because of extensive oxidation of its N‐butyl sidechain, reducing the translational value of rodent experiments. Inhibition of oxidation by piperonyl butoxide (PBO) has previously been reported to increase the half‐life and diuretic activity of bumetanide in rats. Here we studied whether inhibition of bumetanide metabolism by PBO also increases brain levels of bumetanide in rats, and whether this alters pharmacodynamic effects in the kindling model of epilepsy. Furthermore, we studied the effects of PBO in mice. Mice eliminated bumetanide less rapidly than rats (elimination half‐life 47 min vs. 13 min). Pretreatment with PBO increased the half‐life in mice to average values (70 min) previously determined in humans, and markedly elevated brain levels of bumetanide. In rats, the increase in plasma and brain levels of bumetanide by PBO was less marked than in mice. PBO significantly increased the diuretic activity of bumetanide in rats and, less effectively, in mice. In epileptic mice, bumetanide (with PBO) did not suppress spontaneous seizures. In the rat kindling model, bumetanide (with or without PBO) did not exert anticonvulsant effects on fully kindled seizures, but dose‐dependently altered kindling development. These data indicate that PBO offers a simple means to enhance the translational properties of rodent experiments with bumetanide, particularly when using mice.
Breakthrough ideas leading to new futures: prologue
Authors: Willy Christian
Published: November 2013

Since commercialisation almost 20 years ago, negative pressure wound therapy (NPWT; V.A.C.® Therapy; KCI USA, Inc., San Antonio, TX) has been used to treat a wide variety of wound types and continues to evolve as research expands understanding of the mechanisms of action that enable this adjunct therapy to facilitate wound closure. In 2010, the educational International Surgical Wound Forum (ISWF) was created to facilitate discussion among experts from all over the world regarding modern wound treatment challenges and techniques. This is the first of two supplements, which are based on the 2012 and 2013 ISWF presentations and demonstrate the evolution of the role of NPWT in wound care. This first supplement provides an overview of current health care challenges and clinical practice and reviews evidence and experience using NPWT with instillation, which combines NPWT with computer‐controlled delivery and removal of topical solutions and suspensions to cleanse and/or treat wounds.
Tumour necrosis factor-alpha (TNF-α) in the host resistance to mycobacteria of distinct virulence
Authors: APPELBERG R , SARMENTO A , CASTRO A G
Published: November 2013

The relative virulence of different isolates of Mycobacterium avium has been linked to their capacity to trigger the secretion of TNF from the macrophages they infect. Smooth opaque (SmOp) variants of Myco. avium have been shown to trigger higher expression of TNF-α by macrophages in vitro than the smooth transparent (SmTr) variants. To analyse the role of TNF in resistance to infection by Myco. avium, we studied the infection by two different morphotypes of strain 2.151 of Myco. avium both in vitro and in vivo in the presence or absence of neutralizing antibodies to TNF. No effects were found in vitro regarding the growth of either isolate of Myco. avium. In vivo, only the virulent SmTr morphotype showed enhanced growth in the presence of the neutralizing antibodies. This enhancement occurred relatively late when priming for TNF secretion in vivo was evident. Among four isolates of Myco. avium, three virulent ones induced a marked priming for TNF release and one avirulent strain did not. Mycobacterium tuberculosis H37Ra, which is very active in inducing TNF release due to its lipoarabinomannan moiety, was used to compare with the previous results. The growth of H37Ra in macrophages was increased in vitro by the neutralization of TNF and neutralization of either TNF and/or interferon-gamma (IFN-γ) enhanced the in vivo proliferation of this microbe in the spleen and liver of infected animals, whereas only the combination of both anti-TNF and anti-IFN-γ enhanced bacterial proliferation in the lung. We conclude that resistance to the avirulent strains of Myco. avium did not involve TNF, but rather antimicrobial mechanisms expressed consitutively in the mononuclear phagocytes. In contrast, TNF plays an important role in the control of Myco. tuberculosis H37Ra infection.
Fibronectin (FN) decreases glomerular lesions and synthesis of tumour necrosis factor-alpha (TNF-α), platelet-activating factor (PAF) and FN in proliferative glomerulonephritis
Authors: ORTÍZ A , ALONSO J , GÓMEZ-CHIARRI M , LERMA J L , SERON D , CONDOM E , GONZÁLEZ E , EGIDO J
Published: November 2013

We have studied the effect of therapy with plasma FN on glomerular synthesis of PAF, TNF-α and FN, in experimental proliferative glomerulonephritis. Glomerular PAF, TNF-α and FN production were increased in rats with nephritis. Peak glomerular PAF production preceded, while peak glomerular TNF-α bioactivity coincided with maximal proteinuria. Rats treated with FN (5 mg/kg per 48 h) for 15 days had less proteinuria, glomerular and interstitial cell infiltration and glomerular PAF, TNF-α and FN synthesis than non-treated rats. In order to characterize further the mechanisms of action of FN, healthy rats were injected with either FN or saline. Peripheral blood mononuclear cells and neutrophils from healthy rats injected with FN secreted less TNF-α and PAF, respectively, than those obtained from saline-treated rats. Our data suggest that the beneficial effect of FN may be related to decreased number of glomerular leucocytes and decreased synthesis of inflammatory mediators and extracellular matrix.
Strain variation in susceptibility to the development of monoclonal antibody 5-1-6-induced proteinuria in rats
Authors: GOLLNER D , KAWACHI H , OITE T , OKA M , NAGASE M , SHIMIZU F
Published: November 2013

Susceptibility to the development of MoAb 5-1-6-induced proteinuria was investigated in four different rat strains, i.e. Brown-Norway (BN), Lewis (LEW), Sprague-Dawley (SD) and Wistar. An intravenous injection of 5 mg of MoAb 5-1-6 to female 7-week-old rats of a given strain induced massive proteinuria in BN, LEW and Wistar rats. However, SD rats developed almost no proteinuria. A similar tendency was observed in the second experiment, in which the injected dose of MoAb was adjusted according to the body weight of each rat (3 mg/100 g body weight). Immunofluorescence (IF) and immunoelectron microscopy (IEM) revealed no differences between the binding patterns of the MoAbs to normal rat kidneys derived from each strain. Quantitative study using 125I-labelled MoAb showed that there was no significant difference in the amount of antibody bound to the kidney 1 h and 5 days after injection between two rat strains, LEW and SD. Localization of 5-1-6 in vivo and its kinetics were investigated. In IF a linear-like pattern along capillary walls was observed 2 h after injection in both LEW and SD strains. This linear-like pattern was shifted to a granular pattern in proteinuric LEW rats 6 days after injection, whereas it remained linear-like in non-proteinuric SD rats. IEM confirmed this difference in the localization of injected MoAb 6 days after injection to LEW and SD rats also at the ultrastructural level. We conclude that there is a clear-cut strain difference in the development of proteinuria induced by MoAb 5-1-6. SD rats were less susceptible to MoAb-induced glomerular injury than BN, LEW and Wistar rats. Although the exact reason for strain variation in susceptibility to MoAb-induced proteinuria remains to be clarified, the movement of bound MoAb, presumably together with corresponding antigenic molecule along the glomerular epithelial cell surface followed by endocytosis into the epithelial cell, seems to be closely related to the induction of proteinuria.
Human recombinant IL-4 decreases the emergence of non-specific cytolytic cells and favours the appearance of memory cells (CD4+CD45RO+) in the IL-2-driven development of cytotoxic T lymphocytes against autologous ovarian tumour cells
Authors: ROTH A D , DUPUIS S , ALBERTO P
Published: November 2013

As IL-4 and IL-6 have also been reported to promote the development of T lymphocytes such as IL-2, we investigated their role in the development of specific cytotoxic T lymphocytes (CTL) against autologous ovarian tumours in mixed lymphocyte tumour cultures (MLTC). Peripheral blood lymphocytes (PBL) from five ovarian carcinoma (OC) patients were incubated with autologous OC cells at a PBL:OC cell ratio of 20:1 in IL-2 alone (50 U/ml for the first week and 200 U/ml thereafter) or with IL-4 (100 U/ml) and/or IL-6 (5 U/ml). Neither IL-4 nor IL-6 improved lymphocyte proliferation consistently. In contrast, IL-4 reduced significantly the development of LAK activity as assayed against Daudi cell line, and decreased modestly the emergence of natural killer (NK) activity as assayed against K562. This property was not shared by IL-6. The prevention of the development of non-specific cytolytic activity (LAK and NK activities) was much stronger when the MLTC was started with IL-4 in the absence of IL-2 during the first week in culture. A concomitant drop in NKH-1 expression (CD56) was observed. By inhibiting the emergence of non-specific cytotoxicity, IL-4 provided better evidence of the specific cytolytic activity directed at ovarian cells. In parallel, a significant increase in the generation of memory cells (CD4+CD45RO+) was observed with IL-4. In conclusion, in this model, IL-4 added before IL-2 decreases significantly the emergence of non-specific cytotoxic cells, and promotes the generation of memory cells. These properties may be of interest in the design of strategies aimed at obtaining tumour-specific cells for investigational and immunotherapeutic purposes.
In vitro comparison of V‐Loc™ versus Biosyn™ in a one‐layer end‐to‐end anastomosis of equine jejunum
Authors: Nelson Brad B. , Hassel Diana M.
Published: November 2013

Objective

To compare a unidirectional barbed suture (V‐Loc™) to its suture material equivalent (Biosyn™) in a single‐layer end‐to‐end anastomosis of equine jejunum.

Study Design

Experimental in vitro study.

Animals

Jejunal sections from adult horses (n = 5) without gastrointestinal disease.

Methods

Jejunal end‐to‐end anastomoses (n = 9) were performed for each group (V‐Loc™, Biosyn™) with a continuous Lembert pattern with an interruption every 120°. Anastomosis construction time, luminal diameter, and number of suture bites were recorded. Anastomosis constructs were distended with fluid at 1 L/min until failure. Location and intraluminal pressure at failure were recorded and all measurements were compared between groups.

Results

V‐Loc™ anastomoses were significantly faster to perform (13.1 ± 0.35 minutes) when compared to the Biosyn™ group (15.6 ± 0.72 minutes; P = .0004). No differences were observed for anastomotic index or number of suture bites. V‐Loc™ anastomosis constructs had a significantly decreased bursting pressure (160 ± 11.6 mmHg) compared to Biosyn™ constructs (184 ± 16.9 mmHg; P = .01).

Conclusions

V‐Loc™ allowed faster construction time and did not cause a decreased anastomosis luminal diameter when compared with Biosyn™. V‐Loc™ had a decreased bursting strength compared with Biosyn™, albeit well above pathologic pressures encountered clinically. Use of V‐Loc™ may be beneficial for decreasing the amount of exposed suture material because of the absence of knots after construction and has the potential to result in decreased adhesions.
Impact of serving method on the consumption of nutritional supplement drinks: randomized trial in older adults with cognitive impairment
Authors: Allen Victoria J. , Methven Lisa , Gosney Margot
Published: November 2013

Aim

To analyse the influence of serving method on compliance and consumption of nutritional supplement drinks in older adults with cognitive impairment.

Background

Oral nutritional supplement drinks have positive benefits on increasing nutritional status in undernourished older people leading to weight gain. However, consumption of these drinks is low and therefore limits their effectiveness.

Design

This study was a non‐blind randomized control trial where participants either consumed nutritional supplement drinks in a glass/beaker or consumed them through a straw inserted directly into the container.

Method

Participants with long‐standing cognitive impairment were recruited from nursing homes (n = 31) and hospitals (n = 14). Participants were randomized to serving method. Nursing and care staff were instructed to give the supplement drinks three times per day on alternate days over a week by the allocated serving method. The researcher weighed the amount of supplement drink remaining after consumption. Data were collected over 12 months in 2011–2012.

Results

Forty‐five people participated in this study, mean age 86·7 (sd 7·5) years. After randomization, there was no significant difference between the baseline characteristics of the two groups. Participants randomized to consume nutritional drinks from a glass/beaker drank statistically significantly more than those who consumed them via a straw inserted directly into the container. However, supplements allocated to be given in a glass/beaker were more frequently omitted.

Conclusion

Nutritional supplement drinks should be given to people with dementia who are able to feed themselves in a glass or a beaker if staffing resources allow (NIHR CSP ref 31101).
Risk of Sudden Cardiac Death in Chronic Kidney Disease
Authors: POULIKAKOS DIMITRIOS , BANERJEE DEBASISH , MALIK MAREK
Published: November 2013

Sudden Cardiac Death in Chronic Kidney Disease

The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end‐stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes.
Combination treatment for myeloproliferative neoplasms using JAK and pan‐class I PI3K inhibitors
Authors: Choong Meng Ling , Pecquet Christian , Pendharkar Vishal , Diaconu Carmen C. , Yong Jacklyn Wei Yan , Tai Shi Jing , Wang Si Fang , Defour Jean‐Philippe , Sangthongpitag Kanda , Villeval Jean‐Luc , Vainchenker William , Constantinescu Stefan N. , Lee May Ann
Published: November 2013

Current JAK2 inhibitors used for myeloproliferative neoplasms (MPN) treatment are not specific enough to selectively suppress aberrant JAK2 signalling and preserve physiological JAK2 signalling. We tested whether combining a JAK2 inhibitor with a series of serine threonine kinase inhibitors, targeting nine signalling pathways and already used in clinical trials, synergized in inhibiting growth of haematopoietic cells expressing mutant and wild‐type forms of JAK2 (V617F) or thrombopoietin receptor (W515L). Out of 15 kinase inhibitors, the ZSTK474 phosphatydylinositol‐3′‐kinase (PI3K) inhibitor molecule showed strong synergic inhibition by Chou and Talalay analysis with JAK2 and JAK2/JAK1 inhibitors. Other pan‐class I, but not gamma or delta specific PI3K inhibitors, also synergized with JAK2 inhibitors. Synergy was not observed in Bcr‐Abl transformed cells. The best JAK2/JAK1 and PI3K inhibitor combination pair (ruxolitinib and GDC0941) reduces spleen weight in nude mice inoculated with Ba/F3 cells expressing TpoR and JAK2 V617F. It also exerted strong inhibitory effects on erythropoietin‐independent erythroid colonies from MPN patients and JAK2 V617F knock‐in mice, where at certain doses, a preferential inhibition of JAK2 V617F mutated progenitors was detected. Our data support the use of a combination of JAK2 and pan‐class I PI3K inhibitors in the treatment of MPNs.
Motor protein function in skeletal abdominal muscle of cachectic cancer patients
Authors: Taskin Sultan , Stumpf Vera Isabell , Bachmann Jeannine , Weber Cornelia , Martignoni Marc Eric , Friedrich Oliver
Published: November 2013

Cachexia presents with ongoing muscle wasting, altering quality of life in cancer patients. Cachexia is a limiting prognostic factor for patient survival and health care costs. Although animal models and human trials have shown mechanisms of motorprotein proteolysis, not much is known about intrinsic changes of muscle functionality in cancer patients suffering from muscle cachexia, and deeper insights into cachexia pathology in humans are needed. To address this question, rectus abdominis muscle samples were collected from several surgical control, non‐cachectic and cachectic cancer patients and processed for skinned fibre biomechanics, molecular in vitro motility assays, myosin isoform protein compositions and quantitative ubiquitin polymer protein analysis. In pre‐cachectic and cachectic cancer patient samples, maximum force was significantly compromised compared with controls, but showed an unexpected increase in myofibrillar Ca2+ sensitivity consistent with a shift from slow to fast myosin isoform expression seen in SDS‐PAGE analysis and in vitro motility assays. Force deficit was specific for ‘cancer’, but not linked to presence of cachexia. Interestingly, quantitative ubiquitin immunoassays revealed no major changes in static ubiquitin polymer protein profiles, whether cachexia was present or not and were shown to mirror profiles in control patients. Our study on muscle function in cachectic patients shows that abdominal wall skeletal muscle in cancer cachexia shows signs of weakness that can be partially attributed to intrinsic changes to contractile motorprotein function. On protein levels, static ubiquitin polymeric distributions were unaltered, pointing towards evenly up‐regulated ubiquitin protein turnover with respect to ubiquitin conjugation, proteasome degradation and de‐ubiquitination.
Obesity and gastrointestinal liver disorders in Japan
Authors: Matsuura Bunzo , Nunoi Hiroaki , Miyake Teruki , Hiasa Yoichi , Onji Morikazu
Published: November 2013

In Japan, the prevalence of obesity in adult men has increased since the 1970s, while that in adult women has not changed. The prevalence of obesity in 5‐, 8‐, 11‐, and 14‐year‐old boys and girls increased from the late 1980s to late 1990s and has decreased since 2000, while that in 17‐year‐old girls increased in 2002, similar to that for boys, but has since decreased. In 2009, 33.3% of adult men and 25.0% of adult women were obese, and 8–10% of children (age, 5–17 years) were obese. The prevalence of visceral obesity in adults was 50.8% of men and 18.0% of women. Obesity, especially visceral obesity, affects insulin resistance and increases metabolic diseases (diabetes mellitus, dyslipidemia, hypertension, cardiovascular disease, and non‐alcoholic fatty liver disease [NAFLD]) and various cancers. In Japan, with a body mass index (BMI) of 23–25 as the reference category, the hazard ratio of total mortality is 1.36 for a BMI of 30–40 in men and 1.37 with a BMI of 30–40 in women. The frequency of patients with NAFLD has gradually increased in proportion to the increase in the population with obesity. From recent studies in Japan, the number of NAFLD patients is estimated to be 10 million, and around 2 million are considered to have non‐alcoholic steatohepatitis. Dietary and behavioral modification is effective for body weight loss and for improvement of obesity‐related gastrointestinal liver diseases. If necessary, bariatric surgery is useful for obesity treatment.
Iron metabolic disorder in chronic hepatitis C: Mechanisms and relevance to hepatocarcinogenesis
Authors: Hino Keisuke , Nishina Sohji , Hara Yuichi
Published: November 2013

The liver is the major iron storage organ in the body, and therefore, iron metabolic disorder is sometimes involved in chronic liver diseases. Chronic hepatitis C is one of the liver diseases that show hepatic iron accumulation, even though its level should be recognized to be basically mild to moderate and sometimes within the normal range. The mechanisms underlying hepatic iron accumulation in chronic hepatitis C have not been fully elucidated. Reduction of the hepcidin transcription activity by hepatitis C virus (HCV)‐induced reactive oxygen species may in part account for it, but the regulation of hepcidin is very complex and may depend on many variables, including the particular stage of the systemic and/or hepatic inflammatory conditions and the circulating transferrin‐bound iron and intracellular iron stores. This might explain the variations in hepatic iron concentrations reported among patients with HCV‐related chronic liver disease. However, even mild‐to‐moderate iron overload in the liver contributes to disease progression and hepatocarcinogenesis in chronic hepatitis C probably by reinforcing the HCV‐induced oxidative stress through Fenton reaction. The present review highlights the current concept of hepatic iron overload status in chronic hepatitis C and discusses how iron metabolic disorder develops in this disease and the impact of hepatic iron overload on disease progression and its relevance to hepatocarcinogenesis.
Role of FODMAP content in enteral nutrition‐associated diarrhea
Authors: Halmos Emma P
Published: November 2013

Gastrointestinal symptoms including diarrhea are common complications of enteral nutrition (EN); however, the cause is unclear. Mode of EN delivery that alters digestion and possibly absorption is suggested to contribute to the high incidence of diarrhea; however, enteral formula is frequently blamed. Most research has focused on fiber‐supplemented EN, with a meta‐analysis showing that fiber reduces the incidence of diarrhea in non‐intensive care unit studies. Other hypotheses include formula osmolality and FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) content. FODMAPs are poorly absorbed short‐chain carbohydrates that exert an osmotic effect. Dietary FODMAPs have been shown to reduce gastrointestinal symptoms, including diarrhea, in those with irritable bowel syndrome and, given a high‐enough dose, will induce a laxative effect in most people. As FODMAPs are commonly added to enteral formula and EN is frequently used as the main source of nutrition, it is reasonable to hypothesize that EN provides more FODMAPs than usual dietary intake and increases risk for developing diarrhea. This hypothesis was assessed through a retrospective study showing that the standard‐use enteral formula Isosource 1.5 had a protective effect of developing diarrhea. The only characteristic unique to Isosource 1.5 was the lower FODMAP content as determined through methodologies previously validated for food analysis. Methodologies for application to enteral formulas are currently undergoing formal validation. Once confirmed for application in enteral formula, future directions include FODMAP analysis of specific ingredients to increase understanding of potential problems associated with enteral formula and a randomized, controlled trial investigating the role of formula FODMAP content.
Royal College of Physicians Intercollegiate Stroke Working Party evidence‐based guidelines for the nutritional support of patients who have had a stroke
Authors: Gomes F. , Hookway C. , Weekes C. E.
Published: November 2013

Background

Stroke affects 15 million people each year worldwide and is one of the world's leading causes of death and physical disability. Stroke can result in a decline in nutritional status and this is associated with increased mortality and poor outcomes. The present work aimed to systematically review key aspects of the nutritional support of stroke patients at risk of malnutrition and to provide evidence‐based guidelines for use in clinical practice. The work was conducted as part of the process to develop the 4th edition of the Royal College of Physicians' (RCP) ‘National Clinical Guideline (NCG) for Stroke’.

Methods

Questions were generated by the search team, together with contributions from members of the Virtual Stroke Group and the RCP Intercollegiate Stroke Working Party Guideline Development Group. Six questions covering several areas of nutritional support after stroke were defined and searches were conducted through to 31 October 2011 using five electronic databases (Embase, Medline, CINAHL, Cochrane Library and Web of Science). All included studies were assessed for quality and risk of bias using the van Tulder criteria for randomised controlled trials (RCTs) and the Quorum criteria for systematic reviews.

Results

In total, 4215 abstracts were identified, 24 papers were reviewed and 13 systematic reviews and RCTs were included to provide evidence for the nutritional support components of the guidelines. For each question, evidence statements, recommendations and practical considerations were developed.

Conclusions

This systematic review process has resulted in the development of evidence‐based guidelines for use in clinical practice and has identified areas for further research.
Physical Activity and Nutritional Weight Loss Interventions in Obese, Low‐Income Women: An Integrative Review
Authors: Moredich Cheryl A. , Kessler Theresa A.
Published: November 2013

Introduction

Obesity is epidemic in the United States and is considered a public health issue that disproportionally affects low‐income women. Combating obesity among low‐income women presents unique challenges that must be addressed if weight loss interventions are to be successful. The aim of this integrative review was to explore and synthesize the literature that addresses physical activity and nutrition interventions used to combat obesity in obese, low‐income women.

Methods

A search for original research published between 2006 and 2011 was conducted in online databases. In addition, a hand search of references was performed, and one author was contacted to clarify outcome data. Articles that met inclusion criteria targeted obese, low‐income adult women; focused on physical activity or nutrition behavior as an intervention; and measured change in weight as a primary outcome. Studies that focused on women who were postpartum or breastfeeding and those that used pharmacologic or surgical interventions to augment weight loss were excluded.

Results

A total of 7 articles were chosen for critical appraisal. According to a synthesis of the current studies, specific weight loss interventions for physical activity and nutrition behavior change for obese, low‐income women produced the desired outcome of weight loss. Participants among these studies voiced a preference for group interventions led by peers or medical professionals. Interventions led by peer educators were successful and had the advantage of lowering cost and increasing sustainability. Pragmatic nutrition education worked best, especially when cognizant of cost, food preferences, and culture. Even small increases in physical activity augmented weight loss; however, safety concerns prevented some low‐income women from engaging in exercise.

Discussion

According to this synthesis of the best‐available evidence, customized weight loss interventions are effective in obese, low‐income women. By incorporating these evidence‐based interventions, clinicians can be instrumental in decreasing the burden of obesity in obese, low‐income women.