bluuebunny/crossref_metadata_2025 huggingface dataset:
The effectiveness of hypnotherapy in the treatment of anxiety in patients with cancer receiving palliative care
Authors: Plaskota Marek , Lucas Caroline , Pizzoferro Kathleen , Saini Treena , Evans Rosie Evans , Cook Karen
Published: September 2011

Introduction

In palliative care patients, anxiety is usually attributed to a reaction to diagnosis, treatment and its possible outcomes. Despite the support for hypnotherapy as a resource for the alleviation of psychological and emotional distress, there is a paucity of evidences to support the use of hypnotherapy for symptom relief.

Aims

Aims of this study were to assess the benefits of hypnotherapy in the management of anxiety in palliative care patients and to ascertain if hypnotherapy could affect other symptoms including depression and sleep disturbance.

Methods

Participants received four sessions of hypnotherapy and completed the Hospital Anxiety and Depression Scale, Edmonton Symptom Assessment Scale, Verran and Snyder-Halpern Scale, and wrist actigraphy. Out of 21 patients recruited, eleven successfully completed the study.

Results

After the second hypnotherapy session there was a statistically significant reduction in patient-reported anxiety (p=0.0066) and symptoms (p=0.0094), but not in depression (p=0.2910) or sleep disturbance (p=0.0868). After the fourth hypnotherapy session, there was a statistically significant reduction in patient-reported anxiety (p=0.0016), depression (p=0.0466), symptoms (p=0.0329) and sleep disturbance (p=0.0081). Actigraphy did not show a statistically significant improvement in sleep quality.

Discussion

Hypnotherapy intervention appears to have a more immediate impact on anxiety and symptom severity whereas the improvement in depression and sleep quality is more slowly acquired. Actigraphy is a new tool to measure the quality of sleep. Its validation is still in progress and thus the sleep indicators chosen for this study are still a subject of debate. This could explain the result inconsistency.

Conclusion

This study suggests that hypnotherapy can contribute to reduction in anxiety in palliative care patients with the added benefit of improving sleep and severity of psychological and physical symptoms.
Diversifying volunteer roles through the ‘Family Friend’ support service
Authors: Roberts Tina , Thompson Andrew
Published: September 2011

Introduction

Serious illness brings stressful changes for patients and carers. Consultation with our carers identified a ‘gap’ between medical and social care, indicating regular help within the home would sustain coping. Locally, reduced employment opportunities harnessed to Big Society thinking, means there is greater capacity for volunteers to bring their individual skills to support patients' families.

Aims

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Introducing a new role whereby volunteers provide individualised carer support within the home.

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Creating a robust and comprehensive training programme to support volunteer autonomy.

Research methods

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Informal interviews with carers.

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Multi-disciplinary team's identification of carers' needs.

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Qualitative research within hospice sector - indicating concern over health and safety issues.

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Discussion and partnership with local Carer Liaison team.

Results

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A successful proposal to local NHS Trust secured full funding for 1 year.

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Dedicated co-ordinator input enabled the implementation of a robust training programme and supporting policies.

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Development of a comprehensive risk assessment covering a broad range of supportive activities for volunteers to undertake.

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Family Friend volunteers express increasing confidence through required monthly support group meetings.

Discussion

With the project active for a full year, it has been formally evaluated with encouraging feedback. Volunteers state that they value working with greater autonomy and express increased role satisfaction. Carers have identified Family Friend support as contributory towards greater coping and confidence. The service's success is attributed to our ability to identify a shortfall in carer support and our faith in skilled and trained volunteers to meet it.

Conclusion

The hospice believes that diversifying the volunteer role and providing enhanced training and supervision has increased satisfaction for volunteers, patients and families. This information could be used by hospices concerned about managing risk in home support volunteering.
Reflecting identities: using portraiture with people suffering from life threatening illnesses
Authors: Carr Susan
Published: September 2011

“I look in the mirror and I say, ‘who’s that?' I don't really know who I am anymore! I have lost the person I thought I was.” Patient, Prospect Hospice.

Arguably life threatening or chronic illness is not just an attack on the body, it is an attack on the embodied self, and identity, shattering the means by which a person experiences the world, and by which they also are experienced, contributing to a person's sense of powerlessness and ‘loss of self’ (Charmaz, 1983). Therefore negatively affecting a person's ability to continue with their pre-illness activities, relationships and future plans and contributing to their ‘total pain’.

This paper will present case studies, drawn from the author's current PhD research, looking at how working collaboratively with an artist to co-design a portrait of themselves can help people suffering from life threatening or chronic illnesses to increase their self knowledge, build new identities and improve their ‘individual creative capacity’, to adapt to illness, therefore enabling the development of a more coherent sense of self and identity.

When attempting to understand the complex emotions and feelings contained within experiences of illness and loss of self, the use of portraiture as identity work, provides an intervention within which discursive knowledge and non-discursive knowledge can be reintegrated into a more coherent whole. Portraits often capture the ‘essence’ or subjectivity of a person; the trace of a human presence left behind, and can enable people feeling detached from their body after invasive treatment, to recover a sense of autonomy over the bodily image they portray. This intervention also offers ‘time,’ for the building of a collaborative relationship, at a time when relationship is hard to sustain, acknowledging that identity is built and sustained in relationship with others.
‘Opening the electronic gate’: raising spiritual awareness online
Authors: Groves Karen , Baldry Catherine , Smith Brian , Sumner Ken , Rimmer Dominic
Published: September 2011

Background

Following an audit of spiritual and religious needs assessment and care provision across one cancer network area in the Northwest of England in 2006 it was clear that most health professionals working within specialist palliative care services felt that they lacked confidence, and would benefit from further education, in spiritual support. The cancer network supported the development of an interactive learning package for staff. ‘Opening the Spiritual gate’, to meet this expressed need.

Aims

To raise awareness of the spiritual and religious needs of patients and families

To help staff feel more confident in discussing and assessing them.

To provide this education in a format which is easily accessible and available to staff.

Method

A joint project between a cancer network and a university technology department in the Northwest of England resulted in the conversion of the interactive awareness raising course of four sessions, originally delivered face to face (on one day or as a series), into an online course based on a constructivist learning format.

Results

The iterative process involved in the conversion, a description of the online instance and the resulting course along with the qualitative analysis of the pilot are described. The results show that the online platform allowed participants to access the course at a time to suit themselves, from anywhere which had internet access and allowed them to learn at their own pace with time for reflection.

Conclusion

Clearly e-learning does not suit everyone, but this project has shown that conversion of even a course reliant on group interaction is possible as long as sufficient material and activity, to meet all learning styles and preferences, is built in and the course is organised to allow small cohorts of people to form a learning community for its duration.
‘Opening the gate’ – What's the difference?
Authors: Groves Karen , Baldry Catherine
Published: September 2011

Background

NICE Supportive and Palliative Care Improving Outcomes Guidance 2004 states clearly that health professionals should be in a position to assess the spiritual and religious needs of patients and either meet these needs or facilitate others to do so. A cancer network audit in 2006 showed that staff felt quite unprepared for this role.

Aim

To see if a one day interactive course to raise awareness of spiritual and religious needs was effective in increasing staff confidence in this area of support.

Method

A spiritual support education programme was developed, which could be rolled out across the cancer network. The course was then offered to participants who chose to attend. Each participant was asked to complete a pre and post course questionnaire and course evaluation.

Results

159 participants attended the first 12 courses. 156 completed pre and post course questionnaires and 104 completed pre and post course confidence visual analogue scales which were compared. Many of the items suggest improvement from before the course to immediately afterwards, for example, pre course only 6% participants felt that they understood the nature of spiritual assessment ‘very well’, 36% ‘quite well’, 57% ‘a little’ or ‘not at all’. After the course 57% participants scored the answer as ‘very well’, and 40% ‘quite well’ with only 3% ‘a little’. Pre course the mean visual analogue score for confidence in assessing spiritual needs was 4.00 and afterwards 6.76 (where 0 was no confidence) and for assessing religious needs pre course 4.71 and post course 7.07.

Conclusion

It appears that this course was successful in raising awareness and understanding of the nature of spiritual assessment and raises the confidence of participants in assessing spirituals needs. It remains to be seen whether the improvement is maintained once the participants return to the workplace.
Transition to adult services for children and young people with palliative care needs: a systematic review
Authors: Doug M , Adi Y , Williams J , Paul M , Kelly D , Petchey R , Carter Y H
Published: September 2011

Objective

To evaluate the evidence on the transition process from child to adult services for young people with palliative care needs.

Design

Systematic review.

Setting

Child and adult services and interface between healthcare providers.

Patients

Young people aged 13–24 years with palliative care conditions in the process of transition.

Main outcome measures

Young people and their families' experiences of transition, the process of transition between services and its impact on continuity of care and models of good practice.

Results

92 studies included. Papers on transition services were of variable quality when applied to palliative care contexts. Most focussed on common life-threatening and life-limiting conditions. No standardised transition program identified and most guidelines used to develop transition services were not evidence-based. Most studies on transition programs were predominantly condition-specific (eg, cystic fibrosis (CF), cancer) services. CF services offered high-quality transition with the most robust empirical evaluation. There were differing condition-dependent viewpoints on when transition should occur but agreement on major principles guiding transition planning and probable barriers. There was evidence of poor continuity between child and adult providers with most originating from within child settings.

Conclusions

Palliative care was not, in itself, a useful concept for locating transition-related evidence. It is not possible to evaluate the merits of the various transition models for palliative care contexts, or their effects on continuity of care, as there are no long-term outcome data to measure their effectiveness. Use of validated outcome measures would facilitate research and service development.
Living and dying with severe chronic obstructive pulmonary disease: multi-perspective longitudinal qualitative study
Authors: Pinnock Hilary , Kendall Marilyn , Murray Scott A , Worth Allison , Levack Pamela , Porter Mike , MacNee William , Sheikh Aziz
Published: September 2011

Objectives

To understand the perspectives of people with severe chronic obstructive pulmonary disease (COPD) as their illness progresses, and of their informal and professional carers, to inform provision of care for people living and dying with COPD.

Design

Up to four serial qualitative interviews were conducted with each patient and nominated carer over 18 months. Interviews were transcribed and analysed both thematically and as narratives.

Participants

21 patients, and 13 informal carers (a family member, friend, or neighbour) and 18 professional carers (a key health or social care professional) nominated by the patients.

Setting

Primary and secondary care in Lothian, Tayside, and Forth Valley, Scotland, during 2007-9.

Results

Eleven patients died during the study period. Our final dataset comprised 92 interviews (23 conducted with patient and informal carer together). Severe symptoms that caused major disruption to normal life were described, often in terms implying acceptance of the situation as a “way of life” rather than an “illness.” Patients and their informal carers adapted to and accepted the debilitating symptoms of a lifelong condition. Professional carers' familiarity with the patients' condition, typically over many years, and prognostic uncertainty contributed to the difficulty of recognising and actively managing end stage disease. Overall, patients told a “chaos narrative” of their illness that was indistinguishable from their life story, with no clear beginning and an unanticipated end described in terms comparable with attitudes to death in a normal elderly population.

Conclusions

Our findings challenge current assumptions underpinning provision of end of life care for people with COPD. The policy focus on identifying a time point for transition to palliative care has little resonance for people with COPD or their clinicians and is counter productive if it distracts from early phased introduction of supportive care. Careful assessment of possible supportive and palliative care needs should be triggered at key disease milestones along a lifetime journey with COPD, in particular after hospital admission for an exacerbation.
Technical, angiographic and clinical outcomes of Neuroform 1, 2, 2 Treo and 3 devices in stent-assisted coiling of intracranial aneurysms
Authors: Kadkhodayan Yasha , Somogyi Christopher T , Cross DeWitte T , Derdeyn Colin P , Zipfel Gregory J , Chicoine Michael R , Rich Keith M , Grubb Robert L , Dacey Ralph G , Moran Christopher J
Published: September 2011

Background and purpose

Since 2002 the Neuroform stent has expanded endovascular treatment of wide-necked intracranial aneurysms. A study was undertaken to assess the technical success rates and angiographic and clinical outcomes in stent-assisted coiling with Neuroform 1, 2, 2 Treo and 3.

Methods

Patients undergoing Neuroform stent-assisted coiling were enrolled in a prospective registry that included 156 stent deployment attempts in 113 consecutive patients (mean age 53, range 25–78). Deployment success and difficulty, stent movement, procedural complications, immediate/delayed aneurysm occlusion and in-stent stenosis on angiographic follow-up were compared among Neuroform 1, 2, 2 Treo and 3 stents using a log likelihood ratio χ2test.

Results

Of 156 stent attempts, 123 (79%) were deployed (Neuroform 1: 8/9 (89%), Neuroform 2: 50/66 (76%), Neuroform 2 Treo: 9/11 (82%), Neuroform 3: 56/70 (80%)) with a symptomatic complication rate of 1.9% (3/156; 2 transient ischemic attacks, 1 stroke, no deaths). Non-target stent placement (1/8 (13%), 6/50 (12%), 2/9 (22%), 3/56 (5%)), difficult placement (2/8 (25%), 10/50 (20%), 5/9 (56%), 6/56 (11%)), stent movement (1/8 (13%), 4/50 (8%), 0/9 (0%), 4/56 (7%)), procedural complications (1/9 (11%), 7/66 (11%), 2/11 (18%), 2/70 (3%)) and immediate near complete aneurysm occlusion (6/6 (100%), 24/37 (65%), 5/7 (71%), 40/45 (89%)) trended towards improvement with each generation. Improvements in difficult stent placement and immediate aneurysm occlusion were significant (p=0.01 and 0.03, respectively).

Conclusion

Neuroform stent-assisted coiling has evolved through four generations as a safe and effective means of treating wide-necked intracranial aneurysms.
Supernova hemorrhage: obliterative hemorrhage of brain arteriovenous malformations following gamma knife radiosurgery
Authors: Alexander Matthew D , Hetts Steven W , Young William L , Halbach Van V , Dowd Christopher F , Higashida Randall T , English Joey D
Published: September 2011

Hemorrhage represents the most feared complication of cerebral arteriovenous malformations (AVMs) in both untreated patients and those treated with gamma knife radiosurgery. Radiosurgery does not immediately lead to obliteration of the malformation, which often does not occur until years following treatment. Post-obliteration hemorrhage is rare, occurring months to years after radiosurgery, and has been associated with residual or recurrent AVM despite prior apparent nidus elimination. Three cases are reported of delayed intracranial hemorrhage in patients with cerebral AVMs treated with radiosurgery in which no residual AVM was found on catheter angiography at the time of delayed post-treatment hemorrhage. That the pathophysiology of these hemorrhages involves progressive venous outflow occlusion is speculated and the possible mechanistic link to subsequent vascular rupture is discussed.
Surface (sea floor) and near-surface (box cores) sediment mineralogy in Baffin Bay as a key to sediment provenance and ice sheet variations
Authors: Andrews John T. , Eberl D.D.
Published: September 2011

To better understand the glacial history of the ice sheets surrounding Baffin Bay and to provide information on sediment pathways, samples from 82 seafloor grabs and core tops, and from seven box cores were subjected to quantitative X-ray diffraction weight percent (wt.%) analysis of the <2 mm sediment fraction. The samples were collected between 67°N and 78°N, in water depths of 155 to 2375 m and were retrieved on cruises between A.D. 1964 and 2009. Grain size, magnetic characteristics, and colour reflectance data were also obtained on many of the samples. Twenty-one non-clay and 10 clay mineral species were identified; the average wt.% of the non-clay minerals was 70% and was dominated by quartz, various feldspars, and dolomite, whereas the dominant clay minerals were 1 M illite, biotite, and chlorite. Cluster analysis on principal component scores identified three main mineral groups, which also had strong associations with grain size and sediment magnetic properties. Box cores from the deep central basin (>2000 m) all show an abrupt drop in calcite wt.% (post-5 cal ka BP?) following a major peak in detrital carbonate (mainly dolomite). This dolomite-rich detrital carbonate (DC) event in JR175BC06 is possibly coeval with the Younger Dryas cold event. Four possible glacial-sourced end members were employed in a compositional unmixing algorithm to gain insight into down core changes in sediment provenance at the deep central basin. Estimates of the rates of sediment accumulation in the central basin are only in the range of 2 to 4 cm/cal ka, surprisingly low given the glaciated nature of the surrounding land.
A SIMPLE ALGORITHM TO ENFORCE DIRICHLET BOUNDARY CONDITIONS IN COMPLEX GEOMETRIES
Authors: HUBER CHRISTIAN , DUFEK JOSEF , CHOPARD BASTIEN
Published: September 2011

We present a new algorithm to implement Dirichlet boundary conditions for diffusive processes in arbitrarily complex geometries. In this approach, the boundary conditions around the diffusing object is replaced by the fictitious phase transition of a pure substance where the energy cost of the phase transition largely overwhelms the amount of energy stored in the system. The computing cost of this treatment of the boundary condition is independent of the topology of the boundary. Moreover, the implementation of this new approach is straightforward and follows naturally from enthalpy-based numerical methods. This algorithm is compatible with a wide variety of discretization methods, finite differences, finite volume, lattice Boltzmann methods and finite elements, to cite a few. We show, here, using both lattice Boltzmann and finite-volume methods that our model is in excellent agreement with analytical solutions for high symmetry geometries. We also illustrate the advantages of the algorithm to handle more complex geometries.
HIERARCHICAL MAPPING FOR HPC APPLICATIONS
Authors: CHUNG I-HSIN , LEE CHE-RUNG , ZHOU JIAZHENG , CHUNG YEH-CHING
Published: September 2011

As the high performance computing systems scale up, mapping the tasks of a parallel application onto physical processors to allow efficient communication becomes one of the critical performance issues. Existing algorithms were usually designed to map applications with regular communication patterns. Their mapping criterion usually overlooks the size of communicated messages, which is the primary factor of communication time. In addition, most of their time complexities are too high to process large scale problems.

In this paper, we present a hierarchical mapping algorithm (HMA), which is capable of mapping applications with irregular communication patterns. It first partitions tasks according to their run-time communication information. The tasks that communicate with each other more frequently are regarded as strongly connected. Based on their connectivity strength, the tasks are partitioned into supernodes based on the algorithms in spectral graph theory. The hierarchical partitioning reduces the mapping algorithm complexity to achieve scalability. Finally, the run-time communication information will be used again in fine tuning to explore better mappings. With the experiments, we show how the mapping algorithm helps to reduce the point-to-point communication time for the PDGEMM, a ScaLAPACK matrix multiplication computation kernel, up to 20% and the AMG2006, a tier 1 application of the Sequoia benchmark, up to 7%.
INFLUENCE OF LONGITUDINAL MAGNETIC FIELD ON THE FLUCTUATION CONDUCTIVITY IN SLIGHTLY Al-DOPED YBa2Cu3-zAlzO7-δ SINGLE CRYSTALS WITH A GIVEN TOPOLOGY OF PLANE DEFECTS
Authors: VOVK R. V. , OBOLENSKII M. A. , ZAVGORODNIY A. A. , NAZYROV Z. F. , GOULATIS I. L. , KRUGLYAK V. V. , CHRONEOS A.
Published: September 2011

In this work we study the influence of the constant magnetic field up to 14 kOe to the temperature dependence of the electrical conductivity in the ab-plane of aluminium doped YBa 2 Cu 3 O 7-δ single crystals with an unidirectional twin boundaries system. The temperature dependence of the excess para-conductivity is interpreted within the Aslamazov–Larkin theoretical model of the fluctuation conductivity. It was shown that the lack of fan-shaped expansion of the resistive transitions in the magnetic field in these samples may be due to the lack of the non-pinning vortex liquid phase.
ULTRAFAST ELECTRON DIFFRACTIVE VOLTAMMETRY: GENERAL FORMALISM AND APPLICATIONS
Authors: CHANG KISEOK , MURDICK RYAN A. , TAO ZHEN-SHENG , HAN TZONG-RU T. , RUAN CHONG-YU
Published: September 2011

We present a general formalism of ultrafast diffractive voltammetry approach as a contact-free tool to investigate the ultrafast surface charge dynamics in nanostructured interfaces. As case studies, the photoinduced surface charging processes in oxidized silicon surface and the hot electron dynamics in nanoparticle-decorated interface are examined based on the diffractive voltammetry framework. We identify that the charge redistribution processes appear on the surface, sub-surface, and vacuum levels when driven by intense femtosecond laser pulses. To elucidate the voltammetry contribution from different sources, we perform controlled experiments using shadow imaging techniques and N-particle simulations to aid the investigation of the photovoltage dynamics in the presence of photoemission. We show that voltammetry contribution associated with photoemission has a long decay tail and plays a more significant role in the nanosecond timescale, whereas the ultrafast voltammetry are dominated by local charge transfer, such as surface charging and molecular charge transport at nanostructured interfaces. We also discuss the general applicability of the diffractive voltammetry as an integral part of quantitative ultrafast electron diffraction methodology in researching different types of interfaces having distinctive surface diffraction and boundary conditions.
Smooth muscle myosin expression, isoform composition, and functional activities in rat corpus cavernosum altered by the streptozotocin-induced type 1 diabetes
Authors: Zhang Xinhua , Kanika Nirmala D. , Melman Arnold , DiSanto Michael E.
Published: September 2011

Diabetes mellitus (DM) is a quite common chronic disease, and the prevalence of erectile dysfunction (ED) is three times higher in this large population. Although diabetes-related ED has been studied extensively, the actin-myosin contractile apparatus was not examined. The mRNAs encoding smooth muscle myosin (SMM) heavy chains (MHC) and essential light chains (LC17) exist as several different alternatively spliced isoforms with distinct contractile properties. Recently, we provided novel data that blebbistatin (BLEB), a specific myosin II inhibitor, potently relaxed corpus cavernosum smooth muscle (CCSM). In this study, we examine whether diabetes alters SMM expression, alternative splicing, and/or functional activities, including sensitivity to BLEB. By using streptozotocin (STZ)-induced 2-mo diabetic rats, functional activities were tested in vivo by intracavernous pressure (ICP) recording during cavernous nerve stimulation and in vitro via organ bath contractility studies. SMM isoform composition was analyzed by competitive RT-PCR and total SMM, myocardin, and embryonic SMM (SMemb) expression by real-time RT-PCR. Results revealed that the blood glucose level of STZ rats was 407.0 vs. 129.5 mg/dl (control). STZ rats exhibited ED confirmed by significantly increased CCSM contractile response to phenylephrine and decreased ICP response. For STZ rats, SM-B, LC17aand SM2 isoforms, total SMM, and myocardin expression increased, whereas SM-A, LC17b, and SM1 isoforms were decreased, with SMemb unchanged. BLEB was significantly more effective in relaxing STZ CCSM both in vitro and in vivo. Thus we demonstrated a novel diabetes-specific effect on alternative splicing of the SMM heavy chain and essential light chain genes to a SMM isoform composition favoring a heightened contractility and ED. A switch to a more contractile phenotype was supported further by total SMM expression increase. Moreover, the change in CCSM phenotype was associated with an increased sensitivity to BLEB, which may serve as a novel pharmacotherapy for ED.
Effects of raising muscle glycogen synthesis rate on skeletal muscle ATP turnover rate in type 2 diabetes
Authors: Lim Ee L. , Hollingsworth Kieren G. , Smith Fiona E. , Thelwall Peter E. , Taylor Roy
Published: September 2011

Mitochondrial dysfunction has been implicated in the pathogenesis of type 2 diabetes. We hypothesized that any impairment in insulin-stimulated muscle ATP production could merely reflect the lower rates of muscle glucose uptake and glycogen synthesis, rather than cause it. If this is correct, muscle ATP turnover rates in type 2 diabetes could be increased if glycogen synthesis rates were normalized by the mass-action effect of hyperglycemia. Isoglycemic- and hyperglycemic-hyperinsulinemic clamps were performed on type 2 diabetic subjects and matched controls, with muscle ATP turnover and glycogen synthesis rates measured using 31P- and 13C-magnetic resonance spectroscopy, respectively. In diabetic subjects, hyperglycemia increased muscle glycogen synthesis rates to the level observed in controls at isoglycemia [from 19 ± 9 to 41 ± 12 μmol·l−1·min−1 ( P = 0.012) vs. 40 ± 7 μmol·l−1·min−1 in controls]. This was accompanied by a modest increase in muscle ATP turnover rates (7.1 ± 0.5 vs. 8.6 ± 0.7 μmol·l−1·min−1, P = 0.04). In controls, hyperglycemia brought about a 2.5-fold increase in glycogen synthesis rates (100 ± 24 vs. 40 ± 7 μmol·l−1·min−1, P = 0.028) and a 23% increase in ATP turnover rates (8.1 ± 0.9 vs. 10.0 ± 0.9 μmol·l−1·min−1, P = 0.025) from basal state. Muscle ATP turnover rates correlated positively with glycogen synthesis rates ( rs = 0.46, P = 0.005). Changing the rate of muscle glucose metabolism in type 2 diabetic subjects alters demand for ATP synthesis at rest. In type 2 diabetes, skeletal muscle ATP turnover rates reflect the rate of glucose uptake and glycogen synthesis, rather than any primary mitochondrial defect.
Intragastric protein administration stimulates overnight muscle protein synthesis in elderly men
Authors: Groen Bart B. L. , Res Peter T. , Pennings Bart , Hertle Elisabeth , Senden Joan M. G. , Saris Wim H. M. , van Loon Luc J. C.
Published: September 2011

The loss of skeletal muscle mass with aging has been attributed to an impaired muscle protein synthetic response to food intake. Therefore, nutritional strategies are targeted to modulate postprandial muscle protein accretion in the elderly. The purpose of this study was to assess the impact of protein administration during sleep on in vivo protein digestion and absorption kinetics and subsequent muscle protein synthesis rates in elderly men. Sixteen healthy elderly men were randomly assigned to an experiment during which they were administered a single bolus of intrinsically l-[1-13C]phenylalanine-labeled casein protein (PRO) or a placebo (PLA) during sleep. Continuous infusions with l-[ ring-2H5]phenylalanine and l-[ ring-2H2]tyrosine were applied to assess in vivo dietary protein digestion and absorption kinetics and subsequent muscle protein synthesis rates during sleep. We found that exogenous phenylalanine appearance rates increased following protein administration. The latter stimulated protein synthesis, resulting in a more positive overnight whole body protein balance (0.30 ± 0.1 vs. 11.8 ± 1.0 μmol phenylalanine·kg−1·h−1 in PLA and PRO, respectively; P < 0.05). In agreement, overnight muscle protein fractional synthesis rates were much greater in the PRO experiment (0.045 ± 0.002 vs. 0.029 ± 0.002%/h, respectively; P < 0.05) and showed abundant incorporation of the amino acids ingested via the intrinsically labeled protein (0.058 ± 0.006%/h). This is the first study to show that dietary protein administration during sleep is followed by normal digestion and absorption kinetics, thereby stimulating overnight muscle protein synthesis. Dietary protein administration during sleep stimulates muscle protein synthesis and improves overnight whole body protein balance. These findings may provide a basis for novel interventional strategies to attenuate muscle mass loss.
Snapshot of DNA methylation changes associated with hybridization inXenopus
Authors: Koroma Alie Patrick , Jones Raymond , Michalak Pawel
Published: September 2011

Hybridization often results in dramatic genome reconfigurations including epigenetic changes that control gene expression. Here we survey methylation patterns of interspecific Xenopus F1 hybrids relative to parental species X. laevis and X. muelleri, using methyl-sensitive amplification polymorphisms (MSAPs). Out of a total of 546 MSAP markers, 364 were effective in elucidating the difference in methylation patterns between the hybrids and the parental species. Principal coordinate analysis of methylated fragments revealed four distinct clusters with the two parental species separate from hybrid males and females. On average, hybrids were characterized by a higher proportion (70.6%) of methylated fragments compared with the parental species (64.5%), and this difference was consistent with previously observed disruptions of hybrid transcriptomes. The proportion of methylated fragments did not correlate with variation in genome size, as measured with flow cytometry. The levels of methylation in sterile hybrid males (73.8%) were higher than in fertile hybrid females (68.6%), but this difference was not statistically significant. A total of 76 methylated fragments (20.9%) were hybrid-unique, presumably originating from methylation alterations in hybrid genomes.
Towards In Vivo Imaging of Cancer Sialylation
Authors: Martinez-Duncker Ivan , Salinas-Marin Roberta , Martinez-Duncker Carlos
Published: September 2011

In vivo assessment of tumor glucose catabolism by positron emission tomography (PET) has become a highly valued study in the medical management of cancer. Emerging technologies offer the potential to evaluate in vivo another aspect of cancer carbohydrate metabolism related to the increased anabolic use of monosaccharides like sialic acid (Sia). Sia is used for the synthesis of sialylated oligosaccharides in the cell surface that in cancer cells are overexpressed and positively associated to malignancy and worse prognosis because of their role in invasion and metastasis. This paper addresses the key points of the different strategies that have been developed to image Sia expression in vivo and the perspectives to translate it from the bench to the bedside where it would offer the clinician highly valued complementary information on cancer carbohydrate metabolism that is currently unavailable in vivo.
The Phosphatase Inhibitor Menadione (Vitamin K3) Protects Cells from EGFR Inhibition by Erlotinib and Cetuximab
Authors: Perez-Soler Roman , Zou Yiyu , Li Tianhong , Ling Yi He
Published: September 2011

Purpose: Skin toxicity is the main side effect of epidermal growth factor receptor (EGFR) inhibitors, often leading to dose reduction or discontinuation. We hypothesized that phosphatase inhibition in the skin keratinocytes may prevent receptor dephosphorylation caused by EGFR inhibitors and be used as a new potential strategy for the prevention or treatment of this side effect.

Experimental Design: Menadione (Vitamin K3) was used as the prototype compound to test our hypothesis. HaCat human skin keratinocyte cells and A431 human squamous carcinoma cells were used. EGFR inhibition was measured by Western blotting and immunofluorescence. Phosphatase inhibition and reactive oxygen species (ROS) generation were measured by standard ELISA and fluorescence assays.

Results: Menadione caused significant and reversible EGFR activation in a dose-dependent manner starting at nontoxic concentrations. EGFR activation by menadione was associated with reversible protein tyrosine phosphatase inhibition, which seemed to be mediated by ROS generation as exposure to antioxidants prevented both menadione-induced ROS generation and phosphatase inhibition. Short-term coincubation of cells with nontoxic concentrations of menadione and the EGFR inhibitors erlotinib or cetuximab prevented EGFR dephosphorylation. Seventy-two–hour coincubation of cells with the highest nontoxic concentration of menadione and erlotinib provided for a fourfold cell growth inhibitory protection in HaCat human keratinocyte cells.

Conclusions: Menadione at nontoxic concentrations causes EGFR activation and prevents EGFR dephosphorylation by erlotinib and cetuximab. This effect seems to be mediated by ROS generation and secondary phosphatase inhibition. Mild oxidative stress in skin keratinocytes by topical menadione may protect the skin from the toxicity secondary to EGFR inhibitors without causing cytotoxicity. Clin Cancer Res; 17(21); 6766–77. ©2011 AACR.
Risk Profile in Chronic Kidney Disease Stage 3: Older versus Younger Patients
Authors: McIntyre Natasha J. , Fluck Richard J. , McIntyre Christopher W. , Taal Maarten W.
Published: September 2011

Background: The prevalence of chronic kidney disease (CKD) increases with age, but its significance in older patients is uncertain and is regarded by some as part of ‘normal aging’. Moreover, subjects ≥75 years are often excluded from research studies. We therefore undertook a prospective study of patients with CKD stage 3 in primary care to compare the risk profile of older versus younger subjects. Methods: Subjects with an estimated glomerular filtration rate (eGFR) 59–30 ml/min/1.73 m2 on two measurements were recruited from 32 primary care practices. Medical history and demographic data were obtained and participants underwent clinical assessment as well as urine and serum biochemistry tests. Results: 1,741 participants were recruited: mean age 72.9 ± 9 years; 60% female; 98% white; 17% diabetic. Mean eGFR was 52.5 ± 10 ml/min/1.73 m2 and 16.9% had albuminuria. Subjects ≥75 years had a significantly lower eGFR than younger subjects and a higher risk profile characterised by greater albuminuria, more arterial stiffness and higher serum uric acid levels. Conclusion: Older subjects with CKD stage 3 evidenced a higher risk profile for CKD progression and cardiovascular events than younger patients. This implies that CKD is not a benign condition in all elderly patients, but further investigation is required to identify those at greatest risk who may benefit from intervention.
Chyluria Associated with Nephrotic-Range Proteinuria: Pathophysiology, Clinical Picture and Therapeutic Options
Authors: Graziani Giorgio , Cucchiari David , Verdesca Simona , Balzarini Luca , Montanelli Alessandro , Ponticelli Claudio
Published: September 2011

Chyluria denotes the urinary excretion of chyle, which is a lymphatic fluid rich in chylomicrons. Chyle flows from the intestinal lacteals to the left subclavian vein through the thoracic duct. When an abnormal connection between these structures and the urinary tract develops, chyluria appears. The syndrome is often associated with a nephrotic-range proteinuria, and this could be a wrong indication to perform renal biopsy. Chyluria is classified as parasitic or nonparasitic, the former being induced by lymphatic filariasis, whereas the latter is caused by medical, traumatic or inherited diseases. The patient usually reports excretion of milky urines, monolateral flank pain, malnutrition, weight loss and weakness. Urinalysis demonstrates lymphocyturia associated with chylomicrons and triglycerides in the supernatant. The diagnostic approach is aimed to define the site of lymphourinary fistula. A selective ureteral catheterization allows to collect urine samples from each kidney, demonstrating a monolateral source of proteins and lipids and making renal biopsy superfluous. Other diagnostic tools include nuclear magnetic resonance urography and lymphoangiography. Many therapeutic options have been proposed. Sclerosing solution instillation into the renal pelvis and laparoscopic renal pedicle disconnection are the invasive procedures most commonly employed. Among the medical alternatives, a low-fat diet supplemented with medium-chain triglycerides is often followed by complete clinical and biochemical remission.
Marked Heterogeneity in Growth Characteristics of Myoblast Clonal Cultures and Myoblast Mixed Cultures Obtained from the Same Individual
Authors: Maier Andrea B. , Cohen Ron , Blom Joke , van Heemst Diana , Westendorp Rudi G.J.
Published: September 2011

Background: Sarcopenia is defined as an age-related decrease in skeletal muscle mass and function while adjacent satellite cells are unable to compensate for this loss. However, myoblast cultures can be established even in the presence of sarcopenia. Objective: It is yet unknown whether satellite cells from failing muscle in older age are equally affected, as human satellite cells have been assessed using myoblast mixed cultures and not by using myoblast clonal cultures. We questioned to what extent myoblast mixed cultures reflect the in vivo characteristics of single satellite cells from adult skeletal muscle. Methods: We established a myoblast mixed culture and three myoblast clonal cultures out of the same muscle biopsy and cultured these cells for 100 days. Replicative capacity and oxidative stress resistance were compared. Results: We found marked heterogeneity between the myoblast clonal cultures that all had a significantly lower replicative capacity when compared to the mixed culture. Replicative capacity of the clonal cultures was inversely related to the β-galactosidase activity after exposure to oxidative stress. Addition of L-carnosine enhanced the remaining replicative capacity in all cultures with a concomitant marginal decrease in β-galactosidase activity. Conclusions: It is concluded that myoblast mixed cultures in vitro do not reflect the marked heterogeneity between single isolated satellite cells. The consequences of the heterogeneity on muscle performance remain to be established.
RASopathies: Clinical Diagnosis in the First Year of Life
Authors: Digilio M.C. , Lepri F. , Baban A. , Dentici M.L. , Versacci P. , Capolino R. , Ferese R. , De Luca A. , Tartaglia M. , Marino B. , Dallapiccola B.
Published: September 2011

Diagnosis within Noonan syndrome and related disorders (RASopathies) still presents a challenge during the first months of life, since most clinical features used to differentiate these conditions become manifest later in childhood. Here, we retrospectively reviewed the clinical records referred to the first year of life of 57 subjects with molecularly confirmed diagnosis of RASopathy, to define the early clinical features characterizing these disorders and improve our knowledge on natural history. Mildly or markedly expressed facial features were invariably present. Congenital heart defects were the clinical issue leading to medical attention in patients with Noonan syndrome and LEOPARD syndrome. Feeding difficulties and developmental motor delay represented the most recurrent features occurring in subjects with cardiofaciocutaneous syndrome and Costello syndrome. Thin hair was prevalent among SHOC2 and BRAF mutation-positive infants. Café-au-lait spots were found in patients with LS and PTPN11 mutations, while keratosis pilaris was more common in individuals with SOS1, SHOC2 and BRAF mutations. In conclusion, some characteristics can be used as hints for suspecting a RASopathy during the first months of life, and individual RASopathies may be suspected by analysis of specific clinical signs. In the first year of life, these include congenital heart defects, severity of feeding difficulties and delay of developmental milestones, hair and skin anomalies, which may help to distinguish different entities, for their subsequent molecular confirmation and appropriate clinical management.
Mutations in SDCCAG8/NPHP10 Cause Bardet-Biedl Syndrome and Are Associated with Penetrant Renal Disease and Absent Polydactyly
Authors: Schaefer E. , Zaloszyc A. , Lauer J. , Durand M. , Stutzmann F. , Perdomo-Trujillo Y. , Redin C. , Bennouna Greene V. , Toutain A. , Perrin L. , Gérard M. , Caillard S. , Bei X. , Lewis R.A. , Christmann D. , Letsch J. , Kribs M. , Mutter C. , Muller J. , Stoetzel C. , Fischbach M. , Marion V. , Katsanis N. , Dollfus H.
Published: September 2011

The ciliopathies are an expanding group of disorders caused by mutations in genes implicated in the biogenesis and function of primary cilia. Bardet-Biedl syndrome (BBS) is a model ciliopathy characterized by progressive retinal degeneration, obesity, polydactyly, cognitive impairment, kidney anomalies and hypogonadism. Mutations in SDCCAG8(NPHP10) were described recently in patients with nephronophthisis and retinal degeneration (Senior-Loken syndrome; SLS). Given the phenotypic and genetic overlap between known ciliopathy genes, we hypothesized that mutations in SDCCAG8 might also contribute alleles to more severe, multisystemic ciliopathies. We performed genetic and phenotypic analyses of 2 independent BBS cohorts. Subsequent to mutation screening, we made a detailed phenotypic analysis of 5 families mutated for SDCCAG8 (3 homozygous and 2 compound heterozygous mutations) and conducted statistical analyses across both cohorts to examine possible phenotype-genotype correlations with mutations at this locus. All patients with mutations in SDCCAG8 fulfilled the diagnostic criteria for BBS (retinal degeneration, obesity, cognitive defects, renal failure, hypogonadism). Interestingly, none of the patients with primary SDCCAG8 mutations had polydactyly, a frequent but not obligatory BBS feature. In contrast, the same patients displayed early-onset renal failure, obesity, as well as recurrent pulmonary and ENT infections. Comparison of the phenotypes of these families with our entire BBS cohort indicated that renal impairment and absent polydactyly correlated significantly with causal SDCCAG8 mutations. Thus, SDCCAG8 mutations are sufficient to cause BBS in 1–2% of our combined cohorts, and define this gene as the sixteenth BBS locus (BBS16). The absence of polydactyly and the concomitant, apparently fully penetrant association with early kidney failure represents the first significant genotype-phenotype correlation in BBS that potentially represents an indicator for phenotype-driven priority screening and informs specific patient management.
Lifestyle Factors in Relation to Heart Failure Among Finnish Men and Women
Authors: Wang Yujie , Tuomilehto Jaakko , Jousilahti Pekka , Antikainen Riitta , Mähönen Markku , Katzmarzyk Peter T. , Hu Gang
Published: September 2011

Background—

The role of lifestyle factors in explaining the risk of heart failure (HF) is not properly established.

Methods and Results—

The national population-based study included 18 346 Finnish men and 19 729 women who were 25 to 74 years of age and free of HF at baseline. Multivariable Cox proportional hazards regression models was used to examine the association between lifestyle factors (smoking, body mass index [BMI], physical activity, vegetable consumption, fruit consumption, and alcohol consumption) and HF risk. During a median follow-up of 14.1 years (interquartile range, 5.9 to 20.9 years), 638 men and 445 women developed HF. Fruit consumption and alcohol consumption were dropped out of the analyses because no significant associations with the risk of HF were found. When 4 modifiable lifestyle factors (smoking, BMI, physical activity, and vegetable intake) were included in the analysis, the multivariable-adjusted (age, education, systolic blood pressure, total cholesterol, and histories of myocardial infarction, valvular heart disease, diabetes and using antihypertensive drugs) hazard ratios (HRs) of HF associated with engaging in 0, 1, 2, 3, and 4 healthy lifestyle factors were 1.00, 0.69 (95% confidence interval [CI], 0.54 to 0.87), 0.45 (95% CI, 0.35 to 0.58), 0.34 (95% CI, 0.25 to 0.46), and 0.31 (95% CI, 0.17 to 0.56) (
P
<0.001 for trend) for men, and 1.00, 0.53 (95% CI, 0.33 to 0.85), 0.42 (95% CI, 0.26 to 0.67), 0.24 (95% CI, 0.14 to 0.39), and 0.19 (95% CI, 0.09 to 0.40) (
P
<0.001 for trend) for women, respectively.

Conclusions—

The present study demonstrates an inverse association between healthy lifestyle patterns and the risk of HF in Finnish men and women.