bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of long-term clozapine administration. Frequency of cardiomyopathy and hyponatraemia: Two cross-sectional, naturalistic studies
Authors: Serrano Ana , Rangel Nairy , Carrizo Edgardo , Uzcátegui Euderruh , Sandia Ignacio , Zabala Angélica , Fernández Erika , Tálamo Eduardo , Servigna Mercedes , Prieto Dexi , Connell Lisette , Baptista Trino
Published: August 2013

Background:

The antipsychotic drug (APD) clozapine (CLZ) is under-prescribed because of concerns about its safety. We evaluated in separate protocols the frequency of cardiomyopathy and hyponatraemia, which are adverse drug effects, where few comparative studies are available.

Methods:

Cross-sectional studies in subjects treated for at least 3 consecutive months with the same drug were conducted. Cardiomyopathy: Patients undergoing treatment either with CLZ ( n = 125) or with other typical or atypical APDs ( n = 59) were examined by a cardiologist who also recorded echocardiograms and electrocardiograms in order to diagnose cardiomyopathy. Hyponatraemia: Fasting sodium levels were assessed in patients receiving any of the following treatments: CLZ ( n = 88), other atypical APDs ( n = 61), typical APDs ( n = 23), typical + atypical APDs ( n = 11), and other drugs/drug-free ( n = 36).

Results:

Cardiomyopathy: No case of cardiomyopathy was detected. The frequency of abnormal ventricular ejection fraction (< 55%) was similar in both treatment groups ( p = 1). Hyponatraemia: The frequency of hyponatraemia (percentage; 95% CI) was: CLZ (3.4%; –0.7, 7.1); other atypical APDs (4.9%; –0.5, 10.3); typical APDs (26.1%; 8.2, 44.0); typical + atypical APDs (9.1%; –7.8, 26.0); other drugs/drug-free (0%). None of the CLZ hyponatraemia subjects were on monotherapy.

Conclusions:

Our results are at odds with previous studies of CLZ-associated cardiomyopathy. However, they must be compared to further cross-sectional or prospective studies because most published data come from either case reports or pharmacovigilance systems. The frequency of hyponatraemia during CLZ administration was similar to that observed with other atypical APDs, and it was significantly lower than that recorded with typical agents. These results, along with numerous case reports on the effects of CLZ in patients with polydipsia and water intoxication, point to a safe or even positive profile of CLZ on electrolytic regulation.
The subjective experience of community treatment orders: Patients’ views and clinical correlations
Authors: Newton-Howes Giles , Banks Doug
Published: August 2013

Background:

There is little objective evidence to support the use of community treatment orders (CTOs) from randomized controlled trials. Qualitative research indicates more negative than positive responses to the use of CTOs. Nonetheless, the use of CTOs is growing internationally. There is no research to identify for whom CTOs may be a positive experience.

Aim:

To assess patients’ perspectives of CTOs, assessing for correlates with clinical and demographic variables.

Methods:

Patients currently or previously subject to a CTO were assessed quantitatively to identify their experience. Demographic data, the experience of coercion, views of detention, satisfaction with care, social functioning and psychopathology were correlated using SPSS.

Results:

Fifty-three per cent of patients felt that they were, on balance, better off when treated informally in the community. Patients described greater coercion and less satisfaction with care when subject to a CTO. These factors, and being in employment, identified patients whom felt harmed by CTOs 61% of the time.

Conclusions:

This paper highlights that more than half of patients under a CTO consider it negatively. This group is identified by patients who work, experience coercion and are unsatisfied with care. This has implications for the application of CTOs.
Elite Volatility and Change in North Korean Politics: 1997–2010
Authors: Ishiyama John
Published: August 2013

This paper analyzes the change in the composition of the North Korean elite from 1997–2010. It examines 256 public appearances by Kim Jong Il that were reported as an ‘inspection,’ ‘field guidance’ or ‘on-the-spot guidance’ visits. In particular, the paper examines 30 mentioned individuals who accompanied Kim Jong Il at least five times from 1997 to 2010 on these inspection tours. It finds that there was a great deal of volatility and change from 1999–2004 followed by a period of stability. Further, there was a shift away from a conservative perspective to a more moderate and pragmatic perspective surrounding the ‘Dear Leader.’ This has continued under the current leader, Kim Jong Un. The implications of this shift are discussed.
Influence of anesthetic agent, depth of anesthesia and body temperature on cardiovascular functional parameters in the rat
Authors: Redfors Bjorn , Shao Yangzhen , Omerovic Elmir
Published: August 2013

Sedating animals is sometimes necessary in experimental research. This paper presents and discusses the influence of four of the most common anesthetic agents on cardiovascular parameters in rats. We also studied the influence of body temperature. Ten-week-old Sprague-Dawley rats were anesthetized with either isoflurane, pentobarbital, ketamine/xylazine or tiletamine/zolazepam ( n = 12 in each group). A pressure-sensing catheter was placed in the right carotid artery for the continuous measurement of arterial pressure, and echocardiography was performed. Indices of cardiac function were significantly higher in the tiletamine/zolazepam rats compared with the other groups. Heart rate was highest but stroke volume lowest with pentobarbital. Left ventricular diastolic dimension was lower in the pentobarbital and tiletamine/zolazepam rats compared with the isoflurane or ketamine/xylazine rats. Intraventricular diastolic pressure was similar in all groups whereas intraventricular systolic pressure, as well as both systolic and diastolic aortic pressures, was significantly higher in the tiletamine/zolazepam rats compared with the other groups. No hemodynamic indices differed significantly among the isoflurane, pentobarbital and ketamine/xylazine rats. Lowering body temperature significantly reduced heart rate and cardiac output but had no apparent effect on hemodynamic parameters. In conclusion, although cardiac functional parameters differed between the different anesthetic agents in ways that could be of relevance to the researcher, they may all have a role in experimental cardiology. Importantly, tiletamine/zolazepam anesthesia resulted in significantly higher indices of cardiac function and elevated blood pressures compared with the other anesthetic agents, a finding that should be kept in mind when interpreting data obtained in rats sedated on this regimen.
Suicide note on the palm: Three case reports and discussion of medico-legal aspects
Authors: Behera C , Rautji Ravi , Krishna Karthik , Kumar Avishek , Gupta SK
Published: August 2013

Suicide notes are usually written by the victim on paper or readily accessible things such as notebooks, walls or mirrors. Though writing may be found on the body of the deceased, suicide notes in a structured manner written on the palm have not been reported in forensic literature. In all the three cases presented here, we found a handwritten note on the palm of the deceased at the time of autopsy. The victims had written a brief note in their own handwriting, citing the reasons for ending their lives. The suicide note in one case also mentioned details regarding the custody of the victim’s children to be given to her mother. Since we have not found similar cases in the literature, we present and discuss our three cases herein.
Can New Urbanism Create Diverse Communities?
Authors: Cabrera Joseph F. , Najarian Jonathan C.
Published: August 2013

This article examines the differences in diversity between a new urbanist subdivision and a standard suburban subdivision. We examine diversity at the macro level in terms of demographic characteristics such as age, sex, and income. We then examine diversity at the micro level, using a network sample to analyze diversity at the level of the social interaction. We find at the macro level that the new urbanist community is more diverse in a number of factors including education, income, and especially age. However, we find this increased diversity does not translate to diverse social interactions at the micro level.
Applications, value and barriers of common data frameworks in the rail industry of Great Britain
Authors: Golightly David , Easton John M , Roberts Clive , Sharples Sarah
Published: August 2013

In the rail industry, the exchange of data across system and organisational boundaries is an essential step in the delivery of advances such as intelligent infrastructure, end-to-end ticketing, improved passenger information, real-time capacity management and greater interoperability between stakeholders. The industry, however, faces a serious challenge in the form of siloed, legacy ICT systems based around different technologies and data formats. One solution to this problem can be found in the implementation of open data interfaces that use a conceptual representation of the railway network to facilitate the exchange of information while preserving its underlying meaning. The work reported in this paper used two engagement exercises involving industry stakeholders to, first, generate a set of applications for wider information sharing in the rail industry of Great Britain; second, compile a list of the benefits of such an approach to the rail industry; and, third, identify the most significant barriers to implementation. The paper should therefore be valuable for anyone in industry or in academia working on projects that depend on the exchange of data between systems and stakeholders to support rail operations and strategy.
Ulcerating type 1 lepra reaction mimicking lazarine leprosy: an unusual presentation of immune reconstitution inflammatory syndrome in an HIV-infected patient
Authors: Bhat Ramesh , Pinto Malcolm , Dandakeri Sukumar , Kambil Srinath
Published: August 2013

Leprosy maybe “unmasked” in the context of immune reconstitution inflammatory syndrome and treating dermatologists, particularly in highly endemic areas for Hansen’s disease, need to be cognizant to this possibility. It may also reflect emergence of a previously clinically silent infection in the course of immunologic restoration.
Swinging at a Cocktail Party
Authors: Johnsrude Ingrid S. , Mackey Allison , Hakyemez Hélène , Alexander Elizabeth , Trang Heather P. , Carlyon Robert P.
Published: August 2013

People often have to listen to someone speak in the presence of competing voices. Much is known about the acoustic cues used to overcome this challenge, but almost nothing is known about the utility of cues derived from experience with particular voices—cues that may be particularly important for older people and others with impaired hearing. Here, we use a version of the coordinate-response-measure procedure to show that people can exploit knowledge of a highly familiar voice (their spouse’s) not only to track it better in the presence of an interfering stranger’s voice, but also, crucially, to ignore it so as to comprehend a stranger’s voice more effectively. Although performance declines with increasing age when the target voice is novel, there is no decline when the target voice belongs to the listener’s spouse. This finding indicates that older listeners can exploit their familiarity with a speaker’s voice to mitigate the effects of sensory and cognitive decline.
Validating a brief measure of the Zimbardo Time Perspective Inventory
Authors: Zhang Jia Wei , Howell Ryan T. , Bowerman Tom
Published: August 2013

Zimbardo and Boyd (1999) developed the 56-item Zimbardo Time Perspective Inventory (ZTPI). It has become the leading measure used in the study of subjective time. In this article, we report an abbreviated ZTPI that only includes 15 total items (SZTPI-15). We tested the psychometric characteristics of the SZTPI-15 by focusing on: (a) convergent and discriminant validity, (b) external validity, (c) test–retest reliability and (d) self-peer ratings. On the basis of these tests, the results demonstrated that the short version was less reliable than the standard ZTPI but showed impressive psychometric convergence with the standard ZTPI.
In Lieu of Legislation
Authors: Belco Michelle , Rottinghaus Brandon
Published: August 2013

In the legislative process, presidents may negotiate with Congress or use unilateral action as a bargaining tool. When presidents issue a unilateral order during the legislative process, do these orders “preempt” or “support” legislation? We match unilateral orders with related legislative activity and find presidents are more likely to use unilateral orders to “preempt” legislation when the issue is on the president’s agenda or in the second half of their second terms but “support” legislation when of the same party as the bill sponsor. These findings suggest that presidents not only take advantage of Congressional incapacity but also exert unilateral power in support of legislation.
Survey on the Need for Bone Graft in Foot and Ankle Fusion Surgery
Authors: Baumhauer Judith F. , Pinzur Michael S. , Daniels Timothy R. , Lin Sheldon S. , Beasley William , Donahue Rafe M. J. , DiGiovanni Christopher W.
Published: August 2013

Background:

Generally, autologous bone graft is felt to be an important treatment adjunct in the presence of structural deformity, surface irregularities, defects (due to trauma, surgery, or degenerative changes), or underlying comorbidities that predispose the patient to healing challenges. This study assessed the prognostic and predictive factors used in the clinical decision making for bone graft supplementation in foot and ankle fusion surgery.

Methods:

Utilizing standard survey research methodology, key-informant interviews, pretesting, and pilot testing; a survey was constructed. The survey consisted of a web-based 5-point Likert-type scale ( never, seldom, sometimes, almost always, always) listing 14 clinical and 11 radiologic criteria that may influence the use of autologous bone grafting or other biologic augmentation in foot and ankle surgery. This survey was sent to Orthopaedic Foot and Ankle Surgeons in North America and Canada.

Results:

A total of 48 foot and ankle surgeons completed the blinded survey (73% response rate). More than 70% of responders felt bone graft was almost always (AA) or always (A) indicated in prior nonunion of the indicated joint (96%). Fewer than 50% of respondents felt poor soft tissue integrity (20%), prior foot and ankle infection (20%), and current foot and ankle infection (4%) needed bone graft. Radiologic factors marked as AA or A in over 70% of responders include radiographic evidence of nonunion (96%), avascular necrosis (87%), and others. Factors chosen as AA or A by fewer than 50% of surgeons include prior adjacent joint fusions (47%), intra-articular deformity (31%), and extra-articular deformity (13%).

Conclusions:

There was some uniformity of agreement on the number of both clinical and radiologic factors that prompt a surgeon to utilize autologous bone graft to try to avoid the complication of nonunion. Surgeons may wish to consider these factors when making a decision on the use of bone graft to supplement fusion.
Analytical continuum mechanics à la Hamilton–Piola least action principle for second gradient continua and capillary fluids
Authors: Auffray N , dell’Isola F , Eremeyev VA , Madeo A , Rosi G
Published: August 2013

In this paper a stationary action principle is proved to hold for capillary fluids, i.e. fluids for which the deformation energy has the form suggested, starting from molecular arguments. We remark that these fluids are sometimes also called Korteweg–de Vries or Cahn–Allen fluids. In general, continua whose deformation energy depends on the second gradient of placement are called second gradient (or Piola–Toupin, Mindlin, Green–Rivlin, Germain or second grade) continua. In the present paper, a material description for second gradient continua is formulated. A Lagrangian action is introduced in both the material and spatial descriptions and the corresponding Euler–Lagrange equations and boundary conditions are found. These conditions are formulated in terms of an objective deformation energy volume density in two cases: when this energy is assumed to depend on either C and ∇ C or on C−1 and ∇ C−1, where C is the Cauchy–Green deformation tensor. When particularized to energies which characterize fluid materials, the capillary fluid evolution conditions are recovered. A version of Bernoulli’s law valid for capillary fluids is found and useful kinematic formulas for the present variational formulation are proposed. Historical comments about Gabrio Piola’s contribution to analytical continuum mechanics are also presented.
Health research, development and innovation in England from 1988 to 2013: from research production to knowledge mobilization
Authors: Walshe Kieran , Davies Huw TO
Published: August 2013

This paper presents a critical analysis of the development of government policy and practice on health research, development and innovation over the last 25 years – starting from the publication of a seminal report from the House of Lords Science and Technology Committee in 1988. We first set out to map and analyse the trends in ideas and thinking that have shaped research policy and practice over this period, and to put the development of health research, development and innovation in the wider context of health system reforms and changes. We argue that though this has been a transformative period for health research, rather less progress has been made in the domains of development and innovation, and we offer an analysis of why this might be the case. Drawing on advances in our understanding about how research informs practice, we then make the case for a more integrative model of research, development and innovation. This leads us to conclude that recent experiments with Collaborations for Leadership in Applied Health Research and Care and Academic Health Science Centres and Networks offer some important lessons for future policy directions.
A comparison of older workers’ and retired older people’s social capital and sense of mastery
Authors: Nyqvist Fredrica , Forsman Anna K. , Cattan Mima
Published: August 2013

Aim: To assess if older people with higher levels of social capital experience higher levels of sense of mastery than those with lower levels of social capital and to assess whether this association is stronger for retired older people than for older workers. Methods: The data originates from a general population mental health survey conducted among 2610 older people (50 years of age or older) in Finland in 2011. The response rate was 57.1%. The association between sense of mastery, measured by Pearlin’s Sense of Mastery Scale, and social capital, measured by social networks, organisational activities, trust, and sense of belonging, were tested by logistic regression analyses. Results: The results showed that older workers experienced greater sense of mastery than retired older people. Trust and neighbourhood belonging were positively associated with sense of mastery. Conclusions: Inequalities in mental wellbeing between older people included in or excluded from the workforce are a public health challenge. Our findings imply that social capital needs to be prioritised as a means for enhancing mental health. More attention should be paid to promote mental wellbeing in retired older people.
Creativity, anti-humanism and the ‘new sociology of art’
Authors: Fox Nick
Published: August 2013

This article reviews sociology’s uneasy engagement with creativity, using the lens of recent critiques of Bourdieusian art sociology and the call for a more nuanced understanding of the agency of art objects and trajectories of artistic production. I develop and apply an anti-humanist ontology to assert that creativity is profoundly sociologically interesting, and key to the production of human culture, from science and technology to the arts to social forms and institutions. Analysis of auto-ethnographic data on the production of a painting of Australian mallée woodland establishes three propositions for an anti-humanist sociology of creativity: that creative production is part of an open-ended flow of affect between assembled human and non-human elements; that affective flows produce creative capacities to act, feel and desire in bodies; and that products of creativity such as artworks are themselves affects that themselves contribute to the production of social life, the world and human history.
Provider Communication and Role Modeling Related to Patients’ Perceptions and Use of a Federally Qualified Health Center–Based Farmers’ Market
Authors: Friedman Daniela B. , Freedman Darcy A. , Choi Seul Ki , Anadu Edith C. , Brandt Heather M. , Carvalho Natalia , Hurley Thomas G. , Young Vicki M. , Hébert James R.
Published: August 2013

Farmers’ markets have the potential to improve the health of underserved communities, shape people’s perceptions, values, and behaviors about healthy eating, and serve as a social space for both community members and vendors. This study explored the influence of health care provider communication and role modeling for diabetic patients within the context of a farmers’ market located at a federally qualified health center. Although provider communication about diet decreased over time, communication strategies included: providing patients with “prescriptions” and vouchers for market purchases; educating patients about diet; and modeling healthy purchases. Data from patient interviews and provider surveys revealed that patients enjoyed social aspects of the market including interactions with their health care provider, and providers distributed prescriptions and vouchers to patients, shopped at the market, and believed that the market had potential to improve the health of staff and patients of the federally qualified health center. Provider modeling of healthy behaviors may influence patients’ food-related perceptions and dietary behaviors.
Synergistic effects of prostacyclin analogs and phosphodiesterase inhibitors on cyclic adenosine 3′,5′ monophosphate accumulation and adenosine 3′5′ triphosphate release from human erythrocytes
Authors: Knebel Stephanie M , Elrick Mollisa M , Bowles Elizabeth A , Zdanovec Amber K , Stephenson Alan H , Ellsworth Mary L , Sprague Randy S
Published: August 2013

Prostacyclin (PGI2) and phosphodiesterase 5 (PDE5) inhibitors are potent vasodilators that are used alone and in combination for the treatment of pulmonary arterial hypertension (PAH). Although these vasodilators are known to stimulate relaxation of vascular smooth muscle directly, other cells in circulation, including erythrocytes, express prostacyclin receptor (IPR) and contain PDE5. The binding of PGI2 analogs to the erythrocyte IPR results in activation of a signaling pathway that increases cyclic adenosine 3′,5′ monophosphate (cAMP), a requirement for adenosine 3′5′ triphosphate (ATP) release. Within this pathway, cAMP levels are regulated by phosphodiesterase 3 (PDE3), a PDE that is inhibited by cGMP, a cyclic nucleotide regulated by the activity of PDE5. Since inhibition of PDE3 enhances ATP release in response to PGI2 analogs, we investigated if the selective PDE5 inhibitors, zaprinast (ZAP) and tadalafil (TAD), would similarly increase cAMP and ATP release from human erythrocytes in response to the same stimulus. We determined that pretreatment of erythrocytes with one of two chemically dissimilar PDE5 inhibitors (ZAP or TAD, 10 µM) potentiated increases in cAMP and ATP release in response to incubation of human erythrocytes with the PGI2 analog, UT-15C (100 nM). These results suggest that a heretofore unrecognized synergism exists between IPR agonists and PDE5 inhibitors that could provide a new rationale for the co-administration of these agents as vasodilators in humans with PAH.
Sildenafil dilates ophthalmic artery in type 2 diabetic patients
Authors: Zwain Akeel AMH , Hadi Najah R , Al-Mudhaffer Ahmed M
Published: August 2013

Background:

Conflicting reports exist on the effect of sildenafil on ophthalmic artery blood flow; many visual disturbances due to vascular insult were reported with the use of sildenafil in diabetic patients like nonarteritic ischemic optic neuropathy.

Objectives:

The present work aimed to investigate whether sildenafil modulates ophthalmic artery vasoreactivity in patients with type 2 diabetes mellitus. Literature reports on this aspect are lacking.

Methods:

A total of 35 male subjects were enrolled in this study, 18 with type 2 diabetes mellitus matched with 17 normal individuals. Ophthalmic artery was insonated through a transorbital window using colored Doppler equipment with transcranial Doppler facility. Ophthalmic artery reactivity was assessed using breath holding/hyperventilation test, before and after giving 50 mg oral sildenafil.

Results:

It was found that in both normal subjects and diabetic patients, sildenafil increased baseline control of mean flow velocity of ophthalmic artery significantly (p < 0.05), breath holding caused a decrease of MFVopa (p < 0.05), and subsequent hyperventilation caused increase of MFVopa (p < 0.05). There was no statistically significant change in breath holding index and full range of vasodilatation of ophthalmic artery (p > 0.05) after sildenafil, in normal and diabetic groups. There was a significant increase of resistive index of ophthalmic artery flow in diabetic patients compared with that of normal subject (p < 0.05). Sildenafil decreased resistive index of ophthalmic artery flow significantly only in diabetic patients (p < 0.05).

Conclusion:

Sildenafil increased MFVopa, but had no significant effect on vasoreactivity of ophthalmic artery; sildenafil decreased resistive index only in type 2 diabetic patients.
Posterolateral Bundle Reconstruction With Anteromedial Bundle Remnant Preservation in ACL Tears
Authors: Sonnery-Cottet Bertrand , Zayni Rachad , Conteduca Jacopo , Archbold Pooler , Prost Thierry , Carrillon Yannick , Clechet Julien , Thaunat Mathieu
Published: August 2013

Background:

Augmentation consisting of a selective reconstruction of the ruptured bundle while preserving the remnant bundle has been proposed as a treatment option for partial anterior cruciate ligament (ACL) tears. Good clinical outcomes after selective anteromedial (AM) bundle augmentation have been reported, whereas little is known about selective reconstruction of the posterolateral (PL) bundle with preservation of the AM bundle remnant.

Purpose:

The purpose of this study was to evaluate the clinical outcomes and the magnetic resonance imaging (MRI) characteristics of selective PL bundle reconstruction with a median follow-up of 24 months.

Study Design:

Case series; Level of evidence, 4.

Methods:

In a consecutive series of 741 ACL reconstructions, 44 patients underwent a selective PL bundle reconstruction with preservation of the AM remnant. Four patients with contralateral knee ligament surgery and 1 patient who sustained a traumatic rupture of his graft were excluded, leaving 39 patients for final evaluation. Clinical evaluation of knee function and laxity were recorded preoperatively and at a mean 24.2-month follow-up. Magnetic resonance imaging was performed on 35 patients at a mean 25.9-month follow-up for evaluation of graft and remnant bundle continuity, tunnel enlargement, and graft remodeling status by measuring the signal intensity of the graft (contrast/noise quotient [CNQ]).

Results:

Tegner and Lysholm knee scores were significantly improved after surgery. The subjective International Knee Documentation Committee (IKDC) score was 43.5 ± 16.6 preoperatively and 89.9 ± 6.6 at the final follow-up ( P < .01). The objective IKDC score was “B” for 17 patients, “C” for 21 patients, and “D” for 1 patient preoperatively, while it was “A” for 34 patients and “B” for 5 patients postoperatively ( P < .01). The mean side-to-side anteroposterior laxity was 5 mm (range, 4-10 mm) preoperatively and 1.5 mm (range, −1 to 4 mm) at final follow-up ( P < .01). On MRI, the graft was visible and continuous in all cases. No cyclops lesions were noted. The average CNQ for the PL graft and the AM remnant bundle was 3.2 ± 1 and 2.9 ± 1.2, respectively. Minimum bone tunnel enlargement was found.

Conclusion:

Selective PL bundle reconstruction restores knee stability and function. At final follow-up, MRI showed continuity of the PL graft without signs of dramatic tunnel enlargement or cyclops syndrome.
Impact of microRNAs on regulatory networks and pathways in human colorectal carcinogenesis and development of metastasis
Authors: Pizzini Silvia , Bisognin Andrea , Mandruzzato Susanna , Biasiolo Marta , Facciolli Arianna , Perilli Lisa , Rossi Elisabetta , Esposito Giovanni , Rugge Massimo , Pilati Pierluigi , Mocellin Simone , Nitti Donato , Bortoluzzi Stefania , Zanovello Paola
Published: August 2013

Background

Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colon cancer have mainly been demonstrated in primary tumors. Poorly overlapping sets of oncomiRs, tumor suppressor miRNAs and metastamiRs have been linked with distinct stages in the progression of colorectal cancer. To identify changes in both miRNA and gene expression levels among normal colon mucosa, primary tumor and liver metastasis samples, and to classify miRNAs into functional networks, in this work miRNA and gene expression profiles in 158 samples from 46 patients were analysed.

Results

Most changes in miRNA and gene expression levels had already manifested in the primary tumors while these levels were almost stably maintained in the subsequent primary tumor-to-metastasis transition. In addition, comparing normal tissue, tumor and metastasis, we did not observe general impairment or any rise in miRNA biogenesis. While only few mRNAs were found to be differentially expressed between primary colorectal carcinoma and liver metastases, miRNA expression profiles can classify primary tumors and metastases well, including differential expression of miR-10b, miR-210 and miR-708. Of 82 miRNAs that were modulated during tumor progression, 22 were involved in EMT. qRT-PCR confirmed the down-regulation of miR-150 and miR-10b in both primary tumor and metastasis compared to normal mucosa and of miR-146a in metastases compared to primary tumor. The upregulation of miR-201 in metastasis compared both with normal and primary tumour was also confirmed. A preliminary survival analysis considering differentially expressed miRNAs suggested a possible link between miR-10b expression in metastasis and patient survival. By integrating miRNA and target gene expression data, we identified a combination of interconnected miRNAs, which are organized into sub-networks, including several regulatory relationships with differentially expressed genes. Key regulatory interactions were validated experimentally. Specific mixed circuits involving miRNAs and transcription factors were identified and deserve further investigation. The suppressor activity of miR-182 on ENTPD5 gene was identified for the first time and confirmed in an independent set of samples.

Conclusions

Using a large dataset of CRC miRNA and gene expression profiles, we describe the interplay of miRNA groups in regulating gene expression, which in turn affects modulated pathways that are important for tumor development.
A rapid and efficient way to manage hyponatremia in patients with SIADH and small cell lung cancer: treatment with tolvaptan
Authors: Petereit Claudia , Zaba Okan , Teber Ishak , Lüders Heike , Grohé Christian
Published: August 2013

Background

Hyponatremia based on syndrome of inappropriate antidiuretic hormone hypersecretion (SIADH) is observed in up to 15% of patients with small cell lung cancer (SCLC). The electrolyte imbalance is associated with a high morbidity and mortality and often delays appropriate treatment. Management of hyponatremia proved to be challenging until new vasopressin-2 receptor antagonists such as tolvaptan became available. This is the first report which presents a prospective case series with an efficient management of hyponatremia including tolvaptan in ten patients with SCLC and severe SIADH (plasma sodium < 125 mmol/l).

Methods

Ten patients with SCLC and severe SIADH were followed after the onset of clinical symptoms of SIADH. Patients were chosen on the basis of histological proven diagnosis of SCLC and the clinical picture of a neurocognitive deficit caused by SIADH-related hyponatremia. All patient data were monitored for clinical improvement based on ECOG status, commencement of chemotherapy and correction of sodium levels.

Results

The treatment followed a diagnostic and treatment algorithm and lead to a rapid and efficient correction of both clinical symptoms and plasma sodium level.

Conclusions

Based on this algorithm all patients started chemotherapy in time. Subsequently, the treatment with tolvaptan lead to an improvement of the ECOG-performance status. In addition, all patients benefit from the effective management of SIADH which omitted prolonged hospital stays and non-elective hospitalizations due to an unstable clinical condition due to severe hyponatremia. These observations add new insight to management of SIADH in thoracic oncology and are of interest for specialists in oncology, endocrinology and pulmonary medicine.
Shifting perceptions: a pre-post study to assess the impact of a senior resident rotation bundle
Authors: Fabreau Gabriel , Elliott Meghan , Khanna Suneil , Minty Evan , Wallace Jean E , de Grood Jill , Lewin Adriane , Brown Garielle , Bharwani Aleem , Gilmour Janet , Lemaire Jane B
Published: August 2013

Background

Extended duty hours for residents are associated with negative consequences. Strategies to accommodate duty hour restrictions may also have unintended impacts. To eliminate extended duty hours and potentially lessen these impacts, we developed a senior resident rotation bundle that integrates a night float system, educational sessions on sleep hygiene, an electronic handover tool, and a simulation-based medical education curriculum. The aim of this study was to assess internal medicine residents’ perceptions of the impact of the bundle on three domains: the senior residents’ wellness, ability to deliver quality health care, and medical education experience.

Methods

This prospective study compared eligible residents’ experiences (N = 67) before and after a six-month trial of the bundle at a training program in western Canada. Data was collected using an on-line survey. Pre- and post-intervention scores for the final sample (N = 50) were presented as means and compared using the t-test for paired samples.

Results

Participants felt that most aspects of the three domains were unaffected by the introduction of the bundle. Four improved and two worsened perception shifts emerged post-intervention: less exposure to personal harm, reduced potential for medical error, more successful teaching, fewer disruptions to other rotations, increased conflicting role demands and less staff physician supervision.

Conclusions

The rotation bundle integrates components that potentially ease some of the perceived negative consequences of night float rotations and duty hour restrictions. Future areas of study should include objective measures of the three domains to validate our study participants’ perceptions.
First report of a phylogenetic analysis of an autochthonous Plasmodium vivax strain isolated from a malaria case in East Attica, Greece
Authors: Ioannidis Anastasios , Nicolaou Chryssoula , Stoupi Athina , Kossyvakis Athanasios , Matsoukas Petros , Liakata Melina-Vassiliki , Magiorkinis Emmanouil , Petinaki Efthimia , Chatzipanagiotou Stylianos
Published: August 2013

Malaria has become an emerging infection in Greece, which is the doorstep to Europe for thousands of immigrants. With increasing immigration, cases with evidence of domestic transmission (autochthonous) are being reported. In the present study, an isolate of Plasmodium vivax from an autochthonous clinical case was subjected to phylogenetic analysis of the genes encoding the merozoite surface protein 1 (MSP-1) and the circumsporozoite protein (CSP). In the MSP region, the strain was related with strains from Brazil, South Korea, Turkey and Thailand, whereas in the CSP region, with strains from Brazil, Colombia and New Guinea. The present study establishes for the first time in Greece the basis for the creation of a database comprising genotypic and phylogenetic characteristics of Plasmodium spp.
Cancer risk in immune-mediated inflammatory diseases (IMID)
Authors: Beyaert Rudi , Beaugerie Laurent , Van Assche Gert , Brochez Lieve , Renauld Jean-Christophe , Viguier Manuelle , Cocquyt Veronique , Jerusalem Guy , Machiels Jean-Pascal , Prenen Hans , Masson Pierre , Louis Edouard , De Keyser Filip
Published: August 2013

Inflammation and cancer have a profound yet ambiguous relationship. Inflammation - especially chronic inflammation - has protumorigenic effects, but inflammatory cells also mediate an immune response against the tumor and immunosuppression is known to increase the risk for certain tumors.

This article reviews current literature on the role of inflammation in cancer and the cancer risk in immune-mediated inflammatory diseases (IMIDs). We discuss the effect on cancer risk of different drug classes used in the treatment of IMIDs treatment, including biologicals such as tumor necrosis factor (TNF) inhibitors.

Overall cancer incidence and mortality risk are similar to the general population in inflammatory bowel disease (IBD), and slightly increased for rheumatoid arthritis and psoriasis, with risk profiles differing for different tumor types. Increased risk for non-melanoma skin cancer is associated with thiopurine treatment in IBD, with the combination of anti-TNF and methotrexate in rheumatoid arthritis and with PUVA, cyclosporine and anti-TNF treatment in psoriasis. Data on the safety of using biologic or immunosuppressant therapy in IMID patients with a history of cancer are scarce.

This review provides clinicians with a solid background to help them in making decisions about treatment of immune-mediated diseases in patients with a tumor history.

This article is related to another review article in Molecular Cancer:http://www.molecular-cancer.com/content/12/1/86.
Linking neuronal brain activity to the glucose metabolism
Authors: Göbel Britta , Oltmanns Kerstin M , Chung Matthias
Published: August 2013

Background

Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis.

Methods

First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism.

Results

Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis.

Conclusions

The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.
Interactions between HIV-1 Vif and human ElonginB-ElonginC are important for CBF-β binding to Vif
Authors: Wang Xiaodan , Wang Xiaoying , Zhang Haihong , Lv Mingyu , Zuo Tao , Wu Hui , Wang Jiawen , Liu Donglai , Wang Chu , Zhang Jingyao , Li Xu , Wu Jiaxin , Yu Bin , Kong Wei , Yu Xianghui
Published: August 2013

Background

The HIV-1 accessory factor Vif is necessary for efficient viral infection in non-permissive cells. Vif antagonizes the antiviral activity of human cytidine deaminase APOBEC3 proteins that confer the non-permissive phenotype by tethering them (APOBEC3DE/3F/3G) to the Vif-CBF-β-ElonginB-ElonginC-Cullin5-Rbx (Vif-CBF-β-EloB-EloC-Cul5-Rbx) E3 complex to induce their proteasomal degradation. EloB and EloC were initially reported as positive regulatory subunits of the Elongin (SIII) complex. Thereafter, EloB and EloC were found to be components of Cul-E3 complexes, contributing to proteasomal degradation of specific substrates. CBF-β is a newly identified key regulator of Vif function, and more information is needed to further clarify its regulatory mechanism. Here, we comprehensively investigated the functions of EloB (together with EloC) in the Vif-CBF-β-Cul5 E3 ligase complex.

Results

The results revealed that: (1) EloB (and EloC) positively affected the recruitment of CBF-β to Vif. Both knockdown of endogenous EloB and over-expression of its mutant with a 34-residue deletion in the COOH-terminal tail (EloBΔC34/EBΔC34) impaired the Vif-CBF-β interaction. (2) Introduction of both the Vif SLQ → AAA mutant (VifΔSLQ, which dramatically impairs Vif-EloB-EloC binding) and the Vif PPL → AAA mutant (VifΔPPL, which is thought to reduce Vif-EloB binding) could reduce CBF-β binding. (3) EloB-EloC but not CBF-β could greatly enhance the folding of full-length Vif inEscherichia coli. (4) The over-expression of EloB or the N-terminal ubiquitin-like (UbL) domain of EloB could significantly improve the stability of Vif/VifΔSLQ/VifΔPPL through the region between residues 9 and 14.

Conclusion

Our results indicate that the Vif interaction with EloB-EloC may contribute to recruitment of CBF-β to Vif, demonstrating that the EloB C-teminus may play a role in improving Vif function and that the over-expression of EloB results in Vif stabilization.
Development in a naturally acidified environment: Na+/H+-exchanger 3-based proton secretion leads to CO2 tolerance in cephalopod embryos
Authors: Hu Marian Y , Lee Jay-Ron , Lin Li-Yih , Shih Tin-Han , Stumpp Meike , Lee Mong-Fong , Hwang Pung-Pung , Tseng Yung-Che
Published: August 2013

Background

Regulation of pH homeostasis is a central feature of all animals to cope with acid–base disturbances caused by respiratory CO2. Although a large body of knowledge is available for vertebrate and mammalian pH regulatory systems, the mechanisms of pH regulation in marine invertebrates remain largely unexplored.

Results

We used squid (Sepioteuthis lessoniana), which are known as powerful acid–base regulators to investigate the pH regulatory machinery with a special focus on proton secretion pathways during environmental hypercapnia. We cloned a Rhesus protein (slRhP), V-type H+-ATPase (slVHA) and the Na+/H+ exchanger 3 (slNHE3) from S. lessoniana, which are hypothesized to represent key players in proton secretion pathways among different animal taxa. Specifically designed antibodies for S. lessoniana demonstrated the sub-cellular localization of NKA, VHA (basolateral) and NHE3 (apical) in epidermal ionocytes of early life stages. Gene expression analyses demonstrated that slNHE3, slVHA and slRhP are up regulated in response to environmental hypercapnia (pH 7.31; 0.46 kPa p CO2) in body and yolk tissues compared to control conditions (pH 8.1; 0.045 kPa p CO2). This observation is supported by H+ selective electrode measurements, which detected increased proton gradients in CO2 treated embryos. This compensatory proton secretion is EIPA sensitive and thus confirms the central role of NHE based proton secretion in cephalopods.

Conclusion

The present work shows that in convergence to teleosts and mammalian pH regulatory systems, cephalopod early life stages have evolved a unique acid–base regulatory machinery located in epidermal ionocytes. Using cephalopod molluscs as an invertebrate model this work provides important insights regarding the unifying evolutionary principles of pH regulation in different animal taxa that enables them to cope with CO2 induced acid–base disturbances.
The effect of venovenous extra-corporeal membrane oxygenation (ECMO) therapy on immune inflammatory response of cerebral tissues in porcine model
Authors: Chen Qiyi , Yu Wenkui , Shi Jiangliang , Shen Juanhong , Hu Yimin , Gao Tao , Zhang Juanjuan , Xi Fengchan , Gong Jianfeng , Li Jieshou , Li Ning
Published: August 2013

Background

Extra-Corporeal Membrane Oxygenation (ECMO) therapy is associated with high risk of neurologic injury. But the mechanism of neurologic injury during and/or after ECMO therapy is still unclear. Recent animal experiments confirmed that ECMO treatment increases the immune inflammatory response. The aim of this study is to investigate the effect of VV- ECMO on immune inflammatory response of cerebral tissues and neurological impairment.

Methods

18 porcine were randomly divided into control, sham and ECMO group (n = 6/group). ECMO was run 24 h in the ECMO group, and serum collected at 0, 2, 6, 12 and 24 h during ECMO treatment for the analysis of cytokine (IL-1β, IL-6, IL-10, TNF-a) and cerebral injury specific biomarker S100B and NSE. After 24 h ECMO treatment, all animals were euthanized and cerebral tissues (hypothalamus, hippocampus and cortex) were collected for measure of mRNA and protein levels of cytokine (IL-1β, IL-6, IL-10, TNF-a).

Results

The results during ECMO treatment showed that all the pro-inflammation cytokines were increased significantly after 2 h, and anti-inflammation IL-10 showed transient hoist in the first 2 h in serum. After 24 h ECMO therapy, the mRNA levels of pro-inflammation cytokines and anti-inflammation IL-10 were simultaneously up-regulated in cerebral tissues (hypothalamus, hippocampus and cortex). And protein concentrations also showed different increasing levels in cerebral tissues. However, during the ECMO treatment, S100B and NSE protein in serum did not change significantly.

Conclusion

These findings suggest VV-ECMO treatment can not only lead to immune inflammatory response in blood, but can also produce immune and inflammatory response in cerebral tissues. However the extent of immune inflammation was not sufficient to cause significant neurological impairment in this study. But the correlation between cerebral inflammatory response and cerebral impairment need to further explore.