bluuebunny/crossref_metadata_2025 huggingface dataset:
Ethics in Neonatal Pain Research
Authors: Axelin Anna , Salanterä Sanna
Published: May 2008

A literature review of 98 articles concerning clinical pain research in newborn infants was conducted to evaluate how researchers report the ethical issues related to their studies and how journals guide this reporting. The articles were published in 49 different scientific journals. The ethical issues most often mentioned were parental informed consent (94%) and ethical review approval (87%). In 75% of the studies the infants suffered pain during the research when placebo, no treatment or otherwise inadequate pain management was applied. Discussion about benefits versus harm to research participants was lacking. A quarter of the journals did not have any ethical guidelines for submitted manuscripts. We conclude that ethical considerations did not play a significant role in the articles studied. Missing and superficial guidelines enable authors to offer studies with fragile research ethics.
Ethical Issues Related To BRCA Gene Testing in Orthodox Jewish Women
Authors: Mor Pnina , Oberle Kathleen
Published: May 2008

Persons exhibiting mutations in two tumor suppressor genes, BRCA1 and BRCA2, have a greatly increased risk of developing breast and/or ovarian cancer. The incidence of BRCA gene mutation is very high in Ashkenazi Jewish women of European descent, and many issues can arise, particularly for observant Orthodox women, because of their genetic status. Their obligations under the Jewish code of ethics, referred to as Jewish law, with respect to the acceptability of various risk-reducing strategies, may be poorly understood. In this article the moral direction that Jewish law gives to women regarding testing, confidentiality, and other issues is explored. The intent is to broaden nurses' knowledge of how a particular religious tradition could impact on decision making around genetics testing, with the aim of enhancing their understanding of culturally sensitive ethical care.
Guilty But Good: Defending Voluntary Active Euthanasia From a Virtue Perspective
Authors: Begley Ann Marie
Published: May 2008

This article is presented as a defence of voluntary active euthanasia from a virtue perspective and it is written with the objective of generating debate and challenging the assumption that killing is necessarily vicious in all circumstances. Practitioners are often torn between acting from virtue and acting from duty. In the case presented the physician was governed by compassion and this illustrates how good people may have the courage to sacrifice their own security in the interests of virtue. The doctor's action created huge tensions for the nurse, who was governed by the code of conduct and relevant laws. Appraising active euthanasia from a virtue perspective can offer a more compassionate approach to the predicament of practitioners and clients. The tensions arising from the virtue versus rules debate generates irreconcilable difficulties for nurses. A shift towards virtue would help to resolve this problem and support the call for a change in the law. The controversial nature of this position is acknowledged. The argument is put forward on the understanding that many practitioners will not agree with the conclusions reached.
Nurses' Workplace Distress and Ethical Dilemmas in Tanzanian Health Care
Authors: Häggström Elisabeth , Mbusa Ester , Wadensten Barbro
Published: May 2008

The aim of this study was to describe Tanzanian nurses' meaning of and experiences with ethical dilemmas and workplace distress in different care settings. An open question guide was used and the study focused on the answers that 29 registered nurses supplied. The theme, `Tanzanian registered nurses' invisible and visible expressions about existential conditions in care', emerged from several subthemes as: suffering from (1) workplace distress; (2) ethical dilemmas; (3) trying to maintaining good quality nursing care; (4) lack of respect, appreciation and influence; and (5) a heavy workload that did not prevent registered nurses from struggling for better care for their patients. The analysis shows that, on a daily basis, nurses find themselves working on the edge of life and death, while they have few opportunities for doing anything about this situation. Nurses need professional guidance to gain insight and be able to reflect on their situations, so that they do not become overloaded with ethical dilemmas and workplace distress.
Prevention of Unethical Actions in Nursing Homes
Authors: Solum Eva Merethe , Slettebø Åshild , Hauge Solveig
Published: May 2008

Ethical problems regularly arise during daily care in nursing homes. These include violation of patients' right to autonomy and to be treated with respect. The aim of this study was to investigate how caregivers emphasize daily dialogue and mutual reflection to reach moral alternatives in daily care. The data were collected by participant observation and interviews with seven caregivers in a Norwegian nursing home. A number of ethical problems linked to 10 patients were disclosed. Moral problems were revealed as the caregivers acted in ways that they knew were against patients' interest. We used a theoretical interpretation according to Habermas' discourse ethics on the importance of dialogue when deciding moral courses of action for patients. This theory has four basic requirements: communicative competence, equality, self-determination, and openness about motives.
Rekindling the Sociological Imagination as a Pedagogical “Package” in Management Education
Authors: Duarte Fernanda
Published: May 2008

Based on the reflections and insights of a sociologist teaching in a school of management, this article invites management educators to rekindle the sociological imagination, which, albeit more than five decades old, is a concept that has not lost its relevance to make sense of organizational phenomena. It is my contention that C. Wright Mills's sociological imagination is a valuable pedagogical “package” in management education as it encourages contextualization of organizational phenomena and fosters reflection, critical thinking, and reflexivity skills. These skills are a suitable complement to the more normative pedagogical approaches that emphasize the technical and instrumental aspects of management.
The Teaching of Strategy
Authors: Bower Joseph L.
Published: May 2008

Courses in strategy are an outgrowth of the business policy course first taught at Harvard Business School in 1912. This article examines how the teaching of a course concerned with the development and implementation of the goals and policies of a firm changed during three periods in the postwar period: first, with the introduction of the concept of corporate strategy; second, with the evolution of faculty interest in a concept of competitive strategy more closely grounded in industrial organization economics; and third, with the development of a new course in entrepreneurial management more closely linked to business policy's concerns with the general management challenges facing the leaders of modern firms. This history of the course is linked to changes in information technology, financial markets, and the managements of firms as well as related changes in the markets for students and faculty.
Rejoinder
Authors: Barley Stephen R.
Published: May 2008

The articles assembled for the special section on corporations, democracy, and the public good provide a useful starting point for outlining a possible trajectory for future research. Institutional theory can be a solid theoretical foundation, especially when researchers emphasize the role of ideologies and language as well as power and agency. The inner workings of the legal system, and specifically the formation and adjudication of the law, may be a promising arena for empirical work. Finally, meaningful research can be promoted by resisting the temptation to base scholarly work on overly simplistic, uni-dimensional, and naïve conceptualizations of “democracy” and the “public good.”
Hunting Kings
Authors: Betzig Laura
Published: May 2008

Nimrod, the builder of cities from Babel to Calah, was the first “mighty man” on earth, a “mighty hunter before the Lord.” So were other Near Eastern, North African, Far Eastern, European, and New World kings. They hunted everything from lions to guanacos, on four of six continents, from the beginning to the end of recorded time. But why? Hunting provided meat, and perhaps military exercise; but most kings subsisted on domesticated animals and plants, and delegated their wars to specialists. Besides, chasing animals cost money and time, and more than a few kings were killed or maimed in the act of bringing down game. The costs seem to outweigh the benefits. Much about human history seems to have been adaptive. Royal hunts do not. Hunting was the human adaptation on the savannah for hundreds of thousands of years. But it seems to be a vestige most kings can't shake.
Review: Conceptualization and Measurement of Organizational Readiness for Change
Authors: Weiner Bryan J. , Amick Halle , Lee Shoou-Yih Daniel
Published: May 2008

Health care practitioners and change experts contend that organizational readiness for change is a critical precursor to successful change implementation. This article assesses how organizational readiness for change has been defined and measured in health services research and other fields. Analysis of 106 peer-reviewed articles reveals conceptual ambiguities and disagreements in current thinking and writing about organizational readiness for change. Inspection of 43 instruments for measuring organizational readiness for change reveals limited evidence of reliability or validity for most publicly available measures. Several conceptual and methodological issues that need to be addressed to generate knowledge useful for practice are identified and discussed.
A Survey of Hospital Quality Improvement Activities
Authors: Cohen Alan B. , Restuccia Joseph D. , Shwartz Michael , Drake Jennifer E. , Kang Ray , Kralovec Peter , Holmes Sally K. , Margolin Frances , Bohr Deborah
Published: May 2008

Five years after the Institute of Medicine (IOM) called for a redesigned U.S. health care system, relatively little was known about the extent to which hospitals had undertaken quality improvement (QI) efforts to address deficiencies in patient care. To examine the state of hospital QI activities in 2006, the authors designed and conducted a survey of short-term, general hospitals with 25 or more beds. In a sample of 470 hospitals, they found that many were actively engaged in improvement efforts but that these activities varied in method and impact. Hospitals with high levels of perceived quality, as reflected in assessments by their quality managers, were more likely to have embraced QI as a strategic priority, employed quality practices and processes consistent with IOM aims, fostered staff training and involvement in QI methods, engaged in an array of QI activities and clinical QI strategies, and maintained staffing levels favoring fewer patients per nurse.
The Impact of the PICK a Partner Relationship Education Program on Single Army Soldiers
Authors: Van Epp Morgan C. , Futris Ted G. , Van Epp John C. , Campbell Kelly
Published: May 2008

Educating singles on how to develop healthy, romantic relationships can be beneficial to their subsequent dating and marital satisfaction, and for army soldiers, their satisfaction with military life. A new relationship program, the Premarital Interpersonal Choices and Knowledge (PICK) program, was delivered to single army soldiers, and at the conclusion of the program participants demonstrated an increase in their understanding of the crucial areas to explore and discuss in a premarital relationship, gained a better understanding of how to pace their relationship, and exhibited more realistic attitudes and beliefs about marriage and mate selection.
Obliterating Informal Space: The London Olympics and the Lea Valley: A Photo Essay
Authors: Edensor Tim , Christie Caroline , Lloyd Bobby
Published: May 2008

Caroline Christie and Bobby Lloyd have regularly photographed the Lea Valley London Olympic site since 2003. In 2006, they were joined by Tim Edensor for a day of walking and exploring. This article has emerged from this event as well as reflections on the photographs featured here. The area is one of the few remaining informal spaces in London, and the variegated activities and experiences it offers are being replaced by the giant Olympic development. The authors particularly focus on forthcoming loss: of the sensual experience of space, of the numerous possibilities for often improvisatory spatial practices, of an immanent and playful engagement with materiality, of a nondesigned and alternative spatial aesthetics.
Sticking Together
Authors: Hanley Seán , Szczerbiak Aleks , Haughton Tim , Fowler Brigid
Published: May 2008

In this article, we attempt to explain varying patterns of centre—right success between 1990 and 2006 in three post-communist states — Hungary, Poland and the Czech Republic. Success is understood as the ability to construct broad and durable parties. Both macro-institutional explanations, focusing on executive structures and electoral systems, and historical—structural explanations, stressing communist regime legacies, have limited power to explain the observed variance. The introduction of a more sophisticated framework of path dependence, stressing the role of choices and political crafting at critical junctures, adds some insight, but the lack of strong `lock-in' mechanisms required by such approaches makes such a model unconvincing when applied to Central and Eastern European centre—right party development. Other explanations that stress the importance of elite characteristics and capacity are needed to supplement the shortcomings of these approaches, in particular: (a) the presence of cohesive elites able to act as the nucleus of new centre—right formations; and (b) the ability of such elites to craft broad integrative ideological narratives that can transcend diverse ideological positions and unite broad swathes of centre—right activists and voters.
Democracy, Human Rights and History
Authors: Geenens Raf
Published: May 2008

This article offers an overview of the French political philosopher Claude Lefort's oeuvre, arguing that his work should be read as a normative or even universalist justification of democracy and human rights. The notion of history plays a crucial notion in this enterprise, as Lefort demonstrates that there is an ineluctable 'historical' or 'political' condition of human coexistence, a condition that can only be properly accommodated in a regime of democracy and human rights. This reading of Lefort is contrasted with two other interpretations of his work. The first of these, by Sofia Nasstrom, is shown to overlook the importance of history in Lefort's understanding of democracy. The second, by Bernard Flynn, is shown to overlook the universalist implications of Lefort's theory.
Defenders of Liberal Individualism, Republican Virtues and Solidarity
Authors: Dobuzinskis Laurent
Published: May 2008

The intellectual founding fathers of the French Third Republic were innovative thinkers who achieved an original synthesis of republican and liberal principles. This becomes evident when one examines the works of four philosophers who played a crucial role in the French intellectual and political life of the period extending from the 1870s to the early 1900s: Emile Littre, Charles Renouvier, Henry Michel and Alfred Fouillee. Among their many contributions to moral and political philosophy, I highlight two themes: a) a conception of political liberty that grants a pre-eminent place to civic education as a means to free citizens from domination by dogmatic religious authorities, sectarian political movements or unexamined beliefs of any kind; b) the need to implement reasonable social reforms in order to ensure that the many and complex relations of functional interdependence constitutive of modern societies are equitable and realize an ideal of national solidarity. I suggest that these ideas ought to be carefully examined by contemporary proponents of civic republicanism.
Conor Cruise O'Brien's Conservative Anti-Nationalism
Authors: McNally Mark
Published: May 2008

From the early 1970s Conor Cruise O'Brien acquired a reputation in Ireland and internationally as one of the most vociferous critics of nationalism. While many see the origins of his critique in his reaction to the emergence of militant nationalism in Northern Ireland at this time, in this article I argue that the foundations of O'Brien's anti-nationalism had already been laid in the postwar European context. The article illustrates how O'Brien's historical and intellectual experience in the aftermath of the Second World War had an essentially conservative influence on his thought, providing him with a pool of ideas which he would later employ in his attack on nationalism, and Irish nationalism in particular. I therefore maintain that there is a lot more continuity in O'Brien's thought than is sometimes assumed.
Sovereignty, Cosmopolitanism and the Ethics of European Foreign Policy
Authors: Ypi Lea
Published: May 2008

This article explores the tensions between cosmopolitanism and sovereignty as a means to conceptualize the ethics of European foreign policy. It starts by discussing the claim that, in order for the EU to play a meaningful role as an international actor, a definition of the common ethical values orienting its political conduct is required. The question of a European federation of states and its ethical conceptualization emerges clearly in some of the philosophical writings of the 17th and 18th centuries. I seek to provide an outline of the main arguments presented by authors such as Saint Pierre, Rousseau and Kant regarding the implications of the emerging difference between cosmopolitanism and the law of nations in the ethics of international relations. The article focuses on the normative significance of the concept of sovereignty as it emerges in modern political philosophy and highlights its tensions with the ideas of moral and political cosmopolitanism. This exploration serves a double function: theoretical and practical. From the theoretical perspective it leads to a better understanding of the tensions involved in conceptualizing a common ethical orientation for the states of Europe. From the practical standpoint it sheds light on some persistent difficulties the European Union faces in trying to move beyond an intergovernmental political arrangement in the field of foreign policy.
The cytoplasmic tail of CD45 is released from activated phagocytes and can act as an inhibitory messenger for T cells
Authors: Kirchberger Stefanie , Majdic Otto , Blüml Stefan , Schrauf Catharina , Leitner Judith , Gerner Christopher , Paster Wolfgang , Gundacker Nina , Sibilia Maria , Stöckl Johannes
Published: May 2008

CD45 is the prototypic transmembrane protein tyrosine phosphatase (PTP), which is expressed on all nucleated hematopoietic cells and plays a central role in the integration of environmental signals into immune cell responses. Here we report an alternative function for the intracellular domain of CD45. We dis-covered that CD45 is sequentially cleaved by serine/metalloproteinases and γ-secretases during activation of human monocytes and granulocytes by fungal stimuli or phorbol 12-myristate 13-acetate but not by other microbial stimuli. Proteolytic processing of CD45 occurred upon activation of monocytes or granulocytes but not of T cells, B cells, or dendritic cells and resulted in a 95-kDa fragment of the cytoplasmic tail of CD45 (ct-CD45). ct-CD45 was released from monocytes and granulocytes upon activation-induced cell death. Binding studies with ct-CD45 revealed a counter-receptor on preactivated T cells. Moreover, T-cell proliferation induced by dendritic cells or CD3 antibodies was inhibited in the presence of ct-CD45. Taken together, the results of our study demonstrate that fragments of the intracellular domain of CD45 from human phagocytes can function as intercellular regulators of T-cell activation.
A selective sphingosine kinase 1 inhibitor integrates multiple molecular therapeutic targets in human leukemia
Authors: Paugh Steven W. , Paugh Barbara S. , Rahmani Mohamed , Kapitonov Dmitri , Almenara Jorge A. , Kordula Tomasz , Milstien Sheldon , Adams Jeffrey K. , Zipkin Robert E. , Grant Steven , Spiegel Sarah
Published: May 2008

The potent bioactive sphingolipid mediator, sphingosine-1-phosphate (S1P), is produced by 2 sphingosine kinase isoenzymes, SphK1 and SphK2. Expression of SphK1 is up-regulated in cancers, including leukemia, and associated with cancer progression. A screen of sphingosine analogs identified (2R,3S,4E)-N-methyl-5-(4′-pentylphenyl)-2-aminopent-4-ene-1,3-diol, designated SK1-I (BML-258), as a potent, water-soluble, isoenzyme-specific inhibitor of SphK1. In contrast to pan-SphK inhibitors, SK1-I did not inhibit SphK2, PKC, or numerous other protein kinases. SK1-I decreased growth and survival of human leukemia U937 and Jurkat cells, and enhanced apoptosis and cleavage of Bcl-2. Lethality of SK1-I was reversed by caspase inhibitors and by expression of Bcl-2. SK1-I not only decreased S1P levels but concomitantly increased levels of its proapoptotic precursor ceramide. Conversely, S1P protected against SK1-I–induced apoptosis. SK1-I also induced multiple perturbations in activation of signaling and survival-related proteins, including diminished phosphorylation of ERK1/2 and Akt. Expression of constitutively active Akt protected against SK1-I–induced apoptosis. Notably, SK1-I potently induced apoptosis in leukemic blasts isolated from patients with acute myelogenous leukemia but was relatively sparing of normal peripheral blood mononuclear leukocytes. Moreover, SK1-I markedly reduced growth of AML xenograft tumors. Our results suggest that specific inhibitors of SphK1 warrant attention as potential additions to the therapeutic armamentarium in leukemia.
Susceptibility to nontuberculous mycobacterial lung disease: Table 1—
Authors: Sexton P. , Harrison A. C.
Published: May 2008

The nontuberculous mycobacteria (NTM) exhibit heterogeneous pathogenicity in humans. Articles on known and potential human factors capable of producing susceptibility to NTM lung disease (NTMLD) were identified by a systematic search of the medical literature, and are reviewed in the present study.

Patients with pre-existing structural lung disease are known to be at risk of NTMLD. Other susceptible groups have become recognised since the 1980s, in particular middle-aged nonsmokers without previous lung disease (a group including those with Lady Windermere syndrome) and patients with genetically determined defects of cell-mediated immunity, including abnormalities of the interleukin-12/interferon-γ axis, certain human leukocyte antigen alleles, cystic fibrosis transmembrane conductance regulator mutations, and polymorphisms of solute carrier 11A1 (or natural resistance-associated macrophage protein 1) and the vitamin D receptor.

Information is also accruing about acquired systemic causes of susceptibility to NTMLD, including inhibitory antibodies directed against interferon-γ, post-menopausal waning of endogenous oestrogen levels, coeliac disease and exposure to use of dietary phyto-oestrogens. It is not known whether immunosuppressive factors, such as oral corticosteroid treatment, chronic renal failure, diabetes mellitus and other known risk factors for pulmonary tuberculosis, are also risk factors for the development of NTMLD. Caution is appropriate in managing such patients.
Evolution of the CDKN1C-KCNQ1 imprinted domain
Authors: Ager Eleanor I , Pask Andrew J , Gehring Helen M , Shaw Geoff , Renfree Marilyn B
Published: May 2008

Background

Genomic imprinting occurs in both marsupial and eutherian mammals. The CDKN1C and IGF2 genes are both imprinted and syntenic in the mouse and human, but in marsupials only IGF2 is imprinted. This study examines the evolution of features that, in eutherians, regulate CDKN1C imprinting.

Results

Despite the absence of imprinting, CDKN1C protein was present in the tammar wallaby placenta. Genomic analysis of the tammar region confirmed that CDKN1C is syntenic with IGF2. However, there are fewer LTR and DNA elements in the region and in intron 9 of KCNQ1. In addition there are fewer LINEs in the tammar compared with human and mouse. While the CpG island in intron 10 of KCNQ1 and promoter elements could not be detected, the antisense transcript KCNQ1OT1 that regulates CDKN1C imprinting in human and mouse is still expressed.

Conclusion

CDKN1C has a conserved function, likely antagonistic to IGF2, in the mammalian placenta that preceded its acquisition of imprinting. CDKN1C resides in synteny with IGF2, demonstrating that imprinting of the two genes did not occur concurrently to balance maternal and paternal influences on the growth of the placenta. The expression of KCNQ1OT1 in the absence of CDKN1C imprinting suggests that antisense transcription at this locus preceded imprinting of this domain. These findings demonstrate the stepwise accumulation of control mechanisms within imprinted domains and show that CDKN1C imprinting cannot be due to its synteny with IGF2 or with its placental expression in mammals.
Development and optimization of quantitative PCR for the diagnosis of invasive aspergillosis with bronchoalveolar lavage fluid
Authors: Khot Prasanna D , Ko Daisy L , Hackman Robert C , Fredricks David N
Published: May 2008

Background

The diagnosis of invasive pulmonary aspergillosis (IPA) remains challenging. Culture and histopathological examination of bronchoalveolar lavage (BAL) fluid are useful but have suboptimal sensitivity and in the case of culture may require several days for fungal growth to be evident. Detection of Aspergillus DNA in BAL fluid by quantitative PCR (qPCR) offers the potential for earlier diagnosis and higher sensitivity. It is important to adopt quality control measures in PCR assays to address false positives and negatives which can hinder accurate evaluation of diagnostic performance.

Methods

BAL fluid from 94 episodes of pneumonia in 81 patients was analyzed. Thirteen episodes were categorized as proven or probable IPA using Mycoses Study Group criteria. The pellet and the supernatant fractions of the BAL were separately assayed. A successful extraction was confirmed with a human 18S rRNA gene qPCR. Inhibition in each qPCR was measured using an exogenous DNA based internal amplification control (IAC). The presence of DNA from pathogens in the Aspergillus genus was detected using qPCR targeting fungal 18S rRNA gene.

Results

Human 18S rRNA gene qPCR confirmed successful DNA extraction of all samples. IAC detected some degree of initial inhibition in 11 samples. When culture was used to diagnose IPA, the sensitivity and specificity were 84.5% and 100% respectively. Receiver-operating characteristic analysis of qPCR showed that a cutoff of 13 fg of Aspergillus genomic DNA generated a sensitivity, specificity, positive and negative predictive value of 77%, 88%, 50%, 96% respectively. BAL pellet and supernatant analyzed together resulted in sensitivity and specificity similar to BAL pellet alone. Some patients did not meet standard criteria for IPA, but had consistently high levels of Aspergillus DNA in BAL fluid by qPCR.

Conclusion

The Aspergillus qPCR assay detected Aspergillus DNA in 76.9% of subjects with proven or probable IPA when the concentrated BAL fluid pellet fraction was used for diagnosis. There was no benefit from analyzing the BAL supernatant fraction. Use of both extraction and amplification controls provided optimal quality control for interpreting qPCR results and therefore may increase our understanding of the true potential of qPCR for the diagnosis of IPA.
Acute pancreatitis and subdural haematoma in a patient with severe falciparum malaria: Case report and review of literature
Authors: Seshadri Pratibha , Dev Anand Vimal , Viggeswarpu Surekha , Sathyendra Sowmya , Peter John Victor
Published: May 2008

Plasmodium falciparum infection is known to be associated with a spectrum of systemic complications ranging from mild and self-limiting to life-threatening. This case report illustrates a patient who had a protracted course in hospital due to several rare complications of falciparum malaria. A 21-year old man presented with a five-day history of high-grade fever, jaundice and abdominal pain and a two-day history of altered conscious state. A diagnosis of severe falciparum malaria was made based on the clinical presentation and a positive blood smear with parasitaemia of 45%. Despite adequate anti-malarial therapy with artesunate, the patient had persistent and worsening abdominal pain. Investigations suggested a diagnosis of acute pancreatitis, a rare association with falciparum malaria. However, in spite of supportive therapy for acute pancreatitis and a 10-day course of intravenous artesunate and oral doxycycline at recommended doses, he continued to be febrile with peripheral blood smear showing persistence of ring forms. Antimalarial therapy was, therefore, changed to quinine on the suspicion of possible artesunate resistance. On the 17th day of stay in hospital, the patient developed generalized tonic-clonic seizures. Computerized tomography of the brain showed bilateral fronto-parietal subdural haematomas that were surgically drained. His fever persisted beyond 30-days despite broad-spectrum antibiotics, quinine therapy and negative malarial smears. A possibility of drug fever was considered and all drugs were ceased. He subsequently became afebrile and was discharged on the 38th hospital admission day. Recognition of complications and appropriate management at each stage facilitated successful outcome. This report has been presented to highlight the occurrence of several rare complications of falciparum malaria in the same patient.
The elusive link between high sensitivity C-reactive protein and carotid subclinical atherosclerosis in coronary artery bypass grafting candidates: A cross-sectional study
Authors: Shakouri Parvin , Nezami Nariman , Tarzamni Mohammad Kazem , Rashid Reza Javad
Published: May 2008

Background

Previous studies demonstrated a modest association between C-Reactive Protein (CRP), stenosis of carotid artery, and carotid Intima-Media Thickness (IMT) in general population. During present study, we aimed to evaluate the relationship between High Sensitivity C-Reactive Protein (hsCRP) and Common Carotid Intima-Media Thickness (CCIMT) in patients who candidate for Coronary Artery Bypass Grafting (CABG).

Methods

The study subjects were enrolled from patients with coronary arteries disease referred from Shahid Madani Hospital (Tabriz, Iran), who have been candidate for elective CABG from January 2005 to August 2007. The common carotid arteries were evaluated with high-resolution B-mode ultrasonography using a 7.5- MHz linear-array transducer to determine the IMT and grade of stenosis. Serum hsCRP level was measured using commercially available enzyme linked immunosorbent assay kit.

Results

Finally, information of 176 CABG candidates was analysed. The mean age of participants was 62.71 ± 9.45 years with 1.63 male to female ratio. The mean of CCIMT was 0.69 ± 0.54 mm. Although there was no significant correlation between serum hsCRP level and CCIMT in patients without carotid stenosis (p=0.113, r=0.186), participants with common carotid artery stenosis had higher levels of serum hsCRP than participants without stenosis (2.42+/-1.30 vs. 1.20+/-0.97 mg/dl; p=0.009).

Conclusion

Study results showed that there was no correlation between serum hsCRP level and CCIMT in patients without carotid stenosis, but patients with common carotid artery stenosis had higher levels of serum hsCRP than patients without stenosis.
Nef does not contribute to replication differences between R5 pre-AIDS and AIDS HIV-1 clones from patient ACH142
Authors: Olivieri Kevin C , Scoggins Robert M , Broderick Brooks , Powell Maria LC , Alexander Melissa A , Hammarskjöld Marie-Louise , Rekosh David , Camerini David
Published: May 2008

AIDS-associated, CCR5-tropic (R5) HIV-1 clones, isolated from a patient that never developed CXCR4-tropic HIV-1, replicate to a greater extent and cause greater cytopathic effects than R5 HIV-1 clones isolated before the onset of AIDS. Previously, we showed that HIV-1 Env substantially contributed to the enhanced replication of an AIDS clone. In order to determine if Nef makes a similar contribution, we cloned and phenotypically analyzed nef genes from a series of patient ACH142 derived R5 HIV-1 clones. The AIDS-associated Nef contains a series of residues found in Nef proteins from progressors [1]. In contrast to other reports [1–3], this AIDS-associated Nef downmodulated MHC-I to a greater extent and CD4 less than pre-AIDS Nef proteins. Additionally, all Nef proteins enhanced infectivity similarly in a single round of replication. Combined with our previous study, these data show that evolution of the HIV-1 env gene, but not the nef gene, within patient ACH142 significantly contributed to the enhanced replication and cytopathic effects of the AIDS-associated R5 HIV-1 clone.
Differing Alterations of Sodium Currents in Small Dorsal Root Ganglion Neurons after Ganglion Compression and Peripheral Nerve Injury
Authors: Huang Zhi-Jiang , Song Xue-Jun
Published: May 2008

Voltage-gated sodium channels play important roles in modulating dorsal root ganglion (DRG) neuron hyperexcitability and hyperalgesia after peripheral nerve injury or inflammation. We report that chronic compression of DRG (CCD) produces profound effect on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) sodium currents, which are different from that by chronic constriction injury (CCI) of the sciatic nerve in small DRG neurons. Whole cell patch-clamp recordings were obtained in vitro from L4 and/or L5 dissociated, small DRG neurons following in vivo DRG compression or nerve injury. The small DRG neurons were classified into slow and fast subtype neurons based on expression of the slow-inactivating TTX-R and fast-inactivating TTX-S Na+ currents. CCD treatment significantly reduced TTX-R and TTX-S current densities in the slow and fast neurons, but CCI selectively reduced the TTX-R and TTX-S current densities in the slow neurons. Changes in half-maximal potential (V1/2) and curve slope ( k) of steady-state inactivation of Na+ currents were different in the slow and fast neurons after CCD and CCI treatment. The window current of TTX-R and TTX-S currents in fast neurons were enlarged by CCD and CCI, while only that of TTX-S currents in slow neurons was increased by CCI. The decay rate of TTX-S and both TTX-R and TTX-S currents in fast neurons were reduced by CCD and CCI, respectively. These findings provide a possible sodium channel mechanism underlying CCD-induced DRG neuron hyperexcitability and hyperalgesia and demonstrate a differential effect in the Na+ currents of small DRG neurons after somata compression and peripheral nerve injury. This study also points to a complexity of hyperexcitability mechanisms contributing to CCD and CCI hyperexcitability in small DRG neurons.
An optimized high-performance liquid chromatography (HPLC) method for benzoylmesaconine determination in Radix Aconiti Lateralis Preparata (Fuzi, aconite roots) and its products
Authors: Xie Ying , Zhou Hua , Wong Yuen Fan , Liu Zhongqiu , Xu Hongxi , Jiang Zhihong , Liu Liang
Published: May 2008

Background

Benzoylmesaconine (BMA) is the main Aconitum alkaloid in Radix Aconiti Lateralis Preparata (Fuzi, aconite roots) with potent pharmacological activities, such as analgesia and anti-inflammation. The present study developed a simple and reliable method using BMA as a marker compound for the quality control of processed aconite roots and their products.

Methods

After extraction, a high-performance liquid chromatography (HPLC) determination of BMA was conducted on a RP-C18 column by gradient elution with acetonitrile and aqueous phase, containing 0.1% phosphoric acid adjusted with triethylamine to pH 3.0.

Results

A distinct peak profile was obtained and separation of BMA was achieved. Method validation showed that the relative standard deviations (RSDs) of the precision of BMA in all intra-day and inter-day assays were less than 1.36%, and that the average recovery rate was 96.95%. Quantitative analysis of BMA showed that the content of BMA varied significantly in processed aconite roots and their products.

Conclusion

This HPLC method using BMA as a marker compound is applicable to the quality control of processed aconite roots and their products.
Generation of a genomic tiling array of the human Major Histocompatibility Complex (MHC) and its application for DNA methylation analysis
Authors: Tomazou Eleni M , Rakyan Vardhman K , Lefebvre Gregory , Andrews Robert , Ellis Peter , Jackson David K , Langford Cordelia , Francis Matthew D , Bäckdahl Liselotte , Miretti Marcos , Coggill Penny , Ottaviani Diego , Sheer Denise , Murrell Adele , Beck Stephan
Published: May 2008

Background

The major histocompatibility complex (MHC) is essential for human immunity and is highly associated with common diseases, including cancer. While the genetics of the MHC has been studied intensively for many decades, very little is known about the epigenetics of this most polymorphic and disease-associated region of the genome.

Methods

To facilitate comprehensive epigenetic analyses of this region, we have generated a genomic tiling array of 2 Kb resolution covering the entire 4 Mb MHC region. The array has been designed to be compatible with chromatin immunoprecipitation (ChIP), methylated DNA immunoprecipitation (MeDIP), array comparative genomic hybridization (aCGH) and expression profiling, including of non-coding RNAs. The array comprises 7832 features, consisting of two replicates of both forward and reverse strands of MHC amplicons and appropriate controls.

Results

Using MeDIP, we demonstrate the application of the MHC array for DNA methylation profiling and the identification of tissue-specific differentially methylated regions (tDMRs). Based on the analysis of two tissues and two cell types, we identified 90 tDMRs within the MHC and describe their characterisation.

Conclusion

A tiling array covering the MHC region was developed and validated. Its successful application for DNA methylation profiling indicates that this array represents a useful tool for molecular analyses of the MHC in the context of medical genomics.
Conditioning response to granulocyte colony-stimulating factor via the dipeptidyl peptidase IV-adenosine deaminase complex
Authors: Focosi Daniele , Kast Richard Eric , Galimberti Sara , Petrini Mario
Published: May 2008

G-CSF is routinely used to mobilize hematopoietic stem cells (HSCs) from bone marrow (BM) into peripheral blood before aphaeresis, but HSC harvesting can be suboptimal. On the other hand, transplanted HSCs sometimes fail to engraft a recipient BM microenvironment when G-CSF is used after transplantation, as pushing-CSF will push HSCs away from marrow. So, G-CSF action needs to be potentiated by other drugs. Marrow stromal cells establish a local CXCL12 concentration gradient that is the primary homing signal for HSCs. Pharmacological interventions that modify this gradient, therefore, have potential to help HSC mobilization (by decreasing CXCL12) and engraftment (by increasing CXCL12). CXCL12 inactivation is primarily mediated by dipeptidyl peptidase-IV. We review here the currently available drugs affecting this enzyme that could be used in the clinic to achieve phase-specific help for G-CSF.
Separate endocytic pathways regulate IL-5 receptor internalization and signaling
Authors: Lei Jonathan T , Martinez-Moczygemba Margarita
Published: May 2008

Eosinophils are critically dependent on IL-5 for their activation, differentiation, survival, and augmentation of cytotoxic activity. We previously showed that the cytoplasmic domain of the hematopoietic receptor, βc, which is shared by IL-5, IL-3, and GM-CSF, is directly ubiquitinated and degraded by the proteasomes in a JAK2-dependent manner. However, studies describing the spatial distribution, endocytic regulation, and trafficking of βc-sharing receptors in human eosinophils are currently lacking. Using deconvolution microscopy and biochemical methods, we clearly demonstrate that IL-5Rs reside in and are internalized by clathrin- and lipid raft-dependent endocytic pathways. Microscopy analyses in TF1 cells and human eosinophils revealed significant colocalization of βc, IL-5Rα, and Cy3-labeled IL-5 with transferrin- (clathrin) and cholera toxin-B- (lipid raft) positive vesicles. Moreover, whereas internalized IL-5Rs were detected in both clathrin- and lipid raft-positive vesicles, biochemical data revealed that tyrosine phosphorylated, ubiquitinated, and proteasome-degraded IL-5Rs partitioned to the soluble, nonraft fractions (clathrin-containing). Lastly, we show that optimal IL-5-induced signaling requires entry of activated IL-5Rs into the intracellular compartment, as coimmunoprecipitation of key signaling molecules with the IL-5R was completely blocked when either endocytic pathway was inhibited. These data provide the first evidence that IL-5Rs segregate and traffic into two distinct plasma membrane compartments, and they further establish that IL-5R endocytosis regulates signaling both positively and negatively.
Delays in discharging elderly psychiatric in-patients
Authors: Hanif Irfan , Rathod Bhupendra
Published: May 2008

Aims and Method

The issue of elderly psychiatric patients remaining in hospitals after being declared medically fit is of concern to doctors, hospital managers and politicians alike. This article sets out the findings from a study involving elderly psychiatric patients at a district general hospital, undertaken to establish the actual lengths, reasons for and financial implications of delays in discharge. The study involved 50 in-patients, all of whom had been discharged over the 3-month study period.

Results

More than half of the patients in the sample were subject to some delay in discharge and for patients waiting for Elderly Mentally Infirm (EMI) placements this averaged 50 days. Collectively, nearly 25% of the time spent in hospital was due to delay. The cost to the hospital was estimated at more than £700 000 in 1 year.

Clinical Implications

Patients are being put at extra risk in terms of their health by being delayed in hospital. Issues of institutionalisation, nosocomial infections and falls are of primary concern.
Dark side of the moon: a course in mental health and the arts
Authors: Adams Bob
Published: May 2008

In 2005 clinicians were invited to submit proposals for Student Selected Components (SSC) for third and fourth year students at the new Hull and York Medical School. As a consultant psychiatrist with an interest in the arts I proposed a 3-week course in mental health and the arts. I wanted to find ways of promoting psychiatry as an interesting and valid subject for study and practice – as described in a recent Psychiatric Bulletin article (Eagles et al, 2007), medical students' attitudes to psychiatry could be influenced by their undergraduate experience. Eighteen months later, 15 students have completed the course.
Comparative survey of comorbidities in people with learning disability with and without epilepsy
Authors: Pawar Deepak G. , Akuffo Emmanuel O.
Published: May 2008

Aims and Method

To ascertain the prevalence of epilepsy and understand the differences in the comorbidities of non-epileptic and epileptic patients with learning disabilities. A simple comparative survey was undertaken between the two main groups of patients: non-epileptic and epileptic.

Results

The prevalence of epilepsy in the study group was 30%. A total of 70% of patients with any type of challenging behaviour were in the non-epileptic group compared with 59% in the epileptic group. Depression was the most common diagnosis in both groups, being slightly more in the non-epileptic group.

Clinical Implications

Our study suggests that there is no association between epilepsy and the prevalence of challenging behaviour of psychiatric conditions within the learning disabilities population.
Religion and mental health: what should psychiatrists do?
Authors: Koenig Harold G.
Published: May 2008

Religious beliefs and practices of patients have long been thought to have a pathological basis and psychiatrists for over a century have understood them in this light. Recent research, however, has uncovered findings which suggest that to some patients religion may also be a resource that helps them to cope with the stress of their illness or with dismal life circumstances. What are psychiatrists doing with this new information? How is it affecting their clinical practices? Studies of psychiatrists in the UK, Canada and the USA suggest that there remains widespread prejudice against religion and little integration of it into the assessment or care of patients. In this paper I discuss a range of interventions that psychiatrists should consider when treating patients, including taking a spiritual history, supporting healthy religious beliefs, challenging unhealthy beliefs, praying with patients (in highly selected cases) and consultation with, referral to, or joint therapy with trained clergy (Koenig, 2007). Religion is an important psychological and social factor that may serve either as a powerful resource for healing or be intricately intertwined with psychopathology.
James Maguire: Formerly Clinical Director and Consultant Psychiatrist at St Bridget's Hospital, Ardee, County Louth, and Department of Psychiatry, Our Lady's Hospital, Navan, County Meath, Ireland
Authors: Kelly Brendan D.
Published: May 2008

The life and career of Jim Maguire were defined by the qualities that characterised Jim himself: devotion to family and friends, dedication to patient care, and a sense of adventure that was entertaining, thought-provoking and insightful. It was a privilege to know him.
Berberine Acutely Inhibits Insulin Secretion from β-Cells through 3′,5′-Cyclic Adenosine 5′-Monophosphate Signaling Pathway
Authors: Zhou Libin , Wang Xiao , Shao Li , Yang Ying , Shang Wenbin , Yuan Guoyue , Jiang Boren , Li Fengying , Tang Jingfeng , Jing Hua , Chen Mingdao
Published: May 2008

Berberine, a hypoglycemic agent, has recently been shown to activate AMP-activated protein kinase (AMPK) contributing to its beneficial metabolic effects in peripheral tissues. However, whether berberine exerts a regulatory effect on β-cells via AMPK or other signaling pathways and counteracts glucolipotoxicity remains uncertain. In the present study, the impact of berberine on β-cell function was investigated in vivo and in vitro. In high-fat-fed rats, berberine treatment for 6 wk significantly decreased plasma glucose and insulin levels before and after an oral glucose challenge along with the reduction of body weight and improvement of blood lipid profile. In accordance with the in vivo results, berberine acutely decreased glucose-stimulated insulin secretion (GSIS) and palmitate-potentiated insulin secretion in MIN6 cells and rat islets. However, pretreated with berberine for 24 h augmented the response of MIN6 cells and rat islets to glucose and attenuated the glucolipotoxicity. Berberine acutely increased AMPK activity in MIN6 cells. However, compound C, an AMPK inhibitor, completely reversed troglitazone-suppressed GSIS, not berberine-suppressed GSIS. Otherwise, berberine decreased cAMP-raising agent-potentiated insulin secretion in MIN6 cells and rat islets. These results suggest that the activation of AMPK is required for troglitazone-suppressed GSIS, whereas cAMP signaling pathway contributes, at least in part, to the regulatory effect of berberine on insulin secretion.