bluuebunny/crossref_metadata_2025 huggingface dataset:
Palliative care provision for people with intellectual disabilities: a questionnaire survey of specialist palliative care professionals
Authors: Tuffrey-Wijne I , Whelton R , Curfs L , Hollins S
Published: May 2008

There is a growing interest in the palliative care needs of people with intellectual disabilities (ID). There are indications that palliative care staff face particular problems providing care to this group, but empirical data about the extent of the problem are lacking. This study aims to gain insight into the current use of palliative care services by people with ID in London, to identify the prevalence and severity of problems faced by palliative care professionals and to identify strategies that will facilitate an improvement in access and delivery of palliative care services to people with ID. A postal questionnaire was developed for this study and returned by 543 professionals working in 53 specialist palliative care services in London (57% response rate). Sixty-seven percent of respondents had supported a patient with ID at some point in their palliative care career. Problems arising from the patient’s difficulty in understanding the illness and treatment were reported as the most pertinent. Other prevalent problems included difficulty around communication, assessment and patient fear. Respondents emphasised the need for collaboration with carers and other services. Link worker schemes, training and access to background information were seen as most helpful. The authors conclude that palliative care services appear to be under-used by people with ID. There is a distinct set of problems related to the provision of palliative care for people with ID. Palliative care services should assess the nature and level of their service provision for people with ID. Future research should include epidemiological studies to assess need and include people with ID as informants to evaluate the effectiveness of palliative care provision.
Racial disparity in hospice use in the United States in 2002
Authors: Connor SR , Elwert F , Spence C , Christakis NA
Published: May 2008

We used complete Centers for Disease Control death certificate records and the Centers for Medicare and Medicaid Services 100% Standard Analytic File for hospice claims for 2002 to examine differences in hospice utilization between African-American and white decedents living in the United States. White decedents were more likely to use hospice in the year before their death than African-American decedents (29% vs 22%). Cause-specific hospice utilization rates among women were consistently higher than among men within a given race. African-American decedents were consistently less likely to use hospice than white decedents for almost all conditions. Hospice utilization was lower among African-American than among white decedents in 31 of 40 states. The higher the overall hospice utilization in a state, the less the positive difference between white and African-American usage rates; that is, the more accepted hospice is, as measured by ‘market share’, the lower the racial disparity in its use.
Current guidelines and their recommendations for prolactin monitoring in psychosis
Authors: Citrome Leslie
Published: May 2008

Guidelines on the use of second-generation antipsychotics and physical health monitoring have begun to include information on hyperprolactinemia, and generally recommend that patients should be queried about possible symptoms related to elevated prolactin: menstrual abnormalities, galactorrhea and sexual dysfunction. However, with only two exceptions, none of the guidelines suggest performing baseline plasma prolactin levels. Although several of the guidelines mention the potential for hyperprolactinemia to be associated with osteopenia and osteoporosis, there is no guidance how to monitor for this. Product labeling for the different antipsychotics inform the clinician about potential risks but are not helpful with precise monitoring recommendations. The internal medicine literature contains important information regarding the pulsatile secretion of prolactin, differential diagnosis of hyperprolactinemia, and plasma levels of prolactin usually associated with certain symptoms that would be useful for the prescriber of antipsychotics to be aware of. The prudent clinician should consider obtaining a baseline plasma prolactin level and at least one follow-up measurement when starting any patient on a new antipsychotic. This will help guide clinical decisions about antipsychotic dosage, switching antipsychotic medications, or considering ancillary treatments to protect bone mass. These decisions would be within the context of considering other adverse events as well as the overall effectiveness of the antipsychotic medication being used.
Medical causes and consequences of hyperprolactinaemia. A context for psychiatrists
Authors: Holt Richard IG
Published: May 2008

Hyperprolactinaemia is the commonest endocrine disorder of the hypothalamic—pituitary axis and can lead to both short-term sexual dysfunction and galactorrhoea, and long-term loss of bone mineral density. Prolactin is secreted from the anterior pituitary gland under the influence of dopamine, which exerts a tonic inhibitory effect on prolactin secretion. Physiological regulators of prolactin secretion include many different types of `stress' and sleep. Disruption of the normal control of prolactin secretion results in hyperprolactinaemia from pathological and pharmacological causes. The administration of antipsychotic medication is responsible for the high prevalence of hyperprolactinaemia in people with severe mental illness. Physiological hyperprolactinaemia, such as pregnancy and lactation, should be distinguished from pathological causes to prevent unnecessary investigation and treatment. The causes, consequences and management of hyperprolactinaemia are discussed in this article.
Cultural Transfer and National Identity in French Laicity
Authors: Baubérot Jean
Published: May 2008

This article examines the development of the concept of laicity and its specific application within the French political, social and cultural context. In doing so it contends that, far from being a ‘French exception’ as is sometimes perceived in the media, laicity in France drew on concepts and practices already in place in other countries at the time of the 1905 legislation separating church and state. The article concludes by asserting a distinction between laicity and secularism, whereby the former emphasises the separation of the roles of state and religion within a nation, whereas the latter refers to the progressive loss of relevance of religion within a culture. The specific definition of laicity has been enshrined in a recent International Declaration of Laicity in the 21st Century.
The Spread of Alphabetic Scripts (c. 1700—500 BCE)
Authors: Lemaire André
Published: May 2008

This article considers the origins of alphabetic writing, tracing its probable source to ancient Egypt, southern Levant or the Sinai during the Egyptian Middle Kingdom (17th century BCE). It supports the view that the earliest scripts were acrophonic representations of a West-Semitic language, whose use developed under the rule of the Hyksos in Egypt but was arrested there with the expulsion of this foreign dynasty at the end of the 16th century BCE. The development is then traced through the Levant, with particular attention given to the emergence of cuneiform alphabetic scripts in Ugarit (c. 1300 BCE). This form of writing disappeared with the fall of Ugarit, but linear alphabetic scripts were preserved in a variety of Near-Eastern languages, notably Aramaic and Phoenician. These two languages, by becoming linguae francae respectively of the Syria-northern Mesopotamia and the Anatolia-Eastern Mediterranean regions, brought about the spread of alphabetic writing up until the 8th century BCE. The article concludes by examining the influence of the Phoenician script on Greek, Etruscan and ultimately Latin forms of writing.
Melusine and Toyotamahime: Dissemination of a Culture by Sea
Authors: Shinoda Chiwaki
Published: May 2008

Japan's founding myth tells the story of a crocodile princess called Toyotamahime, wife of Prince Hoori. She asks her husband not to look at her as she gives birth, but he disobeys her and so sees that his wife is a crocodile. Finding out that she has been seen, the princess goes back to her country, that is, the bottom of the sea. The tale can be compared to the one about Melusine: in both stories there are common motifs such as the command not to look and disobeying the command, as well as the transformation into a reptile. Both stories are also tales about the founding of a royal house. This paper shows how Japanese myths, closely connected to maritime traditions, are at the crossroad of a cultural circulation extending from China and Korea to Indonesia, India, Arabia and Egypt. The chief actors in these stories are monkeys, hares, crocodiles or turtles.
Transplanting a Different Gardening Style into England: Matteo Ripa and His Visit to London in 1724
Authors: Liu Yu
Published: May 2008

In the second half of the 18th century, the naturalistically planted pleasure ground of England came to be known in France as le jardin anglo-chinois. What the French saw as the Oriental connection of the English landscaping revolution has been denied by English garden historians since Horace Walpole. By way of Matteo Ripa's 1724 visit to London, this paper takes a close look at the issues involved and tries to determine not only whether China was involved at all in the initial change of English gardening taste, but also how specific and crucial that involvement was.
Methylphenidate in Children With Oppositional Defiant Disorder and Both Comorbid Chronic Multiple Tic Disorder and ADHD
Authors: Gadow Kenneth D. , Nolan Edith E. , Sverd Jeffrey , Sprafkin Joyce , Schneider Jayne
Published: May 2008

Our primary objective was to determine if immediate-release methylphenidate is an effective treatment for oppositional defiant disorder diagnosed from mother's report in children with both chronic multiple tic disorder and attention-deficit hyperactivity disorder (ADHD). Children (n = 31) aged 6 to 12 years received placebo and 3 doses of methylphenidate twice daily for 2 weeks each under double-blind conditions and were assessed with ratings scales and laboratory measures. Results indicated significant improvement in both oppositional and ADHD behaviors with medication; however, the magnitude of treatment effect varied considerably as a function of disorder (ADHD > Oppositional behaviors), informant (teacher > mother), assessment instrument, and specific oppositional behavior (rebellious > disobeys rules). Drug response was comparable with that in children (n = 26) who did not have diagnosed oppositional defiant disorder, but comorbidity appeared to alter the perceived benefits for ADHD according to mother's report. Methylphenidate is an effective short-term treatment for oppositional behavior in children with comorbid ADHD and chronic multiple tic disorder.
Megalencephaly, Polymicrogyria, and Hydrocephalus (MPPH) Syndrome: A New Case With Syndactyly
Authors: Pisano Tiziana , Meloni Marta , Cianchetti Carlo , Falchi Melania , Nucaro Annalisa , Pruna Dario
Published: May 2008

Megalencephaly, polymicrogyria, and hydrocephalus (MPPH) syndrome is characterized by megalencephaly, perisylvian polymicrogyria, postaxial polydactyly, and hydrocephalus. Seven cases have been reported. This report presents a new sporadic patient with megalencephaly, polymicrogyria, and hydrocephalus syndrome, a girl born to healthy, nonconsanguineous parents at 38 weeks. Macrocephaly (+4 standard deviation) was present at birth. She had syndactyly instead of the postaxial polydactyly reported in the other patients. Neurologic examination showed severe diffuse hypotonia and profound developmental delay. Magnetic resonance imaging revealed enlarged lateral and third ventricles, with cavum septi pellucidi et vergae, bilateral abnormal white matter intensity, and diffuse polymicrogyria, most prominent in both the frontal and perisylvian regions. A visual evoked potential study showed increased latencies, probably caused by white matter abnormalities. At 16 months, she has never had seizures and shows profound psychomotor retardation. Results of metabolic and genetic studies were normal.
Electricity Regulation in India
Authors: Nair S.K.N.
Published: May 2008

This paper looks at the regulatory component of India's electricity reforms from four perspectives. Concerns about governance standards for the sector that set the context ofreforms are noted first, and the re-allocation of powers that reforms brought about is discussed with particular reference to federal issues and the centre–state interface. The paper then evaluates the impact of regulatory reforms on selected performance parametersof the sector. The finding here is that potential gains largely remain to be realised. Next,the new regulatory architecture is compared with the patterns of reforms undertakenin a group of developed countries to draw the conclusion that the design is sound and appropriate for the country's needs. The reasons for the sub-optimal impact are then taken up: these broadly pertain to large capacity shortcomings and ownership patterns that remain much as before the reforms. The paper concludes by noting a few measures that could help to enhance regulatory effectiveness.
Nurses' Attitudes About the Importance of Families in Nursing Care
Authors: Benzein Eva , Johansson Pauline , Årestedt Kristofer Franzén , Saveman Britt-Inger
Published: May 2008

The purpose of this study was to investigate the attitudes of registered nurses (RNs) about the importance of involving families in nursing care. A sample of 634 randomly selected Swedish RNs completed the instrument, Families' Importance in Nursing Care—Nurses' Attitudes (FINC-NA), and reported holding supportive attitudes about families. High scores were found for the subscales: family as a resource in nursing care, family as a conversational partner, family as a burden, and family as its own resource. Variables that predicted a less supportive attitude about involving families in nursing care included being a newly graduated nurse, having no general approach to the care of families at the place of work, and being a male nurse.
Deploying a Culture Change Programme management approach in support of information and communication technology developments in Greater Glasgow NHS Board
Authors: Frame Joanne , Watson Janice , Thomson Katie
Published: May 2008

This article reports on the project management and Culture Change Programme adopted by the NHS Greater Glasgow Health Board to deliver an electronic patient record (EPR) to support cardiology and stroke clinical services. To achieve its vision for the EPR (`to “really make a difference” to patient care by providing to the right person, the right information, under the right safeguards') the Board recognized that attending to social and organizational issues is at least of equal importance to addressing strictly technical concerns. Consequently, an ICT Culture Change Programme (ICT CCP) was devised and implemented to assist in the management of change, and in particular to facilitate a visionary clinical and cultural environment operating in conjunction with the evolving technical environment. In this article we describe the key components of this approach, outline the benefits we believe have accrued, and describe the steps being taken to build upon lessons learned.
Reframing NGOs: The Identity of an International Relations Non-Starter
Authors: Götz Norbert
Published: May 2008

In this article I aim to provide a better understanding of the concept `non-governmental organization' and its implications for the politics of international relations. As the prevailing confusion about the term stems largely from poor knowledge about the politics behind its introduction and function, the overarching question asks how NGOs have been socially constructed as actors on the margins of the international stage. To this end, a sound insight into the little-known conceptual history and background of the term `NGO' in what might be called a `Westphalian nomenclature' is given. I suggest that the still prevalent NGO terminology is an outcome of political games played by various actors, restricting and containing the signified organizations. The article provides a non-substantial, functional and politics-oriented definition of the term NGO, which differs significantly from previous attempts to attach meaning to it. It also suggests improved choices of terminology for general International Relations theorizing.
Teaching sport education to Russian students: An ecological analysis
Authors: Sinelnikov Oleg , Hastie Peter
Published: May 2008

Given Russian students' general lack of group work and opportunities to develop student responsibility in their prior schooling experiences, the purpose of this study was to examine how a group of Russian high school students responds to novel demands of participation in a sport education season. Forty-two students from two ninth-grade physical education classes participated in basketball seasons lasting 18 lessons. The analysis of video records of lessons, interactive student journals, group and individual interviews demonstrated that these students were highly compliant with the explicit tasks in the managerial and instructional task systems, and became increasingly at ease with the tasks requiring less teacher direction. It was in the student social system that the most dramatic observations were noted. For some, the disruption in their social agenda led to different ways of fun. For others, the season design allowed for team affiliation and achieving goals previously unseen or unavailable during physical education.
Couple Culture and the Production of Singleness
Authors: Budgeon Shelley
Published: May 2008

Historically singleness has operated as a marginalized status while heterosexual couples have occupied a privileged position that confers upon its inhabitants a range of social, economic and symbolic rewards. However, demographics now indicate that single-person households are the fastest growing household formation in the UK, signalling the beginning of what some have termed `the singles' century'. This article will examine how the stigmatized status of singleness is defined and negotiated within a culture that privileges couple relationships. Consideration will be given to whether it is possible for singleness to resist and transcend its `outsider' status within a context where individuals are purportedly able to exercise a greater degree of choice in how they organize their sexual lives. Narratives that single people (across different sexual identities) construct about couple relationships and their own cultures of intimacy, constituted to a significant extent through friendships, are analysed. These narratives indicate that positive single identities are possible despite heteronormative regulations which privilege couple relationships.
Compensated Sex and Sexual Risk: Sexual, Social and Economic Interactions between Homosexually- and Heterosexually-Identified Men of Low Income in Two Cities of Peru
Authors: Fernández-Dávila Percy , Salazar Ximena , Cáceres Carlos F. , Maiorana Andre , Kegeles Susan , Coates Thomas J. , Martinez Josefa
Published: May 2008

This study describes the complex dynamics of the sexual, economic and social interactions between a group of feminized homosexual men and men who have sex with men and self-identify as heterosexual (` mostaceros'), in lower-income peripheral urban areas of Lima and Trujillo, Peru. The study examined sexual risk between these two groups of men, and the significance of the economic exchanges involved in their sexual interactions. Using a Grounded Theory approach, 23 individual interviews and 7 focus groups were analyzed. The results reveal that cultural, economic and gender factors mold sexual and social relations among a group of men who have sex with men in Peru. Compensated sex is part of the behaviors of these men, reflecting a complicated construction of sexuality based on traditional conceptions of gender roles, sexual identity and masculinity. Several factors (e.g. difficulty in negotiating condom use, low self-esteem, low risk perception, alcohol and drug consumption), in the context of compensated sex, play a role in risk-taking for HIV infection.
TGF-β signaling in thymic epithelial cells regulates thymic involution and postirradiation reconstitution
Authors: Hauri-Hohl Mathias M. , Zuklys Saulius , Keller Marcel P. , Jeker Lukas T. , Barthlott Thomas , Moon Anne M. , Roes Jürgen , Holländer Georg A.
Published: May 2008

The thymus constitutes the primary lymphoid organ responsible for the generation of naive T cells. Its stromal compartment is largely composed of a scaffold of different subsets of epithelial cells that provide soluble and membrane-bound molecules essential for thymocyte maturation and selection. With senescence, a steady decline in the thymic output of T cells has been observed. Numeric and qualitative changes in the stromal compartment of the thymus resulting in reduced thymopoietic capacity have been suggested to account for this physiologic process. The precise cellular and molecular mechanisms underlying thymic senescence are, however, only incompletely understood. Here, we demonstrate that TGF-β signaling in thymic epithelial cells exerts a direct influence on the cell's capacity to support thymopoiesis in the aged mouse as the physiologic process of thymic senescence is mitigated in mice deficient for the expression of TGF-βRII on thymic epithelial cells. Moreover, TGF-β signaling in these stromal cells transiently hinders the early phase of thymic reconstitution after myeloablative conditioning and hematopoietic stem cell transplantation. Hence, inhibition of TGF-β signaling decelerates the process of age-related thymic involution and may hasten the reconstitution of regular thymopoiesis after hematopoietic stem cell transplantation.
A universal DNA mini-barcode for biodiversity analysis
Authors: Meusnier Isabelle , Singer Gregory AC , Landry Jean-François , Hickey Donal A , Hebert Paul DN , Hajibabaei Mehrdad
Published: May 2008

Background

The goal of DNA barcoding is to develop a species-specific sequence library for all eukaryotes. A 650 bp fragment of the cytochrome c oxidase 1 (CO1) gene has been used successfully for species-level identification in several animal groups. It may be difficult in practice, however, to retrieve a 650 bp fragment from archival specimens, (because of DNA degradation) or from environmental samples (where universal primers are needed).

Results

We used a bioinformatics analysis using all CO1 barcode sequences from GenBank and calculated the probability of having species-specific barcodes for varied size fragments. This analysis established the potential of much smaller fragments, mini-barcodes, for identifying unknown specimens. We then developed a universal primer set for the amplification of mini-barcodes. We further successfully tested the utility of this primer set on a comprehensive set of taxa from all major eukaryotic groups as well as archival specimens.

Conclusion

In this study we address the important issue of minimum amount of sequence information required for identifying species in DNA barcoding. We establish a novel approach based on a much shorter barcode sequence and demonstrate its effectiveness in archival specimens. This approach will significantly broaden the application of DNA barcoding in biodiversity studies.
Complete Sequence and Analysis of the Mitochondrial Genome of Hemiselmis andersenii CCMP644 (Cryptophyceae)
Authors: Kim Eunsoo , Lane Christopher E , Curtis Bruce A , Kozera Catherine , Bowman Sharen , Archibald John M
Published: May 2008

Background

Cryptophytes are an enigmatic group of unicellular eukaryotes with plastids derived by secondary (i.e., eukaryote-eukaryote) endosymbiosis. Cryptophytes are unusual in that they possess four genomes–a host cell-derived nuclear and mitochondrial genome and an endosymbiont-derived plastid and 'nucleomorph' genome. The evolutionary origins of the host and endosymbiont components of cryptophyte algae are at present poorly understood. Thus far, a single complete mitochondrial genome sequence has been determined for the cryptophyte Rhodomonas salina. Here, the second complete mitochondrial genome of the cryptophyte alga Hemiselmis andersenii CCMP644 is presented.

Results

The H. andersenii mtDNA is 60,553 bp in size and encodes 30 structural RNAs and 36 protein-coding genes, all located on the same strand. A prominent feature of the genome is the presence of a ~20 Kbp long intergenic region comprised of numerous tandem and dispersed repeat units of between 22–336 bp. Adjacent to these repeats are 27 copies of palindromic sequences predicted to form stable DNA stem-loop structures. One such stem-loop is located near a GC-rich and GC-poor region and may have a regulatory function in replication or transcription. The H. andersenii mtDNA shares a number of features in common with the genome of the cryptophyte Rhodomonas salina, including general architecture, gene content, and the presence of a large repeat region. However, the H. andersenii mtDNA is devoid of inverted repeats and introns, which are present in R. salina. Comparative analyses of the suite of tRNAs encoded in the two genomes reveal that the H. andersenii mtDNA has lost or converted its original trnK(uuu) gene and possesses a trnS-derived 'trnK(uuu)', which appears unable to produce a functional tRNA. Mitochondrial protein coding gene phylogenies strongly support a variety of previously established eukaryotic groups, but fail to resolve the relationships among higher-order eukaryotic lineages.

Conclusion

Comparison of the H. andersenii and R. salina mitochondrial genomes reveals a number of cryptophyte-specific genomic features, most notably the presence of a large repeat-rich intergenic region. However, unlike R. salina, the H. andersenii mtDNA does not possess introns and lacks a Lys-tRNA, which is presumably imported from the cytosol.
Global analysis of aberrant pre-mRNA splicing in glioblastoma using exon expression arrays
Authors: Cheung Hannah C , Baggerly Keith A , Tsavachidis Spiridon , Bachinski Linda L , Neubauer Valerie L , Nixon Tamara J , Aldape Kenneth D , Cote Gilbert J , Krahe Ralf
Published: May 2008

Background

Tumor-predominant splice isoforms were identified during comparative in silico sequence analysis of EST clones, suggesting that global aberrant alternative pre-mRNA splicing may be an epigenetic phenomenon in cancer. We used an exon expression array to perform an objective, genome-wide survey of glioma-specific splicing in 24 GBM and 12 nontumor brain samples. Validation studies were performed using RT-PCR on glioma cell lines, patient tumor and nontumor brain samples.

Results

In total, we confirmed 14 genes with glioma-specific splicing; seven were novel events identified by the exon expression array (A2BP1, BCAS1, CACNA1G, CLTA, KCNC2, SNCB, and TPD52L2). Our data indicate that large changes (> 5-fold) in alternative splicing are infrequent in gliomagenesis (< 3% of interrogated RefSeq entries). The lack of splicing changes may derive from the small number of splicing factors observed to be aberrantly expressed.

Conclusion

While we observed some tumor-specific alternative splicing, the number of genes showing exclusive tumor-specific isoforms was on the order of tens, rather than the hundreds suggested previously by in silico mining. Given the important role of alternative splicing in neural differentiation, there may be selective pressure to maintain a majority of splicing events in order to retain glial-like characteristics of the tumor cells.
Control of trichome branching by Chromatin Assembly Factor-1
Authors: Exner Vivien , Gruissem Wilhelm , Hennig Lars
Published: May 2008

Background

Chromatin dynamics and stability are both required to control normal development of multicellular organisms. Chromatin assembly factor CAF-1 is a histone chaperone that facilitates chromatin formation and the maintenance of specific chromatin states. In plants and animals CAF-1 is essential for normal development, but it is poorly understood which developmental pathways require CAF-1 function.

Results

Mutations in all three CAF-1 subunits affect Arabidopsis trichome morphology and lack of CAF-1 function results in formation of trichomes with supernumerary branches. This phenotype can be partially alleviated by external sucrose. In contrast, other aspects of the CAF-1 mutant phenotype, such as defective meristem function and organ formation, are aggravated by external sucrose. Double mutant analyses revealed epistatic interactions between CAF-1 mutants and stichel, but non-epistatic interactions between CAF-1 mutants and glabra3 and kaktus. In addition, mutations in CAF-1 could partly suppress the strong overbranching and polyploidization phenotype of kaktus mutants.

Conclusion

CAF-1 is required for cell differentiation and regulates trichome development together with STICHEL in an endoreduplication-independent pathway. This function of CAF-1 can be partially substituted by application of exogenous sucrose. Finally, CAF-1 is also needed for the high degree of endoreduplication in kaktus mutants and thus for the realization of kaktus' extreme overbranching phenotype.
Phase II trial of isoflavone in prostate-specific antigen recurrent prostate cancer after previous local therapy
Authors: Pendleton John M , Tan Winston W , Anai Satoshi , Chang Myron , Hou Wei , Shiverick Kathleen T , Rosser Charles J
Published: May 2008

Background-

Data exist that demonstrate isoflavones' potent antiproliferative effects on prostate cancer cells. We evaluated the efficacy of isoflavone in patients with PSA recurrent prostate cancer after prior therapy. We postulated that isoflavone therapy would slow the rate of rise of serum PSA.

Methods-

Twenty patients with rising PSA after prior local therapy were enrolled in this open-labeled, Phase II, nonrandomized trial (Trial registration # NCT00596895). Patients were treated with soy milk containing 47 mg of isoflavonoid per 8 oz serving three times per day for 12 months. Serum PSA, testosterone, lipids, isoflavone levels (genistein, daidzein, and equol), and quality of life (QOL) were measured at various time points from 0 to 12 months. PSA outcome was evaluated.

Results-

Within the mixed regression model, it was estimated that PSA had increased 56% per year before study entry and only increased 20% per year for the 12-month study period (p = 0.05). Specifically, the slope of PSA after study entry was significantly lower than that before study entry in 6 patients and the slope of PSA after study entry was significantly higher than before study entry in 2 patients. For the remaining 12 patients, the change in slope was statistically insignificant. Nearly two thirds of the patients were noted to have significant levels of free equol in their serum while on therapy.

Conclusion-

Dietary intervention with isoflavone supplementation may have biologic activity in men with biochemical recurrent prostate cancer as shown by a decline in the slope of PSA. This study may lend support to the literature that nutritional supplements have biologic activity in prostate cancer and therefore, further studies with these agents in randomized clinical trials should be encouraged.
Development and validation of a risk score for hospitalization for heart failure in patients with Type 2 Diabetes Mellitus
Authors: Yang Xilin , Ma Ronald C , So Wing-Yee , Kong Alice P , Ko Gary T , Ho Chun-Shun , Lam Christopher W , Cockram Clive S , Tong Peter C , Chan Juliana C
Published: May 2008

Background

There are no risk scores available for predicting heart failure in Type 2 diabetes mellitus (T2DM). Based on the Hong Kong Diabetes Registry, this study aimed to develop and validate a risk score for predicting heart failure that needs hospitalisation in T2DM.

Methods

7067 Hong Kong Chinese diabetes patients without history of heart failure, and without history and clinical evidence of coronary heart disease at baseline were analyzed. The subjects have been followed up for a median period of 5.5 years. Data were randomly and evenly assigned to a training dataset and a test dataset. Sex-stratified Cox proportional hazard regression was used to obtain predictors of HF-related hospitalization in the training dataset. Calibration was assessed using Hosmer-Lemeshow test and discrimination was examined using the area under receiver's operating characteristic curve (aROC) in the test dataset.

Results

During the follow-up, 274 patients developed heart failure event/s that needed hospitalisation. Age, body mass index (BMI), spot urinary albumin to creatinine ratio (ACR), HbA1c, blood haemoglobin (Hb) at baseline and coronary heart disease during follow-up were predictors of HF-related hospitalization in the training dataset. HF-related hospitalization risk score = 0.0709 × age (year) + 0.0627 × BMI (kg/m2) + 0.1363 × HbA1c(%) + 0.9915 × Log10(1+ACR) (mg/mmol) - 0.3606 × Blood Hb(g/dL) + 0.8161 × CHD during follow-up (1 if yes). The 5-year probability of heart failure = 1-S0(5)EXP{0.9744 × (Risk Score - 2.3961)}. Where S0(5) = 0.9888 if male and 0.9809 if female. The predicted and observed 5-year probabilities of HF-related hospitalization were similar (p > 0.20) and the adjusted aROC was 0.920 for 5 years of follow-up.

Conclusion

The risk score had adequate performance. Further validations in other cohorts of patients with T2DM are needed before clinical use.
An ultrasensitive sorting mechanism for EGF Receptor Endocytosis
Authors: Schmidt-Glenewinkel Hannah , Vacheva Ivayla , Hoeller Daniela , Dikic Ivan , Eils Roland
Published: May 2008

Background

The Epidermal Growth Factor (EGF) receptor has been shown to internalize via clathrin-independent endocytosis (CIE) in a ligand concentration dependent manner. From a modeling point of view, this resembles an ultrasensitive response, which is the ability of signaling networks to suppress a response for low input values and to increase to a pre-defined level for inputs exceeding a certain threshold. Several mechanisms to generate this behaviour have been described theoretically, the underlying assumptions of which, however, have not been experimentally demonstrated for the EGF receptor internalization network.

Results

Here, we present a mathematical model of receptor sorting into alternative pathways that explains the EGF-concentration dependent response of CIE. The described mechanism involves a saturation effect of the dominant clathrin-dependent endocytosis pathway and implies distinct steady-states into which the system is forced for low vs high EGF stimulations. The model is minimal since no experimentally unjustified reactions or parameter assumptions are imposed. We demonstrate the robustness of the sorting effect for large parameter variations and give an analytic derivation for alternative steady-states that are reached. Further, we describe extensibility of the model to more than two pathways which might play a role in contexts other than receptor internalization.

Conclusion

Our main result is that a scenario where different endocytosis routes consume the same form of receptor corroborates the observation of a clear-cut, stimulus dependent sorting. This is especially important since a receptor modification discriminating between the pathways has not been found experimentally. The model is not restricted to EGF receptor internalization and might account for ultrasensitivity in other cellular contexts.
Lessons from Mycobacterium avium complex-associated pneumonitis: a case report
Authors: Zota Victor , Angelis Sheryn M , Fraire Armando E , McNamee Ciaran , Kielbasa Shasta , Libraty Daniel H
Published: May 2008

Introduction

Mycobacterium aviumcomplex (MAC) is an increasingly recognized cause of pulmonary disease in immunocompetent individuals. An acute form of MAC lung disease, MAC-associated pneumonitis, has generally been associated with the use of hot tubs. There is controversy in the literature about whether MAC-associated pneumonitis is a classic hypersensitivity pneumonitis or is a direct manifestation of mycobacterial infection.

Case presentation

We report the second case in the literature of MAC-associated pneumonitis not related to the use of hot tubs. The source of MAC in a 52-year-old immunocompetent patient was an intrapulmonary cyst containing numerous acid-fast bacilli. The patient developed disseminated miliary nodules throughout both lung fields. Histological examination of resected lung tissue revealed well-formed, acid-fast negative granulomas composed predominantly of CD4+T-cells and CD68+histiocytes. The granulomas were strongly positive for tumor necrosis factor-α, a pro-inflammatory cytokine.

Conclusion

The attempt to classify MAC-associated pneumonitis as either a classic hypersensitivity pneumonitis or a direct manifestation of mycobacterial infection is not particularly useful. Our case demonstrates that MAC-associated pneumonitis is characterized by a vigorous T-helper 1-like, pro-inflammatory, immune response to pulmonary mycobacterial infection. The immunopathology provides a rationale for clinical studies of anti-MAC therapy with the addition of anti-inflammatory agents (for example, corticosteroids) to hasten the resolution of infection and symptoms.
Characteristics of T-cell large granular lymphocyte proliferations associated with neutropenia and inflammatory arthropathy
Authors: Prochorec-Sobieszek Monika , Rymkiewicz Grzegorz , Makuch-Łasica Hanna , Majewski Mirosław , Michalak Katarzyna , Rupiński Robert , Warzocha Krzysztof , Maryniak Renata
Published: May 2008

Introduction

The purpose of this study was to analyze the data of patients with T-cell large granular lymphocyte (T-LGL) lymphocytosis associated with inflammatory arthropathy or with no arthritis symptoms.

Methods

Clinical, serological as well as histopathological, immuhistochemical, and flow cytometric evaluations of blood/bone marrow of 21 patients with T-LGL lymphocytosis were performed. The bone marrow samples were also investigated for T-cell receptor (TCR) and immunoglobulin (IG) gene rearrangements by polymerase chain reaction with heteroduplex analysis.

Results

Neutropenia was observed in 21 patients, splenomegaly in 10, autoimmune diseases such as rheumatoid arthritis (RA) in 9, unclassified arthritis resembling RA in 2, and autoimmune thyroiditis in 5 patients. T-LGL leukemia was recognized in 19 cases. Features of Felty syndrome were observed in all RA patients, representing a spectrum of T-LGL proliferations from reactive polyclonal through transitional between reactive and monoclonal to T-LGL leukemia. Bone marrow trephines from T-LGL leukemia patients showed interstitial clusters and intrasinusoidal linear infiltrations of CD3+/CD8+/CD57+/granzyme B+ lymphocytes, reactive lymphoid nodules, and decreased or normal granulocyte precursor count with left-shifted maturation. In three-color flow cytometry (FCM), T-LGL leukemia cells demonstrated CD2, CD3, and CD8 expression as well as a combination of CD16, CD56, or CD57. Abnormalities of other T-cell antigen expressions (especially CD5, CD7, and CD43) were also detected. In patients with polyclonal T-LGL lymphocytosis, T cells were dispersed in the bone marrow and the expression of pan-T-cell antigens in FCM was normal. Molecular studies revealed TCRB and TCRG gene rearrangements in 13 patients and TCRB, TCRG, and TCRD in 4 patients. The most frequently rearranged regions of variable genes were Vβ-Jβ1, Jβ2 and Vγ If Vγ10-Jγ. Moreover, in 4 patients, additional rearrangements of IG kappa and lambda variable genes of B cells were also observed.

Conclusion

RA and neutropenia patients represented a continuous spectrum of T-LGL proliferations, although monoclonal expansions were most frequently observed. The histopathological pattern and immunophenotype of bone marrow infiltration as well as molecular characteristics were similar in T-LGL leukemia patients with and without arthritis.
TIMP-2 mediates the anti-invasive effects of the nitric oxide-releasing prodrug JS-K in breast cancer cells
Authors: Simeone Ann-Marie , McMurtry Vanity , Nieves-Alicea René , Saavedra Joseph E , Keefer Larry K , Johnson Marcella M , Tari Ana M
Published: May 2008

Introduction

Tumor invasion and metastasis remain a major cause of mortality in breast cancer patients. High concentrations of nitric oxide (NO) suppress tumor invasion and metastasis in vivo. NO prodrugs generate large amounts of NO upon metabolism by appropriate intracellular enzymes, and therefore could have potential in the prevention and therapy of metastatic breast cancer.

Methods

The present study was designed to determine the effects of the NO-releasing prodrug O2-(2,4-dinitrophenyl) 1- [(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) on breast cancer invasion and the mechanisms involved. MDA-MB-231, MDA-MB-231/F10, and MCF-7/COX-2 were the three breast cancer cell lines tested. NO levels were determined spectrophotometrically using a NO assay kit. Invasion and the expression of matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs were determined using Matrigel invasion assays, an MMP array kit and ELISAs. The activity and expression of extracellular signal-regulated kinase 1/2, p38, and c-Jun N-terminal kinase mitogen-activated protein kinases were determined using western blot analyses.

Results

Under conditions by which JS-K was not cytotoxic, JS-K significantly decreased (P < 0.05) the invasiveness of breast cancer cells across the Matrigel basement membrane, which was directly correlated with NO production. JS-43-126, a non-NO-releasing analog of JS-K, had no effect on NO levels or invasion. JS-K increased (P < 0.05) TIMP-2 production, and blocking TIMP-2 activity with a neutralizing antibody significantly increased (P < 0.05) the invasive activity of JS-K-treated cells across Matrigel. JS-K decreased p38 activity, whereas the activity and the expression of extracellular signal-regulated kinase 1/2 and c-Jun N-terminal kinase were unaffected.

Conclusion

We report the novel findings that JS-K inhibits breast cancer invasion across the Matrigel basement membrane, and NO production is vital for this activity. Upregulation of TIMP-2 production is one mechanism by which JS-K mediates its anti-invasive effects. JS-K and other NO prodrugs may represent an innovative biological approach in the prevention and treatment of metastatic breast cancer.
Perceiving molecular evolution processes in Escherichia coliby comprehensive metabolite and gene expression profiling
Authors: Vijayendran Chandran , Barsch Aiko , Friehs Karl , Niehaus Karsten , Becker Anke , Flaschel Erwin
Published: May 2008

Background

Evolutionary changes that are due to different environmental conditions can be examined based on the various molecular aspects that constitute a cell, namely transcript, protein, or metabolite abundance. We analyzed changes in transcript and metabolite abundance in evolved and ancestor strains in three different evolutionary conditions - excess nutrient adaptation, prolonged stationary phase adaptation, and adaptation because of environmental shift - in two different strains of bacterium Escherichia coli K-12 (MG1655 and DH10B).

Results

Metabolite profiling of 84 identified metabolites revealed that most of the metabolites involved in the tricarboxylic acid cycle and nucleotide metabolism were altered in both of the excess nutrient evolved lines. Gene expression profiling using whole genome microarray with 4,288 open reading frames revealed over-representation of the transport functional category in all evolved lines. Excess nutrient adapted lines were found to exhibit greater degrees of positive correlation, indicating parallelism between ancestor and evolved lines, when compared with prolonged stationary phase adapted lines. Gene-metabolite correlation network analysis revealed over-representation of membrane-associated functional categories. Proteome analysis revealed the major role played by outer membrane proteins in adaptive evolution. GltB, LamB and YaeT proteins in excess nutrient lines, and FepA, CirA, OmpC and OmpA in prolonged stationary phase lines were found to be differentially over-expressed.

Conclusion

In summary, we report the vital involvement of energy metabolism and membrane-associated functional categories in all of the evolutionary conditions examined in this study within the context of transcript, outer membrane protein, and metabolite levels. These initial data obtained may help to enhance our understanding of the evolutionary process from a systems biology perspective.
CpG island density and its correlations with genomic features in mammalian genomes
Authors: Han Leng , Su Bing , Li Wen-Hsiung , Zhao Zhongming
Published: May 2008

Background

CpG islands, which are clusters of CpG dinucleotides in GC-rich regions, are considered gene markers and represent an important feature of mammalian genomes. Previous studies of CpG islands have largely been on specific loci or within one genome. To date, there seems to be no comparative analysis of CpG islands and their density at the DNA sequence level among mammalian genomes and of their correlations with other genome features.

Results

In this study, we performed a systematic analysis of CpG islands in ten mammalian genomes. We found that both the number of CpG islands and their density vary greatly among genomes, though many of these genomes encode similar numbers of genes. We observed significant correlations between CpG island density and genomic features such as number of chromosomes, chromosome size, and recombination rate. We also observed a trend of higher CpG island density in telomeric regions. Furthermore, we evaluated the performance of three computational algorithms for CpG island identifications. Finally, we compared our observations in mammals to other non-mammal vertebrates.

Conclusion

Our study revealed that CpG islands vary greatly among mammalian genomes. Some factors such as recombination rate and chromosome size might have influenced the evolution of CpG islands in the course of mammalian evolution. Our results suggest a scenario in which an increase in chromosome number increases the rate of recombination, which in turn elevates GC content to help prevent loss of CpG islands and maintain their density. These findings should be useful for studying mammalian genomes, the role of CpG islands in gene function, and molecular evolution.