bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural constraints and opportunities for CAM use and referral by physicians, nurses, and midwives
Authors: Hirschkorn K.A. , Bourgeault I.L.
Published: April 2008

Thisarticleexaminestheattitudesandreportedbehaviorsof physicians, nurses, and midwives regarding complementary and alternative medicine (CAM), with respect to one key theme that emerged from a broader qualitative study. Of central interest are the structural influences identified by study participants that either act as constraints or opportunities for their professional use of or referral for CAM. In an effort to interpret these results, the analysis is situated within the sociology literature that documents the influences of professional socialization, practice philosophy, regulation, and organizations on professional behavior. These influences are classified as either professional-level structures or work/organizational structures. The main conclusion is that future research should pay more attention to such structural dimensions that may be exerting influence on the decisions of providers about whether or not to professionally use or refer for CAM. This article is offered as a conceptual starting point for doing so.
Governing the contagious body: genital herpes, contagion and technologies of the self
Authors: Oster Candice , Cheek Julianne
Published: April 2008

Genital herpes is a prevalent sexually transmitted viral infection. While genital herpes is not life-threatening, it can cause physical discomfort and psychosocial difficulties, and may increase the risk of contracting HIV. Given that genital herpes cannot be cured, both the condition itself, and the possibility of passing it on to others, becomes a part of the everyday reality of those individuals diagnosed with genital herpes. In this article we explore the ways in which people with genital herpes attending the Sexually Transmitted Infections (STI) clinic govern their `contagious bodies'. The discussion draws on the Foucauldian concept of governmentality, and uses Foucault's idea of ethics as a framework to identify the technologies of the self by which individuals with genital herpes govern their own thoughts and behaviours in relation to the contagiousness of the condition. Implications for practice and other ways of thinking about what happens in the STI clinic context are suggested.
A `little world of your own': stigma, gender and narratives of venereal disease contact tracing
Authors: Kampf Antje
Published: April 2008

As in other countries, in order to protect the public from venereal disease (syphilis and gonorrhoea), contact tracing in New Zealand has been a public health strategy since the mid-20th century. So far, scholars have predominantly focused on the aspect of control of the cases traced. Based on a rare interview with a female contact tracer, together with a range of archival material, this article aims to expand the scholarship by focusing on the tracer instead of the patient. Using Erving Goffman's original concept of `courtesy stigma', the article will show that his idea can be nuanced to take into account contact tracers and the ways in which this stigma can be refracted through gender. Working as a tracer had a distinct impact on her life and possibly even her marital status, which were compromised by secrecy, stigma, morality and the demands of public health policies — aspects that were, paradoxically, quite similar to those she traced. The courtesy stigma that contact tracers for venereal disease acquired limited their professional options, as well as isolated them in the non-stigmatized social world.
Medicalization and beyond: the social construction of insomnia and snoring in the news
Authors: Williams Simon. J. , Seale Clive , Boden Sharon , Lowe Pam , Steinberg Deborah Lynn
Published: April 2008

What role do the media play in the medicalization of sleep problems? This article, based on a British Academy funded project, uses qualitative textual analysis to examine representations of insomnia and snoring in a large representative sample of newspaper articles taken from the UK national press from the mid-1980s to the present day. Constructed as `common problems' in the population at large, insomnia and snoring we show are differentially located in terms of medicalizing—healthicizing discourses and debates. Our findings also suggest important differences in the gendered construction of these problems and in terms of tabloid and `broadsheet' newspaper coverage of these issues. Newspaper constructions of sleep, it is concluded, are complex, depending on both the `problem' and the paper in question.
`Bling — the Asians introduced that to the country': gold and its value within a group of families of South Asian origin in Yorkshire
Authors: Pahl Kate , Pollard Andy
Published: April 2008

This visual essay describes an exhibition that collected narratives of migration and artefacts from the homes of families of Pakistani origin from Rotherham, South Yorkshire. 1 The project was collaborative, involving a visual artist — Zahir Rafiq, who designed art work and the website (www.ferhamfamilies.com) — the Clifton Park Museum in Rotherham, Rotherham Central Sure Start and Ferham Primary School.
(In)visible evidence: pictorially enhanced disbelief in the Apollo moon landings
Authors: Perlmutter David D. , Dahmen Nicole Smith
Published: April 2008

When pictures become journalistic, historical, and popular icons, there is a common belief that they also have a single, usable meaning, and media, political, and academic elites typically determine it. Yet, research on how people interpret images suggests that believing is seeing: pre-existing prejudices and experiences affect what meanings we draw from pictures. This is especially so when the viewer seeks out information that confirms strongly held notions, what mainstream audiences might think of in some cases as conspiracy theories. This article examines reaction to one of the most famous sets of images of the past century — photos of the 1969 Apollo moon landing — by proponents of the `moon hoax' theory, those who believe that the landings were faked by NASA. Analysis of moon hoax websites shows that the pictures' visual details are used as evidence that the mainstream interpretation is `visibly' in error.
What has Athens to Do with Patmos? Rhetorical Criticism of the Revelation of John (1980—2005)
Authors: Desilva David A.
Published: April 2008

While Revelation does not immediately recommend itself for analysis along the lines of Greek and Latin rhetoric, scholars have made considerable progress analyzing the persuasive strategies of Revelation from this methodological orientation. Energetic attention has been given to John's strategies for establishing authority for his message and deconstructing the authority of rival 'orators'. A number of articles have identified and analyzed implicit and explicit enthymemes in Revelation, the deployment of typical epideictic and deliberative topics, and the contributions of intertexture to rational persuasion. Study of John's style has demonstrated John's finesse and purposefulness in deploying standard figures of thought and diction, while investigation of rhetorical arrangement has generally proceeded in ways that have respected Revelation's complexity and its distance from the standard forms of oratory. Although critics generally affirm the importance of John's appeals to the emotions, this line of investigation has been the least developed.
Women in Early Judaism: Twenty-five Years of Research and Reenvisioning
Authors: Marks Susan
Published: April 2008

Studies of women in Early Judaism seek to correct and go beyond earlier examinations that had overlooked women. In this they share some important goals with social history, arguing that histories that ignore all but the most prominent individuals offer a distorted presentation of the ancient world. Involving an initial reinvisioning, such explorations partake of the varied methodologies and methodological challenges of other projects in Religious Studies and Jewish Studies. Following the pioneering scholars who first challenged assumptions that only men had merited attention, and their successors who gathered evidence concerning Jewish women, current researchers struggle with post-structuralist questions concerning how much one may read texts as social reality. Responses to these challenges continue to build upon the work of recent decades even as they begin to investigate new possibilities.
Novel, Web-Based, Information-Exploration Approach for Improving Operating Room Logistics and System Processes
Authors: Nagy Paul G. , Konewko Ramon , Warnock Max , Bernstein Wendy , Seagull Jacob , Yan Xiao  , George Ivan , Park Adrian
Published: April 2008

Routine clinical information systems now have the ability to gather large amounts of data that surgical managers can access to create a seamless and proactive approach to streamlining operations and minimizing delays. The challenge lies in aggregating and displaying these data in an easily accessible format that provides useful, timely information on current operations. A Web-based, graphical dashboard is described in this study, which can be used to interpret clinical operational data, allow managers to see trends in data, and help identify inefficiencies that were not apparent with more traditional, paper-based approaches. The dashboard provides a visual decision support tool that assists managers in pinpointing areas for continuous quality improvement. The limitations of paper-based techniques, the development of the automated display system, and key performance indicators in analyzing aggregate delays, time, specialties, and teamwork are reviewed. Strengths, weaknesses, opportunities, and threats associated with implementing such a program in the perioperative environment are summarized.
Communities of Practice
Authors: Denscombe Martyn
Published: April 2008

The mixed methods approach has emerged as a ``third paradigm'' for social research. It has developed a platform of ideas and practices that are credible and distinctive and that mark the approach out as a viable alternative to quantitative and qualitative paradigms. However, there are also a number of variations and inconsistencies within the mixed methods approach that should not be ignored. This article argues the need for a vision of research paradigm that accommodates such variations and inconsistencies. It is argued that the use of ``communities of practice'' as the basis for such a research paradigm is (a) consistent with the pragmatist underpinnings of the mixed methods approach, (b) accommodates a level of diversity, and (c) has good potential for understanding the methodological choices made by those conducting mixed methods research.
Implementing a Mixed Methods Approach to Explore the Financial Implications of Death of a Life Partner
Authors: Corden Anne , Hirst Michael
Published: April 2008

This article describes the development of a mixed methods approach in a study of the financial implications of the death of a partner. The authors seek to integrate analysis and interpretation of quantitative data from the British Household Panel Survey with qualitative, in-depth interviews with recently bereaved people. A key aim is to build a team that is constantly sharing ideas and information from the two components to inform the combined methodology. The article shows how we are trying to mix methods and integrate ways of working, giving details of the practicalities and issues arising thus far. We further reflect on how integrated team working may lead to more inclusive and consensual ways of knowing and influence integrated outputs.
Unrelated donor transplants in adults with Philadelphia-negative acute lymphoblastic leukemia in first complete remission
Authors: Marks David I. , Pérez Waleska S. , He Wensheng , Zhang Mei-Jie , Bishop Michael R. , Bolwell Brian J. , Bredeson Christopher N. , Copelan Edward A. , Gale Robert Peter , Gupta Vikas , Hale Gregory A. , Isola Luis M. , Jakubowski Ann A. , Keating Armand , Klumpp Thomas R. , Lazarus Hillard M. , Liesveld Jane L. , Maziarz Richard T. , McCarthy Philip L. , Sabloff Mitchell , Schiller Gary , Sierra Jorge , Tallman Martin S. , Waller Edmund K. , Wiernik Peter H. , Weisdorf Daniel J.
Published: April 2008

We report the retrospective outcomes of unrelated donor (URD) transplants in 169 patients with acute lymphoblastic leukemia (ALL) in first complete remission (CR1) who received transplants between 1995 and 2004. Median age was 33 years (range, 16-59 years). A total of 50% had a white blood cell count (WBC) more than 30 × 109/L, 18% extramedullary disease, 42% achieved CR more than 8 weeks from diagnosis, 25% had adverse cytogenetics, and 19% had T-cell leukemia. A total of 41% were HLA well-matched, 41% partially matched with their donors, and 18% were HLA-mismatched. At 54-month median follow-up, incidences of acute grade 2-IV, III to IV, and chronic graft-versus-host disease were 50%, 25%, and 43%, respectively. Five-year treatment-related mortality (TRM), relapse, and overall survival were 42%, 20%, and 39%, respectively. In multivariate analyses, TRM was significantly higher with HLA-mismatched donors and T-cell depletion. Relapse risk was higher if the diagnostic WBC was more than 100 × 109/L. Factors associated with poorer survival included WBC more than 100 × 109/L, more than 8 weeks to CR1, cytomegalovirus seropositivity, HLA mismatching, and T-cell depletion. Nearly 40% of adults with ALL in CR1 survive 5 years after URD transplantation. Relapse risks were modest; TRM is the major cause of treatment failure. Selecting closely HLA-matched URD and reducing TRM should improve results.
Comparative transcriptome analysis of Arabidopsis thaliana infested by diamond back moth (Plutella xylostella) larvae reveals signatures of stress response, secondary metabolism, and signalling
Authors: Ehlting Jürgen , Chowrira Sunita G , Mattheus Nathalie , Aeschliman Dana S , Arimura Gen-Ichiro , Bohlmann Jörg
Published: April 2008

Background

Plants are exposed to attack from a large variety of herbivores. Feeding insects can induce substantial changes of the host plant transcriptome. Arabidopsis thaliana has been established as a relevant system for the discovery of genes associated with response to herbivory, including genes for specialized (i.e. secondary) metabolism as well as genes involved in plant-insect defence signalling.

Results

Using a 70-mer oligonulceotide microarray covering 26,090 gene-specific elements, we monitored changes of the Arabidopsis leaf transcriptome in response to feeding by diamond back moth (DBM; Plutella xylostella) larvae. Analysis of samples from a time course of one hour to 24 hours following onset of DBM feeding revealed almost three thousand (2,881) array elements (including 2,671 genes with AGI annotations) that were differentially expressed (>2-fold; p[t-test] < 0.05) of which 1,686 also changed more than twofold in expression between at least two time points of the time course with p(ANOVA) < 0.05. While the majority of these transcripts were up-regulated within 8 h upon onset of insect feeding relative to untreated controls, cluster analysis identified several distinct temporal patterns of transcriptome changes. Many of the DBM-induced genes fall into ontology groups annotated as stress response, secondary metabolism and signalling. Among DBM-induced genes associated with plant signal molecules or phytohormones, genes associated with octadecanoid signalling were clearly overrepresented. We identified a substantial number of differentially expressed genes associated with signal transduction in response to DBM feeding, and we compared there expression profiles with those of previously reported transcriptome responses induced by other insect herbivores, specifically Pieris rapae, Frankliniella occidentalis, Bemisia tabaci,Myzus persicae, and Brevicoryne brassicae.

Conclusion

Arabidopsis responds to feeding DBM larvae with a drastic reprogramming of the transcriptome, which has considerable overlap with the response induced by other insect herbivores. Based on a meta-analysis of microarray data we identified groups of transcription factors that are either affected by multiple forms of biotic or abiotic stress including DBM feeding or, alternatively, were responsive to DBM herbivory but not to most other forms of stress.
Detailed characterization of the mouse embryonic stem cell transcriptome reveals novel genes and intergenic splicing associated with pluripotency
Authors: Kunarso Galih , Wong Kee-Yew , Stanton Lawrence W , Lipovich Leonard
Published: April 2008

Background

Transcriptional control of embryonic stem (ES) cell pluripotency has been a subject of intense study. Transcriptional regulators including Oct4 (Oct3/4 index), Sox2 and Nanog are fundamental for maintaining the undifferentiated state. However, the ES cell transcriptome is not limited to their targets, and exhibits considerable complexity when assayed with microarray, MPSS, cDNA/EST sequencing, and SAGE technologies. To identify novel genes associated with pluripotency, we globally searched for ES transcripts not corresponding to known genes, validated their sequences, determined their expression profiles, and employed RNAi to test their function.

Results

Gene Identification Signature (GIS) analysis, a SAGE derivative distinguished by paired 5' and 3' transcript end tags, identified 153 candidate novel transcriptional units (TUs) distinct from known genes in a mouse E14 ES mRNA library. We focused on 16 TUs free of artefacts and mapping discrepancies, five of which were validated by RTPCR product sequencing. Two of the TUs were revealed by annotation to represent novel protein-coding genes: a PRY-domain cluster member and a KRAB-domain zinc finger. The other three TUs represented intergenic splicing events involving adjacent, functionally unrelated protein-coding genes transcribed in the same orientation, with one event potentially encoding a fusion protein containing domains from both component genes (Clk2 and Scamp3). Expression profiling using embryonic samples and adult tissue panels confirmed that three of the TUs were unique to or most highly expressed in ES cells. Expression levels of all five TUs dropped dramatically during three distinct chemically induced differentiation treatments of ES cells in culture. However, siRNA knockdowns of the TUs did not alter mRNA levels of pluripotency or differentiation markers, and did not affect cell morphology.

Conclusion

Transcriptome libraries retain considerable potential for novel gene discovery despite massive recent cDNA and EST sequencing efforts; cDNA and EST evidence for these ES cell TUs had been limited or absent. RTPCR and full-length sequencing remain essential in resolving the bottleneck between numerous candidate novel transcripts inferred from high-throughput sequencing and the small fraction that can be validated. RNAi results indicate that, despite their strong association with pluripotency, these five transcriptomic novelties may not be required for maintaining it.
Altered regulation of Prox1-gene-expression in liver tumors
Authors: Dudas Jozsef , Mansuroglu Tümen , Moriconi Federico , Haller Florian , Wilting Joerg , Lorf Thomas , Füzesi Laszlo , Ramadori Giuliano
Published: April 2008

Background

Prospero-related homeobox 1 (Prox1) transcription factor was described as a tumor-suppressor gene in liver tumors. In contrast, Prox1 knock out in murine embryos drastically reduces proliferation of hepatoblasts.

Methods

We have studied the expression of Prox1 in normal liver, liver cirrhosis and peritumoral liver samples in comparison to hepatocellular (HCC) and cholangiocellular carcinoma (CCC) at mRNA, protein and functional levels.

Results

Prox1 was found in hepatocytes of normal liver, while normal bile duct epithelial cells were negative. However, Prox1+ cells, which co-expressed biliary epithelial makers and showed ductular morphology, could be detected within fibrotic septa of cirrhotic livers, and in both HCC and CCC. Two Prox1 mRNA isoforms (2.9 kb and 7.9 kb) were identified with a prevalence of the longer isoform in several HCC samples and the shorter in most CCC samples. Evidence was provided that Myc-associated zinc finger protein (MAZ) might significantly contribute to the gene expression of Prox1 in HCC, while neo-expression of Prox1 in CCC remains to be resolved. A point mutation in the prospero domain of Prox1 was found in one HCC sample.

Conclusion

Our study shows dysregulation of Prox1 in liver cirrhosis, HCC and CCC, such as neo-expression in cells with biliary epithelial phenotype in liver cirrhosis, and in CCC. Altered Prox1 mRNA expression is partly regulated by MAZ, and mutation of the prospero domain in HCC indicates an involvement for Prox1 during tumor progression.
Socioeconomic position and risk of short-term weight gain: Prospective study of 14,619 middle-aged men and women
Authors: Purslow Lisa R , Young Elizabeth H , Wareham Nicholas J , Forouhi Nita , Brunner Eric J , Luben Robert N , Welch Ailsa A , Khaw Kay-Tee , Bingham Shelia A , Sandhu Manjinder S
Published: April 2008

Background

The association between socioeconomic position in middle age and risk of subsequent, short-term weight gain is unknown. We therefore assessed this association in a prospective population based cohort study in Norfolk, UK.

Methods

We analysed data on 14,619 middle-aged men and women (aged between 40–75 at baseline) with repeated objective measures of weight and height at baseline (1993–1997) and follow up (1998–2000).

Results

During follow up 5,064 people gained more than 2.5 kg. Compared with the highest social class, individuals in the lowest social class had around a 30% greater risk of gaining more than 2.5 kg (OR 1.29; 95% CI 1.11–1.51; p for trend = 0.002). This association remained statistically significant following adjustment for sex, age, baseline BMI, smoking, and follow up time (OR 1.25; CI 1.07–1.46; p for trend <0.001). We also found no material difference between unadjusted models and those including all confounders and potential mediators.

Conclusion

Individuals of low socioeconomic position are at greatest risk of gaining weight during middle age, which is not explained by classical correlates of socioeconomic position and risk factors for obesity.
Calculating expected years of life lost for assessing local ethnic disparities in causes of premature death
Authors: Aragón Tomás J , Lichtensztajn Daphne Y , Katcher Brian S , Reiter Randy , Katz Mitchell H
Published: April 2008

Background

A core function of local health departments is to conduct health assessments. The analysis of death certificates provides information on diseases, conditions, and injuries that are likely to cause death – an important outcome indicator of population health. The expected years of life lost (Y LL) measure is a valid, stand-alone measure for identifying and ranking the underlying causes of premature death. The purpose of this study was to rank the leading causes of premature death among San Francisco residents, and to share detailed methods so that these analyses can be used in other local health jurisdications.

Methods

Using death registry data and population estimates for San Francisco deaths in 2003–2004, we calculated the number of deaths, Y LL, and age-standardized Y LL rates (ASY Rs). The results were stratified by sex, ethnicity, and underlying cause of death. The Y LL values were used to rank the leading causes of premature death for men and women, and by ethnicity.

Results

In the years 2003–2004, 6312 men died (73,627 years of life lost), and 5726 women died (51,194 years of life lost). The ASY R for men was 65% higher compared to the ASY R for women (8971.1 vs. 5438.6 per 100,000 persons per year). The leading causes of premature deaths are those with the largest average Y LLs and are largely preventable. Among men, these were HIV/AIDS, suicide, drug overdose, homicide, and alcohol use disorder; and among women, these were lung cancer, breast cancer, hypertensive heart disease, colon cancer, and diabetes mellitus. A large health disparity exists between African Americans and other ethnic groups: African American age-adjusted overall and cause-specific Y LL rates were higher, especially for homicide among men. Except for homicide among Latino men, Latinos and Asians have comparable or lower Y LL rates among the leading causes of death compared to whites.

Conclusion

Local death registry data can be used to measure, rank, and monitor the leading causes of premature death, and to measure and monitor ethnic health disparities.
Spatial Cognition and the Brain
Authors: Burgess Neil
Published: April 2008

Recent advances in the understanding of spatial cognition are reviewed, focusing on memory for locations in large‐scale space and on those advances inspired by single‐unit recording and lesion studies in animals. Spatial memory appears to be supported by multiple parallel representations, including egocentric and allocentric representations, and those updated to accommodate self‐motion. The effects of these representations can be dissociated behaviorally, developmentally, and in terms of their neural bases. It is now becoming possible to construct a mechanistic neural‐level model of at least some aspects of spatial memory and imagery, with the hippocampus and medial temporal lobe providing allocentric environmental representations, the parietal lobe egocentric representations, and the retrosplenial cortex and parieto‐occipital sulcus allowing both types of representation to interact. Insights from this model include a common mechanism for the construction of spatial scenes in the service of both imagery and episodic retrieval and a role for the remainder of Papez's circuit in orienting the viewpoint used. In addition, it appears that hippocampal and striatal systems process different aspects of environmental layout (boundaries and local landmarks, respectively) and do so using different learning rules (incidental learning and associative reinforcement, respectively).
The Neural Correlates of Consciousness
Authors: Tononi Giulio , Koch Christof
Published: April 2008

This review examines recent advances in the study of brain correlates of consciousness. First, we briefly discuss some useful distinctions between consciousness and other brain functions. We then examine what has been learned by studying global changes in the level of consciousness, such as sleep, anesthesia, and seizures. Next we consider some of the most common paradigms used to study the neural correlates for specific conscious percepts and examine what recent findings say about the role of different brain regions in giving rise to consciousness for that percept. Then we discuss dynamic aspects of neural activity, such as sustained versus phasic activity, feedforward versus reentrant activity, and the role of neural synchronization. Finally, we briefly consider how a theoretical analysis of the fundamental properties of consciousness can usefully complement neurobiological studies.
The Neural Basis of Moral Cognition
Authors: Moll Jorge , De Oliveira‐Souza Ricardo , Zahn Roland
Published: April 2008

The human moral nature has perplexed laymen and academics for millennia. Recent developments in cognitive neuroscience are opening new venues for unveiling the complex psychological and neurobiological mechanisms underling human morality and its impairments. Here we review these lines of evidence and key topics of debate and explain why investigating the mechanisms of cognition–emotion interaction and of the neural bases of moral sentiments and values will be critical for our understanding of the human moral mind.
Generalization and Differentiation in Semantic Memory
Authors: Lambon Ralph Matthew A. , Patterson Karalyn
Published: April 2008

According to many theories, semantic representations reflect the parallel activation of information coded across a distributed set of modality‐specific association brain cortices. This view is challenged by the neurodegenerative condition known as semantic dementia (SD), in which relatively circumscribed, bilateral atrophy of the anterior temporal lobes results in selective degradation of core semantic knowledge, affecting all types of concept, irrespective of the modality of testing. Research on SD suggests a major revision in our understanding of the neural basis of semantic memory. Specifically, it is proposed that the anterior temporal lobes form amodal semantic representations through the distillation of the multimodal information that is projected to this region from the modality‐specific association cortices. Although cross‐indexing of modality‐specific information could be achieved by a web of direct connections between pairs of these regions, amodal semantic representations enable semantic generalization and inference on the basis of conceptual structure rather than modality‐specific features. As expected from this hypothesis, SD is characterized by impaired semantic generalization, both clinically and in formal assessment. The article describes a comprehensive array of under‐ and overgeneralization errors by patients with SD when engaged in receptive and expressive verbal and nonverbal tasks and everyday behaviors.
Can Neurological Evidence Help Courts Assess Criminal Responsibility? Lessons from Law and Neuroscience
Authors: Aharoni Eyal , Funk Chadd , Sinnott‐Armstrong Walter , Gazzaniga Michael
Published: April 2008

Can neurological evidence help courts assess criminal responsibility? To answer this question, we must first specify legal criteria for criminal responsibility and then ask how neurological findings can be used to determine whether particular defendants meet those criteria. Cognitive neuroscience may speak to at least two familiar conditions of criminal responsibility: intention and sanity. Functional neuroimaging studies in motor planning, awareness of actions, agency, social contract reasoning, and theory of mind, among others, have recently targeted a small assortment of brain networks thought to be instrumental in such determinations. Advances in each of these areas bring specificity to the problems underlying the application of neuroscience to criminal law.
Cognitive Neuroscience of Aging
Authors: Grady Cheryl L.
Published: April 2008

The number of reports on the cognitive neuroscience of aging has increased in recent years, and most of these studies have found many similarities in the patterns of activity in young and old adults, indicating that basic neural mechanisms are maintained into older age. Despite these overall similarities, older adults often have less activity in some regions, such as medial temporal areas during memory processing and visual regions across a variety of cognitive domains. It seems clear that age reductions in cognitive function can be tied, at least in part, to these reductions in brain activity. On the other hand, older adults typically also overrecruit some brain areas, mainly the ventral or dorsal prefrontal cortex during memory tasks, as well as both the frontal and parietal regions during tasks engaging cognitive control processes, such as attention. Sometimes this overrecruitment appears to be in response to altered function in other brain regions and is often seen in those older adults who perform better on the task at hand. These findings have provided rather convincing support for the idea that overrecruitment can be compensatory in the elderly. Nevertheless, not all age increases can be interpreted as compensatory, and some are more indicative of neural inefficiency. The challenge facing future research will be to understand the task conditions that promote compensation in older adults, the role of the various brain areas in aiding cognitive function, and how these compensatory mechanisms can be elicited to enhance quality of life in the elderly.
The Brain's Default Network
Authors: Buckner Randy L. , Andrews‐Hanna Jessica R. , Schacter Daniel L.
Published: April 2008

Thirty years of brain imaging research has converged to define the brain's default network—a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self‐relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
Intention, Choice, and the Medial Frontal Cortex
Authors: Rushworth Matthew F.S.
Published: April 2008

The medial frontal cortex (MFC) has been identified with voluntary action selection. Recent evidence suggests that there are three principal ways in which the MFC is an essential part of the neural circuit for voluntary action selection. First, the MFC represents the reinforcement values of actions and is concerned with the updating of those action values. Because it is particularly concerned with the rate at which action values should be updated, it mediates the influence that the past reinforcement history has over the next choice that is made and it may determine the learning rate. The MFC's representation of action value does not just reflect the potential reward associations of an action but instead represents both the reward and effort costs that are intrinsic to the action. Second, the MFC is important when an exploratory action is generated in order to obtain more information about action values and the environment. Third, the MFC is critical when conflicting information in the immediate environment instructs more than one possible response. In such situations the MFC exerts an influence over how actions will be chosen by other motor regions of the brain.
Insulin Sensitivity Is Correlated with Subcutaneous but Not Visceral Body Fat in Overweight and Obese Prepubertal Children
Authors: Maffeis Claudio , Manfredi Riccardo , Trombetta Maddalena , Sordelli Silvia , Storti Monica , Benuzzi Teresa , Bonadonna Riccardo C.
Published: April 2008

Aim: Our aim was to explore the relationship between insulin sensitivity, body fat distribution, ectopic (liver and skeletal muscle) fat deposition, adipokines (leptin and adiponectin), and inflammation markers (highly sensitive C-reactive protein, IL-6, IL-10, and TNF-α) in prepubertal children.

Subjects and Methods: Thirty overweight and obese children (16 males and 14 females with body mass index z-score range of 1.1–3.2) were recruited. Body fat distribution and fat accumulation in liver and skeletal muscle were measured using magnetic resonance imaging. Insulin sensitivity was assessed by iv glucose tolerance test.

Results: Insulin sensitivity was associated with sc abdominal adipose tissue (SAT) (r = −0.52; P < 0.01) and liver fat content (r = −0.44; P < 0.02) but not with visceral abdominal adipose tissue (VAT) (r = −0.193; P value not significant) and fat accumulation in skeletal muscle (r = −0.210; P value not significant). Adipokines, but not inflammation markers, were significantly correlated to insulin sensitivity. VAT correlated with C-reactive protein (r = 0.55; P < 0.01) as well as adiponectin (r = −0.53; P <0.01). Multiple regression analysis showed that only SAT and liver fat content were independently correlated to insulin sensitivity (P < 0.01; 20 and 16% of explained variance, respectively).

Conclusions: In overweight and moderately obese prepubertal children, insulin sensitivity was negatively correlated with SAT and liver fat content. Furthermore, contrary to adults, VAT and inflammation markers were not correlated with insulin sensitivity in children.
The Aromatase Inhibitor Anastrozole Is Ineffective in the Treatment of Precocious Puberty in Girls with McCune-Albright Syndrome
Authors: Mieszczak Jakub , Lowe Elizabeth S. , Plourde Paul , Eugster Erica A.
Published: April 2008

Context: Precocious puberty (PP) in girls with McCune-Albright syndrome (MAS) is characterized by episodic development of large unilateral ovarian cysts followed by sudden onset of vaginal bleeding. Some patients experience frequent bleeding as well as accelerated linear growth and advanced skeletal maturation. The use of anastrozole for the treatment of PP in this condition has not been well studied.

Objective: The objective of the study was to determine the safety and efficacy of the aromatase inhibitor anastrozole for the treatment of PP in girls with MAS.

Design and Settings: This was a prospective international multicenter study in which subjects received anastrozole 1 mg daily for 1 yr.

Patients: Twenty-eight girls 10 years of age or younger with MAS and progressive PP were enrolled.

Main Outcome Measures: Vaginal bleeding, rate of skeletal maturation (change in bone age over change in chronological age), growth velocity, and uterine/ovarian volumes were measured. These indices were compared with a 6-month pretreatment interval.

Results: No difference in vaginal bleeding (mean number of days per year) was noted. Mean change in ΔBA/ΔCA, which was 1.25 ± 0.77 at baseline, was −0.25 ± 1.02 at study end (P = 0.22). Average growth velocity z score was 1.40 ± 3.15 at study entry and 0.26 ± 2.71 at 12 months (P = 0.10). Mean ovarian/uterine volumes were unaffected by anastrozole, and no significant adverse events occurred.

Conclusions: Although it appears safe, anastrozole for 1 yr was ineffective in halting vaginal bleeding, attenuating rates of skeletal maturation, and linear growth in girls with MAS. Pharmacological strategies other than anastrozole should be pursued for the treatment of PP in this population.
Insulin Intervention in Slowly Progressive Insulin-Dependent (Type 1) Diabetes Mellitus
Authors: Maruyama Taro , Tanaka Shoichiro , Shimada Akira , Funae Osamu , Kasuga Akira , Kanatsuka Azuma , Takei Izumi , Yamada Satoru , Harii Norikazu , Shimura Hiroki , Kobayashi Tetsuro
Published: April 2008

Objective: We tested the hypothesis that insulin therapy rather than sulfonylurea (SU) treatment is preferable to reverse or preserve β-cell function among patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) or latent autoimmune diabetes in adults.

Methods: This multicenter, randomized, nonblinded clinical study screened 4089 non-insulin-dependent diabetic patients for glutamic acid decarboxylase autoantibodies (GADAb). Sixty GADAb-positive non-insulin-requiring diabetic patients with a 5-yr duration or shorter of diabetes were assigned to either the SU group (n = 30) or the insulin group (n = 30). Serum C-peptide responses to annual oral glucose tolerance tests were followed up for a mean of 57 months. The primary endpoint was an insulin-dependent state defined by the sum of serum C-peptide values during the oral glucose tolerance test (ΣC-peptide) less than 4 ng/ml (1.32 nmol/liter).

Results: The progression rate to an insulin-dependent state in the insulin group (three of 30, 10%) was lower than that in the SU group (13 of 30, 43%; P = 0.003, log-rank). Longitudinal analysis demonstrated that ΣC-peptide values were better preserved in the insulin group than in the SU group. Multiple regression analysis demonstrated that insulin treatment, a preserved C-peptide response, and a low GADAb titer at entry were independent factors in preventing progression to an insulin-dependent state. Subgroup analysis suggested that insulin intervention was highly effective for SPIDDM patients with high GADAb titers [≥10 U/ml (180 World Health Organization U/ml)] and preserved β-cell function [ΣC-peptide ≥ 10 ng/ml (3.31 nmol/liter)] at entry. No severe hypoglycemic episodes occurred during the study.

Conclusions: Insulin intervention to preserve β-cell function is effective and safe for patients with SPIDDM or latent autoimmune diabetes in adults.
Treatment of Type 2 Diabetes and Dyslipidemia with the Natural Plant Alkaloid Berberine
Authors: Zhang Yifei , Li Xiaoying , Zou Dajin , Liu Wei , Yang Jialin , Zhu Na , Huo Li , Wang Miao , Hong Jie , Wu Peihong , Ren Guoguang , Ning Guang
Published: April 2008

Context: Berberine, a natural plant alkaloid, is usually used as an antibiotic drug. The potential glucose-lowering effect of berberine was noted when it was used for diarrhea in diabetic patients. In vitro and in vivo studies have then showed its effects on hyperglycemia and dyslipidemia.

Objective: The objective of the study was to evaluate the efficacy and safety of berberine in the treatment of type 2 diabetic patients with dyslipidemia.

Design: One hundred sixteen patients with type 2 diabetes and dyslipidemia were randomly allocated to receive berberine (1.0 g daily) and the placebo for 3 months. The primary outcomes were changes in plasma glucose and serum lipid concentrations. Glucose disposal rate (GDR) was measured using a hyperinsulinemic euglycemic clamp to assess insulin sensitivity.

Results: In the berberine group, fasting and postload plasma glucose decreased from 7.0 ± 0.8 to 5.6 ± 0.9 and from 12.0 ± 2.7 to 8.9 ± 2.8 mm/liter, HbA1c from 7.5 ± 1.0% to 6.6 ± 0.7%, triglyceride from 2.51 ± 2.04 to 1.61 ± 1.10 mm/liter, total cholesterol from 5.31 ± 0.98 to 4.35 ± 0.96 mm/liter, and low-density lipoprotein-cholesterol from 3.23 ± 0.81 to 2.55 ± 0.77 mm/liter, with all parameters differing from placebo significantly (P < 0.0001, P < 0.0001, P < 0.0001, P = 0.001, P < 0.0001, and P <0.0001, respectively). The glucose disposal rate was increased after berberine treatment (P = 0.037), although no significant change was found between berberine and placebo groups (P = 0.063). Mild to moderate constipation was observed in five participants in the berberine group.

Conclusions: Berberine is effective and safe in the treatment of type 2 diabetes and dyslipidemia.
[123I]Iodometomidate for Molecular Imaging of Adrenocortical Cytochrome P450 Family 11B Enzymes
Authors: Hahner Stefanie , Stuermer Andrea , Kreissl Michael , Reiners Christoph , Fassnacht Martin , Haenscheid Heribert , Beuschlein Felix , Zink Martina , Lang Katharina , Allolio Bruno , Schirbel Andreas
Published: April 2008

Background: Due to advances in conventional imaging, adrenal tumors are detected with increasing frequency. However, conventional imaging provides only limited information on the origin of these lesions, which represent a wide range of different pathological entities. New specific imaging methods would therefore be of great clinical value. We, therefore, studied the potential of iodometomidate (IMTO) as tracer for molecular imaging of cytochrome P450 family 11B (Cyp11B) enzymes.

Methods: Inhibition of Cyp11B1 and Cyp11B2 by IMTO, etomidate, metomidate, and fluoroetomidate was investigated in NCI-h295 cells and in Y1 cells stably expressing hsCyp11B1 or hsCyp11B2. Pharmacokinetics and biodistribution after iv injection of [123/125I]IMTO were analyzed in mice in biodistribution experiments and by small-animal single-photon emission computed tomography (SPECT). Furthermore, four patients with known adrenal tumors (two metastatic adrenal adenocarcinomas, one bilateral adrenocortical adenoma, and one melanoma metastasis) were investigated with [123I]iodometomidate-SPECT.

Results: In cell culture experiments, all compounds potently inhibited both Cyp11B1 and Cyp11B2. Adrenals showed high and specific uptake of [123/125I]IMTO and were excellently visualized in mice. In patients, adrenocortical tissue showed high and specific tracer uptake in both primary tumor and metastases with short investigation time and low radiation exposure, whereas the non-adrenocortical tumor did not exhibit any tracer uptake.

Conclusion: We have successfully completed the development of an in vivo detection system of adrenal Cyp11B enzymes by [123I]IMTO scintigraphy in both experimental animals and humans. Our findings suggest that [123I]IMTO is a highly specific radiotracer for imaging of adrenocortical tissue. Due to the general availability of SPECT technology, we anticipate that [123I]IMTO scintigraphy may become a widely used tool to characterize adrenal lesions.
Muscle Adaptation to Short-Term Fasting in Healthy Lean Humans
Authors: Soeters Maarten R. , Sauerwein Hans P. , Dubbelhuis Peter F. , Groener Johanna E. , Ackermans Mariëtte T. , Fliers Eric , Aerts Johannes M. , Serlie Mireille J.
Published: April 2008

Context: It has been demonstrated repeatedly that short-term fasting induces insulin resistance, although the exact mechanism in humans is unknown to date. Intramyocellular sphingolipids (i.e. ceramide) have been suggested to induce insulin resistance by interfering with the insulin signaling cascade in obesity.

Objective: Our objective was to study peripheral insulin sensitivity together with muscle ceramide concentrations and protein kinase B/AKT phosphorylation after short-term fasting.

Main Outcome Measures and Design: After 14- and 62-h fasting, glucose fluxes were measured before and after a hyperinsulinemic euglycemic clamp. Muscle biopsies were performed in the basal state and during the clamp to assess muscle ceramide and protein kinase B/AKT.

Results: Insulin-mediated peripheral glucose uptake was significantly lower after 62-h fasting compared with 14-h fasting. Intramuscular ceramide concentrations tended to increase during fasting. During the clamp the phosphorylation of protein kinase B/AKT at serine473 in proportion to the total amount of protein kinase B/AKT was significantly lower. Muscle ceramide did not correlate with plasma free fatty acids.

Conclusions: Fasting for 62 h decreases insulin-mediated peripheral glucose uptake with lower phosphorylation of AKT at serine473. AKT may play a regulatory role in fasting-induced insulin resistance. Whether the decrease in AKT can be attributed to the trend to higher muscle ceramide remains unanswered.