bluuebunny/crossref_metadata_2025 huggingface dataset:
Tough times, meaningful music, mature performers: popular Billboard songs and performer preferences across social and economic conditions in the USA
Authors: Pettijohn Terry F. , Sacco Donald F.
Published: December 2008

The Billboard number 1 songs for each year from 1955 to 2003 were investigated across changes in US social and economic conditions. Study 1 investigated song characteristics and ratings and found that when social and economic times were relatively threatening, songs that were longer in duration, more meaningful in content, more comforting, more romantic, and slower were most popular. Study 2 explored popular performer facial feature characteristics and found that performers with more mature facial features, including smaller eyes, thinner faces, and larger chins, were popular during relatively threatening social and economic conditions. These facial feature preferences were more pronounced with the onset of music television in the 1980s. Results of the two studies are explained within the context of the Environmental Security Hypothesis.
Diffuse Pontine Glioma in Jordan and Impact of Up-front Prognosis Disclosure With Parents and Families
Authors: Qaddoumi Ibrahim , Ezam Najeeb , Swaidan Maisa , Jaradat Imad , Mansour Asem , Abuirmeileh Najyah , Bouffet Eric , Al-Hussaini Maysa
Published: December 2008

For patients with diffuse pontine glioma, our institution offers local radiotherapy and supportive care only. The prognosis and do-not-resuscitate orders are discussed upfront with patients' parents. To investigate the effectiveness of this policy, we retrospectively reviewed records of patients with diffuse pontine glioma treated at the institution over a 49-month period. This study included 19 children (16 girls and 3 boys). The median age at diagnosis was 7 years. One patient remained alive at the end of the study, 2 were lost to follow-up, and 16 were confirmed dead. The median survival was 8.2 months. Do-not-resuscitate discussion was documented for 14 patients and successfully initiated for 11. None of those confirmed dead had been offered life support. Contrary to the common belief, our study showed that do not resuscitate should be addressed in Muslim patients with high-risk malignancies. We also found that diffuse pontine glioma warrants further study in developing countries.
Parental Education and Late-life Dementia in the United States
Authors: Rogers Mary A. M. , Plassman Brenda L. , Kabeto Mohammed , Fisher Gwenith G. , McArdle John J. , Llewellyn David J. , Potter Guy G. , Langa Kenneth M.
Published: December 2008

We investigated the relation between parental education and dementia in the United States. Participants in the Aging, Demographics, and Memory Study were included, with information regarding parental education obtained from the Health and Retirement Study. The odds of dementia in elderly Americans whose mothers had less then 8 years of schooling were twice (95% CI, 1.1-3.8) that of individuals with higher maternal education, when adjusted for paternal education. Of elderly Americans with less educated mothers, 45.4% (95% CI, 37.4-53.4%) were diagnosed with dementia or ``cognitive impairment, no dementia'' compared to 31.2% (95% CI, 25.0-37.4%) of elderly Americans whose mothers had at least an 8th grade education. The population attributable risk of dementia due to low maternal education was 18.8% (95% CI, 9.4-28.2%). The education of girls in a population may be protective of dementia in the next generation.
Lack of Association of the TP53 Arg72Pro SNP and the MDM2 SNP309 with systemic lupus erythematosus in Caucasian, African American, and Asian children and adults
Authors: Onel KB , Huo D , Hastings D , Fryer-Biggs J , Crow MK , Onel K
Published: December 2008

The p53 tumour suppressor is the central regulator of apoptosis. Previously, the functional TP53 Arg72Pro polymorphism was found to be associated with systemic lupus erythematosus (SLE) in Koreans but not Spaniards. MDM2 is the major negative regulator of p53. An intronic polymorphism in MDM2, the SNP309, attenuates p53 activity and is associated with accelerated tumour development in premenopausal women. Polymorphic variation in MDM2 has never been studied in SLE. The aim of this study is to further assess the contribution of p53-pathway genetic variation to SLE by testing the association of the TP53 Arg72Pro polymorphism and the MDM2 SNP309 with SLE in a well-characterised and ethnically diverse cohort of patients with both childhood- and adult-onset SLE ( n = 314). No association was found between the TP53 Arg72Pro polymorphism and SLE in patients of European descent, Asian descent or in African Americans, nor was an association found between the MDM2 SNP309 and SLE in patients of European descent or in African Americans. In addition, there was no correlation between either variant and early-onset disease or nephritis, an index of severe disease. It is concluded that neither the TP53 Arg72Pro polymorphism nor the MDM2 SNP309 contributes significantly to either susceptibility or disease severity in SLE.
Menstrual and hormonal alterations in juvenile systemic lupus erythematosus
Authors: Medeiros PB , Febrônio MV , Bonfá E , Borba EF , Takiuti AD , Silva CAA
Published: December 2008

Menstrual cycles of 30 patients with juvenile systemic lupus erythematosus (JSLE) were compared with 30 age-matched controls. The mean age of patients with JSLE and controls was similar (17.4 ± 3.2 vs 17.06 ± 2.08 years, P = 0.66). The mean menarche age was higher in JSLE than controls (13.13 ± 1.4 vs 11.56 ± 1.5 years, P = 0.0008). On the contrary, the mean maternal menarche age was similar in both groups ( P = 0.62). Menstrual abnormalities and longer length cycles were more frequently observed in JSLE than controls (63% vs 10%, P = 0.0001; 23% vs 0%, P = 0.0105, respectively). The median of follicle stimulating hormone was significantly higher in patients with JSLE compared with controls (4.6 vs 3.4 IU/L, P = 0.0207), and the median of progesterone was lower (32.5 vs 70 ng/mL, P = 0.0033). The median of luteinizing hormone was lower in patients with JSLE with menstrual abnormalities versus normal cycles (2.9 vs 5.5 IU/L, P = 0.019) and both had a high percentage of decreased progesterone levels (63% vs 73%, P = 0.70). Our findings support the notion that menstrual disturbances are frequent and may be associated with pituitary dysfunction leading to a decreased progesterone production. We also reported that in spite of premature ovarian failure being a rare event in JSLE the follicular reserve seems to be low regardless of intravenous cyclophosphamide treatment.
`How is the Body of Christ a Meaningful Symbol for the Contemporary Christian Community?'
Authors: Johnson SueAnn
Published: December 2008

This essay attempts to answer the question of how the Body of Christ is a meaningful symbol for the contemporary Christian community from a feminist perspective. Following Graham Ward's account of the displaced body of Jesus Christ, the author argues that the Body of Christ is a distinctly Christian symbol that empowers the contemporary community of Christian believers with a radical new identity, one that is multi-gendered and includes a vast continuum of human and divine embodied experience.
Reducing the Costs of Participation
Authors: Giammo Joseph D. , Brox Brian J.
Published: December 2008

The authors address the puzzle of why governments have implemented methods of early voting when those methods appear not to have an effect on turnout. Using an aggregate analysis, the authors find that early voting seems to produce a short-lived increase in turnout that disappears by the second presidential election in which it is available. They also address whether the additional costs to government are worth the negligible increase in participation. They conclude that these reforms merely offer additional convenience for those already likely to vote.
Rights, Contribution, Achievement and the World
Authors: Seglow Jonathan
Published: December 2008

This article explores Axel Honneth's theory of recognition as the most worked out account of recognition available to political philosophy. I argue that Honneth over-estimates the degree to which rights deliver recognition; faces internal problems if his theory is extended to evaluate global injustice; and shows an ambivalence over the criterial basis for esteem. I go on to argue that the institutional fabric of everyday life has a more significant role in delivering recognition than Honneth acknowledges — a point which partially resolves some of the problems identified.
Beyond Dignity and Difference
Authors: Cooke Maeve
Published: December 2008

Revisiting Taylor's 1992 account of the politics of recognition, I argue that he is right to discern a strand in contemporary politics that goes beyond the demand for recognition of dignity. Against Taylor I contend that this is best understood as a concern not for recognition of difference but for the value of something that is not universally shared, such as a particular ethical conception, cultural tradition or religious belief and practice. Using the examples of three social movements I show the relevance of this for contemporary politics. My empirically based argument is supported normatively by a discussion of Hegel's critique of `morality as conscience' in his Phenomenology. Referring to Axel Honneth's theory of recognition I highlight the lack of attention to this kind of concern for recognition in contemporary political and social theory. I conclude by specifying the key features of the concept of recognition most appropriate for responding to it publicly under conditions of value-pluralism.
Recognition, Needs and Wrongness
Authors: Laitinen Arto
Published: December 2008

`Due recognition is a vital human need', argues Charles Taylor. In this article I explore this oft-quoted claim from two complementary and equally appealing perspectives. The bottom—up approach is constructed around Axel Honneth's theory of recognition, and the top—down approach is exemplified by T. M. Scanlon's brief remarks about mutual recognition. The former can be summed up in the slogan `wronging by misrecognizing', the latter in the slogan `misrecognizing by wronging'. Together they provide two complementary readings of the claim that due recognition is a vital human need: one starts from needs, shows how we have a multifarious need for adequate recognition and builds up to a view about wronging; the other starts from wronging and discusses the kind of interest or need that we have of standing in relations where wronging is absent.
A Needs Assessment of Latino Men’s Health Concerns
Authors: Peak Terry , Gast Julie , Ahlstrom Denice
Published: December 2008

Historically, Latino men are an understudied group. Researchers know little about the impact of culture or gender on health concerns. In this study, focus groups with Latino men were held that investigated their health concerns, barriers, motivators, and access to health information and health services. Additionally, the researchers wished to determine if a church-based design might help reach men who might not be responsive to more traditional health education or public health routes. Results included that the Latino male participants in this study wanted health information but wanted it to be more specific and in an accessible format. They also desired more Spanish-speaking health care providers and were acutely interested in low-cost health care. Prevention was not of much interest to these participants. Church-attending participants were interested in church-based health education.
Identifying Grant Funding: Mentored Career Development and Transition Awards
Authors: McDonagh Kevin T.
Published: December 2008

NIH Career Development Awards are designed to provide outstanding, clinically trained professionals with salary support and protected time to pursue a course of intensive, mentored research experience necessary to achieve full scientific independence. The ideal candidate for a career development award is a health scientist nearing the completion of postdoctoral training or in the early years of a faculty position. The K series of NIH awards provide several options for mentored training that are appropriate for investigators interested in laboratory or clinical investigation in the biologic and medical sciences.
Transitioning from Fellowship to a Physician-Scientist Career Track
Authors: Melnick Ari
Published: December 2008

Given the remarkable advances in bio-medicine in recent years, there has never been a better time to devote one’s efforts towards bench to beside medicine. Accordingly, well-trained physician-scientists are in high demand in the private and academic sectors, and there is increasing awareness of the need to support and nurture such individuals. Clinical fellows in hematology, oncology and hematopathology with an interest in the physician-scientist career path must be well prepared to succeed in transitioning from fellowship to their first academic position. This article will discuss some of the key elements that prospective clinical scientists need to assemble in order to survive this critical period.
Clinical Relevance of Anemia and Transfusion Iron Overload in Myelodysplastic Syndromes
Authors: Cazzola Mario , Della Porta Matteo G. , Malcovati Luca
Published: December 2008

Most patients with myelodysplastic syndrome eventually become dependent on regular red cell transfusions. This dependency has a negative impact on clinical outcome, primarily because it may be associated with more severe marrow failure. In addition, however, transfusion dependency may involve clinical consequences of chronic anemia and iron overload. Although transfusion iron is primarily taken up by the reticuloendothelial cells, the metal is later redistributed to parenchymal cells. This redistribution is modulated by several factors, including the degree of ineffective erythropoiesis through its suppressive effect on hepcidin production. Body iron status is routinely assessed by serum ferritin and transferrin saturation, but there is a need of reliable tools for locating iron accumulation in patients. Magnetic resonance imaging T2* provides a non-invasive method for detecting and quantifying both liver and myocardial iron overload. Clinical consequences of parenchymal iron overload have been reported not only in thalassemia major, but also in patients with myelodysplastic syndrome. Transfusion-dependent patients with isolated erythroid dysplasia and low risk of leukemic evolution are more likely to develop parenchymal iron overload and its toxicity, and therefore may benefit from chelation therapy. There may also be a benefit of chelation therapy in patients with transfusion iron overload undergoing allogeneic stem cell transplantation. Deferoxamine and deferasirox are currently available for treatment of transfusion iron overload in patients with myelodysplastic syndrome.
What Do You Do with the “Pink Sheets?”
Authors: Chao Nelson
Published: December 2008

Applying for a grant seems like an enormous challenge, sometimes akin to Sisyphus’ task of rolling the boulder up the hill. In many ways, obtaining funding can be challenging, yet year after year, new investigators do obtain funding, even though there are times when the funding percentage can be low. This review offers some suggestions of what to do after the first or second round of critiques are back. There are some relatively straightforward steps one can take to improve one’s chances of success. The joy of funding is worth it!
Duration of Anticoagulation Therapy for Venous Thromboembolism
Authors: Bounameaux Henri , Perrier Arnaud
Published: December 2008

Treatment of acute deep vein thrombosis and pulmonary embolism-often denominated together as venous thromboembolism (VTE)- consists of parenteral administration of heparin (usually low-molecular-weight heparin or alternatively unfractionated heparin or fondaparinux) overlapped and followed by oral vitamin K antagonists that are administered for a certain period (usually 3 to 12 months). Recommended or suggested durations differ according to guidelines. Practically, the clinical decision in an individual patient depends upon the estimated risks of VTE recurrence and treatment-induced bleeding. The risk of VTE recurrence is higher in idiopathic events (about 10% per year during the first two years and 3% per year thereafter) (odds ratio of 2.4, compared to secondary events); in male subjects (at least before the age of 60, with an odds ratio of 2–4); in patients with persistently elevated D-dimer level (odds ratio of 2.3, compared with normal level); and during the first two years after discontinuation of treatment. The annual risk of major bleeding on anticoagulant treatment vary largely in observational studies with figures of 2% to 29%, depending on the patient characteristics. The case-fatality rate is 8% (DVT), 12% (PE) for recurrent VTE, and about 10% for major bleed. These figures do not support long-term anticoagulant therapy, except in those patients exhibiting a very high risk of recurrence and/or a very low risk of bleeding.

New therapeutic aspects might impact on the duration of anticoagulant therapy after a venous thromboembolic event. They include the possibility of pursuing anticoagulant treatment at a reduced INR after an initial period with an INR 2-3, and the advent of new, more specific and orally active anticoagulants. These features might modify the risk-benefit balance of extending anticoagulant therapy beyond the usual, limited duration.
Skeletal Imaging and Management of Bone Disease
Authors: Roodman G. David
Published: December 2008

Up to 90% of patients with multiple myeloma develop bone lesions. The lesions are purely osteolytic because of increased osteoclast activity and markedly suppressed or absent osteoblast activity. The “gold standard” for imaging myeloma bone lesions is the metastatic bone survey. However, plain radiographs are relatively insensitive and can only demonstrate lytic disease when 30% of trabecular bone loss has occurred. Technicium-99m bone scanning is not appropriate for evaluating myeloma patients since bone scans underestimate the extent of bone involvement in patients with myeloma. The limited reproducibility of bone surveys have led to the use of computerized tomography (CT) scanning, magnetic resonance imaging (MRI) and positron emission tomography (PET) scans to evaluate the extent of bone disease. CT scans are more sensitive than plain radiographs for detecting small lytic lesions, and MRI scans detect marrow involvement by the tumor. PET scans have been used to detect bone lesions in patients with myeloma, are more sensitive than plain radiographs, and have the same sensitivity as MRIs for detecting bone disease in the spine and pelvis. Treatment of myeloma bone disease involves treatment of the underlying malignancy and its manifestations. Current treatments that will be discussed include bisphosphonate therapy, kyphoplasty, vertebroplasty, radiation therapy, and novel agents to suppress osteoclastic bone resorption. In addition, complications with bisphosphonate therapy will be reviewed, in particular, osteonecrosis of the jaw associated with bisphosphonate therapy. As survival of myeloma patients increases, therapies to prevent the complications of aggressive myeloma bone disease become more important.
Chronic Myeloid Leukemia Stem Cells
Authors: Jamieson Catriona H.
Published: December 2008

Chronic myeloid leukemia (CML) is typified by robust marrow and extramedullary myeloid cell production. In the absence of therapy or sometimes despite it, CML has a propensity to progress from a relatively well tolerated chronic phase to an almost uniformly fatal blast crisis phase. The discovery of the Philadelphia chromosome followed by identification of its BCR-ABL fusion gene product and the resultant constitutively active P210 BCR-ABL tyrosine kinase, prompted the unraveling of the molecular pathogenesis of CML. Ground-breaking research demonstrating that BCR-ABL was necessary and sufficient to initiate chronic phase CML provided the rationale for targeted therapy. However, regardless of greatly reduced mortality rates with BCR-ABL targeted therapy, most patients harbor quiescent CML stem cells that may be a reservoir for disease progression to blast crisis. While the hematopoietic stem cell (HSC) origin of CML was first suggested over 30 years ago, only recently have the HSC and progenitor cell–specific effects of the molecular mutations that drive CML been investigated. This has provided the impetus for investigating the genetic and epigenetic events governing HSC and progenitor cell resistance to therapy and their role in disease progression. Accumulating evidence suggests that the acquired BCR-ABL mutation initiates chronic phase CML and results in aberrant stem cell differentiation and survival. This eventually leads to the production of an expanded progenitor population that aberrantly acquires self-renewal capacity resulting in leukemia stem cell (LSC) generation and blast crisis transformation. Therapeutic recalcitrance of blast crisis CML provides the rationale for targeting the molecular pathways that drive aberrant progenitor differentiation, survival and self-renewal earlier in disease before LSC predominate.
New Agents in the Treatment of CLL
Authors: O’Brien Susan
Published: December 2008

Chemoimmunotherapy has resulted in high complete remission rates and long remission duration in patients with chronic lymphocytic leukemia (CLL) but relapses occur and curative strategies still need to be developed. A wealth of new agents with a wide variety of mechanisms of action against CLL are currently in clinical trials. Twelve of these agents, which are in various stages of development varying from Phase I to Phase III trials, will be discussed. These include alkylating agents, monoclonal antibodies, immune modulators, cyclin-dependent kinase (CDK) inhibitors, BCL-2 family member inhibitors, protein kinase C (PKC) inhibitors, SRC inhibitors, HSP-90 inhibitors and small modular immune pharmaceutics (SMIP).
Pain Management in Sickle Cell Disease: Palliative Care Begins at Birth?
Authors: Benjamin Lennette
Published: December 2008

People with sickle cell disease (SCD) are living longer, but their lives are impacted even more by the unpredictable intermittent or constant pain that is often poorly managed over a lifetime. To address this problem, an interdisciplinary team approach is needed that brings the medical professionals together for optimal compassionate care that is coordinated from the beginning of life and throughout the patient’s lifespan.The hematologist, whenever possible, should take the lead. Effective models that have been developed to address SCD pain, such as the Day Hospital, The Recidivism Project and various Home Care models, need to be integrated into an overarching plan on a continuum with an underpinning philosophy that will sustain such a program. While the focus of palliative care has been end of life, its philosophies fit the chronic disease model and support an integrated team approach to the SCD pain management dilemma. The patient-focused and family-oriented interventions can be modeled to fit “any place, any time,” outpatient, inpatient or the home, with homecare and other support systems. Such are the needs in SCD: appropriate, timely and compassionate care to prevent or relieve suffering and to preserve dignity, meaning, value and quality of life with improvement that is translational from birth until the end of life.
Determinants of career aspirations of medical students in southern China
Authors: She LingBing , Wu BingLi , Xu LiYan , Wu JianYi , Zhang PiXian , Li EnMin
Published: December 2008

Background

With recent changes in both the Chinese medical system and compensation of medical doctors, the career aspirations of Chinese medical students have become more diverse. Shantou University Medical College has conducted evaluations and instituted programs to enhance student preparedness to enter a variety of medical careers.

Methods

A survey was conducted with 85 students to evaluate medical career aspirations and their association with family background, personal skills, English language proficiency, and interest in biomedical research, which were considered as possible factors affecting their career interest.

Results

Chinese students aspire to traditional as well as nontraditional medical careers. A significant minority of students are now interested in nontraditional careers such as medical teaching or research. However, poor proficiency in the English language and lack of computer skills may limit their academic and career opportunities.

Conclusion

Career aspirations have changed among medical undergraduates. Although many wish to pursue a traditional clinical doctor career, many are interested in research and teaching careers. Factors such as family background, personal characteristics, school mentoring, and extracurricular support may play a role.
The Demand for, and Impact of, Learning HIV Status
Authors: Thornton Rebecca L
Published: December 2008

This paper evaluates an experiment in which individuals in rural Malawi were randomly assigned monetary incentives to learn their HIV results after being tested. Distance to the HIV results centers was also randomly assigned. Without any incentive, 34 percent of the participants learned their HIV results. However, even the smallest incentive doubled that share. Using the randomly assigned incentives and distance from results centers as instruments for the knowledge of HIV status, sexually active HIV-positive individuals who learned their results are three times more likely to purchase condoms two months later than sexually active HIV-positive individuals who did not learn their results; however, HIV-positive individuals who learned their results purchase only two additional condoms than those who did not. There is no significant effect of learning HIV-negative status on the purchase of condoms. (JEL I12, O15)
Stocks as Lotteries: The Implications of Probability Weighting for Security Prices
Authors: Barberis Nicholas , Huang Ming
Published: December 2008

We study the asset pricing implications of Tversky and Kahneman's (1992) cumulative prospect theory, with a particular focus on its probability weighting component. Our main result, derived from a novel equilibrium with nonunique global optima, is that, in contrast to the prediction of a standard expected utility model, a security's own skewness can be priced: a positively skewed security can be “overpriced” and can earn a negative average excess return. We argue that our analysis offers a unifying way of thinking about a number of seemingly unrelated financial phenomena. (JEL D81, G11, G12)
The Influence of Instrumented Striker Configuration on the Results of Dynamic Toughness Testing
Authors: Lucon Enrico
Published: December 2008

Several studies are available on the influence of the edge radius of instrumented strikers (ASTM — 8 mm or ISO — 2 mm) on the results of both non-instrumented and instrumented Charpy tests. This paper investigates the effect of using either a 2 mm or a 8 mm striker when performing dynamic toughness tests at impact loading rates on precracked Charpy specimens. Existing data from tests run in the ductile-to-brittle region (dynamic Master Curve reference temperature) and in the upper shelf regime (ductile initiation fracture toughness and crack resistance curves) have been analyzed. The results show that 2 mm strikers tend to yield lower cleavage fracture toughness in the transition region (although the effect cannot be considered statistically significant), whereas the influence of striker configuration is negligible in the upper shelf regime when data are generated using the low-blow multiple-specimen technique.
The Endocannabinoid 2-Arachidonoylglycerol Is Responsible for the Slow Self-Inhibition in Neocortical Interneurons
Authors: Marinelli Silvia , Pacioni Simone , Bisogno Tiziana , Di Marzo Vincenzo , Prince David A. , Huguenard John R. , Bacci Alberto
Published: December 2008

In the CNS, endocannabinoids are identified mainly as two endogenous lipids: anandamide, the ethanolamide of arachidonic acid, and 2-arachidonoylglycerol (2-AG). Endocannabinoids are known to inhibit transmitter release from presynaptic terminals; however we have recently demonstrated that they are also involved in slow self-inhibition (SSI) of layer V low-threshold spiking (LTS) interneurons in rat somatosensory cortex. SSI is induced by repetitive firing in LTS cells, which can express either cholecystokinin or somatostatin. SSI is triggered by an endocannabinoid-dependent activation of a prolonged somatodendritic K+conductance and associated hyperpolarization in the same cell. The synthesis of both endocannabinoids is dependent on elevated [Ca2+]isuch as occurs during sustained neuronal activity. To establish whether 2-AG mediates autocrine LTS-SSI, we blocked its biosynthesis from phospholipase C (PLC) and diacylglycerol lipases (DAGLs). Current-clamp recordings from LTS interneurons in acute neocortical slices showed that inclusion of DAGL inhibitors in the whole-cell pipette prevented the long-lasting hyperpolarization triggered by LTS cell repetitive firing. Similarly, extracellular applications of a PLC inhibitor prevented SSI in LTS interneurons. Moreover, metabotropic glutamate receptor-dependent activation of PLC produced a long-lasting hyperpolarization which was prevented by the CB1 antagonist AM251, as well as by PLC and DAGL inhibitors. The loss of SSI in the presence of intracellular DAGL blockers confirms that endocannabinoid production occurs in the same interneuron undergoing the persistent hyperpolarization. Since DAGLs produce no endocannabinoid other than 2-AG, these results identify this compound as the autocrine mediator responsible for the postsynaptic slow self-inhibition of neocortical LTS interneurons.
Neural Markers of Inhibition in Human Memory Retrieval
Authors: Wimber Maria , Bäuml Karl-Heinz , Bergström Zara , Markopoulos Gerasimos , Heinze Hans-Jochen , Richardson-Klavehn Alan
Published: December 2008

Retrieving particular information from memory facilitates the later retrieval of that information, but also impairs the later retrieval of related, interfering information. It has been theorized that this retrieval-induced forgetting reflects inhibition of interfering memory representations. We used event-related fMRI to investigate the functional neuroanatomy of this impaired retrieval, at the time the impairment is observed. Neural activity differences between impaired and facilitated information occurred in left ventrolateral prefrontal cortex (VLPFC, BA 45 and 47), precuneus (BA 7), and right inferior parietal lobule (IPL, BA 40). Activity in left anterior VLPFC (BA 47) and left posterior temporal cortex (BA 22), regions implicated in the controlled retrieval of weak semantic memory representations, predicted the degree of retrieval-induced forgetting. In contrast, activity in precuneus and right IPL predicted the degree of retrieval-induced facilitation. Our findings demonstrate that impairment of interfering memories and facilitation of practiced memories involve distinct neural processes, and suggest that the impairment reflects inhibition that weakens interfering memory representations.
Mutation of a TADR Protein Leads to Rhodopsin and Gq-Dependent Retinal Degeneration inDrosophila
Authors: Ni Lina , Guo Peiyi , Reddig Keith , Mitra Mirna , Li Hong-Sheng
Published: December 2008

TheDrosophilaphotoreceptor is a model system for genetic study of retinal degeneration. Many gene mutations cause fly photoreceptor degeneration, either because of excessive stimulation of the visual transduction (phototransduction) cascade, or through apoptotic pathways that in many cases involve a visual arrestin Arr2. Here we report a gene namedtadr(fortornanddiminishedrhabdomeres), which, when mutated, leads to photoreceptor degeneration through a different mechanism. Degeneration in thetadrmutant is characterized by shrunk and disrupted rhabdomeres, the light sensory organelles of photoreceptor. The TADR protein interactedin vitrowith the major light receptor Rh1 rhodopsin, and genetic reduction of the Rh1 level suppressed thetadrmutation-caused degeneration, suggesting the degeneration is Rh1-dependent. Nonetheless, removal of phospholipase C (PLC), a key enzyme in phototransduction, and that of Arr2 failed to inhibit rhabdomeral degeneration in thetadrmutant background. Biochemical analyses revealed that, in thetadrmutant, the Gqprotein of Rh1 is defective in dissociation from the membrane during light stimulation. Importantly, reduction of Gqlevel by introducing a hypomorphic allele ofGαqgene greatly inhibited thetadrdegeneration phenotype. These results may suggest that loss of a potential TADR-Rh1 interaction leads to an abnormality in the Gqsignaling, which in turn triggers rhabdomeral degeneration independent of the PLC phototransduction cascade. We propose that TADR-like proteins may also protect photoreceptors from degeneration in mammals including humans.
Brain-Derived Neurotrophic Factor Signaling Does Not Stimulate Subventricular Zone Neurogenesis in Adult Mice and Rats
Authors: Galvão Rui P. , Garcia-Verdugo José Manuel , Alvarez-Buylla Arturo
Published: December 2008

In rodents, the adult subventricular zone (SVZ) generates neuroblasts which migrate to the olfactory bulb (OB) and differentiate into interneurons. Recent work suggests that the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) can enhance adult SVZ neurogenesis, but the mechanism by which it acts is unknown. Here, we analyzed the role of BDNF and its receptor TrkB in adult SVZ neurogenesis. We found that TrkB is the most prominent neurotrophin receptor in the mouse SVZ, but only the truncated, kinase-negative isoform (TrkB-TR) was detected. TrkB-TR is expressed in SVZ astrocytes and ependymal cells, but not in neuroblasts. TrkB mutants have reduced SVZ proliferation and survival and fewer new OB neurons. To test whether this effect is cell-autonomous, we grafted SVZ cells from TrkB knock-out mice (TrkB-KO) into the SVZ of wild-type mice (WT). Grafted progenitors generated neuroblasts that migrated to the OB in the absence of TrkB. The survival and differentiation of granular interneurons and Calbindin+periglomerular interneurons seemed unaffected by the loss of TrkB, whereas dopaminergic periglomerular neurons were reduced. Intra-ventricular infusion of BDNF yielded different results depending on the animal species, having no effect on neuron production from mouse SVZ, while decreasing it in rats. Interestingly, mice and rats also differ in their expression of the neurotrophin receptor p75. Our results indicate that TrkB is not essential for adult SVZ neurogenesis and do not support the current view that delivering BDNF to the SVZ can enhance adult neurogenesis.
Potential Network Mechanisms Mediating Electroencephalographic Beta Rhythm Changes during Propofol-Induced Paradoxical Excitation
Authors: McCarthy Michelle M. , Brown Emery N. , Kopell Nancy
Published: December 2008

Propofol, like most general anesthetic drugs, can induce both behavioral and electroencephalographic (EEG) manifestations of excitation, rather than sedation, at low doses. Neuronal excitation is unexpected in the presence of this GABAA-potentiating drug. We construct a series of network models to understand this paradox. Individual neurons have ion channel conductances with Hodgkin–Huxley-type formulations. Propofol increases the maximal conductance and time constant of decay of the synaptic GABAAcurrent. Networks range in size from 2 to 230 neurons. Population output is measured as a function of pyramidal cell activity, with the electroencephalogram approximated by the sum of population AMPA activity between pyramidal cells.

These model networks suggest propofol-induced paradoxical excitation may result from a membrane level interaction between the GABAAcurrent and an intrinsic membrane slow potassium current (M-current). This membrane level interaction has consequences at the level of multicellular networks enabling a switch from baseline interneuron synchrony to propofol-induced interneuron antisynchrony. Large network models reproduce the clinical EEG changes characteristic of propofol-induced paradoxical excitation. The EEG changes coincide with the emergence of antisynchronous interneuron clusters in the model networks. Our findings suggest interneuron antisynchrony as a potential network mechanism underlying the generation of propofol-induced paradoxical excitation. As correlates of behavioral phenomenology, these networks may refine our understanding of the specific behavioral states associated with general anesthesia.
Monitoring FoxO1 Localization in Chemically Identified Neurons
Authors: Fukuda Makoto , Jones Juli E. , Olson David , Hill Jennifer , Lee Charlotte E. , Gautron Laurent , Choi Michelle , Zigman Jeffrey M. , Lowell Bradford B. , Elmquist Joel K.
Published: December 2008

The PI3K-Akt-FoxO1 pathway contributes to the actions of insulin and leptin in several cell types, including neurons in the CNS. However, identifying these actions in chemically identified neurons has proven difficult. To address this problem, we have developed a reporter mouse for monitoring PI3K-Akt signaling in specific populations of neurons, based on FoxO1 nucleocytoplasmic shuttling. The reporter, FoxO1 fused to green fluorescent protein (FoxO1GFP), is expressed under the control of a ubiquitous promoter that is silenced by a loxP flanked transcriptional blocker. Thus, the expression of the reporter in selected cells is dependent on the action ofCrerecombinase. Using this model, we found that insulin treatment resulted in the nuclear exclusion of FoxO1GFP within POMC and AgRP neurons in a dose- and time-dependent manner. FoxO1GFP nuclear exclusion was also observed in POMC neurons followingin vivoadministration of insulin. In addition, leptin induced transient nuclear export of FoxO1GFP in POMC neurons in a dose dependent manner. Finally, insulin-induced nuclear export was impaired in POMC neurons by pretreatment with free fatty acids, a paradigm known to induce insulin resistance in peripheral insulin target tissues. Thus, ourFoxO1GFPmouse provides a tool for monitoring the status of PI3K-Akt signaling in a cell-specific manner under physiological and pathophysiological conditions.
NMDA Receptor Gating of Information Flow through the StriatumIn Vivo
Authors: Pomata Pablo E. , Belluscio Mariano A. , Riquelme Luis A. , Murer M. Gustavo
Published: December 2008

A role of NMDA receptors in corticostriatal synaptic plasticity is widely acknowledged. However, the conditions that allow NMDA receptor activation in the striatumin vivoremain obscure. Here we show that NMDA receptors contribute to sustain the membrane potential of striatal medium spiny projection neurons close to threshold during spontaneous UP statesin vivo. Moreover, we found that the blockade of striatal NMDA receptors reduces markedly the spontaneous firing of ensembles of medium spiny neurons during slow waves in urethane-anesthetized rats. We speculate that recurrent activation of NMDA receptors during UP states allows off-line information flow through the striatum and system level consolidation during habit formation.
Stimulus-Timing-Dependent Plasticity of Cortical Frequency Representation
Authors: Dahmen Johannes C. , Hartley Douglas E. H. , King Andrew J.
Published: December 2008

Adult cortical circuits possess considerable plasticity, which can be induced by modifying their inputs. One mechanism proposed to underlie changes in neuronal responses is spike-timing-dependent plasticity (STDP), an up- or downregulation of synaptic efficacy contingent upon the order and timing of presynaptic and postsynaptic activity. The repetitive and asynchronous pairing of a sensory stimulus with either another sensory stimulus or current injection can alter the response properties of visual and somatosensory neurons in a manner consistent with STDP. To examine whether such plasticity also exists in the auditory system, we recorded from neurons in the primary auditory cortex of anesthetized and awake adult ferrets. The repetitive pairing of pure tones of different frequencies induced shifts in neuronal frequency selectivity, which exhibited a temporal specificity akin to STDP. Only pairs with stimulus onset asynchronies of 8 or 12 ms were effective and the direction of the shifts depended upon the order in which the tones within a pair were presented. Six hundred stimulus pairs (lasting ∼70 s) were enough to produce a significant shift in frequency tuning and the changes persisted for several minutes. The magnitude of the observed shifts was largest when the frequency separation of the conditioning stimuli was < ∼1 octave. Moreover, significant shifts were found only in the upper cortical layers. Our findings highlight the importance of millisecond-scale timing of sensory input in shaping neural function and strongly suggest STDP as a relevant mechanism for plasticity in the mature auditory system.
Raised serum TSH levels in patients with morbid obesity: is it enough to diagnose subclinical hypothyroidism?
Authors: Rotondi Mario , Leporati Paola , La Manna Antonella , Pirali Barbara , Mondello Teresa , Fonte Rodolfo , Magri Flavia , Chiovato Luca
Published: December 2008

Objective

Morbid obesity (body mass index (BMI)≥40 kg/m2) is associated with thyroid function disturbances, with a high rate of subclinical hypothyroidism (SH) being the most consistently reported. We evaluated the circulating thyroid function parameters in morbid obese patients and related the results to the presence of circulating thyroid antibodies (Thyr-Ab).

Design and methods

Morbid obese patients were consecutively enrolled (n=350). Two control groups were used: control group (CG)1, healthy normo-weight subjects (n=50); CG2, normo-weight patients with SH (n=56) matched for TSH with the obese patients with SH. Serum levels of free triiodothyronine (FT3), free thyroxine (FT4), TSH, antithyroglobulin antibodies, and antithyroperoxidase antibodies were measured in all patients.

Results

i) Compared with CG1, obese patients having thyroid function parameters in the normal range and negative Thyr-Ab showed significantly higher serum TSH and lower free thyroid hormones levels, but a similar FT4/FT3 ratio; ii) SH was recorded in 13.7% obese patients; iii) compared with CG2, obese patients with untreated SH had a significantly lower rate of positive Thyr-Ab (32.1 vs 66.1%; P<0.005); iv) no gender prevalence was observed in SH obese patients with negative Thyr-Ab; and v) the comparison of the untreated SH patients (obese and normo-weight) with CG1 demonstrated that in SH obese subjects, unlike normo-weight SH patients, the FT3 levels were significantly lower. This resulted in a normal FT4/FT3 ratio in SH obese patients.

Conclusion

Thyroid autoimmunity is not a major cause sustaining the high rate of SH in morbid obese patients. In these patients, the diagnosis of SH itself, as assessed by a raised TSH alone, appears questionable.
Identification and functional characterization of loss-of-function mutations of the calcium-sensing receptor in four Italian kindreds with familial hypocalciuric hypercalcemia
Authors: Cetani Filomena , Lemmi Monica , Cervia Davide , Borsari Simona , Cianferotti Luisella , Pardi Elena , Ambrogini Elena , Banti Chiara , Brown Edward M , Bagnoli Paola , Pinchera Aldo , Marcocci Claudio
Published: December 2008

Objective

Identification and characterization of calcium-sensing receptor (CASR) mutations in four unrelated Italian kindreds with familial hypocalciuric hypercalcemia.

Design

Clinical evaluation and genetic analysis ofCASRgene. Functional characterization of mutatedCASRs.

Methods

Direct sequencing ofCASRgene in genomic DNA. Studies ofCASR-mediated increases in cytosolic calcium concentration [Ca2+]iinCASR-transfected COS-7 cellsin vitro.

Results

Four unreported heterozygousCASRmutations were identified, including three missense (H595Y, P748H, and C765W) and one splice site (IVS2+1G>C) mutation. The H595Y, P748H, and C765W mutant receptors, although expressed at normal levels on the cell surface, showed a reduced response in [Ca2+]irelative to the wildtype (WT)CASRto increasing extracellular calcium concentrations. Cotransfection experiments showed that the H595Y and P748H mutants did not affect the apparent affinity of the WTCASRfor calcium, suggesting that they do not exert a dominant-negative effect. On the other hand, the co-transfected C765W mutant decreased the maximum response of the WTCASRto calcium, suggesting that it may reduce the effective concentration of the normalCASRon the cell surface or impair its maximal signaling capacity.

Conclusions

FourCASRmutations were identified. The reduced functional responses to extracellular calcium and normal expression of the mutant receptors suggest that conformational changes account for alteredCASRactivity. Moreover, a reduced complement of normalCASRsin these heterozygous patients, perhaps combined with a mutant receptor-induced decrease in maximal activity of the WT receptor, may contribute to defective calcium-sensingin vivo.
The early diagnosis and differential diagnosis of Alzheimer’s disease with clinical methods
Authors: Égerházi Anikó
Published: December 2008

Az Alzheimer-dementia progresszív neurodegeneratív betegség, amelynek progresszióját a jelenleg alkalmazott kezelések a betegség korai szakaszában lassíthatják. Vizsgálatainkkal olyan biológiai markereket kerestünk, amelyek érzékenyek a betegség prodromalis és korai szakaszában. A diagnosztikai rutinvizsgálatok mellett neuropszichológiai tesztet, auditoros kiváltottválasz-vizsgálatot és speciális laboratóriumi teszteket végeztünk Alzheimer-betegségben, vascularis dementiában, enyhe kognitív zavarban és depresszióban egészséges kontrollhoz hasonlítva. A párosított asszociációs tanulás mindegyik betegcsoportban kóros volt, depresszióban reverzíbilisnek látszott. Az auditoros kiváltott P300 komponens latenciája enyhe kognitív zavarban és dementiában megnőtt. A szérumban a paraoxonázaktivitás csökkent, az agy-gerincvelői folyadékban az Nε(γ-glutamil)lizin-izodipeptid koncentrációja emelkedett mindkét dementiacsoportban. Enyhe kognitív zavarban a párosított asszociációs tanulási teszt és a P300 jellegzetes változása az Alzheimer-dementia kialakulásának nagyobb kockázatát jelzi. A paraoxonázaktivitás és az izodipeptidkoncentráció változása érzékeny marker lehet a neurodegeneratív kórfolyamatok kimutatására. Az említett vizsgálatok együttes alkalmazása segítséget nyújthat az Alzheimer-dementia korai felismerésében és előrejelzésében.
Reverse Takotsubo syndrome pattern induced by local anaesthesia
Authors: Tomcsányi János , Arabadzisz Hrisula , Frész Tamás , Sármán Balázs , Bózsik Béla , Zsoldos András , Simor Tamás
Published: December 2008

A szerzők a stressz-cardiomyopathiának, vagy más néven Takotsubo-szindrómának egy új megjelenési formáját ismertetik. Míg a klasszikus Takotsubo-szindróma esetén a szívcsúcs dilatációjának reverzíbilis volta figyelhető meg, a reverz Takotsubo-szindróma esetén pont fordítva, a bazális szegmensek reverzíbilis dilatációja és az apex hiperkinetikus mozgása látható. A reverz Takotsubo-jelenséget egy 36 éves nőbetegnél láttuk, akinél fülplasztikai műtét kapcsán tonogen-lidocainos lokális injekció váltotta ki a panaszokat és tüneteket. A tartós mellkasi fájdalom, EKG-eltérés és troponinpozitivitás hátterében coronariabetegség nem volt, az echokardiográfia a bal kamra bazális szegmenseinek akynesisét és az apex hyperkinesisét mutatta. A falmozgászavarok 3 nap alatt megszűntek.