bluuebunny/crossref_metadata_2025 huggingface dataset:
Cortical Regions Involved in the Generation of Musical Structures during Improvisation in Pianists
Authors: Bengtsson Sara L. , Csíkszentmihályi Mihály , Ullén Fredrik
Published: May 2007

Studies on simple pseudorandom motor and cognitive tasks have shown that the dorsolateral prefrontal cortex and rostral premotor areas are involved in free response selection. We used functional magnetic resonance imaging to investigate whether these brain regions are also involved in free generation of responses in a more complex creative behavior: musical improvisation. Eleven professional pianists participated in the study. In one condition, Improvise, the pianist improvised on the basis of a visually displayed melody. In the control condition, Reproduce, the participant reproduced his previous improvisation from memory. Participants were able to reproduce their improvisations with a high level of accuracy, and the contrast Improvise versus Reproduce was thus essentially matched in terms of motor output and sensory feedback. However, the Improvise condition required storage in memory of the improvisation. We therefore also included a condition FreeImp, where the pianist improvised but was instructed not to memorize his performance. To locate brain regions involved in musical creation, we investigated the activations in the Improvise-Reproduce contrast that were also present in FreeImp contrasted with a baseline rest condition. Activated brain regions included the right dorsolateral prefrontal cortex, the presupplementary motor area, the rostral portion of the dorsal premotor cortex, and the left posterior part of the superior temporal gyrus. We suggest that these regions are part of a network involved in musical creation, and discuss their possible functional roles.
Comprehending Prehending: Neural Correlates of Processing Verbs with Motor Stems
Authors: Rüschemeyer Shirley-Ann , Brass Marcel , Friederici Angela D.
Published: May 2007

The interaction between language and action systems has become an increasingly interesting topic of discussion in cognitive neuroscience. Several recent studies have shown that processing of action verbs elicits activation in the cerebral motor system in a somatotopic manner. The current study extends these findings to show that the brain responses for processing of verbs with specific motor meanings differ not only from that of other motor verbs, but, crucially, that the comprehension of verbs with motor meanings (i.e., greifen, to grasp) differs fundamentally from the processing of verbs with abstract meanings (i.e., denken, to think). Second, the current study investigated the neural correlates of processing morphologically complex verbs with abstract meanings built on stems with motor versus abstract meanings (i.e., begreifen, to comprehend vs. bedenken, to consider). Although residual effects of motor stem meaning might have been expected, we see no evidence for this in our data. Processing of morphologically complex verbs built on motor stems showed no differences in involvement of the motor system when compared with processing complex verbs with abstract stems. Complex verbs built on motor stems did show increased activation compared with complex verbs built on abstract stems in the right posterior temporal cortex. This result is discussed in light of the involvement of the right temporal cortex in comprehension of metaphoric or figurative language.
ERP Evidence of Morphological Analysis from Orthography: A Masked Priming Study
Authors: Lavric Aureliu , Clapp Amanda , Rastle Kathleen
Published: May 2007

There is broad consensus that the visual word recognition system is sensitive to morphological structure (e.g., “hunter” = “hunt” + “er”). Moreover, it has been assumed that the analysis of morphologically complex words (e.g., “hunter”) occurs only if the meaning of the complex form can be derived from the meanings of its constituents (e.g., “hunt” and “er”). However, recent behavioral work using masked priming has suggested that morphological analysis can occur at an early, orthographic level, with little influence from semantics. The present investigation examined the neurophysiological correlates of masked priming in conditions of a genuine morphological relationship (e.g., “hunter”-“HUNT”), an apparent morphological relationship (“corner”-“CORN”), and no morphological relationship (“brothel”-“BROTH”). Neural priming was indexed by the reduction of the N400 ERP component associated with targets preceded by related primes, as compared to targets preceded by unrelated primes. The mere appearance of morphological structure (“corner”-“CORN”) resulted in robust behavioral and neural priming, whose magnitude was similar to that observed in pairs with genuine morphological relationship and greater than that in the nonmorphological pairs. The results support a purely structural morphemic segmentation procedure operating in the early stages of visual word perception.
From Stereotype Threat to Stereotype Threats: Implications of a Multi-Threat Framework for Causes, Moderators, Mediators, Consequences, and Interventions
Authors: Shapiro Jenessa R. , Neuberg Steven L.
Published: May 2007

More than 100 articles have examined the construct of stereotype threat and its implications. However, stereotype threat seems to mean different things to different researchers and has been employed to describe and explain processes and phenomena that appear to be fundamentally distinct. Complementing existing models, the authors posit a Multi-Threat Framework in which six qualitatively distinct stereotype threats arise from the intersection of two dimensions—the target of the threat (the self/one's group) and the source of the threat (the self/outgroup others/ingroup others). The authors propose that these threats constitute the core of the broader stereotype threat construct and provide the foundation for understanding additional, as of yet uncharacterized, stereotype threats. The proposed threats likely differentially peril those with different stigmatizable characteristics, have different eliciting conditions and moderators, are mediated by somewhat different processes, are coped with and compensated for in different ways, and require different interventions to overcome.
How Emotion Shapes Behavior: Feedback, Anticipation, and Reflection, Rather Than Direct Causation
Authors: Baumeister Roy F. , Vohs Kathleen D. , Nathan DeWall C. , Liqing Zhang
Published: May 2007

Fear causes fleeing and thereby saves lives: this exemplifies a popular and common sense but increasingly untenable view that the direct causation of behavior is the primary function of emotion. Instead, the authors develop a theory of emotion as a feedback system whose influence on behavior is typically indirect. By providing feedback and stimulating retrospective appraisal of actions, conscious emotional states can promote learning and alter guidelines for future behavior. Behavior may also be chosen to pursue (or avoid) anticipated emotional outcomes. Rapid, automatic affective responses, in contrast to the full-blown conscious emotions, may inform cognition and behavioral choice and thereby help guide current behavior. The automatic affective responses may also remind the person of past emotional outcomes and provide useful guides as to what emotional outcomes may be anticipated in the present. To justify replacing the direct causation model with the feedback model, the authors review a large body of empirical findings.
Nutrition Review: Relationships of Nutrition With Depression and Anxiety
Authors: Melanson Kathleen J.
Published: May 2007

Although research on relationships of nutrition with depression and anxiety is very limited, both biological plausibility and existing empirical evidence lend strong support to causal links, especially between diet and depression. Clinical deficiencies of several vitamins and minerals result in depression. Nutrients that have received particular attention with relation to depression include omega-3 fatty acids, folate, cobalamin, and zinc. Antioxidant nutrients are other potentially beneficial dietary factors that should be investigated. Body weight issues may be related to depression and anxiety in very complex ways. Dietary strategies to prevent and treat depression are inexpensive and low risk and therefore warrant consideration in future research and clinical applications.
Clinicians' Corner: A Lifestyle Medicine
Authors: Greenstone Clinton L.
Published: May 2007

Anxiety and depression are the 2 leading mental health conditions seen in primary care. They are often underdiagnosed and undertreated in this setting. Primary care physicians must adopt tools and methods of identifying these patients. Office support staff and electronic medical records with reminder systems are helpful in implementing screening and early counseling. Lifestyle medicine approaches to these common conditions are also overlooked as effective primary and adjunctive therapies. Promoting a basic “health formula” (regular physical activity, proper diet, and emotion balance [stress management]) for all of our patients has important implications for not only heart disease and diabetes prevention and treatment, but it also supports treatment for common mental health problems.
Pharmacy Review: Lifestyle Approaches to Anxiety and Depression
Authors: Prevost Rebecca R.
Published: May 2007

Medication is usually the first option of choice for treatment of anxiety and depression. However, the emerging body of evidenced-based research on lifestyle measures to prevent or treat anxiety and depression deserves consideration in all patients. Ways that pharmacists can support lifestyle modification for individuals with anxiety or depressive disorders include the use of screening tools, counseling using open-ended interview techniques, and being aware of reasons people are seeking over-the-counter self-care. Ensuring safe use of prescribed medications and avoiding alcohol or other negatively interacting supplements are other ways. Objective counseling on quantities/ amounts of exercise and proper nutrition and smoking cessation should also be included. Finally, encouraging a healthy environment and outlook is in order. Because mental health disorders affect every aspect of an individual's life, whole-person health measures are vital for overall success.
Physical Activity: Depression, Anxiety, Physical Activity, and Cardiovascular Disease: What's the Connection?
Authors: Zoeller Robert F.
Published: May 2007

Depression and anxiety are major public health problems and have been shown to be associated with increased risk for cardiovascular disease. The prevalence and incidence of depression and anxiety are lower in those who are regularly active. Regular physical activity has also been shown to reduce symptoms of depression and anxiety in those who already suffer from these disorders. Depression and anxiety may increase the risk for cardiovascular disease by a number of mechanisms, including hypertension and reduced vascular function, autonomic nervous system dysfunction, and increased platelet activity and aggregation. Regular physical activity has been demonstrated to lower blood pressure and improve nitric oxide— mediated vascular function, increase heart rate variability and baroreflex sensitivity, increase fibrinolysis, and, possibly, decrease platelet activity. Little or no work has been done to determine the optimal amount or intensity of exercise to prevent or reduce the symptoms of depression and anxiety. Based on the limited data available, a physical activity routine consistent with the 1996 Surgeon General's Report on Physical Activity and Health is appropriate—specifically, at least 30 minutes of moderate-intensity activity on most days, if not every day, of the week. Little evidence supports a dose-response relation between physical activity and depression or any of the physiological mechanisms discussed here. This is not to say that there is no such relationship but, rather, that well-controlled studies are lacking. Studies on anxiety, especially, are lacking. This includes the link with cardiovascular disease, physiological mechanisms, and the effects of regular physical activity.
SNAP-23 and syntaxin-2 localize to the extracellular surface of the platelet plasma membrane
Authors: Flaumenhaft Robert , Rozenvayn Nataliya , Feng Dian , Dvorak Ann M.
Published: May 2007

SNARE proteins direct membrane fusion events required for platelet granule secretion. These proteins are oriented in cell membranes such that most of the protein resides in a cytosolic compartment. Evaluation of SNARE protein localization in activated platelets using immunonanogold staining and electron microscopy, however, demonstrated expression of SNAP-23 and syntaxin-2 on the extracellular surface of the platelet plasma membrane. Flow cytometry of intact platelets confirmed trypsin-sensitive SNAP-23 and syntaxin-2 localization to the extracellular surface of the plasma membrane. Acyl-protein thioesterase 1 and botulinum toxin C light chain released SNAP-23 and syntaxin-2, respectively, from the surface of intact platelets. When resting platelets were incubated with both acyl-protein thioesterase 1 and botulinum toxin C light chain, a complex that included both SNAP-23 and syntaxin-2 was detected in supernatants, indicating that extracellular SNARE proteins retain their ability to bind one another. These observations represent the first description of SNARE proteins on the extracellular surface of a cell.
The human counterpart of zebrafish shiraz shows sideroblastic-like microcytic anemia and iron overload
Authors: Camaschella Clara , Campanella Alessandro , De Falco Luigia , Boschetto Loredana , Merlini Roberta , Silvestri Laura , Levi Sonia , Iolascon Achille
Published: May 2007

Inherited microcytic-hypochromic anemias in rodents and zebrafish suggest the existence of corresponding human disorders. The zebrafish mutant shiraz has severe anemia and is embryonically lethal because of glutaredoxin 5 (GRLX5) deletion, insufficient biogenesis of mitochondrial iron-sulfur (Fe/S) clusters, and deregulated iron-regulatory protein 1 (IRP1) activity. This leads to stabilization of transferrin receptor 1 (TfR) RNA, repression of ferritin, and ALA-synthase 2 (ALAS2) translation with impaired heme synthesis. We report the first case of GLRX5 deficiency in a middle-aged anemic male with iron overload and a low number of ringed sideroblasts. Anemia was worsened by blood transfusions but partially reversed by iron chelation. The patient had a homozygous (c.294A>G) mutation that interferes with intron 1 splicing and drastically reduces GLRX5 RNA. As in shiraz, aconitase and H-ferritin levels were low and TfR level was high in the patient's cells, compatible with increased IRP1 binding. Based on the biochemical and clinical phenotype, we hypothesize that IRP2, less degraded by low heme, contributes to the repression of the erythroblasts ferritin and ALAS2, increasing mitochondrial iron. Iron chelation, redistributing iron to the cytosol, might relieve IRP2 excess, improving heme synthesis and anemia. GLRX5 function is highly conserved, but at variance with zebrafish, its defect in humans leads to anemia and iron overload.
Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia
Authors: Dicker Frank , Haferlach Claudia , Kern Wolfgang , Haferlach Torsten , Schnittger Susanne
Published: May 2007

AML1/RUNX1 is implicated in leukemogenesis on the basis of the AML1-ETO fusion transcript as well as somatic mutations in its DNA-binding domain. Somatic mutations in RUNX1 are preferentially detected in acute myeloid leukemia (AML) M0, myeloid malignancies with acquired trisomy 21, and certain myelodysplastic syndrome (MDS) cases. By correlating the presence of RUNX1 mutations with cytogenetic and molecular aberration in a large cohort of AML M0 (N = 90) at diagnosis, we detected RUNX1 mutations in 46% of cases, with all trisomy 13 cases (n = 18) being affected. No mutations of NRAS or KIT were detected in the RUNX1-mutated group and FLT3 mutations were equally distributed between RUNX1-mutated and unmutated samples. Likewise, a high incidence of RUNX1 mutations (80%) was detected in cases with trisomy 13 from other French-American-British (FAB) subgroups (n = 20). As FLT3 is localized on chromosome 13, we hypothesized that RUNX1 mutations might cooperate with trisomy 13 in leukemogenesis by increasing FLT3 transcript levels. Quantitation of FLT3 transcript levels revealed a highly significant (P < .001) about 5-fold increase in AML with RUNX1 mutations and trisomy 13 compared with samples without trisomy 13. The results of the present study indicate that in the absence of FLT3 mutations, FLT3 overexpression might be a mechanism for FLT3 activation, which cooperates with RUNX1 mutations in leukemogenesis.
primetv: a viewer for reconciled trees
Authors: Sennblad Bengt , Schreil Eva , Berglund Sonnhammer Ann-Charlotte , Lagergren Jens , Arvestad Lars
Published: May 2007

Background

Evolutionary processes, such as gene family evolution or parasite-host co-speciation, can often be viewed as a tree evolving inside another tree. Relating two given trees under such a constraint is known as reconciling them. Adequate software tools for generating illustrations of tree reconciliations are instrumental for presenting and communicating results and ideas regarding these phenomena. Available visualization tools have been limited to illustrations of the most parsimonious reconciliation. However, there exists a plethora of biologically relevant non-parsimonious reconciliations. Illustrations of these general reconciliations may not be achieved without manual editing.

Results

We have developed a new reconciliation viewer, primetv. It is a simple and compact visualization program that is the first automatic tool for illustrating general tree reconciliations. It reads reconciled trees in an extended Newick format and outputs them as tree-within-tree illustrations in a range of graphic formats. Output attributes, such as colors and layout, can easily be adjusted by the user. To enhance the construction of input to primetv, two helper programs, readReconciliation and reconcile, accompany primetv. Detailed examples of all programs' usage are provided in the text. For the casual user a web-service provides a simple user interface to all programs.

Conclusion

With primetv, the first visualization tool for general reconciliations, illustrations of trees-within-trees are easy to produce. Because it clarifies and accentuates an underlying structure in a reconciled tree, e.g., the impact of a species tree on a gene-family phylogeny, it will enhance scientific presentations as well as pedagogic illustrations in an educational setting. primetv is available at http://prime.sbc.su.se/primetv, both as a standalone command-line tool and as a web service. The software is distributed under the GNU General Public License.
Quantitative analysis of Hedgehog gradient formation using an inducible expression system
Authors: Su Vivian F , Jones Kelly A , Brodsky Michael , The Inge
Published: May 2007

Background

The Hedgehog (Hh) family of secreted growth factors are morphogens that act in development to direct growth and patterning. Mutations in human Hh and other Hh pathway components have been linked to human diseases. Analysis of Hh distribution during development indicates that cholesterol modification and receptor mediated endocytosis affect the range of Hh signaling and the cellular localization of Hh.

Results

We have used an inducible, cell type-specific expression system to characterize the three-dimensional distribution of newly synthesized, GFP-tagged Hh in the developing Drosophila wing. Following induction of Hh-GFP expression in posterior producing cells, punctate structures containing Hh-GFP were observed in the anterior target cells. The distance of these particles from the expressing cells was quantified to determine the shape of the Hh gradient at different time points following induction. The majority of cholesterol-modified Hh-GFP was found associated with cells near the anterior/posterior (A/P) boundary, which express high levels of Hh target genes. Without cholesterol, the Hh gradient was flatter, with a lower percentage of particles near the source and a greater maximum distance. Inhibition of Dynamin-dependent endocytosis blocked formation of intracellular Hh particles, but did not prevent movement of newly synthesized Hh to the apical or basolateral surfaces of target cells. In the absence of both cholesterol and endocytosis, Hh particles accumulated in the extracellular space. Staining for the Hh receptor Ptc revealed four categories of Hh particles: cytoplasmic with and without Ptc, and cell surface with and without Ptc. Interestingly, mainly cholesterol-modified Hh is detected in the cytoplasmic particles lacking Ptc.

Conclusion

We have developed a system to quantitatively analyze Hh distribution during gradient formation. We directly demonstrate that inhibition of Dynamin-dependent endocytosis is not required for movement of Hh across target cells, indicating that transcytosis is not required for Hh gradient formation. The localization of Hh in these cells suggests that Hh normally moves across both apical and basolateral regions of the target cells. We also conclude that cholesterol modification is required for formation of a specific subset of Hh particles that are both cytoplasmic and not associated with the receptor Ptc.
Auxin and nitric oxide control indeterminate nodule formation
Authors: Pii Youry , Crimi Massimo , Cremonese Giorgia , Spena Angelo , Pandolfini Tiziana
Published: May 2007

Background

Rhizobia symbionts elicit root nodule formation in leguminous plants. Nodule development requires local accumulation of auxin. Both plants and rhizobia synthesise auxin. We have addressed the effects of bacterial auxin (IAA) on nodulation by using Sinorhizobium meliloti and Rhizobium leguminosarum bacteria genetically engineered for increased auxin synthesis.

Results

IAA-overproducing S. meliloti increased nodulation in Medicago species, whilst the increased auxin synthesis of R. leguminosarum had no effect on nodulation in Phaseolus vulgaris, a legume bearing determinate nodules. Indeterminate legumes (Medicago species) bearing IAA-overproducing nodules showed an enhanced lateral root development, a process known to be regulated by both IAA and nitric oxide (NO). Higher NO levels were detected in indeterminate nodules of Medicago plants formed by the IAA-overproducing rhizobia. The specific NO scavenger cPTIO markedly reduced nodulation induced by wild type and IAA-overproducing strains.

Conclusion

The data hereby presented demonstrate that auxin synthesised by rhizobia and nitric oxide positively affect indeterminate nodule formation and, together with the observation of increased expression of an auxin efflux carrier in roots bearing nodules with higher IAA and NO content, support a model of nodule formation that involves auxin transport regulation and NO synthesis.
Marital status and mortality among Japanese men and women: the Japan Collaborative Cohort Study
Authors: Ikeda Ai , Iso Hiroyasu , Toyoshima Hideaki , Fujino Yoshihisa , Mizoue Tetsuya , Yoshimura Takesumi , Inaba Yutaka , Tamakoshi Akiko ,   JACC Study Group
Published: May 2007

Background

Several studies have indicated a significant association between marital status and mortality risks. However, most of these studies have compared married and unmarried people without differentiating among single, divorced and widowed status. Moreover, gender differences in mortality rates associated with marital status have not been sufficiently clarified. With significant increases in the percentages of divorced and widowed people and a corresponding drop in the marriage rate in Japan during the past two or three decades, it can be expected that these changes will have a significant impact on mortality rates.

Methods

This investigation used a prospective study of a total of 94,062 Japanese men and women aged 40–79 who completed self-administered questionnaires at baseline and during a followed-up of 9.9-years.

Results

Compared with married men, never-married men showed higher risks of mortality from cardiovascular disease [relative risk (RR) = 3.05, 95% confidence interval (CI) 2.03–4.60], respiratory disease (RR = 2.43, 95%CI 1.27–4.63), external causes (RR = 2.18, 95%CI 1.05–4.54) and all causes (RR = 1.91, 95%CI 1.51–2.42) after adjustment for potentially confounding variables. For never-married women, there was a smaller but significantly higher risk of mortality from all causes (RR = 1.46, 95%CI 1.15–1.84). Divorced and widowed men showed moderately higher risks of mortality from cardiovascular disease, external causes and all causes compared with married men, but such a trend was not observed in women.

Conclusion

Single status was associated with a higher risk of mortality than was married status for both men and women. Divorce and widowhood were associated with elevated risk for men, but not for women. These findings suggest single, divorce and widowhood status constitute potentially adverse health effects.
Hospitalisations at the end of life: using a sentinel surveillance network to study hospital use and associated patient, disease and healthcare factors
Authors: Van den Block Lieve , Deschepper Reginald , Drieskens Katrien , Bauwens Sabien , Bilsen Johan , Bossuyt Nathalie , Deliens Luc
Published: May 2007

Background

Hospital deaths following several hospital admissions or long hospital stays may be indicative of a low quality of dying. Although place of death has been extensively investigated at population level, hospital use in the last months of life and its determinants have been studied less often, especially in Europe and with a general end-of-life patient population. In this study we aim to describe hospital use in the last three months of life in Belgium and identify associated patient, disease and healthcare factors.

Methods

We conducted a retrospective registration study (13 weeks in 2004) with the Belgian Sentinel Network of General Practitioners, an epidemiological surveillance system representative of all GPs in Belgium, covering 1.75% of the total Belgian patient population. All registered non-sudden or expected deaths of patients (aged one year or older) at the GPs' practices were included. Bivariate and regression analyses were performed.

Results

The response rate was 87%. The GPs registered 319 deaths that met inclusion criteria. Sixty percent had been hospitalised at least once in the last three months of life, for a median of 19 days. The percentage of patients hospitalised increased exponentially in the last weeks before death; one fifth was admitted in the final week of life. Seventy-two percent of patients hospitalised at least once in the final three months died in hospital. A palliative treatment goal, death from cardiovascular diseases, the expression of a wish to die in an elderly home and palliative care delivery by the GP were associated with lower hospitalisation odds.

Conclusion

Hospital care plays a large role in the end of patients' lives in Belgium, especially in the final weeks of life. The result is a high rate of hospital deaths, showing the institutionalised nature of dying. Patients' clinical conditions, the expression of preferences and also healthcare characteristics such as being treated as a palliative care patient, seem to be associated with hospital transfers. It is recommended that hospitalisation decisions are only made after careful consideration. Short admissions in the final days of life should be prevented in order to make dying at home more feasible.
Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE
Authors: Eltayeb Sana , Berg Anna-Lena , Lassmann Hans , Wallström Erik , Nilsson Maria , Olsson Tomas , Ericsson-Dahlstrand Anders , Sunnemark Dan
Published: May 2007

Background

The CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.

Methods

The expression of CCR1, CCR2 and CCR5 mRNA was studied within situhybridization using radio labelled cRNA probes in combination with immunohistochemical staining for phenotypic cell markers. Spinal cord sections from healthy rats and rats with MOG-EAE (acute phase, remission phase, relapse phase) were analysed. In defined lesion stages, the number of cells expressing CCR1, CCR2 and CCR5 mRNA was determined. Data were statistically analysed by the nonparametric Mann-Whitney U test.

Results

In MOG-EAE rats, extensive up-regulation of CCR1 and CCR5 mRNA, and moderate up-regulation of CCR2 mRNA, was found in the spinal cord during episodes of active inflammation and demyelination. Double staining with phenotypic cell markers identified the chemokine receptor mRNA-expressing cells as macrophages/microglia. Expression of all three receptors was substantially reduced during clinical remission, coinciding with diminished inflammation and demyelination in the spinal cord. Healthy control rats did not show any detectable expression of CCR1, CCR2 or CCR5 mRNA in the spinal cord.

Conclusion

Our results demonstrate that the acute and chronic-relapsing phases of MOG-EAE are associated with distinct expression of CCR1, CCR2, and CCR5 mRNA by cells of the macrophage/microglia lineage within the CNS lesions. These data support the notion that CCR1, CCR2 and CCR5 mediate recruitment of both infiltrating macrophages and resident microglia to sites of CNS inflammation. Detailed knowledge of expression patterns is crucial for the understanding of therapeutic modulation and the validation of CCR1, CCR2 and CCR5 as feasible targets for therapeutic intervention in MS.
Surgical Complications Associated With Sentinel Lymph Node Dissection (SLND) Plus Axillary Lymph Node Dissection Compared With SLND Alone in the American College of Surgeons Oncology Group Trial Z0011
Authors: Lucci Anthony , McCall Linda Mackie , Beitsch Peter D. , Whitworth Patrick W. , Reintgen Douglas S. , Blumencranz Peter W. , Leitch A. Marilyn , Saha Sukumal , Hunt Kelly K. , Giuliano Armando E.
Published: May 2007

Purpose

The American College of Surgeons Oncology Group trial Z0011 was a prospective, randomized, multicenter trial comparing overall survival between patients with positive sentinel lymph nodes (SLNs) who did and did not undergo axillary lymph node dissection (ALND). The current study compares complications associated with SLN dissection (SLND) plus ALND, versus SLND alone.

Patients and Methods

From May 1999 to December 2004, 891 patients were randomly assigned to SLND + ALND (n = 445) or SLND alone (n = 446). Information on wound infection, axillary seroma, paresthesia, brachial plexus injury (BPI), and lymphedema was available for 821 patients.

Results

Adverse surgical effects were reported in 70% (278 of 399) of patients after SLND + ALND and 25% (103 of 411) after SLND alone (P ≤ .001). Patients in the SLND + ALND group had more wound infections (P ≤ .0016), seromas (P ≤ .0001), and paresthesias (P ≤ .0001) than those in the SLND-alone group. At 1 year, lymphedema was reported subjectively by 13% (37 of 288) of patients after SLND + ALND and 2% (six of 268) after SLND alone (P ≤ .0001). The difference between the two groups' lymphedema, assessed by arm measurements at 30 days (P = .36), 6 months (P = .22), and 1 year (P = .078), although close to the cutoff for significance at 1 year, was not significant. BPIs occurred in less than 1% of patients.

Conclusion

In trial Z0011, the use of SLND + ALND resulted in more wound infections, axillary seromas, and paresthesias than SLND alone. Lymphedema was more common after SLND + ALND but was significantly different only by subjective report. The use of SLND alone resulted in fewer complications.
Evaluation of Cognitive Function Associated With Chemotherapy: A Review of Published Studies and Recommendations for Future Research
Authors: Vardy Janette , Rourke Sean , Tannock Ian F.
Published: May 2007

Purpose

There is evidence that some cancer survivors suffer cognitive impairment after chemotherapy. Determining if a patient has cognitive impairment is challenging, especially because impairment is usually subtle.

Patients and Methods

We assessed the design of studies evaluating cognitive function during or after chemotherapy in adult patients with solid tumors. We also reviewed methods used to evaluate cognitive function in subjects with other diseases and make recommendations for future studies.

Results

We identified 22 studies that met our criteria: 82% included women with breast cancer. Eight studies were longitudinal, 12 were cross-sectional, and two were follow-ups of cross-sectional studies. Sixteen studies used a battery of neuropsychological (NP) tests to assess subjects, and 13 included a control group. Ten studies (45%) had no explicit definition of cognitive impairment; most others used z scores or T scores and defined impairment based on standard deviations below the mean, but there was no consistency in for the cutoff point used or the number of tests required.

Conclusion

There is no consistency in defining cognitive impairment, in the NP batteries used, or in statistical methods in studies of cognitive function of cancer patients. We suggest guidelines to define criteria for cognitive impairment. Use of summary scores and control groups is recommended. Practice effect should be adjusted for in longitudinal studies. A balance is needed between comprehensive batteries and briefer tests, which still need to be sensitive to mild impairment.
Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Authors: Montoto Silvia , Davies Andrew John , Matthews Janet , Calaminici Maria , Norton Andrew J. , Amess John , Vinnicombe Sarah , Waters Rachel , Rohatiner Ama Z.S. , Lister T. Andrew
Published: May 2007

Purpose

To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL).

Patients and Methods

From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%.

Results

The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed.

Conclusion

Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.
Breast Cancer in the Elderly
Authors: Crivellari Diana , Aapro Matti , Leonard Robert , von Minckwitz Gunter , Brain Etienne , Goldhirsch Aron , Veronesi Andrea , Muss Hyman
Published: May 2007

Screening and adjuvant postoperative therapies have increased survival among women with breast cancer. These tools are seldom applied in elderly patients, although the usually reported incidence of breast cancer is close to 50% in women 65 years or older, reaching 47% after 70 years in the updated Surveillance, Epidemiology, and End Results (SEER) database. Elderly breast cancer patients, even if in good medical health, were frequently excluded from adjuvant clinical trials. Women age 70 years who are fit actually have a median life expectancy of 15.5 years, ie, half of them will live much longer and will remain exposed for enough time to the potentially preventable risks of a relapse and specific death. In the last few years, a new concern about this issue has developed. Treatment now faces two major end points, as in younger women: to improve disease-free survival in the early stages, and to palliate symptoms in advanced disease. However, in both settings, the absolute benefit of treatment is critical because protecting quality of life and all its related aspects (especially functional status and independence), is crucial in older persons who have more limited life expectancy. Furthermore, the new hormonal compounds (aromatase inhibitors) and chemotherapeutic drugs (capecitabine, liposomal doxorubicin), are potentially less toxic than and equally as effective as older more established therapies. These new treatments bring new challenges including higher cost, and defining their benefit in elderly breast cancer must include an analysis of the cost/benefit ratio. These issues emphasize the urgent need to develop and support clinical trials for this older population of breast cancer patients both in the adjuvant and metastatic settings, a move that will take us from a prejudiced, age-based medicine to an evidence-based medicine.
Prospective, Randomized Study of Single Compared With Double Autologous Stem-Cell Transplantation for Multiple Myeloma: Bologna 96 Clinical Study
Authors: Cavo Michele , Tosi Patrizia , Zamagni Elena , Cellini Claudia , Tacchetti Paola , Patriarca Francesca , Di Raimondo Francesco , Volpe Ettore , Ronconi Sonia , Cangini Delia , Narni Franco , Carubelli Affra , Masini Luciano , Catalano Lucio , Fiacchini Mauro , de Vivo Antonio , Gozzetti Alessandro , Lazzaro Antonio , Tura Sante , Baccarani Michele
Published: May 2007

Purpose

We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM).

Patients and Methods

A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B).

Results

As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70).

Conclusion

In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
Adjuvant Therapy in the Elderly: Making the Right Decision
Authors: Muss Hyman B. , Biganzoli Laura , Sargent Daniel J. , Aapro Matti
Published: May 2007

Adjuvant chemotherapy has led to improvements in relapse-free and overall survival in patients with breast, colon, and non–small-cell lung cancer, yet many older patients are not offered these potentially life-saving treatments. Moreover, older patients have been either excluded or under-represented in most adjuvant trials, limiting the generalizability of these treatments to older populations. Limited data in elders suggest that older patients derive significant benefits from adjuvant therapies provided they have life expectancies exceeding 5 years. Making treatment decisions in elders is challenging. Many have major comorbidities that may substantially limit life expectancy and minimize or negate the benefits of adjuvant chemotherapy. In this review, we discuss the potential benefits of adjuvant treatment in older patients with solid tumors with a focus on general principles involved in the selection of adjuvant therapy for patients with breast, colon, and non–small-cell lung cancer. In addition, we discuss the role of comorbidity and how it factors in treatment decisions. Finally, we discuss future research directions and funding for elders with cancer.
Older Female Cancer Patients: Importance, Causes, and Consequences of Undertreatment
Authors: Bouchardy Christine , Rapiti Elisabetta , Blagojevic Stina , Vlastos Anne-Thérèse , Vlastos Georges
Published: May 2007

Despite increased interest in treatment of senior cancer patients, older patients are much too often undertreated. This review aims to present data on treatment practices of older women with breast and gynecologic cancers and on the consequences of undertreatment on patient outcome. We also discuss the reasons and validity of suboptimal care in older patients. Numerous studies have reported suboptimal treatment in older breast and gynecologic cancer patients. Undertreatment displays multiple aspects: from lowered doses of adjuvant chemotherapy to total therapeutic abstention. Undertreatment also concerns palliative care, treatment of pain, and reconstruction. Only few studies have evaluated the consequences of nonstandard approaches on cancer-specific mortality, taking into account other prognostic factors and comorbidities. These studies clearly showed that undertreatment increased disease-specific mortality for breast and ovarian cancers. For other gynecological cancers, data were insufficient to draw conclusions. Objective reasons at the origin of undertreatment were, notably, higher prevalence of comorbidity, lowered life expectancy, absence of data on treatment efficacy in clinical trials, and increased adverse effects of treatment. More subjective reasons were putative lowered benefits of treatment, less aggressive cancers, social marginalization, and physician's beliefs. Undertreatment in older cancer patients is a well-documented phenomenon responsible for preventable cancer deaths. Treatments are still influenced by unclear standards and have to be adapted to the older patient's general health status, but should also offer the best chance of cure.
Radiation Therapy and the Geriatric Oncology Patient
Authors: Horiot Jean-Claude
Published: May 2007

Delivering radiotherapy to the geriatric cancer patient raises several questions: Are there objective reasons to consider the elderly population as potentially more vulnerable to radiation therapy than younger people? In practice, how are geriatric patients treated when radiotherapy is indicated? Recent data from French tumor registries on rectal cancers are reviewed to illustrate the evolution of the practices during a 20-year period up to 2000. Is there a changing landscape in radiotherapy research protocols in the elderly? Thirty-one European Organisation for Research and Treatment of Cancer (Brussels, Belgium) radiotherapy protocols are analyzed regarding compliance to the 1996 recommendation of having no upper age limit when other eligibility factors are fulfilled. To conclude, specific recommendations for optimal radiotherapeutic management of geriatric patients are made for some common cancers in the elderly.
International Society of Geriatric Oncology Chemotherapy Taskforce: Evaluation of Chemotherapy in Older Patients—An Analysis of the Medical Literature
Authors: Lichtman Stuart M. , Wildiers Hans , Chatelut Etienne , Steer Christopher , Budman Daniel , Morrison Vicki A. , Tranchand Brigitte , Shapira Iuliana , Aapro Matti
Published: May 2007

The elderly comprise the majority of patients with cancer and are the recipients of the greatest amount of chemotherapy. Unfortunately, there is a lack of data to make evidence-based decisions with regard to chemotherapy. This is due to the minimal participation of older patients in clinical trials and that trials have not systematically evaluated chemotherapy. This article reviews the available information with regard to chemotherapy and aging provided by a task force of the International Society of Geriatric Oncology (SIOG). Due to the lack of prospective data, the conclusions and recommendations made are a consensus of the participants. Extrapolation of data from younger to older patients is necessary, particularly to those patients older than 80 years, for which data is almost entirely lacking. The classes of drugs reviewed include alkylators, antimetabolites, anthracyclines, taxanes, camptothecins, and epipodophyllotoxins. Clinical trials need to incorporate an analysis of chemotherapy in terms of the pharmacokinetic and pharmacodynamic effects of aging. In addition, data already accumulated need to be reanalyzed by age to aid in the management of the older cancer patient.
Effects of temperature on tuning of the auditory pathway in the cicadaTettigetta josei(Hemiptera, Tibicinidae)
Authors: Fonseca P. J. , Correia T.
Published: May 2007

The effects of temperature on hearing in the cicada Tettigetta josei were studied. The activity of the auditory nerve and the responses of auditory interneurons to stimuli of different frequencies and intensities were recorded at different temperatures ranging from 16°C to 29°C.

Firstly, in order to investigate the temperature dependence of hearing processes, we analyzed its effects on auditory tuning, sensitivity, latency and Q10dB. Increasing temperature led to an upward shift of the characteristic hearing frequency, to an increase in sensitivity and to a decrease in the latency of the auditory response both in the auditory nerve recordings (periphery) and in some interneurons at the metathoracic–abdominal ganglionic complex (MAC). Characteristic frequency shifts were only observed at low frequency (3–8 kHz). No changes were seen in Q10dB. Different tuning mechanisms underlying frequency selectivity may explain the results observed.

Secondly, we investigated the role of the mechanical sensory structures that participate in the transduction process. Laser vibrometry measurements revealed that the vibrations of the tympanum and tympanal apodeme are temperature independent in the biologically relevant range(18–35°C). Since the above mentioned effects of temperature are present in the auditory nerve recordings, the observed shifts in frequency tuning must be performed by mechanisms intrinsic to the receptor cells.

Finally, the role of potassium channels in the response of the auditory system was investigated using a specific inhibitor of these channels,tetraethylammonium (TEA). TEA caused shifts on tuning and sensitivity of the summed response of the receptors similar to the effects of temperature. Thus,potassium channels are implicated in the tuning of the receptor cells.