bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duration of untreated symptoms in common mental disorders: association with outcomes
Authors: Kisely Stephen , Scott Anita , Denney Jennifer , Simon Gregory 
Published: June 2006

SummaryStudies have assessed the association between a longer duration of untreated symptoms and outcome for psychoses in specialist care. We investigated the effect of longer duration on the outcome of common psychiatric disorders in primary care, where most patients are treated. Patients presenting to primary care for new episodes in 10 countries were recruited into a prospective cohort study. Information on duration of untreated symptoms and psychosocial status was collected for 351 individuals using standardised instruments and this was repeated 1 year later. At 1-year follow-up, longer duration was associated with worse psychiatric outcome even after controlling for potential confounders.
Beyond the Kraepelinian dichotomy: acute and transient psychotic disorders and the necessity for clinical differentiation
Authors: Marneros Andreas 
Published: June 2006

SummaryThe concept of acute and transient psychoses is, together with that of schizoaffective disorders, a challenge by the Kraepelinian dichotomy. Although these conditions have some similarities to schizophrenia, they differ significantly from schizophrenia regarding onset, duration, prognosis, gender and premorbid adaptation. They show some similarities with bipolar disorders. They do not fit into the dichotomous concept.
Switching from immediate- to sustained-release psychostimulants in routine treatment of children with attention-deficit hyperactivity disorder
Authors: Thompson Anne E. , Nazir Saeed A. , Abbas Mohammed J. , Clarke Julie 
Published: June 2006

Aims and MethodTo investigate the effectiveness of switching children with attention-deficit hyperactivity disorder (ADHD) from immediate- to sustained-release psychostimulants (Concerta XL, a novel methylphenidate hydro-chloride) and to examine factors associated with treatment success or failure. This was a retrospective study of all such children known to four clinicians in Lincolnshire, over a 2-year period. The initial response to treatment and the response to slow-release psychostimulant as judged by the clinicians were recorded. Data were analysed using the Statistical Package for the Social Sciences version 12.ResultsOf the children who were switched (n=97) and on whom clinical judgement was available (n=92), a statistically significant number (32%) responded poorly (P<0.001). In 26 out of the 97 patients, the switching was considered as a treatment failure and they were switched back to the original immediate-release stimulants. There was no significant-difference with possible confounding variables between children who responded well and those who responded poorly after switching to sustained-release drug.Clinical ImplicationsIn a real-life clinical situation there is a significant failure rate when a child with ADHD is switched from an immediate- to sustained-release psychostimulant. Further studies are needed.
Phase I Trial of Intravesical Docetaxel in the Management of Superficial Bladder Cancer Refractory to Standard Intravesical Therapy
Authors: McKiernan James M. , Masson Puneet , Murphy Alana M. , Goetzl Manlio , Olsson Carl A. , Petrylak Daniel P. , Desai Manisha , Benson Mitchell C. 
Published: June 2006

Purpose Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent. Patients and Methods This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging. Results Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression. Conclusion Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.
Isolated CNS Relapse of Acute Lymphoblastic Leukemia Treated With Intensive Systemic Chemotherapy and Delayed CNS Radiation: A Pediatric Oncology Group Study
Authors: Barredo Julio C. , Devidas Meenakshi , Lauer Stephen J. , Billett Amy , Marymont MaryAnne , Pullen Jeanette , Camitta Bruce , Winick Naomi , Carroll William , Ritchey A. Kim 
Published: June 2006

Purpose Prognosis and outcome of children with isolated CNS relapse of acute lymphoblastic leukemia (ALL) has depended on duration of first complete remission (CR1). This study intensified systemic therapy by delaying CNS radiation for 12 months and tailored CNS radiation by CR1 duration. Patients and Methods Seventy-six children with first isolated CNS relapse of ALL were treated with systemic chemotherapy that effectively penetrates into the CSF and intrathecal chemotherapy for 12 months. Patients with CR1 of less than 18 months received craniospinal radiation (24 Gy cranial/15 Gy spinal), whereas those with CR1 of 18 months or more received cranial radiation only (18 Gy), followed by maintenance chemotherapy. Additionally, asymptomatic patients were enrolled in a thiotepa up-front therapeutic window. Results Seventy-four (97.4%) of 76 eligible patients achieved a second remission. Overall 4-year event-free survival (EFS) for the 71 precursor B-cell patients was 70.1% ± 5.8%. CR1 duration and National Cancer Institute (NCI; National Institutes of Health, Bethesda, MD) risk group at initial diagnosis predicted outcome. Patients with CR1 of less than 18 months and 18 months or more had a 4-year EFS of 51.6% ± 11.3% and 77.7% ± 6.4% (P = .027), respectively. NCI high- versus standard-risk 4-year EFS was 51.4% ± 10.8% and 80.2% ± 6.3% (P = .0018), respectively. A significant difference in EFS between standard risk/CR1 of at least 18 months and both high risk/CR1 of less than 18 months and high risk/CR1 of at least 18 months groups was detected (P = .0068 and .0314, respectively). Response rate to thiotepa was 78%. Most relapses involved the bone marrow, and three second malignancies were reported. Conclusion Twelve months of intensive systemic chemotherapy with reduced dose cranial radiation (18 Gy) is highly effective for children with isolated CNS relapse and CR1 of 18 months or more. Novel strategies are needed for patients with CR1 of less than 18 months.
Placebo-Controlled Phase III Trial of Immunologic Therapy with Sipuleucel-T (APC8015) in Patients with Metastatic, Asymptomatic Hormone Refractory Prostate Cancer
Authors: Small Eric J. , Schellhammer Paul F. , Higano Celestia S. , Redfern Charles H. , Nemunaitis John J. , Valone Frank H. , Verjee Suleman S. , Jones Lori A. , Hershberg Robert M. 
Published: June 2006

Purpose Sipuleucel-T (APC8015) is an investigational immunotherapy product designed to stimulate T-cell immunity against prostatic acid phosphatase. A phase III study was undertaken to evaluate the safety and efficacy of sipuleucel-T in a placebo-controlled study. Patients and Methods A total of 127 patients with asymptomatic metastatic hormone refractory prostate cancer (HRPC) were randomly assigned in a 2:1 ratio to receive three infusions of sipuleucel-T (n = 82) or placebo (n = 45) every 2 weeks. On disease progression, placebo patients could receive APC8015F, a product made with frozen leukapheresis cells. Results Of the 127 patients, 115 patients had progressive disease at the time of data analysis, and all patients were followed for survival for 36 months. The median for time to disease progression (TTP) for sipuleucel-T was 11.7 weeks compared with 10.0 weeks for placebo (P = .052, log-rank; hazard ratio [HR], 1.45; 95%CI, 0.99 to 2.11). Median survival was 25.9 months for sipuleucel-T and 21.4 months for placebo (P = .01, log-rank; HR, 1.70; 95%CI, 1.13 to 2.56). Treatment remained a strong independent predictor of overall survival after adjusting for prognostic factors using a Cox multivariable regression model (P = .002, Wald test; HR, 2.12; 95%CI, 1.31 to 3.44). The median ratio of T-cell stimulation at 8 weeks to pretreatment was eight-fold higher in sipuleucel-T-treated patients (16.9 v 1.99; P < .001). Sipuleucel-T therapy was well tolerated. Conclusion While the improvement in the primary end point TTP did not achieve statistical significance, this study suggests that sipuleucel-T may provide a survival advantage to asymptomatic HRPC patients. Supportive studies are underway.
Metabolic and neuroendocrine effects on diurnal urea excretion in the mangrove killifishRivulus marmoratus
Authors: Rodela Tammy M. , Wright Patricia A. 
Published: June 2006

SUMMARYIn mangrove killifish Rivulus marmoratus, urea excretion(Jurea) follows a distinct diurnal pattern with the highest rates between 12:00 h and 18:00 h. We investigated the regulating mechanisms that underlie temporal rhythms in Jurea in R. marmoratus. We hypothesized that the daily pattern of Jurea in R. marmoratus is (1) due to diurnal changes in urea synthesis rates and ultimately metabolic rate and/or (2)controlled by neuroendocrine messengers. Oxygen consumption and whole body urea content in R. marmoratus demonstrated a clear diurnal pattern with maximum rates for both parameters occurring at 12:00 h. A strong synchrony between diurnal patterns of oxygen consumption, whole body urea content and Jurea implicated metabolic regulation of the diurnal Jurea pattern. Ketanserin, a 5-HT2receptor antagonist, and RU-486, a cortisol receptor antagonist, were used to test the second hypothesis. Increasing antagonist concentrations of either ketanserin or RU-486 resulted in dose-dependent decreases in Jurea. Application of a single dose of either antagonist significantly decreases Jurea for up to 12 and 6 h for ketanserin and RU-48, respectively. Repeated exposure to doses of either ketanserin or RU-486 did not abolish the diurnal pattern in Jurea; however, there was a significant decrease in the amplitude of the rates. Taken together, these findings indicate that the diurnal pattern of Jurea in R. marmoratus are regulated by both metabolic and neuroendocrine factors. We propose that cortisol and 5-HT influence the absolute rate of urea excretion by altering the permeability of the gill membrane to urea and/or the rate of urea synthesis.
The cellular response to heat stress in the gobyGillichthys mirabilis: a cDNA microarray and protein-level analysis
Authors: Buckley Bradley A. , Gracey Andrew Y. , Somero George N. 
Published: June 2006

SUMMARYThe cellular response to stress relies on the rapid induction of genes encoding proteins involved in preventing and repairing macromolecular damage incurred as a consequence of environmental insult. To increase our understanding of the scope of this response, a cDNA microarray, consisting of 9207 cDNA clones, was used to monitor gene expression changes in the gill and white muscle tissues of a eurythermic fish, Gillichthys mirabilis(Gobiidae) exposed to ecologically relevant heat stress. In each tissue, the induction or repression of over 200 genes was observed. These genes are associated with numerous biological processes, including the maintenance of protein homeostasis, cell cycle control, cytoskeletal reorganization,metabolic regulation and signal transduction, among many others. In both tissues, the molecular chaperones, certain transcription factors and a set of additional genes with various functions were induced in a similar manner;however, the majority of genes displayed tissue-specific responses. In gill,thermal stress induced the expression of the major structural components of the cytoskeleton, whereas these same genes did not respond to heat in muscle. In muscle, many genes involved in promoting cell growth and proliferation were repressed, perhaps to conserve energy for repair and replacement of damaged macromolecules, but a similar repression was not observed in the gill. Many of the observed changes in gene expression were similar to those described in model species whereas many others were unexpected. Measurements of the concentrations of the protein products of selected genes revealed that in each case an induction in mRNA synthesis correlated with an increase in protein production, though the timing and magnitude of the increase in protein was not consistently predicted by mRNA concentration, an important consideration in assessing the condition of the stressed cell using transcriptomic analysis.
Division of labor in the honey bee (Apis mellifera): the role of tyramine β-hydroxylase
Authors: Lehman Herman K. , Schulz David J. , Barron Andrew B. , Wraight Lydia , Hardison Chris , Whitney Sandra , Takeuchi Hideaki , Paul Rajib K. , Robinson Gene E. 
Published: June 2006

SUMMARYThe biogenic amine octopamine (OA) is involved in the regulation of honey bee behavioral development; brain levels are higher in foragers than bees working in the hive, especially in the antennal lobes, and treatment causes precocious foraging. We measured brain mRNA and protein activity of tyramineβ-hydroxylase (T βh), an enzyme vital for OA synthesis, in order to begin testing the hypothesis that this enzyme is responsible for the rising levels of OA during honey bee behavioral development. Brain OA levels were greater in forager bees than in bees engaged in brood care, as in previous studies, but T βh activity was not correlated with bee behavior. Tβh mRNA levels, however, did closely track OA levels during behavioral development, and T βh mRNA was localized to previously identified octopaminergic neurons in the bee brain. Our results show that the transcription of this neurotransmitter synthetic enzyme is associated with regulation of social behavior in honey bees, but other factors may be involved.
Behavioral responses of Drosophila to biogenic levels of carbon dioxide depend on life-stage, sex and olfactory context
Authors: Faucher Cécile , Forstreuter Manfred , Hilker Monika , de Bruyne Marien 
Published: June 2006

SUMMARY
Drosophila melanogaster (Meigen) detects and uses many volatiles for its survival. Carbon dioxide (CO2) is detected in adults by a special class of olfactory receptor neurons, expressing the gustatory receptor Gr21a. The behavioral responses to CO2 were investigated in a four-field olfactometer bioassay that is new for Drosophila. We determined (1) whether the sensitivity of this response changes with odor context, and (2) if it depends on sex and life stage. When CO2 was added to ambient air in one field and tested against ambient air in the three other fields, individually observed adults avoided CO2 (0.1-1%above ambient), but did not respond to a low rise of 0.02%. We relate this behavior to measurements of CO2 production in bananas and flies. When 0.02% CO2 was combined with the odor of apple cider vinegar in one field of the olfactometer and tested against ambient air in the three other fields, the addition of CO2 did not affect the attractiveness of apple cider vinegar alone. However, this combination of CO2 and vinegar became repellent when it was tested against vinegar at ambient CO2 concentrations in the three other fields. This `odor background effect' was female-specific, revealing a sexually dimorphic behavior. The new assay allowed us to test larvae under similar conditions and compare their behavior to that of adults. Like adults, they avoided CO2, but with lower sensitivity. Larvae lacking neurons expressing Gr21a lost their avoidance behavior to CO2, but kept their positive response to vinegar odor. Hence, Gr21a-expressing neurons mediate similar behaviors in larvae and adults.
Nitric oxide and cnidarian bleaching: an eviction notice mediates breakdown of a symbiosis
Authors: Perez Santiago , Weis Virginia 
Published: June 2006

SUMMARYNitric oxide (NO) is a free radical implicated in numerous cell signaling,physiological and pathophysiological processes of eukaryotic cells. Here, we describe the production of NO as part of the cellular stress response of the symbiotic sea anemone Aiptasia pallida, which hosts dinoflagellates from the genus Symbiodinium. We show that exposure to elevated temperatures induces symbiotic anemones to produce high levels of NO, leading to the collapse of the symbiosis. These results shed light on the poorly understood cellular mechanism through which elevated seawater temperature causes the release of symbiotic algae from symbiotic cnidarians, a detrimental process known as coral (cnidarian) bleaching. The results presented here show that the host cell is a major source of NO during exposure to elevated temperatures and that this constitutes a cytotoxic response leading to bleaching. These results have important evolutionary implications as the observed NO production in these basal metazoans displays many parallels to the cytotoxic inflammatory response to pathogens, a well-understood process in mammalian model systems.
Mitochondrial proton leak rates in the slow, oxidative myotomal muscle and liver of the endothermic shortfin mako shark (Isurus oxyrinchus)and the ectothermic blue shark (Prionace glauca) and leopard shark(Triakis semifasciata)
Authors: Duong Cindy A. , Sepulveda Chugey A. , Graham Jeffrey B. , Dickson Kathryn A. 
Published: June 2006

SUMMARYMitochondrial proton leak was assessed as a potential heat source in the slow, oxidative (red) locomotor muscle and liver of the shortfin mako shark(Isurus oxyrinchus), a regional endotherm that maintains the temperature of both tissues elevated above ambient seawater temperature. We hypothesized that basal proton leak rates in red muscle and liver mitochondria of the endothermic shortfin mako shark would be greater than those of the ectothermic blue shark (Prionace glauca) and leopard shark(Triakis semifasciata). Respiration rate and membrane potential in isolated mitochondria were measured simultaneously at 20°C using a Clark-type oxygen electrode and a lipophilic probe(triphenylmethylphosphonium, TPMP+). Succinate-stimulated respiration was titrated with inhibitors of the electron transport chain, and the non-linear relationship between respiration rate and membrane potential was quantified. Mitochondrial densities of both tissues were measured by applying the point-contact method to electron micrographs so that proton leak activity of the entire tissue could be assessed. In all three shark species,proton leak occurred at a higher rate in red muscle mitochondria than in liver mitochondria. For each tissue, the proton leak curves of the three species overlapped and, at a membrane potential of 160 mV, mitochondrial proton leak rate (nmol H+ min-1 mg-1 protein) did not differ significantly between the endothermic and ectothermic sharks. This finding indicates that red muscle and liver mitochondria of the shortfin mako shark are not specialized for thermogenesis by having a higher proton conductance. However, mako mitochondria did have higher succinate-stimulated respiration rates and membrane potentials than those of the two ectothermic sharks. This means that under in vivo conditions mitochondrial proton leak rates may be higher in the mako than in the ectothermic species, due to greater electron transport activity and a larger proton gradient driving proton leak. We also estimated each tissue's total proton leak by combining mitochondrial proton leak rates at 160 mV and tissue mitochondrial density data with published values of relative liver or red muscle mass for each of the three species. In red muscle, total proton leak was not elevated in the mako shark relative to the two ectothermic species. In the liver, total proton leak would be higher in the mako shark than in both ectothermic species, due to a lower proton conductance in the blue shark and a lower liver mitochondrial content in the leopard shark, and thus may contribute to endothermy.
Why are so many adhesive pads hairy?
Authors: Federle Walter 
Published: June 2006

SUMMARYMany arthropods and vertebrates possess tarsal adhesive pads densely covered with setae. The striking morphological convergence of `hairy' pads in lizards, spiders and several insect orders demonstrates the advantage of this design for substrate adhesion. Early functional explanations of hairy adhesive organs focused on the performance on rough substrates, where flexible setae can make more intimate contact. Recent theoretical and experimental work shows that the hairy design can also help to achieve self-cleaning properties,controllable detachment and increased adhesion. Several arguments have been proposed to explain why adhesive forces are maximised. First, the `Force scaling' hypothesis states that when adhesive forces scale linearly with the dimensions of the contact, adhesion is increased by dividing the contact zone into many microscopic subunits. Second, the `Fracture mechanics' argument implies that adhesion is maximised when the size of adhesive contacts is smaller than the critical crack length. Third, the `Work of adhesion' model suggests that adhesion increases due to the bending and stretching of setae and associated energy losses during detachment.Several morphological traits of hairy adhesive pads can be explained by the need to maximise the work of adhesion, while avoiding the sticking of setae to each other (self-matting). Firstly, if setae are oblique and convex toward the foot tip as typical of most hairy pads, arrays should achieve greater adhesion. Secondly, a branched seta morphology not only confers the advantage that setae can adapt to roughness at different length scales but also prevents self-matting and increases the work of adhesion.It is predicted from the `Work of adhesion' model that adhesion of pads with unbranched setae cannot be increased by subdividing the contact zone into ever finer subcontacts, because this would increasingly cause self-matting. However, contact splitting can increase adhesion if setae are branched. The greater density of setae in large animals has been interpreted by `Force scaling'. However, the existing data can be explained by the effect of seta branching and by a fundamental difference between `wet' and `dry' adhesive systems. As insects employ adhesive fluids, they can cope with small-scale surface roughness even with relatively blunt seta tips, whereas the dry systems of lizards and spiders require extremely fine endings.