bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of [18F]fluorinated sigma receptor ligands in the conscious monkey brain
Authors: Elsinga P.H. , Tsukada H. , Harada N. , Kakiuchi T. , Kawamura K. , Vaalburg W. , Kimura Y. , Kobayashi T. , Ishiwata K.
Published: January 2004

PET‐imaging of the sigma receptors is very helpful to understand processes, e.g., several central nervous system (CNS)‐diseases in which the sigma receptors are involved. The [18F]fluoroethylated analogs of SA4503 and SA5845 ([18F]FE‐SA4503 and [18F]FE‐SA5845) were evaluated in conscious monkeys to estimate its suitability for human application for PET. Conscious monkeys (Macaca Mulatta) were either scanned with [18F]FE‐SA4503 or [18F]FE‐SA5845 (n = 3 for both groups, 220–802 MBq). After a dynamic study of 120 min, radioactivity was displaced by intravenous (i.v.) injection of haloperidol (1 mg/kg). One month later the same set of three monkeys were scanned with [18F]FE‐SA4503 for 120 min and “cold” SA4503 (1 mg/kg) was infused to displace the radioactivity, and the other three monkeys were pretreated with haloperidol (1 mg/kg) before the 120‐min PET‐scan with [18F]FE‐SA5845. Cortical areas (cingulate, frontal, occipital, parietal, temporal), striatum, and thalamus showed high radioactivity uptake. Infusion of haloperidol displaced the radioactivity levels of the two radioligands. The same effect was found for [18F]FE‐SA4503 after SA4503 displacement. Pretreatment with haloperidol blocked the [18F]FE‐SA5845 binding to give PET‐images with low and uniform uptake in the brain. The findings demonstrated the reversible binding of the two radioligands. Metabolite analysis showed that 14% and 23% parent compound of [18F]FE‐SA5845 and [18F]FE‐SA4503, respectively, at 120 min postinjection was present in plasma. Kinetic analysis showed that the binding potential of [18F]FE‐SA5845 was higher in all brain regions than that of [18F]FE‐SA4503 (4.75–8.79 vs. 1.65–4.04). The highest binding potential was found in the hippocampus, followed by the cortical regions, thalamus, cerebellar hemisphere, striatum and vermis. Both [18F]FE‐SA compounds bound specifically to cerebral sigma receptors of the monkey and have potential for mapping sigma receptors in the human brain. Synapse 52:29–37, 2004. © 2004 Wiley‐Liss, Inc.
DsdA (D‐serine deaminase): a new heterologous MX cassette for gene disruption and selection in Saccharomyces cerevisiae
Authors: Vorachek‐Warren Mara K. , McCusker John H.
Published: January 2004

Dominant drug resistance markers offer experimental flexibility in the study of Saccharomyces cerevisiae by eliminating the dependence on auxotrophic mutations and, because they are phenotypically neutral, avoid the deleterious effects of auxotrophic mutations. We have developed a new dominant resistance marker, dsdAMX4, for use in the genetic manipulation of S. cerevisiae. The dsdA gene, which is derived from Escherichia coli and encodes a D‐serine deaminase, confers to S. cerevisiae resistance to D‐serine and the ability to use D‐serine as a nitrogen source. Here we describe the construction of a dsdAMX4 cassette, capable of expression in S. cerevisiae, and the characterization of this new marker for use in chromosomal gene disruption. The unique selection properties of the dsdAMX4 cassette make it an important addition to the existing array of S. cerevisiae genetic tools. Copyright © 2004 John Wiley & Sons, Ltd.
Monofunctional catalase P of Paracoccidioides brasiliensis: identification, characterization, molecular cloning and expression analysis
Authors: Moreira Sabrina F. I. , Bailão Alexandre M. , Barbosa Mônica S. , Jesuino Rosalia S. A. , Felipe M. Sueli Soares , Pereira Maristela , Soares Célia Maria de Almeida
Published: January 2004

Within the context of studies on genes from Paracoccidioides brasiliensis (Pb) potentially associated with fungus–host interaction, we isolated a 61 kDa protein, pI 6.2, that was reactive with sera of patients with paracoccidioidomycosis. This protein was identified as a peroxisomal catalase. A complete cDNA encoding this catalase was isolated from a Pb cDNA library and was designated PbcatP. The cDNA contained a 1509 bp ORF containing 502 amino acids, whose molecular mass was 57 kDa, with a pI of 6.5. The translated protein PbCATP revealed canonical motifs of monofunctional typical small subunit catalases and the peroxisome‐PTS‐1‐targeting signal. The deduced and the native PbCATP demonstrated amino acid sequence homology to known monofunctional catalases and was most closely related to catalases from other fungi. The protein and mRNA were diminished in the mycelial saprobic phase compared to the yeast phase of infection. Protein synthesis and mRNA levels increased during the transition from mycelium to yeast. In addition, the catalase protein was induced when cells were exposed to hydrogen peroxide. The identification and characterization of the PbCATP and cloning and characterization of the cDNA are essential steps for investigating the role of catalase as a defence of P. brasiliensis against oxygen‐dependent killing mechanisms. These results suggest that this protein exerts an influence in the virulence of P. brasiliensis. Copyright © 2004 John Wiley & Sons, Ltd.
Liver Trauma: Experience in 348 Cases
Authors: Gao Jing‐mou , Du Ding‐yuan , Zhao Xing‐ji , Liu Guo‐long , Yang Jun , Zhao Shan‐hong , Lin Xi
Published: January 2004

Liver trauma, the main cause of death in patients suffering abdominal injury, remains an unresolved problem, especially in its most severe forms. The objective of this study was to probe effective surgical procedures and improve the outcome for patients with severe hepatic injury. A retrospective study of 348 patients with hepatic trauma seen in our institution during the past 12 years was carried out. Of these 348 patients, 259 (74.4%) underwent surgery. To manage severe liver trauma (American Association for the Surgery of Trauma grade III to grade V), procedures such as packing of the laceration with omentum, hepatectomy or direct control of bleeding vessels within the liver substance by means of the Pringle maneuver, selective hepatic artery ligation, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing were selected and combined based on the specific injury. In the 259 patients treated operatively, the survival rate was 86.9% (225/259); and 15 of 40 with retrohepatic venous injury (RHVI) were cured with the maximum blood transfusion of 60 units. In 42 patients treated by perihepatic packing, the bleeding was stopped in 20 of 25 (80%) with RHVI and in 14 of 17 (82%) without such injury (p > 0.75). The percentage of failure of nonoperative management was 17.2% (17/99); and it was 46.7% (14/30) in patients with grade III–V injury. Death occurred in 3 (50%) of 6 failures of grade IV–V injury. The overall mortality rate was 11.8% (41/348), and 51% of the deaths were due to exsanguination. The results suggest that severe hepatic injuries, especially grade IV–V injuries, usually require surgical intervention; reasonable surgical procedures based on classification of liver trauma and combined application of techniques can increase the survival rate; and perihepatic packing is effective in dealing with RHVI.
Acute Compartment Syndrome of the Lower Leg: Retrospective Study on Prevalence, Technique, and Outcome of Fasciotomies
Authors: Heemskerk Jeroen , Kitslaar Peter
Published: January 2004

The acute compartment syndrome is caused by bleeding or edema in a closed muscle compartment surrounded by fascia and bone. It is characterized by increased intracompartmental pressure and decreased tissue perfusion. Well‐known causative incidents are acute trauma and reperfusion after treatment for acute arterial obstruction. Most commonly the lower leg is involved. Inadequate therapy of the syndrome usually leads to muscle ischemia, rhabdomyolysis, and renal insufficiency. Perioperative morbidity and mortality are high. Although compartment syndromes can be caused by various factors, up until now no comparative studies have been published on clinical outcome of compartment syndromes of different origin. In this retrospective study we analyzed 40 successive cases of fasciotomy for acute lower leg compartment syndrome to study whether different causes of the syndrome lead to different clinical outcomes. We also studied other predictive factors for clinical outcome. The causes for the compartment syndromes were trauma, vascular deobstruction, cardiac surgery, and gastrointestinal surgery in lithotomy position. Clinical outcome showed a mortality of 15% and serious overall morbidity. Multivariate analysis showed the only significant predictive determinant of outcome to be the age of the patient. Fasciotomy for acute compartment syndrome is associated with serious morbidity and mortality. No correlation between causative factors and clinical outcome could be found.
Accuracy of Laparoscopy in the Diagnosis and Staging of Lymphoproliferative Diseases
Authors: Silecchia Gianfranco , Raparelli Luigi , Perrotta Nicola , Fantini Aldo , Fabiano Paolo , Monarca Bruno , Basso Nicola
Published: January 2004

Laparoscopy seems to be playing an emerging role in the management of lymphoproliferative diseases. The aim of this study was to prospectively analyze personal experience evaluating the role and limits of laparoscopy in the management of lymphomas. From July 1993 to December 2000, 131 consecutive patients were referred to our institution for primary diagnosis (group A, n = 70), suspected relapse (reassessment) (group B, n = 54), or staging/restaging of lymphoproliferative diseases (group C, n = 7). Diagnostic and/or operative laparoscopy was performed in all patients. To assess the accuracy of laparoscopy, the results were analyzed according to the indications for surgery. In all, 128 procedures were completed laparoscopically (95.5%). Conversion was required in 7 cases (5.1%). Causes of the conversions were severe obesity (body mass index 62.5), uncontrolled intraoperative bleeding (HIV+), nondiagnostic tissue sampling (2 cases), perisplenic inflammation and perisplenic abscesses (3 cases). The results of this study highlight the safety of diagnostic and staging laparoscopy and laparoscopic splenectomy in patients with lymphoproliferative diseases (major complications 2.9%, perioperative mortality 0%). In all, 96.4% of patients from group A and 100% of patients from group B were treated on the basis of laparoscopic findings. No false negative diagnosis occurred. Laparoscopy may become the “gold standard” in the management of lymphoproliferative disease in the following settings: for the differential diagnosis of hepatic and/or splenic focal lesions; when percutaneous needle biopsy fails and/or genetic analysis is needed for therapeutic decision; for the primary diagnosis and abdominal staging of patients with diffuse retroperitoneal lymphadenopathy in the absence of peripheral lymphadenopathy; for cases of abdominal restaging after concurrent chemoradiotherapy and in cases of suspected relapse when percutaneous biopsy is not technically possible; and for patients with lymphoproliferative disease when splenectomy is required. Marked splenomegaly with perisplenic inflammatory reaction and lymphadenopathy in HIV+ patients should be considered possible causes of failure of the laparoscopic approach.
Nihilism: A Benign Denial
Authors: Skandalakis John E. , Mirilas Petros
Published: January 2004

Nihilism is the belief that all possible knowledge on a given topic has been amassed and codified. Ranging from benign denial to deliberate attempts at excommunication, nihilism is often encountered in the history of medicine. Eustachius, Columbus, and Sylvius strongly criticized Vesalius and defended the authority of Galen. Riolan fervently rejected Harvey’s monumental work on the circulation of blood. Gross stated that no honest and sensible surgeon would ever sanction thyroidectomy. Sandstrom’s discovery of the parathyroids was met with silence. Transplantation of parathyroids by Mandl was not appreciated when announced. Aristotle’s dictum that the heart cannot withstand serious injury led to Paget’s statement that cardiac surgery had reached the limits set by nature, which no new techniques could overcome. The first Billroth I operation was welcomed as, “Hopefully, also the last.” Pancreatic surgery was opposed because the organ was of no clinical interest and was impossible for surgeons to reach. Pancreatic transplantation was rejected for many years, despite good results. When Blundell used blood transfusion for postpartum hemorrhage, critics averred that his next exploit would be radical removal of the spleen. Bassini stated that it could be risky to publish more about radical treatment of inguinal hernias. Carcinomas of the lower sigmoid and upper rectum were deemed untreatable because of their inaccessibility. Colostomy during pediatric surgery was rejected many times. Although it is difficult for the human mind to move from a familiar point of view, this propensity should not infect science, thereby impeding advancement.
Pain thresholds during and after treatment of severe depression with electroconvulsive therapy
Authors: Gormsen Lise , Ribe Anette Riisgaard , Raun Peter , Rosenberg Raben , Videbech Poul , Vestergaard Per , Bach Flemming W. , Jensen Troels S.
Published: January 2004

Pain and depression are often associated suggesting that both conditions share a common neurobiological mechanism, which modulate emotional function and processing of noxious information. Pain thresholds are hypothesized to be altered in depressed patients and normalized with the amelioration of depression. The purpose of this study was therefore to determine pain thresholds in patients during and after treatment with electroconvulsive therapy (ECT) of severe depression and in healthy controls. Seventeen depressed patients (Hamilton depression score > 18) and an age and gender matched control group of same size participated in the study. Pain detection and tolerance thresholds to pressure and pain tolerance thresholds to the Cold Pressor Test by exposure to ice‐water was measured twice in depressed patients during and after ECT and twice in controls with a similar time interval. While ECT significantly improved Hamilton depression score (from mean 23.9 (SD:5) to mean 12.5 (SD:5.7)) there was no significant change in pain thresholds during and after ECT in the patient group. However, depressed patients had significantly lower pain tolerance in the Cold Pressor Test on both examinations and on pressure pain tolerance on the second examination day than their corresponding control subjects. The differential effect of ECT on depression score and pain processing indicate that mood and noxious processing are not medicated directly by the same systems but that a complex relationship between pain and depression exists.
Size at maturity of the smallnose fanskate Sympterygia bonapartii (Müller & Henle, 1841) (Pisces, Elasmobranchii, Rajidae) in the SW Atlantic
Authors: Oddone María Cristina , Velasco Gonzalo
Published: January 2004

The smallnose fanskate Sympterygia bonapartii is found in coastal and shelf waters between southern Brazil and southern Argentina. Since 1994 it has become an alternative and commercially important target of demersal fisheries. In Uruguayan waters, the onset of sexual maturity in the species is at 65.5 cm for females and at 50–57 cm for males.
The study of international political economy in Russia
Authors: Tkachenko Stanislav L.
Published: January 2004

The author argues that international political economy (IPE), however prominent in the West, has not been established in Russia as an academic discipline. In the Russian policy community, the main debate is between liberal institutionalists, who advocate the country’s integration into the global economy, and the so-called dirigists, who promote relative economic autonomy. These two schools, however, only now begin to find their way in academia. Three main problems impede IPE development in Russia—the excessive separation of political science from economics, the deficit of theoretical generalization, and the weakness of educational curricula.
Defining the p53 DNA‐binding domain/Bcl‐xL‐binding interface using NMR
Authors: Petros Andrew M , Gunasekera Angelo , Xu Nan , Olejniczak Edward T , Fesik Stephen W
Published: January 2004

p53 exerts its tumor suppressor activity through both transcription‐dependent and transcription‐independent processes. Although the transcription‐dependent activity of p53 has been extensively studied, the mechanism for transcription‐independent p53‐mediated tumor suppression is less well known. Recently, it was reported that p53 can directly induce mitochondrial permeabilization and promote apoptosis. This occurs through complexation of the DNA‐binding region of p53 with the anti‐apoptotic proteins Bcl‐xL and Bcl‐2 (Mihara, M. et al. (2003) Mol. Cell 11, 577–590). Using nuclear magnetic resonance (NMR) spectroscopy we show that the interaction surface on p53 involves the same region that is used by the protein to contact DNA. The p53‐binding site on Bcl‐xL consists of the carboxy‐terminus of the first α‐helix, the loop between α3 and α4, and the loop between α5 and α6 of Bcl‐xL. Furthermore, the interaction of p53 with Bcl‐xL is blocked by the binding of a 25‐residue peptide derived from the BH3 region of the pro‐apoptotic protein referred to as Bad.
PI 3‐kinase and MAP kinase regulate bradykinin induced prostaglandin E2 release in human pulmonary artery by modulating COX‐2 activity
Authors: Bradbury D.A , Corbett L , Knox A.J
Published: January 2004

Here we studied the role of phosphoinositide 3‐kinase (PI 3‐kinase) and mitogen activated protein (MAP) kinase in regulating bradykinin (BK) induced prostaglandin E2 (PGE2) production in human pulmonary artery smooth muscle cells (HPASMC). BK increased PGE2 in a three step process involving phospholipase A2 (PLA2), cyclooxygenase (COX) and PGE synthase (PGES). BK stimulated PGE2 release in cultured HPASMC was inhibited by the PI 3‐kinase inhibitor LY294002 and the p38 MAP kinase inhibitor SB202190. The inhibitory mechanism used by LY294002 did not involve cytosolic PLA2 activation or COX‐1, COX‐2 and PGES protein expression but rather a novel effect on COX enzymatic activity. SB202190 also inhibited COX activity.
The origin and significance of an indent on wheat leaves
Authors: LOCK A. A.
Published: January 2004

The origin and significance of an indent on laminae of wheat is unknown. The constancy, position and emergence of a leaf indent was recorded on a range of winter wheat cultivars sown on two dates in 1998/99 and three dates in 1999/2000. The time when the indent developed was also examined in 1999/2000.

The indent appeared to be caused by tissue in the region of the ligule on the previous leaf swelling as the ligule formed. The synchrony between a ligule on one leaf and an indent on the next generally lasted until the ligule appeared from within the previous leaf sheath. The date of plant emergence influenced the pattern of tip to indent length throughout the life of the plant and different varieties also showed different patterns. There was strong correlation between the length of a leaf sheath and the length of the next (younger) lamina from the ligule to the indent.
Earliness per se and its dependence upon temperature in diploid wheat lines differing in the major gene Eps-Am1 alleles
Authors: APPENDINO M. L. , SLAFER G. A.
Published: January 2004

Differences in development among wheat cultivars are not only restricted to photoperiod and vernalization responses. When both requirements are fully satisfied differences may still arise due to earliness per se. It is not clear at present to what extent this trait is ‘intrinsically’ expressed (a constitutive trait) independently of the environmental conditions so that it might be selected under any thermal condition or if it may be altered to the extent of showing a crossover interaction with temperature in which the ranking of wheat genotypes may be altered. The present study assessed the influence of temperature on the intrinsic earliness for lines of diploid wheat characterized for their differences in a major gene for intrinsic earliness, but also possibly differing in their genetic background for other factors controlling this polygenic trait. To do so the lines were grown individually in two temperature regimes (16 and 23°C) under long days having previously been fully vernalized. Multiple comparisons analyses were carried out among lines of the same allelic group for the Eps-Am1 gene. Results indicated that within each group there were lines that did not differ in their earliness per se, others differed but without exhibiting any line×temperature interaction and finally different types of interaction were shown, including cases where the ranking of lines was altered depending on the growing temperature. It is thus possible that the selection of a genotype based on its earliness per se in an environment might not represent the same performance in another location where temperature varied significantly.
The effects of waterlogging on growth, photosynthesis and biomass allocation in perennial ryegrass (Lolium perenne L.) genotypes with contrasting root development
Authors: MCFARLANE N. M. , CIAVARELLA T. A. , SMITH K. F.
Published: January 2004

Perennial ryegrass (Lolium perenne L.) is often subject to transient waterlogging during winter under dryland conditions and summer when flood-irrigated. Despite this, little is known about the physiological responses of perennial ryegrass genotypes to waterlogging. In a pot experiment, four perennial ryegrass genotypes with contrasting root growth characteristics were subjected to waterlogging for 0, 3, 7, 14, 21 or 28 days. The masses of roots and shoots of the genotype Aurora6 were not significantly (P>0·05) reduced by waterlogging, throughout the experiment. All other genotypes exhibited reductions in root and shoot biomass between 14 and 21 days after waterlogging was imposed. The masses of laminae and roots of susceptible genotypes were reduced by up to 70% after 28 days of waterlogging. Aurora6 was also able to maintain photosynthesis for longer into the waterlogging period. However, after 28 days of waterlogging, photosynthesis of all genotypes was reduced by 30–50%. The waterlogging tolerance of Aurora6 was not due to its relatively poor root growth, as its progeny (2178), which also had poor root growth under control conditions, was susceptible to waterlogging. These findings show that there is variation in physiological processes and herbage yield of perennial ryegrass under waterlogged conditions. The implications of these findings for the genetic improvement of waterlogging tolerance of perennial ryegrass are discussed.
Agronomic performance of maize (Zea mays L.) breeding lines derived from a low nitrogen maize population
Authors: KAMARA A. Y. , KLING J. G. , MENKIR A. , IBIKUNLE O.
Published: January 2004

Eighteen S1 lines of maize (Zea mays L.) derived from a low nitrogen tolerant pool and two inbred lines were evaluated for agronomic performance under moderate N conditions in the southern Guinea savannah of Nigeria. Generally, the breeding lines differed in yield, growth, vertical root-pulling resistance, N-uptake and N-use efficiency. Breeding lines with high vertical root-pulling resistance took up more N and utilized it more efficiently. They also showed better agronomic performance and recorded higher yields. Principal component and cluster analyses classified the breeding lines into six groups. The results of principal components analyses (PCA) suggest that the most important variables for the classification of the S1 lines were grain yield, plant height, total dry matter during the grain-filling period and at maturity, N-accumulation, N-uptake and N-use efficiency. Other important traits were days to silking, anthesis-silking interval, ears per plant, harvest index and vertical root-pulling resistance. Two groups containing a total of 14 S1 lines that had higher agronomic performance than others are recommended for further evaluation under severe N stress to ascertain their tolerance of low N stress before recombination to form a new population for the next cycle of selection.
Influence of ‘historic’ photoperiod during stem elongation on the number of fertile florets in wheat
Authors: MIRALLES D. J. , SLAFER G. A. , RICHARDS R. A.
Published: January 2004

Extending the duration of the late reproductive phase in wheat has been proposed as a possible avenue to improve spike fertility. There is a positive correlation between the number of fertile florets and the duration of the stem elongation phase when this phase is varied by extended photoperiod. Photoperiod treatments imposed during the vegetative period also influence the duration of stem elongation. The present study analysed the effect of long photoperiod (19 h) of different duration (10, 12, 14, 18 or 22 d) imposed before the onset of stem elongation on floret fertility in wheat. It was found that the length of the stem elongation phase was modified by earlier ‘historic’ photoperiod treatments imposed during previous phases. However, neither the number of fertile florets per spike nor the spikelet fertility was affected significantly by these historic treatments. The results of the study therefore showed that an increased duration of the late reproductive phase was ineffective in increasing the number of fertile florets, unless the length of that phase was directly altered by current photoperiod.
Psychological consequences of road traffic accidents for children and their mothers
Authors: BRYANT B. , MAYOU R. , WIGGS L. , EHLERS A. , STORES G.
Published: January 2004

Background. Little is known about the psychological and behavioural consequences of road traffic accidents for children. The study aimed to determine the outcome of road traffic accidents on children and their mothers.

Method. A 1-year cohort study of consecutive child attenders aged 5–16 years at an Accident and Emergency Department. Data were extracted from medical notes and from interview and self-report at baseline, 3 months and 6 months.

Results. The children had an excellent physical outcome. Fifteen per cent suffered acute stress disorder; 25% suffered post-traumatic stress disorder at 3 months and 18% at 6 months. Travel anxiety was frequent. Post-traumatic consequences for mothers were common.

Conclusion. Psychological outcome was poor for a minority of children and associated with disability, especially for travel. There were significant family consequences. There is a need for changes in clinical care to prevent, identify and treat distressing and disabling problems.
Understanding delay in treatment for first-episode psychosis
Authors: NORMAN R. M. G. , MALLA A. K. , VERDI M. B. , HASSALL L. D. , FAZEKAS C.
Published: January 2004

Background. A lengthy delay often occurs between the onset of symptoms of psychotic disorders and initiation of adequate treatment. In this paper we examine the extent to which this represents a delay in individuals contacting health professionals or a delay in receiving treatment once such contact is made.

Method. Pathways to care were examined in 110 patients of the Prevention and Early Intervention Program for Psychosis in London, Canada. Data were collected using structured interviews with patients, family members, consultation with clinicians and review of case records.

Results. Family physicians and hospital emergency rooms were prominent components of pathways to care. Both delay to contact with a helping professional and delay from such contact to initiation of adequate treatment appear to be about equally important for the sample as a whole, but some individuals appear to be at risk for particularly lengthy delay in the second component. Individuals with younger age of onset, or who had initial contact with professional helpers before the onset of psychosis and were being seen on an ongoing basis at the time of onset of psychosis, had longer delays from first service contact after onset to initiation of adequate treatment. The greater delay to treatment for those being seen at the onset of psychosis does not appear to reflect differences in age, gender, symptoms, drug use or willingness to take medication.

Conclusions. Interventions to reduce treatment delay should increase the public's awareness of the symptoms of psychotic illness and the need to seek treatment, but of equal importance is the education of service providers to recognize such illness and the potential benefits of earlier intervention.
Neurocognitive function in users of MDMA: the importance of clinically significant patterns of use
Authors: HANSON KAREN L. , LUCIANA MONICA
Published: January 2004

Background. Use of MDMA (ecstasy), a serotonin neurotoxin, has been associated with memory impairment and psychological dysfunction. This study examined cognitive functioning in abstinent MDMA users and MDMA-naïve controls.

Method. Participants completed measures of intelligence, motor function, attention, memory span, verbal fluency, immediate and delayed verbal memory, and working memory. They were also assessed for the presence of psychopathology. In addition to comparing cognitive function in MDMA users relative to controls, the possibility that clinically dysfunctional MDMA use increases the risk of cognitive impairment was examined.

Results. MDMA users exhibited relative deficits in mnemonic and executive functions. Additionally, users that met DSM-IV substance use disorder criteria for lifetime MDMA abuse or dependence exhibited a number of additional deficits relative to those who did not meet these criteria.

Conclusion. These findings suggest that clinically dysfunctional, rather than purely recreational, MDMA use is associated with cognitive impairment. Future research studies of diverse samples of users may shed light on the mechanisms that underlie these differences.
Pathways to care of first-admitted subjects with psychosis in South-Western France
Authors: COUGNARD A. , KALMI E. , DESAGE A. , MISDRAHI D. , ABALAN F. , BRUN-ROUSSEAU H. , SALMI L. R. , VERDOUX H.
Published: January 2004

Background. A limited number of studies have assessed the pathways to care of patients with first-episode psychosis. The aim of the study was to describe the pathways to care of subjects with psychosis between onset of psychosis and first admission, and to examine the demographic and clinical factors influencing access to care.

Method. Number and type of helping contacts since onset of first psychotic symptoms were assessed using multiple sources of information in 86 subjects with psychosis first-admitted in two hospitals of South-Western France. Characteristics independently associated with long delays between onset of symptoms and first helping contact, first treatment and first admission were explored using logistic regressions.

Results. Twelve per cent of subjects were first admitted without any previous helping contact. The patients were seen by a median of two helpers (maximum 7). For most patients (70%), the first helping contact was a health care professional, and the same proportion of patients had a first contact with a GP or a psychiatrist. The type of first contact was not predicted by demographic or clinical characteristics. Subjects with poor pre-morbid functioning or at-risk behaviour were more likely to have a delayed access to care.

Conclusions. The delay in access to care may not be totally attributed to inadequate management by health professionals, but may be a characteristic of the disease itself, at least in part independent of the organization of the health system.
Parental separation at birth and depression in adulthood: a long-term follow-up of the Finnish Christmas Seal Home Children
Authors: VEIJOLA J. , MÄKI P. , JOUKAMAA M. , LÄÄRÄ E. , HAKKO H. , ISOHANNI M.
Published: January 2004

Background. Early separation of a child from the mother has been considered a risk factor for later depression. We investigated the association between very early separation and depression in adulthood in a unique dataset.

Method. The index cohort consisted of 3020 subjects born in 1945–1965 in Finland, isolated from their family due to tuberculosis in the family and placed in special nurseries, immediately after birth, for an average time of 7 months. Those subjects alive at 1 January, 1971 were identified. For every index subject two reference subjects were chosen, the matching criteria being sex, year of birth and place of birth. Data on depression were obtained from the Finnish Hospital Discharge Register by the end of year 1998.

Results. In males, 4·2% of the index subjects and 2·6% (Adjusted Rate Ratio RR 1·7, 95% CI 1·3–2·3) of the reference subjects had been treated in hospital due to a depressive episode. In females the respective figures were 3·9% for index subjects and 3·6% (RR 1·1, 95% CI 0·8–1·5) for reference subjects.

Conclusions. The index subjects had an elevated risk for hospital treated depression in adulthood. One explanation may be that the very early temporal separation from the mother at birth may have unfavourable effects on later psychological development. On the other hand, separation from the parents at birth was not found to be strongly associated with severe adulthood depression.
Post-traumatic stress disorder among patients with chronic pain and chronic fatigue
Authors: ROY-BYRNE P. , SMITH W. R. , GOLDBERG J. , AFARI N. , BUCHWALD D.
Published: January 2004

Background. Fibromyalgia (FM), a chronic pain condition of unknown aetiology often develops following a traumatic event. FM has been associated with post-traumatic stress disorder (PTSD) and major depression disorder (MDD).

Method. Patients seen in a referral clinic (N=571) were evaluated for FM and chronic fatigue syndrome (CFS) criteria. Patients completed questionnaires, and underwent a physical examination and a structured psychiatric evaluation. Critical components of the diagnostic criteria of FM (tender points and diffuse pain) and CFS (persistent debilitating fatigue and four of eight associated symptoms) were examined for their relationship with PTSD.

Results. The prevalence of lifetime PTSD was 20% and lifetime MDD was 42%. Patients who had both tender points and diffuse pain had a higher prevalence of PTSD (OR=3·4, 95% CI 2·0–5·8) compared with those who had neither of these FM criteria. Stratification by MDD and adjustment for sociodemographic factors and chronic fatigue revealed that the association of PTSD with FM criteria was confined to those with MDD. Patients with MDD who met both components of the FM criteria had a three-fold increase in the prevalence of PTSD (95% CI 1·5–7·1); conversely, FM patients without MDD showed no increase in PTSD (OR=1·3, 95% CI 0·5–3·2). The components of the CFS criteria were not significantly associated with PTSD.

Conclusion. Optimal clinical care for patients with FM should include an assessment of trauma in general, and PTSD in particular. This study highlights the importance of considering co-morbid MDD as an effect modifier in analyses that explore PTSD in patients with FM.
Analysing the contributions of genes and parent–child interaction to childhood behavioural and emotional problems: a model for the children of twins
Authors: SILBERG J. L. , EAVES L. J.
Published: January 2004

Background. Despite the demonstrable influence of both genes and the family environment on children's behavioural and emotional development, the mechanisms by which these factors are transmitted from parents to their children are not known. Numerous aspects of the family have long been associated with behavioural and emotional problems in children; it is not clear, however, whether these family variables represent genuine environmental risks or secondary consequences of the underlying genetic liability shared between parents and their children.

Method. In this study we present a model for analysing the non-genetic contributions of family background to risk for childhood and adolescent depression and conduct disturbance using simulated data on adult MZ and DZ twins, their spouses and children.

Results. The twin offspring design provides substantial power to detect remarkably small non-genetic effects on parent–offspring resemblance against the background of genetic transmission. As presented, the model is able to resolve the direction of transmission from both parent to child (passive genotype–environment correlation) and child to parent (evocative genotype–environment correlation).

Conclusions. Unlike many other genetic studies, a study of twins and their children can sort out which putative family environmental risk factors do actually have a significant environmental impact on the child and which ones only appear to do so because they are associated with genetic mediation.
Advances in biomolecular simulations: methodology and recent applications
Authors: Norberg Jan , Nilsson Lennart
Published: January 2004

1. Introduction 258

2. Set-up of MD simulations 260

2.1 Constant-pressure dynamics 260

2.2 Grand-canonical dynamics 261

2.3 Boundary conditions 261

3. Force fields 262

3.1 Proteins 262

3.2 Nucleic acids 265

3.3 Carbohydrates 266

3.4 Phospholipids 266

3.5 Polarization 267

4. Electrostatics 267

4.1 Spherical truncation methods 268

4.2 Ewald summation methods 269

4.3 Fast multipole (FM) methods 271

4.4 Reaction-field methods 271

5. Implicit solvation models 271

6. Speeding-up the simulation 273

6.1 SHAKE and its relatives 273

6.2 Multiple time-step algorithms 274

6.3 Other algorithms 275

7. Conformational space sampling 275

7.1 Multiple copy simultaneous search (MCSS) and locally enhanced sampling (LES) 275

7.2 Steered or targeted MD 276

7.3 Self-guided MD 276

7.4 Leaving the standard 3D Cartesian coordinate system: 4D MD and internal coordinate MD 277

7.5 Temperature variations 277

8. Thermodynamic calculations 278

8.1 Lambda (λ) dynamics 278

8.2 Extracting thermodynamic information from simulations 279

8.3 Non-Boltzmann thermodynamic integration (NBTI) 279

8.4 Other methods 279

9. QM/MM calculations 282

10. MD simulations of protein folding and unfolding 283

10.1 High-temperature effects 284

10.2 Co-solvent and polarization effects 288

10.3 External force effects 288

11. On the horizon 291

12. Acknowledgements 292

13. References 292

Molecular dynamics simulations are widely used today to tackle problems in biochemistry and molecular biology. In the 25 years since the first simulation of a protein computers have become faster by many orders of magnitude, algorithms and force fields have been improved, and simulations can now be applied to very large systems, such as protein–nucleic acid complexes and multimeric proteins in aqueous solution. In this review we give a general background about molecular dynamics simulations, and then focus on some recent technical advances, with applications to biologically relevant problems.
Electron tunneling through proteins
Authors: Gray Harry B. , Winkler Jay R.
Published: January 2004

1. History 342

2. Activation barriers 343

2.1 Redox potentials 344

2.2 Reorganization energy 344

3. Electronic coupling 345

4. Ru-modified proteins 348

4.1 Reorganization energy 349

4.1.1 Cyt c 349

4.1.2 Azurin 350

4.2 Tunneling timetables 352

5. Multistep tunneling 357

6. Protein–protein reactions 359

6.1 Hemoglobin (Hb) hybrids 359

6.2 Cyt c/cyt b5 complexes 360

6.3 Cyt c/cyt c peroxidase complexes 360

6.4 Zn–cyt c/Fe–cyt c crystals 361

7. Photosynthesis and respiration 362

7.1 Photosynthetic reaction centers (PRCs) 362

7.2 Cyt c oxidase (CcO) 364

8. Concluding remarks 365

9. Acknowledgments 366

10. References 366

Electron transfer processes are vital elements of energy transduction pathways in living cells. More than a half century of research has produced a remarkably detailed understanding of the factors that regulate these ‘currents of life’. We review investigations of Ru-modified proteins that have delineated the distance- and driving-force dependences of intra-protein electron-transfer rates. We also discuss electron transfer across protein–protein interfaces that has been probed both in solution and in structurally characterized crystals. It is now clear that electrons tunnel between sites in biological redox chains, and that protein structures tune thermodynamic properties and electronic coupling interactions to facilitate these reactions. Our work has produced an experimentally validated timetable for electron tunneling across specified distances in proteins. Many electron tunneling rates in cytochrome c oxidase and photosynthetic reaction centers agree well with timetable predictions, indicating that the natural reactions are highly optimized, both in terms of thermodynamics and electronic coupling. The rates of some reactions, however, significantly exceed timetable predictions; it is likely that multistep tunneling is responsible for these anomalously rapid charge transfer events.
The communication and psychosocial perceptions of older adults with sensory loss: a qualitative study
Authors: HEINE CHYRISSE , BROWNING COLETTE J.
Published: January 2004

Sensory loss (visual and/or hearing loss) is prevalent in older adults. Decreased vision and/or hearing acuity often result in poor communication and psychosocial functioning. This qualitative study explores the communication and psychosocial perceptions of a group of older adults with single or dual sensory loss. The aims were to identify the communication difficulties and conversational strategies used by the subjects, and to explore their perceptions of their social adjustment, quality of life and physical and mental well-being. The participants were all older adults with sensory loss who attended the Vision Australia Foundation. In-depth interviews revealed that the participants experienced frequent communication difficulties. They identified the personal, situational and environmental triggers responsible for communication breakdown, and they described the compensation and avoidance strategies that they used. The participants acknowledged that frequent communication breakdown resulted in decreased socialisation. The problems of adjusting to sensory loss, depression, anxiety, lethargy and social dissatisfaction were cited as factors that affected their physical and mental well-being, while being optimistic, coping with their sensory loss, and maintaining social contact contributed to an improved quality of life. All participants expressed interest in being involved in further communication intervention programmes.
Verotoxins in commensal Escherichia coli in cattle: the effect of injectable subcutaneous oxytetracycline in addition to in-feed chlortetracycline on prevalence
Authors: O'CONNOR A. M. , ZIEBELL K. A. , POPPE C. , McEWEN S. A.
Published: January 2004

Using a self-paired observational study, the association between therapeutic oxytetracycline use and the prevalence of virulence genes in commensal Escherichia coli (E. coli) from cattle was examined. Faeces were collected from 39 yearling bulls prior to and after treatment with oxytetracycline and from 44 untreated animals. Between samplings all animals received in-feed chlortetracycline for 16 days. Five E. coli were isolated from each sample and tested by a polymerase chain reaction (PCR) capable of detecting all verotoxin (vt) genes. Positive isolates were further tested with a multiplex PCR to detect vt1, vt2, eaeA and hlyA. For vt, 23 animals were positive at both samplings, 26 negative at both samplings, 22 negative animals became positive and 12 positive animals became negative. Sixty-eight per cent of the discordant pairs changed from vt-negative to vt-positive (95% CI 48–80) suggesting pressure toward becoming vt-positive perhaps due to the transfer of genes due to mixing of cattle in the months between samplings or an effect of chlortetracycline.
Duration and magnitude of faecal shedding of Shiga toxin-producing Escherichia coli from naturally infected cattle
Authors: WIDIASIH D. A. , IDO N. , OMOE K. , SUGII S. , SHINAGAWA K.
Published: January 2004

To clarify the epidemiological relationship between cattle and human infections of Shiga toxin-producing Escherichia coli (STEC), we studied the duration and magnitude of the excretion of STEC O157 and STEC O26 with rectal faeces from naturally infected cattle at a breeding farm in the Tohoku area of Japan, using microbiological methods. The prevalence of STEC O157 was 3·5% (11/324), whereas that of STEC O26 was 7·9% (14/178). Faecal shedding of STEC O157 persisted for <1 week to 10 weeks, whereas STEC O26 persisted from <1 week to <3 weeks. The magnitude of faecal shedding (per 10 g) ranged from 4 to >110000 c.f.u. for STEC O157 and from 3 to 2400 c.f.u. for STEC O26. All isolates of both STEC serotypes contained the stx1 or stx2 genes. Pulsed-field electrophoretic analysis of both STEC serotypes identified predominantly STEC O157 type III and STEC O26 type I in isolates, suggesting that a single STEC strain may be mutated in the intestinal tract of calves. These results indicate that STEC O157 is secreted for longer periods and in higher numbers than STEC O26 from healthy calves with natural infections, suggesting that STEC O157 may have more opportunities than STEC O26 to induce human disease.
Characterization and dry deposition of carbonaceous aerosols in a wet tropical forest canopy
Authors: Loescher H. W. , Bentz J. A. , Oberbauer S. F. , Ghosh T. K. , Tompson R. V. , Loyalka S. K.
Published: January 2004

Carbon aerosol concentration was measured using an impactor on a 42 m tower over a wet tropical forest in northeast Costa Rica. Samples were collected at three different heights, 42, 21, and 2 m, for 2 months during the wet season in 1998. Winds originated from two directions, southeast from the Caribbean Sea and west from the continental isthmus. Concentrations were normalized by the fraction of dry sampling time during the collection. The distribution was negatively skewed for the range of aerodynamic diameter aerosols measured. The main size constituent was in the class 4.7–3.3 μm, accounting for ∼0.70 μg C mol−1. No significant difference was found in the distribution of aerosol carbon with height, suggesting a well‐mixed column of air, minimal resuspension, and that the source was from surrounding land use types. Functional relationships were developed to describe the loading of aerosols to the atmosphere and the removal by precipitation. Deposition was estimated using these relationships, combined with three different estimates of velocity deposition derived from (1) aerodynamic and canopy conductance, (2) aerodynamic and momentum conductance, and (3) traditional estimates of gravitational settling diffusion, impaction, and interception. Annual deposition estimates were 2.9, 5.0, and 9.6 kg ha−1 yr−1, respectively. Concentrations of carbon aerosols reported here are as much as two orders of magnitude higher than those reported elsewhere. Annual dry deposition estimates, however, were within the range of other estimates but were likely underestimated. Potential effects on deposition caused by seasonal burns and El Niño–Southern Oscillation are discussed.