bluuebunny/crossref_metadata_2025 huggingface dataset:
Galanin and galanin‐like peptide modulate neurite outgrowth via protein kinase C‐mediated activation of extracellular signal‐related kinase
Authors: Hawes Jessica J. , Narasimhaiah Roopashree , Picciotto Marina R.
Published: June 2006

The neuropeptide galanin is widely distributed in the central nervous system and plays a role in a number of processes in the adult brain. Galanin also has neurotrophic effects in the developing nervous system and after nerve injury. The current study investigated the mechanism by which galanin promotes neurite outgrowth in the neuronal cell line PC12 and in neurospheres derived from adult hippocampal progenitor cells. We demonstrated that galanin can induce extracellular signal‐related kinase (ERK) phosphorylation transiently in a concentration‐dependent manner in neurons. Galanin‐like peptide, which is thought to signal primarily through the GalR2 receptor subtype, induced ERK phosphorylation with similar kinetics to galanin. In functional studies, the ability of galanin and galanin‐like peptide to induce neurite outgrowth was dependent on activation of both protein kinase C and ERK. This study identified a novel physiological role for galanin‐induced ERK phosphorylation and identified ERK and protein kinase C as important signaling components in the galanin‐mediated modulation of neurite outgrowth.
Aquaporin 4 changes in rat brain with severe hydrocephalus
Authors: Mao Xiaoyan , Enno Terry L. , Del Bigio Marc R.
Published: June 2006

Hydrocephalus is characterized by impaired cerebrospinal fluid (CSF) flow with enlargement of the ventricular cavities of the brain and progressive damage to surrounding tissue. Bulk water movement is altered in these brains. We hypothesized that increased expression of aquaporins, which are water‐permeable channel proteins, would occur in these brains to facilitate water shifts. We used quantitative (real‐time) RT‐PCR, Western blotting and immunohistochemistry to evaluate the brain expression of aquaporins (AQP) 1, 4, and 9 mRNA and protein in Sprague–Dawley rats rendered hydrocephalic by injection of kaolin into cistern magna. AQP4 mRNA was significantly up‐regulated in parietal cerebrum and hippocampus 4 weeks and 9 months after induction of hydrocephalus (P < 0.05). Although Western blot analysis showed no significant change, there was more intense perivascular AQP4 immunoreactivity in cerebrum of hydrocephalic brains at 3–4 weeks after induction. We did not detect mRNA or protein changes in AQP1 (located in choroid plexus) or AQP9 (located in select neuron populations). Kir4.1, a potassium channel protein linked to water flux, exhibited enhanced immunoreactivity in the cerebral cortex of hydrocephalic rats; the perineuronal distribution was entirely different from that of AQP4. These results suggest that brain AQP4 up‐regulation might be a compensatory response to maintain water homeostasis in hydrocephalus.
Localization of the GoLoco motif carrier regulator of G‐protein signalling 12 and 14 proteins in monkey and rat brain
Authors: López‐Aranda Manuel F. , Acevedo Maria J. , Carballo Francisco J. , Gutiérrez Antonia , Khan Zafar U.
Published: June 2006

Regulator of G‐protein signalling (RGS)12 and ‐14 proteins possess the RGS domain, Ras‐binding domains and the GoLoco motif. Emerging evidence suggests that these proteins are involved in several cellular functions in addition to stimulation of GTPase activity of G‐protein α subunits. However, our understanding of the role of the two proteins in brain function remains marginal. Here, we have studied the expression pattern of RGS12 and RGS14 proteins in brain at regional, cellular and subcellular levels. Both proteins were expressed throughout the brain regions, including cortex, hippocampus, striatum, thalamus and substantia nigra. The most intense immunostaining for RGS12 was seen in cortex and that of RGS14 was found in striatum. In cortex, RGS12 and RGS14 proteins were associated with pyramidal and nonpyramidal cell types. Apical dendrites of pyramidal cells were also labelled. RGS12 was found in both nuclear and cytoplasmic compartments. In contrast to RGS12 protein, RGS14 was localized in astrocytes in addition to neurons. Pyramidal cells in the CA1 area showed labelling for both RGS proteins. The presence of RGS12 was predominantly nuclear in the striatum of rat brain; however, the labelling of this protein was non‐nuclear in adult monkey brain. To our surprise, in 1‐month‐old monkey brain the immunostaining pattern of the same protein was changed to nuclear. Non‐nuclear staining for RGS12 was also evident in thalamus of adult monkey brain; however, in 1‐month‐old monkey brain, it was seen into two different populations, one with nuclear and the other with cytoplasmic staining. Both RGS12 and RGS14 were exclusively localized at postsynaptic sites of excitatory synapses. Our results demonstrate a highly dynamic expression pattern of RGS12 and RGS14 proteins in the central nervous system, and support the view that these proteins may participate not only in G‐protein receptor signalling pathways but also in other cellular activities.
Improved cortical entrainment to infant communication calls in mothers compared with virgin mice
Authors: Liu Robert C. , Linden Jennifer F. , Schreiner Christoph E.
Published: June 2006

There is a growing interest in the use of mice as a model system for species‐specific communication. In particular, ultrasonic calls emitted by mouse pups communicate distress, and elicit a search and retrieval response from mothers. Behaviorally, mothers prefer and recognize these calls in two‐alternative choice tests, in contrast to pup‐naïve females that do not have experience with pups. Here, we explored whether one particular acoustic feature that defines these calls − the repetition rate of calls within a bout − is represented differently in the auditory cortex of these two animal groups. Multiunit recordings in anesthetized CBA/CaJ mice revealed that: (i) neural entrainment to repeated stimuli extended up to the natural pup call repetition rate (5 Hz) in mothers; but (ii) neurons in naïve females followed repeated stimuli well only at slower repetition rates; and (iii) entrained responses to repeated pup calls were less sensitive to natural pup call variability in mothers than in pup‐naïve females. In the broader context, our data suggest that auditory cortical responses to communication sounds are plastic, and that communicative significance is correlated with an improved cortical representation.
Selective loss of dopaminergic neurons and formation of Lewy body‐like aggregations in α‐synuclein transgenic fly neuronal cultures
Authors: Park Soon S. , Lee Daewoo
Published: June 2006

A key pathological feature of Parkinson's disease (PD) is the selective loss of dopaminergic neurons accompanied by the formation of Lewy bodies (LB). Given the complex nature of the disease, it is imperative to develop a model system suitable for molecular and cellular manipulation in order to study the mechanisms underlying the pathogenesis of PD. Here, we report that a new in vitro model of PD has been developed by using Drosophila melanogaster primary neuronal cultures expressing a human mutant α‐synuclein (α‐Syn; A30P). The selective loss of dopaminergic (DA) neurons was observed when α‐Syn was pan‐neuronally expressed while non‐dopaminergic neurons (e.g. GABAergic) were not influenced. This degeneration was also observed even when α‐Syn was specifically expressed in DA neurons, demonstrating α‐Syn toxicity is DA cell‐autonomous. In all experiments, cultures 5 days or older showed clear degeneration of DA neurons whereas this degeneration was not significant in 3‐day‐old cultures. In addition, there were intracellular aggregations in 5‐day or older α‐Syn neurons that were recognized by anti‐α‐Syn or ubiquitin antibodies, demonstrating the formation of LB‐like inclusions. By contrast, no such aggregations were found in 3‐day‐old neurons. The results demonstrate that mutated human α‐Syn expressed in Drosophila primary neuronal cultures causes the selective loss of DA neurons and the formation of cellular aggregations. Therefore, this is one of the first in vitro models recapitulating two important cellular features of PD and will be useful in examining mechanisms underlying selective neurodegeneration mediated by α‐Syn.
Interaction of LDL receptor‐related protein 4 (LRP4) with postsynaptic scaffold proteins via its C‐terminal PDZ domain‐binding motif, and its regulation by Ca2+/calmodulin‐dependent protein kinase II
Authors: Tian Qing‐Bao , Suzuki Tatsuo , Yamauchi Takashi , Sakagami Hiroyuki , Yoshimura Yoshiyuki , Miyazawa Shoko , Nakayama Kohzo , Saitoh Fuminori , Zhang Jing‐Ping , Lu Yonghao , Kondo Hisatake , Endo Shogo
Published: June 2006

We cloned here a full‐length cDNA of Dem26[Tian et al. (1999)Mol. Brain Res., 72, 147–157], a member of the low‐density lipoprotein (LDL) receptor gene family from the rat brain. We originally named the corresponding protein synaptic LDL receptor‐related protein (synLRP) [Tian et al. (2002) Soc. Neurosci. Abstr., 28, 405] and have renamed it LRP4 to accord it systematic nomenclature (GenBankTM accession no. AB073317). LRP4 protein interacted with postsynaptic scaffold proteins such as postsynaptic density (PSD)‐95 via its C‐terminal tail sequence, and associated with N‐methyl‐d‐aspartate (NMDA)‐type glutamate receptor subunit. The mRNA of LRP4 was localized to dendrites, as well as somas, of neuronal cells, and the full‐length protein of 250 kDa was highly concentrated in the brain and localized to various subcellular compartments in the brain, including synaptic fractions. Immunocytochemical study using cultured cortical neurons suggested surface localization in the neuronal cells both in somas and dendrites. Ca2+/calmodulin‐dependent protein kinase II (CaMKII) phosphorylated the C‐terminal cytoplasmic region of LRP4 at Ser1887 and Ser1900, and the phosphorylation at the latter site suppressed the interaction of the protein with PSD‐95 and synapse‐associated protein 97 (SAP97). These findings suggest a postsynaptic role for LRP4, a putative endocytic multiligand receptor, and a mechanism in which CaMKII regulates PDZ‐dependent protein–protein interactions and receptor dynamics.
Sequential patterns of colonization of coarse woody debris byIps pini(Say) (Coleoptera: Scolytidae) following a major ice storm in Ontario
Authors: Ryall K. L. , De Groot P. , Smith S. M.
Published: June 2006

Abstract 

It is widely known that many bark and wood‐boring beetle species use nonresistant coarse woody debris (CWD) created by disturbances; however, the ability of these secondary species to cause mortality in healthy trees following a build‐up of their populations remains unclear. We characterized the pattern of colonization byIps pini(Say) following a major ice storm that created large amounts of CWD varying in resistance to colonization (i.e. ranging from snapped tops with no resistance to heavily damaged trees with intact root systems). A major question was how the beetles responded to the different types of storm‐damaged material and whether healthy undamaged trees were colonized and killed following increases in beetle populations.

Six red pine,Pinus resinosaAit., plantations in eastern Ontario were monitored from 1998 to 2001 inclusive: three with high storm damage (approximately 120 m3/ha CWD) and three with minimal damage (approximately 20 m3/ha CWD). Transects (200 × 2 m) were sampled yearly in each plantation to assess the type and amount of damaged pine brood material colonized by the pine engraver beetle,I. pini.

Beetles preferentially infested the most nonresistant material available each year (i.e. all snapped tops in year 1, all standing snags, up‐rooted trees and many bent trees by year 2, but still less than 50% of trees blown over but with intact root systems by year 3). By years 3 and 4, the majority (approximately 75%) of severely damaged trees (with > 50% crown loss) died prior to beetle colonization.

The size of the beetle population tracked the abundance of available woody material from year‐to‐year within a plantation; populations were very large in the first 2 years, and declined significantly in the last 2 years.

Healthy standing red pines were apparently resistant to colonization by the beetles, despite the significant build‐up in their populations. Hence, the results of the present study suggest that native bark beetle populations will not cause further tree mortality following such a disturbance in this region.
Seasonal changes in the distribution of green spruce aphid Elatobium abietinum (Walker) (Homoptera: Aphididae) in the canopy of Sitka spruce
Authors: Straw Nigel , Fielding Nick , Green Gill , Price John
Published: June 2006

1 Seasonal changes in the distribution of green spruce aphid Elatobium abietinum (Walker) within the canopy of 20–25‐year‐old Sitka spruce are described based on data from two low‐altitude sites (310–420 m above sea‐level), two mid‐altitude sites (500–550 m a.s.l) and one high‐altitude site (610 m a.s.l).

2 Aphids were counted throughout the canopy on shoots representative of all needle age‐classes present at each whorl of branches. Counts were made during the middle week of each month from September to July for 4 years (1999–2003), and mean E. abietinum densities at each canopy position were calculated separately for each month and for the low‐, mid‐ and high‐altitude sites.

3 During September to November, the highest densities of E. abietinum occurred on 3–4‐year‐old needles on branches low in the canopy. Over the winter and spring, the centre of the aphid’s distribution shifted outward and upward, so that by June of the next year the highest aphid densities occurred on current and 1‐year‐old needles on branches near the top of the tree.

4 The aphid distribution was re‐set each year during July, at the time when the nutrient quality of the host was in decline and E. abietinum populations were decreasing. Aphid densities decreased less on 3–4‐year‐old needles than on current and 1‐year‐old needles, suggesting that older needles were a superior food resource at this time of year and in the autumn. However, other factors, such as higher temperatures in the upper canopy during the summer or differential mortality caused by natural enemies, could also have contributed to the change in distribution.

5 The outward and upward shift in the aphid distribution over the winter period provided no evidence that aphids at positions lower and deeper in the canopy were better insulated from freezing temperatures and had higher over‐winter survival rates. Mean air temperatures at the top and bottom of the canopy during the winter were also found to differ by only 0.1–0.2 °C.

6 The percentage of the total aphids per tree that occurred on current or 1‐year‐old needles varied widely between seasons and between sites. Consequently, sampling programmes designed to estimate total population numbers of E. abietinum have little option but to sample needles throughout the canopy, and at regular intervals during the period when the aphid is abundant.
Cryotherapy in the treatment of pyogenic granuloma
Authors: Mirshams M , Daneshpazhooh M , Mirshekari A , Taheri A , Mansoori P , Hekmat S
Published: June 2006

Background  Pyogenic granuloma is a benign, acquired, proliferative vascular lesion of the skin and mucous membranes. Many different treatments have been used for pyogenic granuloma with variable success rates.

Objectives  To evaluate the efficacy of cryotherapy in the treatment of pyogenic granuloma.

Methods  In a prospective observational study, 135 patients with pyogenic granuloma were treated with cryotherapy using liquid nitrogen. The patients were followed up every 3 weeks until 3 months after disappearance of the lesion.

Results  Complete resolution of the pyogenic granuloma was achieved in all patients after a mean of 1.58 treatments (range, 1–4 treatments). At the end of follow‐up period, there was a flat imperceptible scar, smaller than the treated lesion, in 16 patients (11.8%). A hypertrophic scar, 3 mm in diameter, was observed in one patient. Hypopigmentation was observed in seven patients (5.1%). No other complication or side‐effect was recorded in the study.

Conclusions  We believe that pyogenic granuloma can be treated simply and effectively with cryotherapy.
Epidermal thickness assessed by optical coherence tomography and routine histology: preliminary results of method comparison
Authors: Gambichler T , Boms S , Stücker M , Kreuter A , Moussa G , Sand M , Altmeyer P , Hoffmann K
Published: June 2006

Background  Optical coherence tomography (OCT) is a promising non‐invasive imaging technique for studying the epidermis and upper dermis in vivo. As proposed previously by Welzel et al. (J Am Acad Dermatol 1997; 37: 958–963), distance measurements between the entrance peak and the second peak of the A‐scan seem to correspond to epidermal thickness (ET). However, there is a lack of systematic studies comparing OCT with histology.

Methods  Sixteen healthy subjects were included in this pilot study. OCT assessments were conducted on the upper back. To determine ET by OCT, the distance between the entrance peak and the second peak of the A‐scan was calculated (ET‐OCT). After OCT measurement a 4 mm punch biopsy was taken on each subject from the same site previously assessed. The maximum thickness of the epidermis (ET‐Histo) was determined microscopically using routine histological slices (formalin‐paraffin technique, haematoxylin–eosin staining). Correlation and agreement between the two methods were assessed by means of the Pearson correlation procedure and Bland–Altman plots, respectively.

Results  ET‐Histo was 79.4 ± 21.9 µm, including a stratum corneum thickness of 20 ± 12.1 µm. OCT measurements resulted in an ET of 106 ± 15.4 µm. No correlation between ET‐Histo and ET‐OCT was observed (r = 0.29, P = 0.27). There was a considerable lack of agreement between histology and OCT measurements as expressed in a high bias of 26.63 µm [95% confidence interval (CI) 14.49–38.77]. Furthermore, the lower 95% limits of agreement were −18.03 µm (95% CI −37.11 to 1.05) and the upper 95% limits of agreement were 71.28 µm (95% CI 52.2–90.36) indicating that ET‐OCT may be 71.28 µm above or 18.03 µm below ET‐Histo.

Conclusions  Our preliminary data suggest that the above‐described OCT algorithm is probably not a valid measure for the evaluation of ET. The second peak of the A‐scan seems not to correspond to the dermo‐epidermal junction zone, but rather to fibrous structures in the upper dermis. Nevertheless, further systematic comparison studies between OCT and histology are warranted, using different OCT algorithms for ET determination and cryopreparation, which has a higher reliability than the formalin‐paraffin technique.
Prevalence and predictors of psychosocial morbidity in patients with chronic pruritic skin diseases
Authors: Van Os‐Medendorp H , Eland‐de Kok PCM , Grypdonck M , Bruijnzeel‐Koomen CAFM , Ros WJG
Published: June 2006

Background  Itch is a major symptom of many skin diseases and causes patients considerable distress, adversely affecting quality of life. Feelings of helplessness and lack of control can influence the perceived itch and psychosocial complaints.

Objectives  To determine the prevalence of psychosocial morbidity among patients with pruritic skin diseases, and the influence of itch‐related variables, coping strategies, and demographic variables on psychosocial morbidity.

Patients and methods  One hundred and sixty‐eight patients with pruritic skin diseases from five hospitals in the Netherlands participated in the study. Skin‐related psychosocial morbidity was measured with the Adjustment to Chronic Skin Diseases questionnaire (ACS); general psychosocial morbidity was measured with the Symptom Checklist‐90 (SCL‐90). The frequency and intensity of itching and scratching was recorded in diaries. Itch‐related coping was measured with the Itching Cognitions Questionnaire (ICQ). Multiple regression analyses were used.

Results  Patients with pruritic skin diseases had higher SCL‐90 scores than a healthy Dutch population. All patients had psychosocial complaints as measured with the ACS. Thirty‐nine per cent of the variance in skin‐related psychosocial morbidity was explained by ‘catastrophizing and helpless coping’; another 11% was explained by itching and scratching. Age and sex together explained another 10%. The frequency of itching and scratching (11%), ‘catastrophizing and helpless coping’ (19%) and skin‐related psychosocial morbidity (10%) explained the variance in general psychosocial morbidity.

Conclusions  Patients with a pruritic skin disease have a high level of psychosocial morbidity. Catastrophizing and helpless coping are the most important predictors of psychosocial morbidity, with itching, scratching and demographic variables having a limited influence.
Acute neuropsychological effects of methylphenidate in stimulant drug‐naïve boys with ADHD II – broader executive and non‐executive domains
Authors: Rhodes Sinéad M. , Coghill David R. , Matthews Keith
Published: June 2006

Background:  Accumulating evidence supports methylphenidate‐induced enhancement of neuropsychological functioning in attention deficit hyperactivity disorder (ADHD). The present study was designed to investigate the acute effects of the psychostimulant drug, methylphenidate (MPH), on neuropsychological performance in stimulant naïve boys with ADHD.

Methods:  Seventy‐three drug‐naïve boys (age 7–15) with ADHD (combined type) completed neuropsychological tasks from the CANTAB battery under randomised, placebo controlled, double‐blind conditions following an acute challenge with either placebo (n = 24), .3 (n = 25) or .6 (n = 24) mg/kg oral MPH.

Results:  MPH did not impair performance on any task. MPH (.6 mg/kg) lengthened response latencies on a task of Spatial Recognition, shortened response times on a Reaction Time task and restored performance on a Delayed Matching to Sample visual, non‐working memory task. Contrary to predictions, MPH did not enhance performance on tasks with a prominent executive component, including Go/NoGo, Spatial Working Memory, Stockings of Cambridge and Attentional Set shifting tasks.

Conclusions:  Acute administration of MPH to drug‐naïve boys with ADHD did not impair neuropsychological performance. Acute MPH enhanced performance on some aspects of non‐executive functioning. MPH‐induced slowing of responding on a relatively complex Spatial Recognition memory task and quickened responding on a reaction time task requiring less cognitive resources suggests that MPH may act by improving self‐regulatory ability. MPH may not exert its effects on neuropsychological functioning by enhancing executive processes.
Trajectories of aggression from toddlerhood to age 9 predict academic and social functioning through age 12
Authors: Campbell Susan B. , Spieker Susan , Burchinal Margaret , Poe Michele D. ,   The NICHD Early Child Care Research Network
Published: June 2006

Background:  Using longitudinal data from the NICHD Study of Early Child Care and Youth Development, we examined behavior problems and social and academic outcomes from ages 9 through 12 in children classified into five trajectories of physical aggression, on the basis of maternal ratings obtained from 24 months through 9 years (N = 1195).

Methods:  Outcome data were obtained from teacher reports, observations of children's behavior, and children's self‐reports.

Results:  Children on the high‐stable aggression trajectory (3% of sample) showed the most severe adjustment problems, including poorer social skills, higher levels of externalizing problems, and more self‐reported peer problems; those on the moderate‐stable aggression trajectory (15%) showed poor regulation and inattention. Although children with moderate levels of early aggression that decreased sharply by school entry (12%) appeared well adjusted at follow‐up, those who showed a low level of stable aggression (25%) evidenced some unanticipated social and behavior problems. Children in the contrast group (45%) were consistently very low in aggression from toddlerhood onward.

Conclusions:  Results highlight links between different patterns (stable or decreasing) and levels (high, moderate, low, very low) of aggression across childhood and children's later adjustment. For example, even quite low aggression that is stable appears to be a risk factor for some social problems; in contrast, moderate aggression that decreases sharply to no aggression by school entry is associated with good adjustment at age 12.
Processing emotional facial expressions influences performance on a Go/NoGo task in pediatric anxiety and depression
Authors: Ladouceur Cecile D. , Dahl Ronald E. , Williamson Douglas E. , Birmaher Boris , Axelson David A. , Ryan Neal D. , Casey B.J.
Published: June 2006

Background:  This study investigated whether processing emotionally salient information such as emotional facial expressions influences the performance on a cognitive control task in pediatric anxiety and depression.

Methods:  The sample included 68 participants between 8 and 16 years of age selected into three diagnostic groups: Anxiety Disorder (ANX, n = 23), Major Depressive Disorder (MDD, n = 19), and Low‐Risk Normal Control (LRNC, n = 26). Participants completed an Emotional Go/NoGo task in which participants must either respond to (Go trials) or not respond to (NoGo trials) specific facial expressions (angry, fearful, sad, happy, neutral). In order to manipulate the level of cognitive control needed to perform the task, the probability of occurrence of the Go trials was varied across 3 probability conditions (low, moderate, high).

Results:  Analyses showed that the MDD group had significantly faster reaction times to sad face Go trials embedded in neutral face NoGo trials in the moderate probability condition and that the ANX group had significantly slower reaction times to neutral face Go trials embedded in angry face NoGo trials in the low probability condition.

Conclusions:  These data demonstrate that processing emotional facial expressions influences the performance on a cognitive control task in children and adolescents diagnosed with an anxiety disorder and major depression.
Reproductive seasonality in the Tete veld rat (Aethomys ineptus) (Rodentia: Muridae) from southern Africa
Authors: Muteka S. P. , Chimimba C. T. , Bennett N. C.
Published: June 2006

Very little is known about the reproductive biology of the recently recognized Tete veld rat Aethomys ineptus. In the present study, we investigated the seasonality of reproduction in this newly recognized rodent using a number of histological and endocrinological parameters. Body mass, reproductive tract morphometrics, gonadal histology, and plasma testosterone concentrations in males and plasma oestradiol‐17β and progesterone concentrations in females were assessed from a population in the north‐central part of South Africa over a 12‐month period in order to ascertain the pattern of reproduction in the species. Seminiferous tubule diameters in 59 males were significantly larger between September and February relative to between March and August. Although spermatogenesis was prevalent in the southern hemisphere winter (June–August), the number of spermatozoa in the epididymides decreased in the southern hemisphere spring (September–November), summer (December–February) and autumn (March–May). Testicular mass relative to body mass and testicular volume regressed between May and September but exhibited recrudescence between September and April, whereas plasma testosterone concentrations increased significantly between September and February relative to between March and August. Ovarian histology of 67 females showed corpora lutea to be present throughout the year, but decreased in number during winter, whereas mean plasma progesterone concentration increased significantly between August and November and again between February and April. This bimodal pattern of progesterone concentration suggests that up to two litters per breeding season may be raised by the Tete veld rat. Gravid females were found between October and April, whereas gravid or lactating females were conspicuously absent between May and September. Collation of all these data suggests that the Tete veld rat is a seasonal breeder with reproduction confined predominantly to summer and autumn months of the southern hemisphere. However, the presence of follicular development in females and the presence of corpora lutea outside the breeding season imply that the Tete veld rat may undergo spontaneous ovulation.
Strategic interaction among courts within the preliminary reference process – Stage 1: National court preemptive opinions
Authors: NYIKOS STACY A.
Published: June 2006

Abstract.  While scholars today are well‐acquainted with how the European Community preliminary reference process works, little research has been done to investigate strategic court interaction – that is, intentional, procedural court behaviour employed to influence the substantive direction of legal evolution, within that process. The present investigation, which is part of a larger project examining such court behaviour throughout the referral process, focuses on the initial stage: the decision to refer. Within that stage lies the opportunity for national courts to stack the interpretive deck for the entire decision‐making process via a preemptive opinion, the submission of which is neither required, suggested nor prohibited by written procedural guidelines. It is assumed that courts are strategic institutions that seek to maximize their policy objectives, and therefore, national courts submit preemptive opinions to obtain that goal. Such strategic behaviour, however, is influenced by intervening factors – namely the acceptance of European Court of Justice intervention, national judicial procedure, issue complexity and individual court experience.
Teamwork as an Essential Component of High‐Reliability Organizations
Authors: Baker David P. , Day Rachel , Salas Eduardo
Published: June 2006

Organizations are increasingly becoming dynamic and unstable. This evolution has given rise to greater reliance on teams and increased complexity in terms of team composition, skills required, and degree of risk involved. High‐reliability organizations (HROs) are those that exist in such hazardous environments where the consequences of errors are high, but the occurrence of error is extremely low. In this article, we argue that teamwork is an essential component of achieving high reliability particularly in health care organizations. We describe the fundamental characteristics of teams, review strategies in team training, demonstrate the criticality of teamwork in HROs and finally, identify specific challenges the health care community must address to improve teamwork and enhance reliability.
Creating High Reliability in Health Care Organizations
Authors: Pronovost Peter J. , Berenholtz Sean M. , Goeschel Christine A. , Needham Dale M. , Sexton J. Bryan , Thompson David A. , Lubomski Lisa H. , Marsteller Jill A. , Makary Martin A. , Hunt Elizabeth
Published: June 2006

Objective. The objective of this paper was to present a comprehensive approach to help health care organizations reliably deliver effective interventions.

Context. Reliability in healthcare translates into using valid rate‐based measures. Yet high reliability organizations have proven that the context in which care is delivered, called organizational culture, also has important influences on patient safety.

Model for Improvement. Our model to improve reliability, which also includes interventions to improve culture, focuses on valid rate‐based measures. This model includes (1) identifying evidence‐based interventions that improve the outcome, (2) selecting interventions with the most impact on outcomes and converting to behaviors, (3) developing measures to evaluate reliability, (4) measuring baseline performance, and (5) ensuring patients receive the evidence‐based interventions. The comprehensive unit‐based safety program (CUSP) is used to improve culture and guide organizations in learning from mistakes that are important, but cannot be measured as rates.

Conclusions. We present how this model was used in over 100 intensive care units in Michigan to improve culture and eliminate catheter‐related blood stream infections—both were accomplished. Our model differs from existing models in that it incorporates efforts to improve a vital component for system redesign—culture, it targets 3 important groups—senior leaders, team leaders, and front line staff, and facilitates change management—engage, educate, execute, and evaluate for planned interventions.
Making Noncatastrophic Health Care Processes Reliable: Learning to Walk before Running in Creating High‐Reliability Organizations
Authors: Resar Roger K.
Published: June 2006

Health care clinicians successfully apply proven medical evidence in common acute, chronic, or preventive care processes less than 80 percent of the time. This low level of reliability at the basic process level means that health care's efforts to improve reliability start from a different baseline from most other industries, and therefore may require a different approach. This paper describes The Institute for Healthcare Improvement's (IHI) current approach to improving health care reliability, including a useful nomenclature for levels of reliability, and a focus on improving reliability of basic health care processes before moving on to more sophisticated high reliability organization concepts. Early IHI work with a community of health care reliability innovators has identified four themes in health care settings that help to explain at least a portion of the gap in process reliability between health care and other industries. These include extreme dependence on hard work and personal vigilance, a focus on mediocre benchmark outcomes rather than process, great tolerance of provider autonomy, and failure to create systems that are specifically designed to reach articulated reliability goals. This paper describes our recommendations for the initial steps health care organizations' might take, based on these four themes, as they begin to move toward higher reliability.
Effects of water discharge and temperature on the seaward migration of anadromous browntrout, Salmo trutta, smolts
Authors: Hembrel B. , Arnekleiv J. V. , L'Abée‐Lund J. H.
Published: June 2006

Abstract
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The smolt run of anadromous brown trout (Sulmo trutta) in a Norwegian river was studied for three consecutive years. The main run occurred in a period of 7–10 days in the middle or second half of May. Support was found for the hypothesis that high water discharge and temperature triggered the run. Few smolts descended when the discharge was low (<50 m3· s−1) and the water temperature was below 4°C. The maximum number were caught when the discharge was moderate (70–150 m3· s−1) and the water temperature high (68°C). The relative importance of these factors varied from year to year. The first‐year discharge explained 38% of the variation in the number of smolts migrating. Discharge and temperature together explained 61% in 1992 and 28% in the second and third year, respectively.
Role of calcium in the gating of isoproterenol‐induced arylalkylamine N‐acetyltransferase gene expression in the mouse pineal gland
Authors: Chansard Mathieu , Liang Jian , Iwahana Eiko , Baker Tabari , Whittaker Joseph , Fukuhara Chiaki
Published: June 2006

Abstract:  Melatonin and its autonomic regulation serve important physiological functions. We recently demonstrated that stimulation of beta‐adrenergic receptors only increases nighttime arylalkylamine N‐acetyltransferase (Aa‐Nat, the rate‐limiting enzyme in melatonin synthesis) mRNA levels in mouse pineal gland in vitro, which suggests that pineal clocks may gate Aa‐Nat gene expression. In the present study, our data reveal that cAMP analog increased Aa‐Nat at any time of day but only in the presence of ionomycin. Using Fura‐2AM in ratiometric calcium measurements, we show that isoproterenol stimulation increased intracellular free calcium levels at night, contrary to previous reports. Further, intra‐ or extracellular calcium depletion suppressed the isoproterenol‐induced calcium responses as well as Aa‐Nat gene expression. These results suggest calcium may be a critical factor in isoproterenol‐induced Aa‐Nat gene expression, which may be limited in the daytime. We also found that basal intracellular calcium levels were lower during the night and responses to isoproterenol and KCl depolarization were more robust. In addition, pineals of Cryptochrome mutant mice exhibited no significant difference between day and nighttime basal calcium or isoproterenol response. Together, these results suggest that basal calcium levels in the pineal may be controlled by the endogenous pineal clock, which may influence calcium dynamics, cellular homeostasis and sensitivity to external stimulation. Although the mechanism underlying Aa‐Nat gene expression has been well studied, the role of calcium as a link between the pineal clock and Aa‐Nat gene expression has been underestimated in rodent pineals.
Melatonin induces apoptosis in human neuroblastoma cancer cells
Authors: García‐Santos Guillermo , Antolín Isaac , Herrera Federico , Martín Vanesa , Rodriguez‐Blanco Jezabel , Carrera Maria del Pilar , Rodriguez Carmen
Published: June 2006

Abstract:  Low concentrations (nanomolar) of melatonin had been previously shown to inhibit cell proliferation in several cancer cell lines as well as in experimental animal models. Additionally, cell growth inhibition and differentiation of prostate cancer cell lines by high concentrations (micromolar to millimolar) of melatonin have been recently reported. In the present paper, we show the induction of apoptosis by high doses of melatonin in the human neuroblastoma cell line SK‐N‐MC. We found accumulation of cells in the G2/M cell cycle phase and induction of cellular death, measured as lactate dehydrogenase (LDH) released into the culture medium, under millimolar concentration of melatonin. Apoptosis was evaluated using 4,6‐diamidino‐2‐phenylindole staining, DNA gel electrophoresis, electron microscopy, and annexin V binding. Apoptosis progressed through the classical pathway, which involves caspase‐3 activation. Cell death was dose and time‐dependent; the lowest effective concentration of melatonin was 100 μm. Treatment with 1 mm melatonin for 6 days induced cell death in 75% of the cells. This novel finding shows that a nontoxic natural indoleamine may be potential therapy for some types of human neuroblastomas.
Injury switches melatonin production source from endocrine (pineal) to paracrine (phagocytes) – melatonin in human colostrum and colostrum phagocytes
Authors: Pontes Gerlândia N. , Cardoso Elaine C. , Carneiro‐Sampaio Magda M. S. , Markus Regina P.
Published: June 2006

Abstract:  A large number of data show that melatonin has immunomodulatory properties and is produced by immunocompetent cells; also, some evidence suggests a ‘feedback’ of the activated immune system on the pineal gland. In this paper, we studied immune–pineal interactions in colostrum obtained from healthy puerperae and mothers with mastitis taking into account that, (a) melatonin levels in milk reflects pineal activity and (b) colostrum quiescent mononuclear and polymorphonuclear phagocytes from healthy mothers in culture are adequate for evaluating the ability of immunocompetent cells to produce melatonin. Here we compared the diurnal and nocturnal melatonin levels in colostrum from healthy puerperae and mothers with mastitis; this is a unique noninvasive model for determining pineal activity in the proinflammatory phase of a defense response. In addition, we determined the ‘in vitro’ production of melatonin by colostrum immunocompetent cells stimulated by enteropathogenic Escherichia coli or zymosan. Suppression of nocturnal melatonin rise in mothers with mastitis was highly correlated with increased tumor necrosis factor‐α (TNF‐α) secretion. This result, interpreted taking into account the presence of the transcription factor nuclear factor kappa B in pineal gland, suggest that the proinflammatory cytokine can inhibit nocturnal pineal melatonin production. On the other hand, stimulated, but not quiescent, immunocompetent cells secreted in the colostrum produced melatonin in vitro. In addition, this production ceases after bacteria killing. These results suggest that during the response to an injury the production of melatonin can be transiently shifted from an endocrine (pineal) to a paracrine (immunocompetent cells) source.
Melatonin ameliorates nonalcoholic fatty liver induced by high‐fat diet in rats
Authors: Pan Min , Song Yu‐Lin , Xu Jian‐Ming , Gan Hui‐Zhong
Published: June 2006

Abstract:  Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized condition that may progress to end‐stage liver disease, which ranges from simple steatosis to steatohepatitis, advanced fibrosis, and cirrhosis. Oxidative stress and lipid peroxidation are key pathophysiological mechanisms in NAFLD. We investigate the preventive effects of intraperitoneal administration of melatonin (2.5, 5, 10 mg/kg, daily, respectively) in NAFLD rats induced by high‐fat diets for 12 wk. Liver damage was evaluated by serological analysis, serum and hepatic lipid assay as well as hematoxylin–eosin staining in liver sections. Oxidative stress and lipid peroxidation were assessed by measuring malondialdehyde (MDA) levels and superoxide dismutase (SOD) and glutathione peroxidase (GSH‐Px) activities in liver. The results showed that high‐fat diet induced oxidative stress with extensive liver steatosis in rats. Melatonin (5 or 10 mg/kg) was effective in reducing hepatic steatosis and inflammation with lowering serum alanine aminotransferase, aspartate aminotransferase, and levels liver total cholesterol and triglycerides in high‐fat diet rats. Moreover, melatonin (2.5, 5, 10 mg/kg) increased SOD and GSH‐Px activities and the 10 mg/kg dose of melatonin reduced MDA levels in liver. This study shows that melatonin exerts protective effects against fatty liver in rats induced by high‐fat diet possibly through its antioxidant actions.
Perceptions of Death and Management of Grief in People with Intellectual Disability
Authors: Meeusen‐van de Kerkhof Rianne , Van Bommel Hanneke , Van De Wouw Werner , Maaskant Marian
Published: June 2006

Abstract  The authors examine the way in which people with intellectual disability (ID) handle death and mourning, and note that the way in which death and bereavement are being experienced depends – among other things – upon the intellectual and socio‐emotional age of the individual. The authors used the theories formulated by Piaget (cognitive development), Došen (socio‐emotional development), Timmers‐Huigens (strategies of ordering experience), and Fowler (stages of faith) to frame an explanation of how people with ID perceive and experience death. This ranges from hardly any understanding (among persons with profound ID) to a clear realization (among persons with mild ID) of death. Within this framework, the authors offer suggestions and tools for counselors that can be used to help people with ID to manage grief, contingent on their degree of emotional‐cognitive‐social development (e.g., offering closeness and physical contact, using specific rituals, making use of stories and photographs, and allowing participation in farewell rituals).
Promoting Self‐Determination in Health and Medical Care: A Critical Component of Addressing Health Disparities in People with Intellectual Disabilities
Authors: Shogren Karrie A. , Wehmeyer Michael L. , Reese R. Matthew , O’Hara David
Published: June 2006

Abstract As increased attention has been directed toward the disparities experienced by people with intellectual disabilities in achieving positive health outcomes, the importance of promoting the active involvement of people with intellectual disabilities in efforts to reduce such disparities and promote positive health and wellness outcomes has been acknowledged by researchers and policymakers. This parallels the larger movement within the disability field to promote the self‐determination and empowerment of people with intellectual disabilities. The authors more explicitly discuss the implications of self‐determination, as it has been conceptualized in the disability field, for promoting positive health and wellness outcomes in people with intellectual disabilities. They review the current research on self‐determination and its impact on health, as well as the implications of this research for the development of strategies that promote self‐determination in the achievement of health and wellness outcomes in people with intellectual disabilities. The authors posit the need to extend an understanding of the implications of self‐determination for promoting health in people with disabilities not only to the disability field, but also to the medical and public health fields. They also provide recommendations for future research and practice.
Attitudes of Research Ethics Committee Members Toward Individuals with Intellectual Disabilities: The Need for More Research
Authors: Lai Roxanne , Elliott Deborah , Ouellette‐Kuntz Hélène
Published: June 2006

Abstract Select research areas affecting individuals with intellectual disabilities (ID) are understudied, resulting in their often being routinely excluded from drug trials and other medically based research. Many factors contributing to this exclusion have been identified, but little has been written about the effects of research ethics committees on inhibiting ID research. By exploring the role of ethics committees in research, and reviewing the ethical guidelines and other factors that direct their decisions, this article argues that committee members’ attitudes toward ID often affect their response to proposals involving this group of individuals. The authors note that in many countries, research ethics guidelines provide little direction on how to weigh conflicting ethical duties toward vulnerable individuals. As a result, committee members often adopt unsystematic approaches toward ethical dilemmas, creating an environment where their attitudes can have a disproportionate effect on their decisions. The authors suggest that the attitudes of research ethics committee members toward individuals with ID must be studied in further detail if we are to understand and address the exclusion of individuals with ID from medical research.
Implementation of Goal Attainment Scaling in Community Intellectual Disability Services
Authors: Chapman Melanie , Burton Mark , Hunt Victoria , Reeves David
Published: June 2006

Abstract  The authors describe the evaluation of the implementation of an outcome measurement system (Goal Attainment Scaling – GAS) within the context of an interdisciplinary and interagency intellectual disability services setting. The GAS database allowed analysis of follow‐up goals and indicated the extent of implementation, while a rater study evaluated the quality of goals. While staff were able to produce adequate goals and scales, fewer goals were set than anticipated, and the overall quality was not high. Although implementation resulted in a number of perceived benefits, various barriers to implementation were experienced. These hinged on staff perceptions of the value, ease of use, appropriateness, and soundness of the method. Widespread adoption of GAS in community intellectual disability teams is not supported by the findings of this study. The authors suggest that staff perceptions, ease of use, and the implementation process play a key role in the successful adoption of an outcome measurement system. They conclude that alternative ways of measuring individually oriented outcomes may be more useful.