bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal plasma or human serum albumin in wash buffer enhances enrichment and ex vivo expansion of human umbilical cord blood CD34+ cells
Authors: Kwok Yvonne K. , Tang Mary H. Y. , Law Helen K. W. , Ngai Cora S. , Lau Yu Lung , Lau Elizabeth T.
Published: May 2007

Umbilical cord blood is a valuable source of haemopoietic stem/progenitor cells (HSC) for transplantation. This study explored the effect of maternal plasma/human serum albumin (HSA) in the purification and culture conditions of CD34+ cells derived from human umbilical cord blood. During CD34+ cell enrichment, including maternal plasma or HSA instead of fetal bovine serum (FBS) in the wash buffer, significantly increased the purity and the fold expansion of CD34+ cells. The increase in fold expansion of CD34+ cells was independent of CD34+ cell purity before expansion. With FBS, the mean fold expansion of CD34+ cells and total nucleated cells on day 7 was 9·7 ± 5·5 and 39·7 ± 13·7 respectively. The use of maternal plasma increased the mean fold expansion of CD34+ cells and total nucleated cells on day 7 to 28·2 ± 6·7 and 71·5 ± 15·4 respectively. When HSA was added to wash buffer, the mean fold expansion of CD34+ cells and total nucleated cells were 30·4 ± 10·5 and 83·5 ± 24·8 respectively. No statistical significance was found between using HSA and maternal plasma on total cell and CD34+ cell expansion. We propose that HSA in maternal plasma was responsible for the positive effect on CD34+ cell enrichment and expansion.
Detecting zones of abrupt change in soil data, with an application to an agricultural field
Authors: Gabriel E. , Allard D. , Mary B. , Guérif M.
Published: May 2007

We propose a new method for estimating and testing the zones where a variable has discontinuities or sharp changes in the mean. Such zones are called Zones of Abrupt Change (ZACs). Our method is based on the statistical properties of the estimated gradient of the variable. The local gradient is first interpolated by kriging. Then we test whether the estimated local gradient exceeds some critical threshold computed under the null hypothesis of a constant mean. The locations where the local test is rejected define the potential ZACs, which are then tested globally. Using this method, we analysed soil data from an agricultural field. The analysis of the main soil components of the ploughed layer (clay, silt and sand particles and calcium carbonate content) reveals the structural variations in the field, linked to boundaries between soil types. Its application to non‐permanent variables (soil water and mineral nitrogen content of the soil profile to 120 cm taken at several dates) shows that water content has the same ZACs for all dates, whereas mineral nitrogen has none.
A conceptual model of HIV/AIDS stigma from five African countries
Authors: Holzemer William L. , Uys Leana , Makoae Lucy , Stewart Anita , Phetlhu René , Dlamini Priscilla S. , Greeff Minrie , Kohi Thecla W. , Chirwa Maureen , Cuca Yvette , Naidoo Joanne
Published: May 2007

Title. A conceptual model of HIV/AIDS stigma from five African countries

Aim.  This paper is a report on the development of a conceptual model delineating contexts and processes of HIV/AIDS stigma as reported by persons living with HIV/AIDS and nurses from African countries. It is part of a larger study to increase understanding of HIV/AIDS stigma.

Background.  Researchers have defined stigma, explored determinants and outcomes of stigma and attempted to measure its multiple dimensions. This literature is difficult to synthesize, and often does not distinguish adequately between experiences of stigma and its causes and outcomes.

Method.  Forty‐three focus groups were held with persons living with HIV/AIDS and nurses in five African countries in 2004. Focus group recordings were transcribed and coded. The data were organized into a conceptual model of HIV/AIDS stigma.

Findings.  Two components were identified in the data: contextual factors – environment, healthcare system, agents – that influence and affect stigma and the stigma process itself. The stigma process included four dimensions: triggers of stigma, stigmatizing behaviours, types of stigma and the outcomes of stigma.

Conclusion.  A conceptual model is presented that delineates the dynamic nature of stigma as reported by study participants. The model may be used to identify areas appropriate for the design and testing of stigma reduction interventions that have a goal of reducing the burden of HIV/AIDS stigma.
Correlates of consequences of intergenerational caregiving in Taiwan
Authors: Lee Ming‐Der
Published: May 2007

Title. Correlates of consequences of intergenerational caregiving in Taiwan

Aim.  This paper is a report of a study to test a theoretical model of factors related to consequences of intergenerational caregiving among Taiwanese caregivers of cognitively impaired ageing relatives.

Background.  With the ageing of the population worldwide, care of elders has become a pressing issue. Intergenerational caregiving behaviours may reflect cultural values and beliefs, but create conflict for adult children between traditional obligations to ageing parents and the capacity to provide care.

Methods.  Adult caregivers (n = 130) of cognitively impaired ageing relatives were recruited from three home care agencies in northern Taiwan between September 2003 and February 2004. Role and attachment theories were combined to extend the understanding of the consequences of intergenerational caregiving.

Results.  Caregiving consequences (role strain and role reward) were not polar opposites on a unidimensional continuum. Caregiver role conflict and role performance had positive relationships with role strain, whereas caregiving resources and role expectation had an inverse relationship. For caregiver role reward, only role performance and secure‐attached style were positively correlated. Role demand was not a statistically significant predictor of either role strain or role reward. Furthermore, secure‐attached style explained additional variance in role strain and role reward. Moderating effects involving secure attachment with other predictors of role strain and role reward were supported.

Conclusion.  By incorporating role and attachment theories, our model gives a more complete view of intergenerational caregiving in an Asian culture. These findings may be applicable to other countries with Chinese populations.
Nursing students’ career preferences: a Norwegian study
Authors: Kloster Torill , Høie Magnhild , Skår Randi
Published: May 2007

Title. Nursing students’ career preferences: a Norwegian study

Aim.  This paper is a report of a study to identify Norwegian undergraduate nursing students’ career preferences at the beginning and end of their nursing education programme, together with their reasons for these preferences.

Background.  International studies have shown that recruitment and retention of nurses in areas such as aged care and psychiatric nursing is difficult. It is important to know why some working areas are popular whilst others are not, so that nursing schools produce graduates who meet the needs of the community.

Methods.  All students starting their nursing education programme in 2001/2002 in five Norwegian university colleges were invited to complete questionnaires at the beginning and end of their nursing education programme. In phase 1, 620 of 782 commencing students completed questionnaires (response rate 79·2%). In their third year, phase 2, 473 questionnaires were distributed (response rate 82·6%, n = 386). The questionnaire included closed questions about career preferences and open‐ended questions seeking the reasons for the preferences.

Results.  The study revealed changes in preferences between the beginning and the end of the nursing education programme. In phase 1, midwifery and paediatric nursing were ranked highest and in phase 2 working in medical/surgical ward, midwifery and psychiatric nursing were preferred. Working in aged care institutions remained unpopular throughout. Clinical experiences and professional challenges were often given as reasons for preferences.

Conclusion.  Nursing educators, clinical nurses and policymakers must reconsider their priorities and improve working conditions for nurses in aged care in order to meet society's need for nurses.
Using a conceptual model in nursing research – mitigating fatigue in cancer patients
Authors: Mock Victoria , St. Ours Christine , Hall Sue , Bositis Amy , Tillery Miriam , Belcher Anne , Krumm Sharon , McCorkle Ruth
Published: May 2007

Title.  Using a conceptual model in nursing research – mitigating fatigue in cancer patients

Aim.  This paper is a discussion of the use of the Levine Conservation Model to guide the investigation of an exercise intervention to mitigate cancer‐related fatigue.

Background.  Researchers use conceptual models or theoretical frameworks to provide an organizing structure for their studies, to guide the development and testing of hypotheses, and to place research finding within the context of science. Selection of an appropriate and useful framework is an essential step in the development of a research project.

Method.  A descriptive approach is used to present the components of the conceptual model and details of the articulation of the study intervention and outcomes with the model.

Findings.  The Levine Conservation Model provided a useful framework for this investigation, conducted in 2002–2006, of the effects of exercise on fatigue and physical functioning in cancer patients. The four conservation principles of the model guided the development of the exercise intervention, the identification of salient outcomes for patients, and the selection of appropriate instruments to measure study variables. The model is also proving useful in the analysis and interpretation of data in relation to the conservation principles.

Conclusion.  Use of an appropriate conceptual model facilitates the design and testing of theory‐based interventions and the development of science to support nursing practice.
Phylogeography of the high alpine plant Senecio halleri (Asteraceae) in the European Alps: in situ glacial survival with postglacial stepwise dispersal into peripheral areas
Authors: BETTIN O. , CORNEJO C. , EDWARDS P. J. , HOLDEREGGER R.
Published: May 2007

Whether alpine plant species survived Pleistocene glaciations in situ on high alpine nunatak mountains is still under debate. To test this hypothesis, Senecio halleri, a high alpine and endemic species with a narrow distribution range in the European Alps, was chosen as a model organism. Polymerase chain reaction‐restriction fragment length polymorphisms of chloroplast DNA (cpDNA PCR‐RFLPs) were used in a phylogeographic analysis of 14 populations of S. halleri, covering its total distribution area. The results of haplotype diversity and distribution gave evidence of in situ glacial survival on siliceous central‐alpine nunatak mountains in two areas, southwest and northeast of the Aosta valley. According to the absence of genetic differentiation between these two nunatak areas (based on amova), nested clade analysis implied a history of preglacial gene flow, in situ survival and extinction of intermediate populations during glaciation and postglacial stepwise recolonization of peripheral and intermediate areas.
Fine‐scale genetic structure and dispersal in the common vole (Microtus arvalis)
Authors: SCHWEIZER MANUEL , EXCOFFIER LAURENT , HECKEL GERALD
Published: May 2007

The genetic structure and demography of local populations is tightly linked to the rate and scale of dispersal. Dispersal parameters are notoriously difficult to determine in the field, and remain often completely unknown for smaller organisms. In this study, we investigate spatial and temporal genetic structure in relation to dispersal patterns among local populations of the probably most abundant European mammals, the common vole (Microtus arvalis). Voles were studied in six natural populations at distances of 0.4–2.5 km in three different seasons (fall, spring, summer) corresponding to different life‐history stages. Field observations provided no direct evidence for movements of individuals between populations. The analysis of 10 microsatellite markers revealed a persistent overall genetic structure among populations of 2.9%, 2.5% and 3%FST in the respective season. Pairwise comparisons showed that even the closest populations were significantly differentiated from each other in each season, but there was no evidence for temporal differentiation within populations or isolation by distance among populations. Despite significant genetic structure, assignment analyses identified a relatively high proportion of individuals as being immigrants for the population where they were captured. The immigration rate was not significantly lower for females than for males. We suggest that a generally low and sex‐dependent effective dispersal rate as the consequence of only few immigrants reproducing successfully in the new populations together with the social structure within populations may explain the maintenance of genetic differentiation among populations despite migration.
Genetic structure of hybrid zones betweenSilene latifoliaandSilene dioica(Caryophyllaceae): evidence for introgressive hybridization
Authors: MINDER A. M. , ROTHENBUEHLER C. , WIDMER A.
Published: May 2007

Natural hybrid zones provide a valuable tool to study introgressive hybridization, because they can contain a wide variety of genotypes that result from many generations of recombination. Here we used molecular markers and morphological variation to describe the structure of two natural hybrid zones betweenSilene latifoliaandSilene dioicain the Swiss Alps.Populations in both hybrid zones consisted of few intermediate hybrids and were dominated by backcross hybrids. The latter were also found in the parental populations at the margins of the hybrid zones. Out of 209 amplified fragment length polymorphism (AFLP) markers scored in 390 individuals, only 7 (3.3%) were species specific. These results indicate that introgression betweenS. dioicaandS. latifoliais extensive, and that hybrid zones act as bridges to gene flow between these two species. Analysis of linkage disequilibrium identified few populations in which hybridization is ongoing, whereas in most populations linkage disequilibrium has eroded. Where hybridization is ongoing, strong changes in species‐specific marker frequencies and morphological traits were observed. Plastid introgression into the hybrid zone was found to be bidirectional, but only theS. latifoliaplastid haplotype was found in a nuclearS. dioicabackground. This unidirectional plastid introgression fromS. latifoliaintoS. dioicais most likely due to pollen‐flow fromS. dioicaontoS. latifolia, and results in plastid capture. Comparisons between the molecular and the morphological hybrid indices revealed that morphology in this study system is useful for identifying hybrids, but not for detailed analysis of hybrid zone structure.
Outcomes following surgery for congenital heart disease in low‐birthweight infants
Authors: Dimmick Simon , Walker Karen , Badawi Nadia , Halliday Robert , Cooper Stephen G , Nicholson Ian A , Sherwood Megan , Chard Richard B , Hawker Richard , Lau Kai C , Jones Owen , Grant Peter W , Sholler Gary F , Winlaw David S ,   Neonatal Intensive Care Units Study (NICUS) of the New South Wales Pregnancy and Newborn Services Network
Published: May 2007

Aim:  To describe cardiac surgery, survival and outcomes for low‐birthweight (≤2500 g) infants undergoing surgery for congenital heart disease.

Methods:  Using data from a prospectively collected population‐based database of admissions to neonatal intensive care units in New South Wales and the Australian Capital Territory, we identified all low‐birthweight infants undergoing cardiac surgery between 1992 and 2001. Infants with only a persistent ductus arteriosus were excluded. Two‐year cardiac and neurodevelopmental outcome data were sought from hospital medical records.

Results:  A total of 121 low‐birthweight infants underwent cardiac surgery, of whom 34% had a congenital syndrome or non‐cardiac birth defect. Most (81%) underwent a palliative surgical procedure in the neonatal period. There were 19 early (15.7%) and 19 late deaths giving a 2‐year mortality of 31%. Factors associated with mortality included birthweight below 1500 g (P = 0.006), low weight at surgery (P = 0.028) and Apgar score at 1 min (P = 0.019). No single factor predicted 30‐day mortality. By 2 years of age, 27 (33% of survivors) were known to have neurodevelopmental delay. Although 22 children are known to be developing normally, the neurodevelopmental status of 34 children was not known.

Conclusions:  These surgical data were comparable to previous single‐institution studies. This group had a high risk of disability due to prematurity, low birthweight and associated conditions. There is a need to prospectively assess and manage neurodevelopmental outcomes in this group.
Activation of the canonical Wnt pathway by the antipsychotics haloperidol and clozapine involves dishevelled‐3
Authors: Sutton Laurie P. , Honardoust Dariush , Mouyal Joanne , Rajakumar Nagalingam , Rushlow Walter J.
Published: May 2007

Protein kinase B (Akt), glycogen synthase kinase‐3 (GSK‐3) and members of the Wnt signal transduction pathway were recently found to be altered in schizophrenia and targeted by antipsychotic drugs. In the current study, selected Wnt signalling proteins were investigated to determine if they are altered by the antipsychotics clozapine or haloperidol in the rat prefrontal cortex. Pheochromocytoma (PC12) and neuroblastoma (SH‐SY5Y) cells were also used to elucidate how antipsychotics generated the pattern of changes observedin vivo. Western blotting (WB) revealed that treatment with haloperidol or clozapine caused an up‐regulation of Wnt‐5a, dishevelled‐3, Axin, total and phosphorylated GSK‐3 and β‐catenin protein levels. Treatment of PC12 and SH‐SY5Y cells with a variety of pharmacological agents as well as the over‐expression of several Wnt related proteins failed to mimic the pattern observedin vivofollowing antipsychotic treatment. However, the over‐expression of dishevelled‐3 nearly perfectly duplicated the changes observedin vivo. Immunoprecipitations (IP) conducted using protein isolated from the rat prefrontal cortex indicated that dishevelled‐3 is associated with the D2dopamine receptor thereby suggesting that antipsychotics may act on dishevelled‐3 via D2dopamine receptors to initiate a cascade of downstream changes involving Axin, GSK‐3 and β‐catenin that may help to alleviate psychosis in schizophrenic patients.
NeuroD1: developmental expression and regulated genes in the rodent pineal gland
Authors: Muñoz Estela M. , Bailey Michael J. , Rath Martin F. , Shi Qiong , Morin Fabrice , Coon Steven L. , Møller Morten , Klein David C.
Published: May 2007

NeuroD1/BETA2, a member of the bHLH transcription factor family, is known to influence the fate of specific neuronal, endocrine and retinal cells. We report here that NeuroD1 mRNA is highly abundant in the developing and adult rat pineal gland. Pineal expression begins in the 17‐day embryo at which time it is also detectable in other brain regions. Expression in the pineal gland increases during the embryonic period and is maintained thereafter at levels equivalent to those found in the cerebellum and retina. In contrast, NeuroD1 mRNA decreases markedly in non‐cerebellar brain regions during development. Pineal NeuroD1 levels are similar during the day and night, and do not appear to be influenced by sympathetic neural input. Gene expression analysis of the pineal glands from neonatalNeuroD1knockout mice identifies 127 transcripts that are down‐regulated (>twofold,p < 0.05) and 16 that are up‐regulated (>twofold,p < 0.05). According to quantitative RT‐PCR, the most dramatically down‐regulated gene is kinesin family member 5C (∼100‐fold) and the most dramatically up‐regulated gene is glutamic acid decarboxylase 1 (∼fourfold). Other impacted transcripts encode proteins involved in differentiation, development, signal transduction and trafficking. These findings represent the first step toward elucidating the role ofNeuroD1in the rodent pinealocyte.
Role of matrix metalloproteinase and tissue inhibitor of MMP in methamphetamine‐induced behavioral sensitization and reward: implications for dopamine receptor down‐regulation and dopamine release
Authors: Mizoguchi Hiroyuki , Yamada Kiyofumi , Mouri Akihiro , Niwa Minae , Mizuno Tomoko , Noda Yukihiro , Nitta Atsumi , Itohara Shigeyoshi , Banno Yoshiko , Nabeshima Toshitaka
Published: May 2007

Matrix metalloproteinases (MMPs) and its inhibitors (TIMPs) function to remodel the pericellular environment. We have demonstrated that methamphetamine (METH)‐induced behavioral sensitization and reward were markedly attenuated in MMP‐2‐ and MMP‐9 deficient [MMP‐2‐(−/−) and MMP‐9‐(−/−)] mice compared with those in wild‐type mice, suggesting that METH‐induced expression of MMP‐2 and MMP‐9 in the brain plays a role in the development of METH‐induced sensitization and reward. In the present study, we investigated the changes in TIMP‐2 expression in the brain after repeated METH treatment. Furthermore, we studied a role of MMP/TIMP system in METH‐induced behavioral changes and dopamine neurotransmission. Repeated METH treatment induced behavioral sensitization, which was accompanied by an increase in TIMP‐2 expression. Antisense TIMP‐2 oligonucleotide (TIMP‐AS) treatment enhanced the sensitization, which was associated with the potentiation of METH‐induced dopamine release in the nucleus accumbens (NAc). On the other hand, MMP‐2/‐9 inhibitors blocked the METH‐induced behavioral sensitization and conditioned place preference, a measure of the rewarding effect, and reduced the METH‐increased dopamine release in the NAc. Dopamine receptor agonist‐stimulated [35S]GTPγS binding was reduced in the frontal cortex of sensitized rats. TIMP‐AS treatment potentiated, while MMP‐2/‐9 inhibitor attenuated, the reduction of dopamine D2 receptor agonist‐stimulated [35S]GTPγS binding. Repeated METH treatment also reduced dopamine D2 receptor agonist‐stimulated [35S]GTPγS binding in wild‐type mice, but such changes were significantly attenuated in MMP‐2‐(−/−) and MMP‐9‐(−/−) mice. These results suggest that the MMP/TIMP system is involved in METH‐induced behavioral sensitization and reward, by regulating dopamine release and receptor signaling.
Deciphering adaptor specificity in GFL‐dependent RET‐mediated proliferation and neurite outgrowth
Authors: Gustin Jason A. , Yang Mao , Johnson Eugene M. , Milbrandt Jeffrey
Published: May 2007

Glial cell derived neurotrophic factor (GDNF)‐dependent receptor tyrosine kinase RET activity is required for proper development of the nervous system and genitourinary tract. Loss‐of‐function mutations in RET are associated with enteric nervous system abnormalities (Hirschsprung disease) and renal deficits (Potter’s syndrome), whereas activating mutations lead to hereditary cancer syndromes (multiple endocrine neoplasia type 2A and type 2B). RET activation is crucial for the proper regulation of a variety of cellular processes including cell migration, proliferation and neurite outgrowth. By analyzing a series of RET mutants we found that Y1062 was critical for stimulating GDNF‐mediated proliferation as well as proliferation stimulated by GDNF‐independent oncogenic forms of RET. Studies using small interfering RNA driven by lentivirus to knock‐down expression of particular adaptor proteins that interact with RET phospho‐Y1062, demonstrated that only Src‐homology 2 and growth factor receptor binding protein 2 were necessary for RET‐mediated proliferation by wild type and oncogenic forms of RET. Interestingly, we discovered that Y1062 was also required for GDNF‐stimulated neurite outgrowth. However, small interfering RNAs to either Src‐homology 2 or growth factor receptor binding protein 2 or a panel of other adaptor proteins known to interact with RET Y1062 were incapable of blocking GDNF‐stimulated neurite formation, indicating that differential use of intracellular adaptors is responsible for regulating alternative RET‐stimulated cellular events such as proliferation versus a differentiation response like neurite outgrowth.
Calcium‐induced precipitate formation in brain mitochondria: composition, calcium capacity, and retention
Authors: Kristian Tibor , Pivovarova Natalia B. , Fiskum Gary , Andrews S. Brian
Published: May 2007

Both isolated brain mitochondria and mitochondria in intact neurons are capable of accumulating large amounts of calcium, which leads to formation in the matrix of calcium‐ and phosphorus‐rich precipitates, the chemical composition of which is largely unknown. Here, we have used inhibitors of the mitochondrial permeability transition (MPT) to determine how the amount and rate of mitochondrial calcium uptake relate to mitochondrial morphology, precipitate composition, and precipitate retention. Using isolated rat brain (RBM) or liver mitochondria (RLM) Ca2+‐loaded by continuous cation infusion, precipitate composition was measured in situ in parallel with Ca2+ uptake and mitochondrial swelling. In RBM, the endogenous MPT inhibitors adenosine 5′‐diphosphate (ADP) and adenosine 5′‐triphosphate (ATP) increased mitochondrial Ca2+ loading capacity and facilitated formation of precipitates. In the presence of ADP, the Ca/P ratio approached 1.5, while ATP or reduced infusion rates decreased this ratio towards 1.0, indicating that precipitate chemical form varies with the conditions of loading. In both RBM and RLM, the presence of cyclosporine A in addition to ADP increased the Ca2+ capacity and precipitate Ca/P ratio. Following MPT and/or depolarization, the release of accumulated Ca2+ is rapid but incomplete; significant residual calcium in the form of precipitates is retained in damaged mitochondria for prolonged periods.
Amyloid precursor protein intracellular domain modulates cellular calcium homeostasis and ATP content
Authors: Hamid Runa , Kilger Ellen , Willem Michael , Vassallo Neville , Kostka Markus , Bornhövd Carsten , Reichert Andreas S. , Kretzschmar Hans A. , Haass Christian , Herms Jochen
Published: May 2007

Consecutive cleavages of amyloid precursor protein (APP) generate APP intracellular domain (AICD). Its cellular function is still unclear. In this study, we investigated the functional role of AICD in cellular Ca2+ homeostasis. We could confirm previous observations that endoplasmic reticulum Ca2+ stores contain less calcium in cells with reduced APP γ‐secretase cleavage products, increased AICD degradation, reduced AICD expression or in cells lacking APP. In addition, we observed an enhanced resting cytosolic calcium concentration under conditions where AICD is decreased or missing. In view of the reciprocal effects of Ca2+ on mitochondria and of mitochondria on Ca2+ homeostasis, we analysed further the cellular ATP content and the mitochondrial membrane potential. We observed a reduced ATP content and a mitochondrial hyperpolarisation in cells with reduced amounts of AICD. Blockade of mitochondrial oxidative phosphorylation chain in control cells lead to similar alterations as in cells lacking AICD. On the other hand, substrates of Complex II rescued the alteration in Ca2+ homeostasis in cells lacking AICD. Based on these observations, our findings indicate that alterations observed in endoplasmic reticulum Ca2+ storage in cells with reduced amounts of AICD are reciprocally linked to mitochondrial bioenergetic function.
Sympathetic predominance of cardiovascular regulation during mild orthostatic stress in adolescents with chronic fatigue
Authors: Wyller Vegard B. , Saul J. P. , Amlie Jan P. , Thaulow Erik
Published: May 2007

Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS‐patients by analysing RR‐interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non‐stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age‐ and sex distribution underwent 15 min of 20° head‐up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low‐frequency (LF) band (0·04–0·15 Hz) and the high‐frequency (HF) band (0·15–0·4 Hz) using an adaptive autoregressive algorithm to obtain a time‐varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P≤0·001) and normalized LF power of RRI (P≤0·01), and a larger decrease in normalized HF power (P≤0·01) of RRI than controls. CFS patients also had trends towards a larger decrease in absolute HF power of RRI and a larger increase in normalized LF power of DBP. These findings suggest that adolescents with CFS have sympathetic predominance of cardiovascular regulation during very mild orthostatic stress. Possible underlying mechanisms are moderate hypovolemia, abnormalities of reflex control or physical de‐conditioning.
Neuromuscular and hormonal responses to a single session of whole body vibration exercise in healthy young men
Authors: Erskine Julie , Smillie Ian , Leiper John , Ball Derek , Cardinale Marco
Published: May 2007

Whole body vibration (WBV) has been proposed as an alternative exercise stimulus to produce adaptive responses similar to resistance exercise. Few studies have analysed acute hormonal responses to WBV.

Purpose  To evaluate neuromuscular and hormonal responses to an acute bout of isometric half‐squat exercise with and without superimposition of WBV.

Methods  Seven healthy males (22·3 ± 2·7 years) performed 10 sets of half squat isometric exercise for 1 min with 1‐min rest between sets. Two separate trials were conducted either with WBV [30 Hz; 3·5 g (1 g = 9·81 m·s2)] or without vibration (Control). Salivary concentration of testosterone and cortisol was collected and maximal isometric unilateral knee extensions (MVC) were completed before, immediately after, 1, 2 and 24 h after treatment.

Results  Significant decreases in MVC were observed immediately after (229·4 ± 53·2 Nm), 1 h (231·6 ± 59·9 Nm), and 2 h (233·0 ± 59·1 Nm) after WBV compared with baseline (252·7 ± 56·4 Nm; P<0·05). No significant change in MVC was recorded in Control. Rate of torque development in the first 200 ms (RTD200 ms), and salivary testosterone and cortisol concentrations were unaffected in both conditions. However, there was a trend for change over time in cortisol (P = 0·052), with an increase after WBV and decrease after Control.

Conclusion  A 10 min session of intermittent WBV was shown to produce an acute reduction in MVC in healthy individuals, which recovered after 24 h. No significant changes were identified in salivary concentration of testosterone and cortisol suggesting that WBV with low acceleration does not represent a stressful stimulus for the neuroendocrine system.
Rash from Antiepileptic Drugs: Influence by Gender, Age, and Learning Disability
Authors: Alvestad Silje , Lydersen Stian , Brodtkorb Eylert
Published: May 2007

Summary:  Purpose: Cutaneous adverse reactions from antiepileptic drugs (AEDs) are common, but have received little scientific attention from a clinical point of view. We wanted to study the incidence of skin reactions of current AEDs and to explore their relation to clinical parameters such as gender, age, and learning disability.

Methods: Consecutive patients with epilepsy were studied retrospectively. A detailed survey of medical records concerning all treatment with AEDs was performed.

Results: A total of 663 patients were included with altogether 2,567 exposures to 15 different AEDs. Skin reactions were found in 14% of the patients and in 5% of the exposures. Ninety‐seven percent of the reactions occurred to either carbamazepine (CBZ, 11%), phenytoin (PHT, 8%), lamotrigine (LTG, 8%), oxcarbazepine (8%), or phenobarbital (2%). Skin reactions developed significantly more often in females than in males (19% vs. 8%), and significantly less often in patients with learning disability than in other patients (7% vs. 16%). These differences were significant for CBZ, PHT, and LTG when analyzed separately. Females displayed higher rash frequency during the reproductive years, while men experienced less frequent rash in the same phase of life.

Conclusions: Fertile females have a higher risk for skin reactions compared to males, probably due to hormonal factors. Patients with learning disability appeared to have a lower risk than other patients in this study. Hygiene factors may possibly be underlying.
The Natural History and Treatment of Epilepsy in a Murine Model of Tuberous Sclerosis
Authors: Erbayat‐Altay Ebru , Zeng Ling‐Hui , Xu Lin , Gutmann David H. , Wong Michael
Published: May 2007

Summary:  Purpose: Patients with tuberous sclerosis complex (TSC) often have severe epilepsy that is intractable to available therapies. The development of novel treatments for epilepsy in TSC would benefit greatly from a suitable animal model, but most animal models of TSC to date have few reported neurological abnormalities, such as epilepsy. We previously described a novel model of TSC, due to conditional inactivation of the Tsc1 gene in glia (Tsc1GFAPCKO mice), in which mice develop epilepsy and premature death. Here, we characterize the natural history of the epilepsy in Tsc1GFAPCKO mice in more detail and report acute effects of treatment with standard antiepileptic drugs on seizures in these mice.

Methods: Video‐EEG recordings were obtained from Tsc1GFAPCKO mice on a weekly basis, starting at 4 weeks of age until death, to monitor progression of interictal EEG abnormalities and seizures. In separate experiments, Tsc1GFAPCKO mice were monitored for interictal EEG abnormalities and seizures before and during treatment with phenobarbital, phenytoin, or saline.

Results: Tsc1
GFAPCKO mice developed seizures around 4–6 weeks of age and subsequently had progressive worsening of the interictal EEG background and seizure frequency over a month, culminating in death. Treatment with phenobarbital or phenytoin caused a reduction in seizure frequency, but did not improve EEG background or prevent death.

Conclusions: Tsc1
GFAPCKO mice develop progressive epilepsy. Acute treatment with standard antiepileptic drugs suppresses seizures in these mice, but does not affect long‐term prognosis. Tsc1GFAPCKO mice represent a good model to test other drugs that may have true antiepileptogenic actions in TSC.
Epilepsy in Phenylketonuria: A Complex Dependence on Serum Phenylalanine Levels
Authors: Martynyuk Anatoly E. , Ucar Deniz A. , Yang Dawn D. , Norman Wendy M. , Carney Paul R. , Dennis Donn M. , Laipis Philip J.
Published: May 2007

Summary:  Purpose: Phenylketonuria (PKU) is a disorder of phenylalanine (Phe) metabolism that frequently results in epilepsy if a low Phe diet was not implemented at birth. The mechanisms by which Phe affects the brain are poorly understood.

Methods: Audiogenic seizures (AGS) were studied in female homozygous Pahenu2 BTBR (PKU) mice.

Results: Adult PKU mice, 18–20 weeks of age, in contrast to wild‐type and heterozygous counterparts, exhibited a full range of AGS. Younger PKU mice, 5–7 weeks of age, had higher serum Phe levels (2.22 ± 0.20 mM) in comparison with the adult animals (1.72 ± 0.05 mM) and were not susceptible to AGS. Among adult mice, animals susceptible to AGS had significantly lower serum Phe levels (1.62 ± 0.06 mM) in comparison with those resistant to AGS (1.86 ± 0.07 mM). Susceptibility to AGS tended to increase in the afternoon when serum Phe concentration decreased in comparison to evening and morning. Normalization of serum Phe level by instituting a low Phe diet generally prevented susceptibility to AGS within 12 h. Although return to a standard diet raised Phe levels to hyperphenylalaninemic within 12 h in animals treated with a low Phe diet for 2 weeks, more than 7 weeks were needed for a complete resumption of AGS.

Conclusions: Transient decrease in Phe levels within hyperphenylalaninemic range may be a necessary condition for PKU‐related seizures to occur. A low Phe diet prevents susceptibility to seizures, which can resume with the significant delay after termination of dietary treatment.
Pharmacoresistance in Epilepsy: A Pilot PET Study with the P‐Glycoprotein SubstrateR‐[11C]verapamil
Authors: Langer Oliver , Bauer Martin , Hammers Alexander , Karch Rudolf , Pataraia Ekaterina , Koepp Matthias J. , Abrahim Aiman , Luurtsema Gert , Brunner Martin , Sunder‐Plassmann Raute , Zimprich Friedrich , Joukhadar Christian , Gentzsch Stephan , Dudczak Robert , Kletter Kurt , Müller Markus , Baumgartner Christoph
Published: May 2007

Summary: Purpose and Methods:Regional overexpression of the multidrug transporter P‐glycoprotein (P‐gp) in epileptic brain tissue may lower target site concentrations of antiepileptic drugs and thus contribute to pharmacoresistance in epilepsy. We used the P‐gp substrateR‐[11C]verapamil and positron emission tomography (PET) to test for differences in P‐gp activity between epileptogenic and nonepileptogenic brain regions of patients with drug‐resistant unilateral temporal lobe epilepsy (n = 7). We comparedR‐[11C]verapamil kinetics in homologous brain volumes of interest (VOIs) located ipsilateral and contralateral to the seizure focus.Results:Among different VOIs, radioactivity was highest in the choroid plexus. The hippocampal VOI could not be used for data analysis because it was contaminated by spill‐in of radioactivity from the adjacent choroid plexus. In several other temporal lobe regions that are known to be involved in seizure generation and propagation ipsilateral influx rate constantsK1and efflux rate constantsk2ofR‐[11C]verapamil were descriptively increased as compared to the contralateral side. Parameter asymmetries were most prominent in parahippocampal and ambient gyrus (K1, range: −3.8% to +22.3%;k2, range: −2.3% to +43.9%), amygdala (K1, range: −20.6% to +31.3%;k2, range: −18.0% to +38.9%), medial anterior temporal lobe (K1, range: −8.3% to +14.5%;k2, range: −14.5% to +31.0%) and lateral anterior temporal lobe (K1, range: −20.7% to +16.8%;k2, range: −24.4% to +22.6%). In contrast to temporal lobe VOIs, asymmetries were minimal in a region presumably not involved in epileptogenesis located outside the temporal lobe (superior parietal gyrus,K1, range: −3.7% to +4.5%;k2, range: −4.2% to +5.8%). In 5 of 7 patients, ipsilateral efflux (k2) increases were more pronounced than ipsilateral influx (K1) increases, which resulted in ipsilateral reductions (10%–26%) ofR‐[11C]verapamil distribution volumes (DV). However, for none of the examined brain regions, any of the differences inK1,k2andDVbetween the epileptogenic and the nonepileptogenic hemisphere reached statistical significance (p > 0.05, Wilcoxon matched pairs test).Conclusions:Even though we failed to detect statistically significant differences inR‐[11C]verapamil model parameters between epileptogenic and nonepileptogenic brain regions, it cannot be excluded from our pilot data in a small sample size of patients that regionally enhanced P‐gp activity might contribute to drug resistance in some patients with temporal lobe epilepsy.
Typical versus Atypical Absence Seizures: Network Mechanisms of the Spread of Paroxysms
Authors: Velazquez Jose L. Perez , Huo Jeanne Zhen , Dominguez L. Garcia , Leshchenko Yevgen , Snead III O. Carter
Published: May 2007

Summary: Purpose:Typical absence seizures differ from atypical absence seizures in terms of semiology, EEG morphology, network circuitry, and cognitive outcome, yet have the same pharmacological profile. We have compared typical to atypical absence seizures, in terms of the recruitment of different brain areas. Our initial question was whether brain areas that do not display apparent paroxysmal discharges during typical absence seizures, are affected during the ictal event in terms of synchronized activity, by other, distant areas where seizure activity is evident. Because the spike‐and‐wave paroxysms in atypical absence seizures invade limbic areas, we then asked whether an alteration in inhibitory processes in hippocampi may be related to the spread seizure activity beyond thalamocortical networks, in atypical seizures.

Methods:We used two models of absence seizures in rats: one of typical and the other of atypical absence seizures. We estimated phase synchronization, and evaluated inhibitory transmission using a paired‐pulse paradigm.

Results:In typical absence seizures, we observed an increase in synchronization between hippocampal recordings when spike‐and‐wave discharges occurred in the cortex and thalamus. This indicates that seizure activity in the thalamocortical circuitry enhances the propensity of limbic areas to synchronize, but is not sufficient to drive hippocampal circuitry into a full paroxysmal discharge. Lower paired‐pulse depression was then found in hippocampus of rats that displayed atypical absence seizures.

Conclusions:These observations suggest that circuitries in brain areas that do not display apparent seizure activity become synchronized as seizures occur within thalamocortical circuitry, and that a weakened hippocampal inhibition may predispose to develop synchronization into full paroxysms during atypical absence seizures.
Interobserver Reliability of Video Recording in the Diagnosis of Nocturnal Frontal Lobe Seizures
Authors: Vignatelli Luca , Bisulli Francesca , Provini Federica , Naldi Ilaria , Pittau Francesca , Zaniboni Anna , Montagna Pasquale , Tinuper Paolo
Published: May 2007

Summary:  Background: Nocturnal frontal lobe seizures (NFLS) show one or all of the following semeiological patterns: (1) paroxysmal arousals (PA: brief and sudden recurrent motor paroxysmal behavior); (2) hyperkinetic seizures (HS: motor attacks with complex dyskinetic features); (3) asymmetric bilateral tonic seizures (ATS: motor attacks with dystonic features); (4) epileptic nocturnal wanderings (ENW: stereotyped, prolonged ambulatory behavior).

Objective: To estimate the interobserver reliability (IR) of video‐recording diagnosis in patients with suspected NFLS among sleep medicine experts, epileptologists, and trainees in sleep medicine.

Methods: Sixty‐six patients with suspected NFLS were included. All underwent nocturnal video‐polysomnographic recording. Six doctors (three experts and three trainees) independently classified each case as “NFLS ascertained” (according to the above specified subtypes: PA, HS, ATS, ENW) or “NFLS excluded”. IR was calculated by means of Kappa statistics, and interpreted according to the standard classification (0.0–0.20 = slight agreement; 0.21–0.40 = fair; 0.41–0.60 = moderate; 0.61–0.80 = substantial; 0.81–1.00 = almost perfect).

Results: The observed raw agreement ranged from 63% to 79% between each pair of raters; the IR ranged from “moderate” (kappa = 0.50) to “substantial” (kappa = 0.72). A major source of variance was the disagreement in distinguishing between PA and nonepileptic arousals, without differences in the level of agreement between experts and trainees.

Conclusions: Among sleep experts and trainees, IR of diagnosis of NFLS, based on videotaped observation of sleep phenomena, is not satisfactory. Explicit video‐polysomnographic criteria for the classification of paroxysmal sleep motor phenomena are needed.
Conditional Likelihood Methods for Haplotype‐Based Association Analysis Using Matched Case–Control Data
Authors: Chen Jinbo , Rodriguez Carmen
Published: May 2007

Summary Genetic epidemiologists routinely assess disease susceptibility in relation to haplotypes, that is, combinations of alleles on a single chromosome. We study statistical methods for inferring haplotype‐related disease risk using single nucleotide polymorphism (SNP) genotype data from matched case–control studies, where controls are individually matched to cases on some selected factors. Assuming a logistic regression model for haplotype‐disease association, we propose two conditional likelihood approaches that address the issue that haplotypes cannot be inferred with certainty from SNP genotype data (phase ambiguity). One approach is based on the likelihood of disease status conditioned on the total number of cases, genotypes, and other covariates within each matching stratum, and the other is based on the joint likelihood of disease status and genotypes conditioned only on the total number of cases and other covariates. The joint‐likelihood approach is generally more efficient, particularly for assessing haplotype‐environment interactions. Simulation studies demonstrated that the first approach was more robust to model assumptions on the diplotype distribution conditioned on environmental risk variables and matching factors in the control population. We applied the two methods to analyze a matched case–control study of prostate cancer.
Exact Sample Size Needed to Detect Dependence in 2 × 2 × 2 Tables
Authors: Dai Jianliang , Li Li , Kim Sangkyu , Kimball Beth , Jazwinski S. Michal , Arnold Jonathan ,   for the Georgia Centenarian Study
Published: May 2007

Summary In the Georgia Centenarian Study (Poon et al., Exceptional Longevity, 2006), centenarian cases and young controls are classified according to three categories (age, ethnic origin, and single nucleotide polymorphisms [SNPs] of candidate longevity genes), where each factor has two possible levels. Here we provide methodologies to determine the minimum sample size needed to detect dependence in 2 × 2 × 2 tables based on Fisher's exact test evaluated exactly or by Markov chain Monte Carlo (MCMC), assuming only the case total L and the control total N are known. While our MCMC method uses serial computing, parallel computing techniques are employed to solve the exact sample size problem. These tools will allow researchers to design efficient sampling strategies and to select informative SNPs. We apply our tools to 2 × 2 × 2 tables obtained from a pilot study of the Georgia Centenarians Study, and the sample size results provided important information for the subsequent major study. A comparison between the results of an exact method and those of a MCMC method showed that the MCMC method studied needed much less computation time on average (10.16 times faster on average for situations examined with S.E. = 2.60), but its sample size results were only valid as a rule for larger sample sizes (in the hundreds).
Analysis of Pulsatile Hormone Concentration Profiles with Nonconstant Basal Concentration: A Bayesian Approach
Authors: Johnson Timothy D.
Published: May 2007

SummaryMany challenges arise in the analysis of pulsatile, or episodic, hormone concentration time series data. Among these challenges is the determination of the number and location of pulsatile events and the discrimination of events from noise. Analyses of these data are typically performed in two stages. In the first stage, the number and approximate location of the pulses are determined. In the second stage, a model (typically a deconvolution model) is fit to the data conditional on the number of pulses. Any error made in the first stage is carried over to the second stage. Furthermore, current methods, except two, assume that the underlying basal concentration is constant. We present a fully Bayesian deconvolution model that simultaneously estimates the number of secretion episodes, as well as their locations, and a nonconstant basal concentration. This model obviates the need to determine the number of events a priori. Furthermore, we estimate probabilities for all “candidate” event locations. We demonstrate our method on a real data set.