bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion
Authors: Argent Richard H. , Hale James L. , El-Omar Emad M. , Atherton John C.
Published: August 2008

Helicobacter pylori strains from East Asia have an ‘East Asian’ type of CagA that is more active and predominantly comprises a single type. Strains from other countries have a ‘western’ type of CagA, which is less active and comprises many different types generated by intragenomic recombination. Co-culture of AGS gastric epithelial cells with isolates of western strains that displayed microevolution in CagA showed that isolates with additional copies of the C motif induced significantly more interleukin (IL)-8 secretion. Co-culture of AGS cells with western and East Asian strains, each expressing CagA with a single copy of the C or D motif, showed that East Asian strains induced significantly more IL-8 secretion. Analysis of the different CagA types from data deposited in GenBank and from the literature showed that western CagA is significantly more likely to undergo duplication of tyrosine phosphorylation motif C than East Asian CagA is of the corresponding D motif. Taken together, the data suggest that the already highly active East Asian CagA with one D motif has no requirement to increase its virulence, whereas the less active western CagA displays flexibility in its capacity to increase its number of tyrosine phosphorylation motifs to become more virulent.
Identification of virulence determinants in uropathogenic Proteus mirabilis using signature-tagged mutagenesis
Authors: Himpsl Stephanie D. , Lockatell C. Virginia , Hebel J. Richard , Johnson David E. , Mobley Harry L. T.
Published: August 2008

The Gram-negative bacterium Proteus mirabilis causes urinary tract infections (UTIs) in individuals with long-term indwelling catheters or those with functional or structural abnormalities of the urinary tract. Known virulence factors include urease, haemolysin, fimbriae, flagella, DsbA, a phosphate transporter and genes involved in cell-wall synthesis and metabolism, many of which have been identified using the technique of signature-tagged mutagenesis (STM). To identify additional virulence determinants and to increase the theoretical coverage of the genome, this study generated and assessed 1880 P. mirabilis strain HI4320 mutants using this method. Mutants with disruptions in genes vital for colonization of the CBA mouse model of ascending UTI were identified after performing primary and secondary in vivo screens in approximately 315 CBA mice, primary and secondary in vitro screens in both Luria broth and minimal A medium to eliminate mutants with minor growth deficiencies, and co-challenge competition experiments in approximately 500 CBA mice. After completion of in vivo screening, a total of 217 transposon mutants were attenuated in the CBA mouse model of ascending UTI. Following in vitro screening, this number was reduced to 196 transposon mutants with a probable role in virulence. Co-challenge competition experiments confirmed significant attenuation for 37 of the 93 transposon mutants tested, being outcompeted by wild-type HI4320. Following sequence analysis of the 37 mutants, transposon insertions were identified in genes including the peptidyl-prolyl isomerases surA and ppiA, glycosyltransferase cpsF, biopolymer transport protein exbD, transcriptional regulator nhaR, one putative fimbrial protein, flagellar M-ring protein fliF and hook protein flgE, and multiple metabolic genes.
Serum antibodies to West Nile virus in naturally exposed and vaccinated horses
Authors: Magnarelli Louis A. , Bushmich Sandra L. , Anderson John F. , Ledizet Michel , Koski Raymond A.
Published: August 2008

A polyvalent ELISA and plaque reduction neutralization tests (PRNTs) were used to measure serum antibodies to West Nile virus (WNV) in horses naturally exposed to or vaccinated against this flavivirus in Connecticut and New York State, USA. Relying on a PRNT as a ‘gold standard’, the main objective was to validate a modified ELISA containing a recombinant WNV envelope protein antigen. It was also important to assess specificity by testing sera from horses that had other, undiagnosed illnesses. Sera for the latter study were obtained from 43 privately owned horses during 1995–1996. Analyses by an ELISA and a PRNT confirmed the presence of WNV antibodies in 21 (91 %) of 23 sera from naturally exposed horses and in 85 % of the 20 vaccinated subjects; overall results for both study groups were highly concordant (91 % agreement). Humoral responses of naturally exposed and immunized horses were similar. Both serological tests were useful in confirming past infections with WNV, but there was no evidence that horses with undiagnosed illnesses were exposed to WNV prior to a 1999 outbreak in Connecticut, USA.
Rh-PIP2;1, a Rose Aquaporin Gene, Is Involved in Ethylene-Regulated Petal Expansion
Authors: Ma Nan , Xue Jingqi , Li Yunhui , Liu Xiaojing , Dai Fanwei , Jia Wensuo , Luo Yunbo , Gao Junping
Published: August 2008

Aquaporins are water channel proteins that facilitate the passage of water through biological membranes and play a crucial role in plant growth. We showed that ethylene treatment significantly reduced petal size, inhibited expansion of petal abaxial subepidermal cells, and decreased petal water content in rose (Rosa hybrida ‘Samantha’). Here, we report the isolation of a plasma membrane aquaporin (PIP) gene, Rh-PIP2;1, and characterized its potential role in ethylene-inhibited petal expansion. Rh-PIP2;1 is mainly localized on the plasma membrane and belongs to the class 2 subfamily of PIP proteins. We show that Rh-PIP2;1 is an active water channel. The transcripts of Rh-PIP2;1 are highly abundant in petal epidermal cells, especially in the abaxial subepidermal cells. The expression of Rh-PIP2;1 is highly correlated with petal expansion and tightly down-regulated by ethylene. Furthermore, we demonstrate that in Rh-PIP2;1-silenced flowers, petal expansion was greatly inhibited and anatomical features of the petals were similar to those of ethylene-treated flowers. We argue that Rh-PIP2;1 plays an important role in petal cell expansion and that ethylene inhibits petal expansion of roses at least partially by suppressing Rh-PIP2;1 expression.
Reconfiguration of the Achene and Receptacle Metabolic Networks during Strawberry Fruit Development
Authors: Fait Aaron , Hanhineva Kati , Beleggia Romina , Dai Nir , Rogachev Ilana , Nikiforova Victoria J. , Fernie Alisdair R. , Aharoni Asaph
Published: August 2008

The anatomy of strawberry (Fragaria × ananassa) fruit, in which the achene is found on the outer part of the fruit, makes it an excellent species for studying the regulation of fruit development. It can provide a model for the cross talk between primary and secondary metabolism, whose role is of pivotal importance in the process. By combining gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry with the aim of addressing the metabolic regulation underlying fruit seed development, we simultaneously analyzed the composition of primary and secondary metabolites, separately, in achene and receptacle during fruit ripening of strawberry cultivar Herut. The results from these analyses suggest that changes in primary and secondary metabolism reflect organ and developmental specificities. For instance, the receptacle was characterized by increases in sugars and their direct derivatives, while the achene was characterized by a major decrease in the levels of carbon- and nitrogen-rich compounds, with the exception of storage-related metabolites (e.g. raffinose). Furthermore, the receptacle, and to a lesser extent the achene, exhibited dynamic fluctuations in the levels and nature of secondary metabolites across the ripening process. In the receptacle, proanthocyanidins and flavonol derivatives characterized mainly early developmental stages, while anthocyanins were abundant in the mature red stage; in the achene, ellagitannin and flavonoids were abundant during early and late development, respectively. Correlation-based network analysis suggested that metabolism is substantially coordinated during early development in either organ. Nonetheless, a higher degree of connectivity within and between metabolic pathways was measured in the achenes. The data are discussed within the context of current models both of the interaction of primary and secondary metabolism and of the metabolic interaction between the different plant organs.
Chloroplast Outer Envelope Protein CHUP1 Is Essential for Chloroplast Anchorage to the Plasma Membrane and Chloroplast Movement
Authors: Oikawa Kazusato , Yamasato Akihiro , Kong Sam-Geun , Kasahara Masahiro , Nakai Masato , Takahashi Fumio , Ogura Yasunobu , Kagawa Takatoshi , Wada Masamitsu
Published: August 2008

Chloroplasts change their intracellular distribution in response to light intensity. Previously, we isolated the chloroplast unusual positioning1 (chup1) mutant of Arabidopsis (Arabidopsis thaliana). This mutant is defective in normal chloroplast relocation movement and shows aggregation of chloroplasts at the bottom of palisade mesophyll cells. The isolated gene encodes a protein with an actin-binding motif. Here, we used biochemical analyses to determine the subcellular localization of full-length CHUP1 on the chloroplast outer envelope. A CHUP1-green fluorescent protein (GFP) fusion, which was detected at the outermost part of mesophyll cell chloroplasts, complemented the chup1 phenotype, but GFP-CHUP1, which was localized mainly in the cytosol, did not. Overexpression of the N-terminal hydrophobic region (NtHR) of CHUP1 fused with GFP (NtHR-GFP) induced a chup1-like phenotype, indicating a dominant-negative effect on chloroplast relocation movement. A similar pattern was found in chloroplast OUTER ENVELOPE PROTEIN7 (OEP7)-GFP transformants, and a protein containing OEP7 in place of NtHR complemented the mutant phenotype. Physiological analyses of transgenic Arabidopsis plants expressing truncated CHUP1 in a chup1 mutant background and cytoskeletal inhibitor experiments showed that the coiled-coil region of CHUP1 anchors chloroplasts firmly on the plasma membrane, consistent with the localization of coiled-coil GFP on the plasma membrane. Thus, CHUP1 localization on chloroplasts, with the N terminus inserted into the chloroplast outer envelope and the C terminus facing the cytosol, is essential for CHUP1 function, and the coiled-coil region of CHUP1 prevents chloroplast aggregation and participates in chloroplast relocation movement.
Characterization of an Autonomously Activated Plant ADP-Glucose Pyrophosphorylase
Authors: Boehlein Susan K. , Shaw Janine R. , Stewart Jon D. , Hannah L. Curtis
Published: August 2008

ADP-glucose pyrophosphorylase (AGPase) catalyzes the rate-limiting step in starch biosynthesis in plants and changes in its catalytic and/or allosteric properties can lead to increased starch production. Recently, a maize (Zea mays)/potato (Solanum tuberosum) small subunit mosaic, MP [Mos(1–198)], containing the first 198 amino acids of the small subunit of the maize endosperm enzyme and the last 277 amino acids from the potato tuber enzyme, was expressed with the maize endosperm large subunit and was reported to have favorable kinetic and allosteric properties. Here, we show that this mosaic, in the absence of activator, performs like a wild-type AGPase that is partially activated with 3-phosphoglyceric acid (3-PGA). In the presence of 3-PGA, enzyme properties of Mos(1–198)/SH2 are quite similar to those of the wild-type maize enzyme. In the absence of 3-PGA, however, the mosaic enzyme exhibits greater activity, higher affinity for the substrates, and partial inactivation by inorganic phosphate. The Mos(1–198)/SH2 enzyme is also more stable to heat inactivation. The different properties of this protein were mapped using various mosaics containing smaller portions of the potato small subunit. Enhanced heat stability of Mos(1–198) was shown to originate from five potato-derived amino acids between 322 and 377. These amino acids were shown previously to be important in small subunit/large subunit interactions. These five potato-derived amino acids plus other potato-derived amino acids distributed throughout the carboxyl-terminal portion of the protein are required for the enhanced catalytic and allosteric properties exhibited by Mos(1–198)/SH2.
Transition to adult care: experiences and expectations of adolescents with a chronic illness
Authors: Tuchman L. K. , Slap G. B. , Britto M. T.
Published: August 2008

Background  Effective means of transitioning adolescent patients with chronic illness from paediatric to adult medical care are poorly documented and supported by limited evidence. The purpose of this study is to describe expectations and concerns of adolescents with chronic illness regarding transition from subspecialty paediatric to adult‐centred care during the transition process in order guide effective programme design and implementation.

Methods  Qualitative content and thematic analysis of semi‐structured individual interviews with 22 adolescents with chronic illness, including cystic fibrosis, sickle cell disease, juvenile rheumatoid arthritis, and inflammatory bowel disease. Interviews took place at 1–3 time points over an 18‐month study period.

Results  Transition topics included: timing of transfer to adult care, the transition process, attitudes about transition, and factors that might aid transition. During the study period, one‐third of participants made the transition to adult‐oriented health care. All participants who had transitioned to adult‐oriented care reported participating in a structured transition programme. Concerns of those who had not initiated the transition process centred on re‐establishing relationships and bringing a new team ‘up to speed’. Most adolescents anticipating transfer to adult care identified only downsides and felt unprepared to transition at the time of the interview. Subjects who had transitioned noted benefits of the adult‐oriented system, even if they had been ambivalent prior to transfer of care. Participants suggested that earlier discussions about transition, opportunities to meet new healthcare teams and visits to adult‐oriented venues prior to transition might aid in the transition process.

Conclusions  Subspecialty paediatric providers should anticipate common fears and concerns of adolescents and discuss the benefits of transfer to adult‐oriented care. Further evaluation of existing transition programmes is an area for future study and is necessary for improvement of the continuum of care for adolescents with chronic medical conditions.
Is there a relationship between preferred posture and positioning in early life and the direction of subsequent asymmetrical postural deformity in non ambulant people with cerebral palsy?
Authors: Porter David , Michael Shona , Kirkwood Craig
Published: August 2008

Background  It has been suggested that asymmetrical positioning of an infant with reduced mobility may lead to postural deformity becoming established over time. However, evidence to support or question this line of thinking is lacking. Therefore, the aim of this retrospective cohort study was to test the association between asymmetrical positioning in the first 12 months of life and the subsequent direction of postural deformity in non‐ambulant people with cerebral palsy.

Methods  The direction of scoliosis, pelvic obliquity and windswept hip pattern and also the side of unilateral hip subluxation/dislocation were determined for 246 young people ranging in age from 1 year and 2 months to 19 years (median age 10 years and 3 months). Parents/carers of the participants were interviewed to establish holding and feeding positions and preferred lying posture adopted in early life. Univariate analyses and multivariate logistic regression analyses were carried out.

Results  The study provided evidence of an association between asymmetrical lying posture adopted in the first year of life and the direction of the subsequent pattern of postural deformity. If the child's head had been rotated to the right during supine lying, it was more likely that the scoliosis would be convex to the left, pelvic obliquity would be lower on the left, windswept hip pattern would be to the right and hip subluxation/dislocation would occur on the left. The likelihood of the deformities occurring in the same direction was also increased if consistent side lying on the right had been preferred.

Conclusions  Clinicians should be aware of positioning for children with severe disabilities particularly those who prefer supine lying with their head rotated to the side and those who prefer consistent side lying.
Outcome of Newborn Hearing Screening Programme delivered by health visitors
Authors: Basu S. , Evans K. L. , Owen M. , Harbottle T.
Published: August 2008

Background  The Newborn Hearing Screening Programme (NHSP) was introduced in England in 2001 to detect congenital hearing loss in the newborn. The screen is either hospital‐ or community‐based.

Objectives  This is the first large‐scale study of community‐based NHSP published in the United Kingdom which aims to evaluate the performance of the community‐based screen and compare it against national targets for NHSP and the outcome of national pilot projects.

Method  Hearing screening data recorded for 10 074 well babies between March 2004 and December 2005 were analysed. Babies who were admitted to the Special Care Baby Unit were excluded. The case notes of all children who failed the initial hearing screen, either unilateral or bilateral, were reviewed retrospectively. Specific performance measures include coverage rate, referral rate and yield. Reasons for failure to complete the screen were identified.

Results  The community programme met all the standards set by the NHSP and the results are comparable with the average of the pilot sites reported in 2004.

Conclusion  The data demonstrate that a community‐based hearing screening programme conducted by Health Visitors meets all the current national standards and could be implemented across wider areas in this country. Its advantages include a low false positive rate and convenience for parents living in rural areas. The babies identified can be diagnosed and rehabilitated in a time which meets national standards.
Transitions in the lives of young people with complex healthcare needs
Authors: Kirk S.
Published: August 2008

Background  The disabled child population now incorporates a group of children and young people with complex healthcare needs, many of whom are supported by medical devices and technologies. Little is known about their experiences and perspectives, particularly in relation to transitions.

Methods  Twenty‐eight young people aged between 8 and 19 years old were recruited via Community Children's Nursing Teams. Data were collected by in‐depth qualitative interviews and analysed using Grounded Theory principles and procedures.

Results  Young people with complex healthcare needs experience multiple and often concurrent transitions in their lives. As well as moving from childhood to adulthood, they experience different organizational and illness transitions. This paper focuses on their experiences of moving from children to adult services and moving from parental care to self‐care. Moving to adult services was characterized as a time of uncertainty because of lack of information and involvement in transition planning. Concerns were expressed about the continuity of support packages into adult services and whether specialist expertise would be available. Young people in adult services described how they had needed to adjust to a different culture and way of working and the loss of relationships with familiar, trusted professionals. In addition to becoming socially independent, young people were in the process of acquiring control over their healthcare and support needs. The acquisition of responsibility for managing therapies and devices was described as an evolving, individually negotiated process. However, responsibility for decision‐making and liasing with services could be acquired suddenly on transfer to adult services and not as part of an integrated self‐care transition process.

Conclusions  Transition is often too focused on service transition and transfer rather than conceptualizing it holistically as part of the process of moving to adulthood and independence. Young people with complex healthcare needs may have support needs that are unfamiliar for adult services at present. Multi‐agency personalized planning that involves parents and young people is essential to ensure continuity of support and integration with other life transitions.
Stress in mothers of preterm infants in Bangladesh: associations with family, child and maternal factors and children's neuro‐development
Authors: Khan N. Z. , Muslima H. , Bhattacharya M. , Parvin R. , Begum N. , Jahan M. , Begum D. , Akhtar S. , Ahmed A. S. M. N. U. , Darmstadt G. L.
Published: August 2008

Background  The aim of this paper was to ascertain stress experienced by mothers of prospectively followed up preterm infants, and associations with family, child and maternal factors and children's neuro‐development.

Methods  Within a follow‐up study of preterm infants <33 weeks gestational age at a Child Development Center in Dhaka Shishu Hospital, mothers were interviewed with the Self‐Report Questionnaire (SRQ) at each visit. Association between SRQ scores and child, family and maternal variables at first and final visit and children's neuro‐developmental outcomes was determined.

Results  Low income mothers were more compliant (54%) compared with the defaulters (31%) (P = 0.0001) among the 159 mothers enrolled. Of the 88 mothers who were followed up until a mean age of 22 months of their child, 29.3% were at high risk for psychiatric morbidity at first visit compared with 23.9% on their last visit. Use of abortifacients (P = 0.026) and higher maternal age (P = 0.040) were significantly associated with maternal stress at first visit; while at last follow‐up, total number of visits had the most significant association (P = 0.041). Twenty‐five per cent and 19% of mothers were at risk for psychiatric morbidity in children developing normally and those with neuro‐developmental impairments respectively.

Conclusions  Mothers at risk for psychiatric morbidity can be helped through follow‐up support within public hospitals close to their homes, which is most availed by low income families. Neuro‐developmental monitoring of high‐risk infants closer to homes may be more feasible in resource poor countries than reliance on hospital visits, which increase stress. Biological markers of stress and coping strategies need further research.
Serious injuries in children: variation by area deprivation and settlement type
Authors: Reading Richard
Published: August 2008

.
 
Edwards P.,
Green J.,
Lachowycz K.,
Grundy C. &
Roberts I.
(
2008
)

,
93
,
485
–
489
.
 
DOI: 10.1136/adc.2007.116541
.

Objective  To examine the variation in serious injuries in children by the level of deprivation in an area and by types of settlement.

Methods  Hospital admission rates for serious injury to children aged 0–15 years in census lower super output areas in England during the 5‐year period 1 April 1999 to 31 March 2004 were analysed.

Results  Rates of serious injury in children were higher in the most deprived areas than in the least deprived for pedestrians [rate ratio (RR) 4.1; 95% CI 2.8–6.0] and cyclists (RR 3.0; 95% CI 1.9–4.7). Rates of serious pedestrian injury were lower in towns and fringe areas (RR 0.67; 95% CI 0.53–0.86) and in village (RR 0.64; 95% CI 0.50–0.83) areas than in urban areas. The rate of serious injury to cyclists was lower in London than in other urban areas (RR 0.78; 95% CI 0.62–0.98). The rate of serious injury to car occupants was higher in village than in urban areas (RR 1.51; 95% CI 1.05–2.17). Rates of serious injury caused by falls were higher in London (RR 1.60; 95% CI 1.47–1.75) and lower in villages (RR 0.76; 95% CI 0.66–0.88) than in urban areas. Steeper socio‐economic gradients in serious injury rates were identified in rural areas for cyclists and for children suffering falls.

Conclusions  Socio‐economic inequalities in serious injury exist across the whole of England, particularly for child pedestrians. Rates of serious injury vary by settlement type, and inequalities vary by cause of injury between rural and urban settings.
Effects of prenatal cocaine exposure on special education in school‐aged children
Authors: Reading Richard
Published: August 2008

.
 
Levine T. P.,
Liu J.,
Das A.,
Lester B.,
Lagasse L.,
Shankaran S.,
Bada H. S.,
Bauer C. R. &
Higgins R.
(
2008
)

.
Published online
.
 
DOI: 10.1542/peds.2007‐2826
.

Objective  The objective of this study was to evaluate the effects of prenatal cocaine exposure on special education at age 7 with adjustment for covariates.

Methods  As part of the prospective, longitudinal, multi‐site study of children with prenatal cocaine exposure (Maternal Lifestyle Study), school records were reviewed for 943 children at 7 years to determine involvement in special education outcomes: (1) individualized education plan; (2) special education conditions; (3) support services; (4) special education classes; and (5) speech and language services. Logistic regression was used to examine the effect of prenatal cocaine exposure on these outcomes with environmental, maternal and infant medical variables as covariates, as well as with and without low child IQ.

Results  Complete data for each analysis model were available for 737–916 children. When controlling for covariates including low child IQ, prenatal cocaine exposure had a significant effect on individualized education plan. When low child IQ was not included in the model, prenatal cocaine exposure had a significant effect on support services. Male gender, low birthweight, white race and low child IQ also predicted individualized education plan. Low birthweight and low child IQ were significant in all models. White race was also significant in speech and language services. Other covariate effects were model specific. When included in the models, low child IQ accounted for more of the variance and changed the significance of other covariates.

Conclusions  Prenatal cocaine exposure increased the likelihood of receiving an individualized education plan and support services, with adjustment for covariates. Low birthweight and low child IQ increased the likelihood of all outcomes. The finding that white children were more likely to get an individualized education plan and speech and language services could indicate a greater advantage in getting educational resources for this population.
Explaining educational inequalities in preterm birth. The Generation R Study
Authors: Reading Richard
Published: August 2008

.
 
Jansen P.,
Tiemeier H.,
Jaddoe V.,
Hofman A.,
Steegers E.,
Verhulst F.,
Mackenbach J. &
Raat H.
(
2008
)

.
Published online
.
 
DOI: 10.1136/adc.2007.136945
.

Background  Although a low socio‐economic status has consistently been associated with an increased risk of preterm birth, little is known about the pathways through which socio‐economic disadvantage influences preterm birth.

Aim  To examine mechanisms that might underlie the association between the educational level of pregnant women as an indicator of socio‐economic status, and preterm birth.

Methods  The study was nested in a population‐based cohort study in the Netherlands. Information was available for 3830 pregnant women of Dutch origin.

Findings  The lowest educated pregnant women had a statistically significant higher risk of preterm birth [OR = 1.89 (95% CI: 1.28, 2.80)] than the highest educated women. This increased OR was reduced by up to 22% after separate adjustment for age, height, pre‐eclampsia, intrauterine growth restriction, financial concerns, long‐lasting difficulties, psychopathology, smoking habits, alcohol consumption and BMI of the pregnant women. Joint adjustment for these variables resulted in a reduction of 89% of the increased risk of preterm birth among low educated pregnant women [fully adjusted OR = 1.10 (95% CI: 0.66, 1.84)].

Conclusions  Pregnant women with a low educational level have a nearly twofold higher risk of preterm birth than women with a high educational level. This elevated risk could largely be explained by pregnancy characteristics, indicators of psychosocial well‐being and lifestyle habits. Apparently, educational inequalities in preterm birth go together with an accumulation of multiple adverse circumstances among women with a low education. A number of explanatory mechanisms unravelled in the present study seem to be modifiable by intervention programmes.
LRP5 in premature adrenarche and in metabolic characteristics of prepubertal children
Authors: Lappalainen Saila , Saarinen Anne , Utriainen Pauliina , Voutilainen Raimo , Jääskeläinen Jarmo , Mäkitie Outi
Published: August 2008

Objective  Premature adrenarche (PA) is associated with unfavourable metabolic characteristics. We hypothesized that genetic variation in low density lipoprotein (LDL) receptor‐related protein 5 (LRP5), which is involved in Wnt signalling in the adrenal cortex and in cholesterol metabolism, plays a role in the pathogenesis of PA.

Design and patients  We performed a cross‐sectional association study in 73 Finnish children with PA and 97 age‐ and gender‐matched healthy controls.

Measurements  LRP5 genotypes were determined by direct sequencing. Single‐marker associations with clinical‐metabolic characteristics, including adrenocortical function, glucose tolerance and lipid profile, were examined with age and gender as covariates.

Results  Nineteen single nucleotide polymorphisms (SNPs) in LRP5 were found in the 170 children. No significant differences in the genotype distributions were observed between the PA and control groups. SNPs A1330V and N740N were associated with higher serum dehydroepiandrosterone sulphate (DHEAS) levels in the control subjects (A/A vs. A/a; mean 0·8 vs. 1·4 µmol/l, P = 0·01). They were also associated with higher plasma levels of total (4·2 vs. 4·7 mmol/l, P = 0·02) and LDL cholesterol (2·4 vs. 2·9 mmol/l, P = 0·02) in the control group, as was SNP V1119V (P = 0·04 and P = 0·03, respectively). SNPs F549F and V1119V were associated with higher systolic blood pressure (P = 0·04 and P = 0·02, respectively). There were no differences in the parameters of glucose metabolism between the genotype groups.

Conclusions  Genetic variation in LRP5 did not predispose to PA but was associated with metabolic characteristics, especially lipid profile, in healthy prepubertal children.
Variability in bleeding phenotype in Amish carriers of haemophilia B with the 31008 C→T mutation
Authors: SHARATHKUMAR A. , HARDESTY B. , GREIST A. , SALTER J. , KERLIN B. , HEIMAN M. , SULKIN M. , SHAPIRO A.
Published: August 2008

Summary.  The aim of this study was to characterize the variability of bleeding phenotype and its association with plasma factor IX coagulant activity (FIX:C) in haemophilia B carriers in a large Amish pedigree with a unifying genetic mutation, C‐to‐T transition at base 31008 of the factor IX gene (Xq27.1–27.2). A cross‐sectional survey of haemophilia B carriers included a multiple choice questionnaire evaluating symptoms of mucocutaneous bleeding, joint bleeding and bleeding after haemostatic stress [menstruation, postpartum haemorrhage (PPH), dental extractions and invasive surgeries]. Severity of bleeding was graded as 0 to 4, 0 being no bleeding whereas 4 being severe bleeding. Association between total bleeding scores and the FIX:C was evaluated. Sixty‐four haemophilia B carriers participated in this study. Median age: 18 years (range 1–70 years); median bleeding score: 1 (range 0–8). Besides PPH, isolated symptoms of bruising, epistaxis, menorrhagia and postsurgical bleeding including dental extraction were not associated with lower FIX:C. Bleeding score ≥3 was associated with involvement of at least two bleeding sites and a lower mean FIX:C of 42 ± 10.3% (95% CI 36.4–47.7) while a score >3 had involvement of ≤2 sites and higher mean FIX:C of 54.9 ± 21.5% (95% CI 49–61), P = 0.005. Subcutaneous haematoma formation and bleeding after haemostatic stress requiring treatment were associated with bleeding scores ≥3. Phenotypic variability existed among the carriers of haemophilia B who belonged to a single pedigree carrying a single unifying mutation. The utility of bleeding scores to define bleeding phenotype precisely in haemophilia B carriers needs further evaluation.
Exercise and sport in the treatment of haemophilic patients: a systematic review
Authors: GOMIS M. , QUEROL F. , GALLACH J. E. , GONZÁLEZ L. M. , AZNAR J. A.
Published: August 2008

Summary.  In haemophiliacs, the physical condition, muscular strength, aerobic resistance, anaerobic resistance and proprioception have all diminished. Muscle atrophy and instability, being more vulnerable to stressful motor demands, increase the risk of lesion and establish a vicious circle that is hard to break: pain, immobility, atrophy, articular instability and repeated bleeding episodes. In haemophilia, physical and/or sporting activities were not recommended until the seventies. Nowadays, the overall policy is to recommend certain physical activities, especially swimming, to improve the patient’s quality of life, thanks to prophylaxis programmes. The objective of this study is to perform a systematic review of the exercise and sporting activities recommended for haemophiliacs. Experimental and observational studies and clinical assays about rehabilitation for haemophiliacs with exercise and sporting activities have been included. The relevant studies were identified in Medline, Cinahl, Embase and SportDiscus, and key words were: haemophilia, exercise and sport (with no language restrictions). Works were independently analysed by reviewers and the following were identified: of 3603 studies, 103 were included in this review: 29 (28.15%) were experimental, 27 (26.21%) were observational and 47 (45.63%) were clinical. Physiotherapy, physical activity and sport are basic elements to improve quality of life and the physical condition, increase strength and resistance and to reduce the risk of musculoskeletal lesions and to prevent haemophilic atrophy. In general, professionals in haemophilia believe that regular exercise and rehabilitation with physiotherapy is fundamental, particularly in countries where replacement therapy is not readily available.
Emotional outcome after intensive care: literature review
Authors: Rattray Janice E. , Hull Alastair M.
Published: August 2008

Title.  Emotional outcome after intensive care: literature review.

Aim.  This paper is a report of a literature review to identify (a) the prevalence of emotional and psychological problems after intensive care, (b) associated factors and (c) interventions that might improve this aspect of recovery.

Background.  Being a patient in intensive care has been linked to both short‐ and long‐term emotional and psychological consequences.

Data sources.  The literature search was conducted during 2006. Relevant journals and databases were searched, i.e. Medline and CINAHL, between the years 1995 and 2006.

Review methods.  The search terms were ‘anxiety’, ‘depression’, posttraumatic stress’, ‘posttraumatic stress disorder’ and ‘intensive care’.

Results.  Fifteen papers were reviewed representing research studies of anxiety, depression and posttraumatic stress, and seven that represented intensive care follow‐up clinics and patient diaries. Being in intensive care can result in significant emotional and psychological problems for a number of patients. For the majority of patients, symptoms of distress will decrease over time but for a number these will endure for some years. Current evidence indicates that emotional problems after intensive care are related to both subjective and objective indicators of a patient’s intensive care experience. Evidence suggests some benefit in an early rehabilitation programme, daily sedation withdrawal and the use of patient diaries. However, additional research is required to support such findings.

Conclusion.  Our understanding of the consequences of intensive care is improving. Psychological care for intensive care patients has lagged behind care for physical problems. We now need to focus on developing and evaluating appropriate interventions to improve psychological outcome in this patient group.
Haemangiomas and associated congenital malformations in a large population‐based sample of infants
Authors: Bukowinski Anna T. , Ryan Margaret A. K. , Slymen Donald J. , Sevick Carter J. , Alcaraz John E. , Smith Tyler C.
Published: August 2008

Haemangiomas are common, benign, vascular tumours, observed in 4–12% of infants during the first year of life. Most cases progress without complication, yet a small proportion experience life‐threatening complications. Concomitant congenital malformations have been reported in a small but significant proportion of haemangioma patients. This study aimed to describe haemangioma cases and to identify patterns of congenital malformations associated with these diagnoses in a large population. Diagnoses of haemangiomas and 21 congenital malformations were extracted from electronic medical records of 467 295 singleton infants born to US military families from 1998 to 2003. Cluster analysis was used to group cases according to these diagnoses. Multivariable logistic regression was used to further explore the associations of the 21 congenital malformations with the diagnosis of haemangioma and to assess the adjusted relationships between a number of characteristics of interest and diagnosis of haemangioma.

Clusters found to be associated with haemangioma were characterised by anomalies of the cervix, vagina, and external female genitalia, anophthalmia or microphthalmia, hydrocephalus without spina bifida, and reduction deformities of the brain. Logistic regression identified three congenital malformations significantly associated with haemangioma diagnosis: spina bifida without anencephalus, hydrocephalus without spina bifida, and anomalies of the cervix, vagina and external female genitalia. Characteristics significantly associated with haemangioma included female gender, preterm birth, white non‐Hispanic race/ethnicity and increasing maternal age. This exploratory study identified a number of important associations between haemangiomas and congenital malformations that may provide insight into the pathogenesis of these disorders and have possible implications for clinical care.
Role of volatiles and metasomatized subcontinental lithospheric mantle in the genesis of magmatic Ni–Cu–PGE mineralization: insights from in situ H, Li, B analyses of hydromagmatic phases from the Valmaggia ultramafic pipe, Ivrea‐Verbano Zone (NW Italy)
Authors: Fiorentini M. L. , Beresford S. W.
Published: August 2008

In situ trace element and isotopic data of hydromagmatic phases from the Valmaggia peridotite pipe provide insights into the origin of the metasomatic fluids that affected the Ivrea‐Verbano Zone (NW Italy) during the late Carboniferous and shed new light on genetic models for the formation of Ni–Cu–PGE deposits. Volatiles implicated in the formation of hydromagmatic phases are not hydrothermal and did not derive from crustal assimilation. Low boron concentrations exclude the implication of fluids derived from dehydration of a subducted slab and indicate an origin from mantle‐derived juvenile water. Metasomatism introduced elevated contents of alkalis, Cu, PGEs and S into the depleted mantle of the Ivrea‐Verbano Zone. Increased water activity caused the harzburgite to undergo partial melting, thus producing pockets of volatile‐rich sulphide‐bearing ultramafic magma that evolved to form independent intrusions that host Ni–Cu–PGE mineralization.
Unexpected Jurassic to Neogene vertical movements in ‘stable’ parts of NW Africa revealed by low temperature geochronology
Authors: Ghorbal B. , Bertotti G. , Foeken J. , Andriessen P.
Published: August 2008

In Morocco, it is generally considered that post‐Hercynian vertical movements were limited to the Atlas system, the passive continental margin and the Rif. Apatite FT and He ages from the Moroccan Meseta (Rehamna and Zaer Massif) document instead two episodes of subsidence and exhumation in Jurassic‐Early Cretaceous and during the Late Cretaceous to Neogene. The Meseta subsided to >3 km depth during the Late Triassic to Middle Jurassic and was exhumed to the surface before the Late Cretaceous, during the rift and post‐rift stages of Central Atlantic opening. Erosion of the exhuming rocks is responsible for a thick package of terrigenous sands found in the Moroccan offshore and elsewhere along the NW Africa margin. About 1 km of subsidence affected the Meseta during the Late Cretaceous to Eocene. During the Neogene, these areas were brought back to the surface in association with bimodal folding with wavelengths of 100–150 km and >500 km.
Late stage differential exhumation of crustal blocks in the central Eastern Alps: evidence from fission track and (U–Th)/He thermochronology
Authors: Wölfler Andreas , Dekant Christian , Danišík Martin , Kurz Walter , Dunkl István , Putiš Marián , Frisch Wolfgang
Published: August 2008

Thermal history modelling based on zircon‐ and apatite fission track and apatite (U–Th)/He data constrain and refine the near‐surface exhumation of the south‐eastern Tauern Window (Penninic units) and neighbouring Austroalpine basement units in the Eastern Alps. Fast exhumation on both sides of the Penninic/Austroalpine boundary coincides with a period of lateral extrusion and tectonic denudation of the Penninic units in Miocene time (22–12 Ma). The jump to older ages occurs within the Austroalpine unit along the Polinik fault, which therefore defines the boundary between the tectonically denuded units and the hangingwall at that time. According to the different (U–Th)/He ages between the Penninic Hochalm‐ and Sonnblick Domes we demonstrate a differential cooling history of these two domes in the latest Miocene and early Pliocene.
Palaeomagnetic evidence of a Variscan age for the epigenetic Galmoy zinc–lead deposit, Ireland
Authors: Pannalal S. J. , Symons D. T. A. , Sangster D. F.
Published: August 2008

Palaeomagnetism of 273 specimens from 24 sites isolated a well‐defined characteristic remanent magnetization (ChRM) direction on AF and thermal demagnetization in seven host carbonate and 14 ore mineralization sites from the Galmoy Zn–Pb deposit. Thermal decay and saturation remanence data show that the ChRM is carried dominantly by single domain magnetite. Palaeomagnetic field stability tests indicate a post‐brecciation and post‐folding ChRM. The ChRM directions from the host rock and mineralized sites are indistinguishable at 95% confidence and give a palaeopole at 41.5°S, 8.4°W (dp = 1.5°, dm = 3.0°) with an age of 290 ± 9 Ma on the Laurentian apparent polar wander path. This Early Permian age at Galmoy records Variscan orogenesis and suggests an epigenetic model in which mineralization occurred during cooling from the regional Variscan thermal episode.
Therapy of uncomplicated malaria in children: a review of treatment principles, essential drugs and current recommendations
Authors: Deen Jacqueline L. , Von Seidlein Lorenz , Dondorp Arjen
Published: August 2008

Understanding the optimal treatment of uncomplicated malaria in children is challenging because of the availability of new drugs and the shift to combination therapies. This is a review of the guiding principles for the treatment of uncomplicated malaria, the essential anti‐malarial drugs for children, and the treatment regimens currently recommended.
Pharmacovigilance through consumer feedback (reporting) in the mass treatment of lymphatic filariasis using diethylcarbamazine and albendazole in two districts of Sri Lanka
Authors: Gunawardena Sharmini , Ranganathan Shalini Sri , Fernandopulle Rohini
Published: August 2008

Objective  To document the types and severity of adverse drug reactions to diethylcarbamazine and albendazole in randomly selected urban populations from Colombo and rural populations from Gampaha, Sri Lanka.

Methods  Interviewers administered a pre‐tested questionnaire to elicit information about the type and severity of adverse drug reactions experienced by recipients. Seeking medical treatment and requiring hospital admission for the adverse drug reactions were used as indicators for severity. The sample population was selected using the cluster sampling method.

Results  Two thousand three hundred and nineteen persons aged 10 to 90 years (median 40.0) responded to the questionnaire; 63.9% of them had received and ingested the drugs. 12.6% reported that they had experienced adverse drug reactions, the proportion being similar in urban and rural areas (χ2 = 0.05; p = 0.82). Commonly reported reactions were drowsiness (34.7%), headache (23.1%), gastrointestinal symptoms (18.7%) and dizziness or faintness (11.9%). However, most symptoms were mild (96.3%) and did not interfere with daily activities or require medical attention. 3.2% said that they sought medical advice for their symptoms; one person (0.5%) who had severe abdominal pain was hospitalized.

Conclusions  Fewer people experienced adverse drug reactions than in previous years, possibly due to lower microfilariaemia prevalence after several rounds of mass drug administration against filariasis. Community awareness of adverse drug reactions is essential for improving compliance and for the success of the filariasis elimination programme.
After a decade of annual dose mass ivermectin treatment in Cameroon and Uganda, onchocerciasis transmission continues
Authors: Katabarwa Moses , Eyamba Albert , Habomugisha Peace , Lakwo Tom , Ekobo Same , Kamgno Joseph , Kuete Thomas , Ndyomugyenyi Richard , Onapa Ambrose , Salifou Mkpouwoueiko , Ntep Marcelline , Richards Frank O.
Published: August 2008

Objective  To evaluate the effectiveness of 10 years’ annual single dose ivermectin treatment on onchocerciasis transmission in hyperendemic areas of Cameroon and Uganda.

Methods  Baseline nodule and microfilaria (‘skin snip’) prevalence data were available from 10 hyperendemic sentinel communities in Cameroon (from 1996) and hyperendemic 20 sentinel communities in Uganda (from 1993). We returned to these villages in 2005, 10 months after the last annual ivermectin distribution, to repeat the cross‐sectional surveys. Each sentinel community reported a mean interval treatment coverage of eligible persons of >88% (range 37–100%). Data were analyzed for more than 6200 person examinations. In Cameroon, 719 people ≥10 years were examined at the baseline survey in 1996 and 838 at the follow‐up survey in 2005. In Uganda, 1590 people ≥10 years were examined at the baseline survey in 1993 and 2122 people at the follow‐up survey in 2005. We also examined children under 10 in Cameroon (1996, n = 185; 2005, n = 448) and Uganda (1993, n = 177; 2005, n = 130). In Uganda, the vitality of worms was judged using standard histological criteria in 80 nodules excised in 2005.

Results  The prevalence of microfilaria carriers among older children and adults (≥10 years) in Cameroon sentinel communities dropped from 70.1% to 7.04% (P < 0.0001) over the 10‐year treatment period; that of nodule carriers from 58% to 9.55% (P < 0.0001). Similarly, in Uganda, the prevalence of microfilaria carriers fell from 71.9% to 7.49% (P < 0.0001) over the 13‐year treatment period, and that of nodule carriers from 53.21% to 9.66% (P < 0.0001). The number of microfilaria carriers among children <10 years in Cameroon decreased from 29.73% to 3.8% (P < 0.0001), and in Uganda from 33.89% to 3.1% (P < 0.0001). In 2005, worms excised from nodules in Uganda, 81.4% of males remained alive, and 64% of females, with 24% of them inseminated.

Conclusion  A decade or more of annual single dose ivermectin treatment in hyperendemic areas has reduced onchocerciasis to ‘hypoendemicity’, but onchocerciasis transmission persists. For now, annual treatment with ivermectin should be continued in formerly mesoendemic and hyperendemic zones.