bluuebunny/crossref_metadata_2025 huggingface dataset:
The protein factors MBNL1 and U2AF65 bind alternative RNA structures to regulate splicing
Authors: Warf M. Bryan , Diegel Julien V. , von Hippel Peter H. , Berglund J. Andrew
Published: May 2009

Myotonic dystrophy type 1 (DM1) is a genetic disorder linked to a (CTG)
n
repeat expansion in the 3′ untranslated region of the
DMPK
gene. Upon transcription in the nucleus, the CUG repeats form a stable RNA stem-loop that sequesters the RNA-binding protein MBNL1 from its normal function in the cell. MBNL1 regulates the alternative splicing of many pre-mRNAs, and upon MBNL1's sequestration, the alternative splicing of many genes is mis-regulated, leading to disease symptoms. MBNL1 is known to bind directly to at least 3 of the pre-mRNAs that it regulates, but how MBNL1 binding mechanistically regulates alternative splicing is unclear. Here, we demonstrate that MBNL1 controls the splicing of exon 5 in the cardiac troponin T (cTNT) pre-mRNA by competing directly with the essential splicing factor U2AF65 for binding at the 3′ end of intron 4. When U2AF65 is prevented from binding to the pre-mRNA, the U2 snRNP can no longer be recruited and the following exon is skipped. Furthermore, MBNL1 and U2AF65 appear to compete by binding to mutually exclusive RNA structures. When bound by splicing factors, the 3′ end of intron 4 can form either a stem-loop or a single-stranded structure. MBNL1 binds a portion of the intron as a stem-loop, whereas U2AF65 binds the same region in a single-strand structure. Mutations that strengthen the stem-loop decrease U2AF65 binding affinity and also repress exon 5 inclusion, independently of MBNL1. Thus, U2AF65 binding can be blocked either by MBNL1 binding or by the stabilization of RNA secondary structure.
Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells
Authors: Burzio Verónica A. , Villota Claudio , Villegas Jaime , Landerer Eduardo , Boccardo Enrique , Villa Luisa L. , Martínez Ronny , Lopez Constanza , Gaete Fancy , Toro Viviana , Rodriguez Ximena , Burzio Luis O.
Published: May 2009

We reported the presence in human cells of a noncoding mitochondrial RNA that contains an inverted repeat (IR) of 815 nucleotides (nt) covalently linked to the 5′ end of the mitochondrial 16S RNA (16S mtrRNA). The transcript contains a stem-loop structure and is expressed in human proliferating cells but not in resting cells. Here, we demonstrate that, in addition to this transcript, normal human proliferating cells in culture express 2 antisense mitochondrial transcripts. These transcripts also contain stem-loop structures but strikingly they are down-regulated in tumor cell lines and tumor cells present in 17 different tumor types. The differential expression of these transcripts distinguishes normal from tumor cells and might contribute a unique vision on cancer biology and diagnostics.
Development and diversification of retinal amacrine interneurons at single cell resolution
Authors: Cherry Timothy J. , Trimarchi Jeffrey M. , Stadler Michael B. , Cepko Constance L.
Published: May 2009

The vertebrate retina uses diverse neuronal cell types arrayed into complex neural circuits to extract, process, and relay information from the visual scene to the higher order processing centers of the brain. Amacrine cells, a class of interneurons, are thought to mediate much of the processing of the visual signal that occurs within the retina. Although amacrine cells display extensive morphological diversity, the molecular nature of this diversity is largely unknown. Furthermore, it is not known how this diversity arises during development. Here, we have combined in vivo genetic labeling, single cell genome-wide expression profiling, and classical birthdating to (
i
) identify specific molecular types of amacrine cells, (
ii
) demonstrate the molecular diversity of the amacrine cell class, and (
iii
) show that amacrine cell diversity arises at least in part through temporal patterning.
Recent progress in fast ion studies on JET
Authors: Kiptily V.G. , Perez von Thun C.P. , Pinches S.D. , Sharapov S.E. , Borba D. , Cecil F.E. , Darrow D. , Goloborod'ko V. , Craciunescu T. , Johnson T. , Nabais F. , Reich M. , Salmi A. , Yavorskij V. , Cecconello M. , Gorini G. , Lomas P. , Murari A. , Parail V. , Popovichev S. , Saibene G. , Sartori R. , Syme D.B. , Tardocchi M. , de Vries P. , Zoita V.L.
Published: May 2009

This paper presents recent results on fast ion studies on JET. A set of diagnostics for both confined and lost fast ions was employed for investigating the response of fast ions to MHD modes and for studying their behaviour in plasmas with toroidal field ripple and in shear-reversed plasmas. A dependence of the losses on MHD mode amplitude was deduced from the experimental data. A study of various plasma scenarios has shown that a significant redistribution of the fast ions happens during changes in the profile of the safety factor from shear-reversed to monotonic. Significant changes in the losses of ICRH accelerated protons were found to be associated with L–H confinement transitions in plasmas. After an L–H transition, an abrupt decrease in the ICRH proton losses was observed. In plasmas with an internal transport barrier, the loss of ICRH accelerated ions was found to increase as the barrier forms. Further results concerning fast ion losses were obtained during JET experiments in which the magnitude of the TF ripple was varied. The ripple losses of fusion products appear similar to classical losses, and are in agreement with modelling.
Off-axis neutral beam current drive for advanced scenario development in DIII-D
Authors: Murakami M. , Park J.M. , Petty C.C. , Luce T.C. , Heidbrink W.W. , Osborne T.H. , Prater R. , Wade M.R. , Anderson P.M. , Austin M.E. , Brooks N.H. , Budny R.V. , Challis C.D. , DeBoo J.C. , deGrassie J.S. , Ferron J.R. , Gohil P. , Hobirk J. , Holcomb C.T. , Hollmann E.M. , Hong R.M. , Hyatt A.W. , Lohr J. , Lanctot M.J. , Makowski M.A. , McCune D.C. , Politzer P.A. , Scoville J.T. , St John H.E. , Suzuki T. , Taylor T.S. , West W.P. , Unterberg E.A. , Van Zeeland M.A. , Yu J.H.
Published: May 2009

Modification of the two existing DIII-D neutral beamlines is planned to allow vertical steering to provide off-axis neutral beam current drive (NBCD) peaked as far off-axis as half the plasma minor radius. New calculations for a downward-steered beam indicate strong current drive with good localization off-axis so long as the toroidal magnetic field, B
T, and the plasma current, I
p, point in the same direction. This is due to good alignment of neutral beam injection (NBI) with the local pitch of the magnetic field lines. This model has been tested experimentally on DIII-D by injecting equatorially mounted NBs into reduced size plasmas that are vertically displaced with respect to the vessel midplane. The existence of off-axis NBCD is evident in the changes seen in sawtooth behaviour in the internal inductance. By shifting the plasma upwards or downwards, or by changing the sign of the toroidal field, off-axis NBCD profiles measured with motional Stark effect data and internal loop voltage show a difference in amplitude (40–45%) consistent with differences predicted by the changed NBI alignment with respect to the helicity of the magnetic field lines. The effects of NBI direction relative to field line helicity can be large even in ITER: off-axis NBCD can be increased by more than 30% if the B
T direction is reversed. Modification of the DIII-D NB system will strongly support scenario development for ITER and future tokamaks as well as provide flexible scientific tools for understanding transport, energetic particles and heating and current drive.
A detailed study of kinetic effects of energetic particles on resistive MHD linear stability
Authors: Takahashi R. , Brennan D.P. , Kim C.C.
Published: May 2009

The effects of energetic particles on MHD instabilities is a key issue in the basic physics that will be important in burning plasma experiments such as ITER. Recently, experiments (JET, JT-60U and DIII-D) have shown that the kinetic effects of energetic particles can play a crucial role in the stability of the m/n = 2/1 tearing mode, where the fraction of energetic particle βfrac ≡ βh/β is high (β = 2μ0
P/B
2, P is pressure, B is magnetic field and βh is the energetic particle β). For the study of the kinetic effects of energetic particles on resistive MHD stability, using model equilibria based on DIII-D experimental reconstructions, the non-ideal MHD linear stability of cases unstable to the 2/1 mode is investigated including a δf PIC model for the energetic particles coupled to the nonlinear 3D resistive MHD code NIMROD (Kim et al 2008 Phys. Plasmas
15 072507). The growth of unstable modes is calculated at a series of β, βfrac and S = τR/τA (the ratio of the resistive time to Alfvén time), spanning from the resistive to the ideal unstable regime of the mode, up to and above βfrac = 0.25, and well into the asymptotic regime of the resistivity. It is observed that energetic particles have significant damping and stabilizing effects at experimentally relevant β, βfrac and S, and less damping and stabilizing effects at the ideal unstable regime. It is also observed that energetic particles excite a real frequency of the 2/1 mode. The growth rates significantly reduce at experimentally relevant β, βfrac and S due to the mode interacting with the trapped particles and ‘barely passing’ particles. Furthermore, extrapolation of the results is discussed for implications for JET and ITER, where the effects are projected to be significant.
Treevolution: visual analysis of phylogenetic trees
Authors: Santamaría Rodrigo , Therón Roberto
Published: May 2009

Summary: Treevolution is a tool for the representation and exploration of phylogenetic trees that facilitates visual analysis. There are several useful tools to visualize phylogenetic trees, but their level of interaction is usually low, especially in the case of radial representations. Highly interactive visualizations can improve the exploration and understanding of phylogenetic trees. Treevolution implements strategies to interact with phylogenetic trees in order to allow a more thorough analysis by users.

Availability: Treevolution is available at http://vis.usal.es/treevolution. Additional figures, a user's guide, a video demo and some examples are available at the same site.

Contact:  rodri@usal.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
CORAL: aligning conserved core regions across domain families
Authors: Fong Jessica H. , Marchler-Bauer Aron
Published: May 2009

Motivation: Homologous protein families share highly conserved sequence and structure regions that are frequent targets for comparative analysis of related proteins and families. Many protein families, such as the curated domain families in the Conserved Domain Database (CDD), exhibit similar structural cores. To improve accuracy in aligning such protein families, we propose a profile–profile method CORAL that aligns individual core regions as gap-free units.

Results: CORAL computes optimal local alignment of two profiles with heuristics to preserve continuity within core regions. We benchmarked its performance on curated domains in CDD, which have pre-defined core regions, against COMPASS, HHalign and PSI-BLAST, using structure superpositions and comprehensive curator-optimized alignments as standards of truth. CORAL improves alignment accuracy on core regions over general profile methods, returning a balanced score of 0.57 for over 80% of all domain families in CDD, compared with the highest balanced score of 0.45 from other methods. Further, CORAL provides E-values to aid in detecting homologous protein families and, by respecting block boundaries, produces alignments with improved ‘readability’ that facilitate manual refinement.

Availability: CORAL will be included in future versions of the NCBI Cn3D/CDTree software, which can be downloaded at http://www.ncbi.nlm.nih.gov/Structure/cdtree/cdtree.shtml.

Contact:  fongj@ncbi.nlm.nih.gov.

Supplementary information:  Supplementary data are available at Bioinformatics online.
Enhanced long-term and impaired short-term spatial memory in GluA1 AMPA receptor subunit knockout mice: Evidence for a dual-process memory model
Authors: Sanderson David J. , Good Mark A. , Skelton Kathryn , Sprengel Rolf , Seeburg Peter H. , Rawlins J. Nicholas P. , Bannerman David M.
Published: May 2009

The GluA1 AMPA receptor subunit is a key mediator of hippocampal synaptic plasticity and is especially important for a rapidly-induced, short-lasting form of potentiation. GluA1 gene deletion impairs hippocampus-dependent, spatial working memory, but spares hippocampus-dependent spatial reference memory. These findings may reflect the necessity of GluA1-dependent synaptic plasticity for short-term memory of recently visited places, but not for the ability to form long-term associations between a particular spatial location and an outcome. This hypothesis is in concordance with the theory that short-term and long-term memory depend on dissociable psychological processes. In this study we tested GluA1−/− mice on both short-term and long-term spatial memory using a simple novelty preference task. Mice were given a series of repeated exposures to a particular spatial location (the arm of a Y-maze) before their preference for a novel spatial location (the unvisited arm of the maze) over the familiar spatial location was assessed. GluA1−/− mice were impaired if the interval between the trials was short (1 min), but showed enhanced spatial memory if the interval between the trials was long (24 h). This enhancement was caused by the interval between the exposure trials rather than the interval prior to the test, thus demonstrating enhanced learning and not simply enhanced performance or expression of memory. This seemingly paradoxical enhancement of hippocampus-dependent spatial learning may be caused by GluA1 gene deletion reducing the detrimental effects of short-term memory on subsequent long-term learning. Thus, these results support a dual-process model of memory in which short-term and long-term memory are separate and sometimes competitive processes.
A discrete population of neurons in the lateral amygdala is specifically activated by contextual fear conditioning
Authors: Wilson Yvette M. , Murphy Mark
Published: May 2009

There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the fos-tau-lacZ (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral amygdala that are activated specifically following learning. These neurons have the morphology of principal neurons of the amygdala, and are immunoreactive for glutamate. The highly specific localization of these neurons within the lateral amygdala suggests that these neurons may be a discrete population of neurons involved in fear learning.
Memory deficits are associated with impaired ability to modulate neuronal excitability in middle-aged mice
Authors: Kaczorowski Catherine C. , Disterhoft John F.
Published: May 2009

Normal aging disrupts hippocampal neuroplasticity and learning and memory. Aging deficits were exposed in a subset (30%) of middle-aged mice that performed below criterion on a hippocampal-dependent contextual fear conditioning task. Basal neuronal excitability was comparable in middle-aged and young mice, but learning-related modulation of the post-burst afterhyperpolarization (AHP)—a general mechanism engaged during learning—was impaired in CA1 neurons from middle-aged weak learners. Thus, modulation of neuronal excitability is critical for retention of context fear in middle-aged mice. Disruption of AHP plasticity may contribute to contextual fear deficits in middle-aged mice—a model of age-associated cognitive decline (AACD).
Posterior parietal cortex and episodic retrieval: Convergent and divergent effects of attention and memory
Authors: Hutchinson J. Benjamin , Uncapher Melina R. , Wagner Anthony D.
Published: May 2009

Functional neuroimaging studies of humans engaged in retrieval from episodic memory have revealed a surprisingly consistent pattern of retrieval-related activity in lateral posterior parietal cortex (PPC). Given the well-established role of lateral PPC in subserving goal-directed and reflexive attention, it has been hypothesized that PPC activation during retrieval reflects the recruitment of parietal attention mechanisms during remembering. Here, we evaluate this hypothesis by considering the anatomical overlap of retrieval and attention effects in lateral PPC. We begin by briefly reviewing the literature implicating dorsal PPC in goal-directed attention and ventral PPC in reflexive attention. We then discuss the pattern of dorsal and ventral PPC activation during episodic retrieval, and conclude with consideration of the degree of anatomical convergence across the two domains. This assessment revealed that predominantly divergent subregions of lateral PPC are engaged during acts of episodic retrieval and during goal-directed and reflexive attention, suggesting that PPC retrieval effects reflect functionally distinct mechanisms from these forms of attention. Although attention must play a role in aspects of retrieval, the data reviewed here suggest that further investigation into the relationship between processes of attention and memory, as well as alternative accounts of PPC contributions to retrieval, is warranted.
Changes in soil organic matter composition are associated with forest encroachment into grassland with long‐term fire history
Authors: Dümig A. , Knicker H. , Schad P. , Rumpel C. , Dignac M.‐F. , Kögel‐Knabner I.
Published: May 2009

This study investigates if Araucaria forest (C3 metabolism) expansion on frequently burnt grassland (C4 metabolism) in the southern Brazilian highland is linked to the chemical composition of soil organic matter (SOM) in non‐allophanic Andosols. We used the 13C/12C isotopic signature to group heavy organo‐mineral fractions according to source vegetation and 13C NMR spectroscopy, lignin analyses (CuO oxidation) and measurement of soil colour lightness to characterize their chemical compositions. Large proportions of aromatic carbon (C) combined with small contents of lignin‐derived phenols in the heavy fractions of grassland soils and grass‐derived lower horizons of Araucaria forest soils indicate the presence of charred grass residues in SOM. The contribution of this material may have led to the unusual increase in C/N ratios with depth in burnt grassland soils and to the differentiation of C3‐ and C4‐derived SOM, because heavy fractions from unburnt Araucaria forest and shrubland soils have smaller proportions of aromatic C, smaller C/N ratios and are paler compared with those with C4 signatures. We found that lignins are not applicable as biomarkers for plant origin in these soils with small contents of strongly degraded and modified lignins as the plant‐specific lignin patterns are absent in heavy fractions. In contrast, the characteristic contents of alkyl C and O/N‐alkyl C of C3 trees or shrubs and C4 grasses are reflected in the heavy fractions. They show consistent changes of the (alkyl C)/(O/N‐alkyl C) ratio and the 13C/12C isotopic signature with soil depth, indicating their association with C4 and C3 vegetation origin. This study demonstrates that soils may preserve organic matter components from earlier vegetation and land‐use, indicating that the knowledge of past vegetation covers is necessary to interpret SOM composition.
The importance of scent and nectar filters in a specialized wasp‐pollination system
Authors: Shuttleworth Adam , Johnson Steven D.
Published: May 2009

1. Plants with open flowers and exposed nectar should attract a wide diversity of flower visitors, yet, for reasons that are not yet well understood, some plants with these ‘generalist’ floral traits have highly specialized pollination systems.

2. We investigated this problem in the African milkweed Pachycarpus grandiflorus which has open flowers that produce copious amounts of exposed and concentrated nectar, yet is visited almost exclusively by spider‐hunting wasps in the genus Hemipepsis.

3. These wasps were the only visitors found to consistently carry pollinaria and a cage experiment showed that they are capable of successfully pollinating this plant. Furthermore, experimental hand‐pollinations showed that P. grandiflorus is genetically self‐incompatible and thus reliant on pollinators for seed set.

4. We investigated the roles of chemical (nectar and floral scent) and spectral properties in the selective attraction of wasps and the filtering out of other potential flower visitors. Nectar palatability experiments showed that the nectar is unpalatable to honeybees but palatable to the wasps. Choice experiments conducted in the field and using a Y‐maze in the laboratory showed that wasps are attracted primarily by scent rather than visual cues. Analysis of scent using Gas Chromatography‐Mass Spectrometry showed that these inflorescences produce 36 different compounds, mostly monoterpenes and aliphatics. Analysis of spectral reflectance showed that flowers have similar colouring to the background vegetation.

5. We conclude that P. grandiflorus is specialized for pollination by Hemipepsis wasps, and in the absence of morphological filters, achieves specialization through unpalatable nectar, cryptic colouring and scent as a selective pollinator attractant.

6. This study demonstrates that plants whose flowers are not morphologically adapted to exclude particular floral visitors can achieve specialization through non‐morphological filters.
Methane hydrates in controlled‐source electromagnetic surveys – analysis of a recent data example
Authors: Zach J. J. , Brauti K.
Published: May 2009

Data from a recently acquired sea‐bed logging deep‐water survey are analysed for resistive bodies at depths below mudline shallower than about 300 m. A model consistent with known methane hydrate properties is found to explain near‐offset structures over an offset scale of a few hundred metres observed in the data. The lateral near‐seabed resolution of the sea‐bed logging method was determined to less than 100 m for source frequencies of up to 10 Hz. The importance of accurate hydrate maps to improve data processing is demonstrated by placing synthetic reservoirs below hydrates and observing their effects on reference model processing. The phase is shown to be less perturbed by shallow resistors than the amplitude, which is an important quality control of standard anomaly maps. While patchy shallow resistors can generally be mapped with simple normalized magnitude‐versus‐offset and phase‐versus‐offset difference analyses, large area distributions of hydrates over kilometres are hard to distinguish from deeper structures using controlled‐source electromagnetic data only, short of conducting a full 3D inversion of a sufficiently large survey. Beyond, the study confirms the applicability of controlled‐source electromagnetic techniques in general to map shallow resistive structures for drilling hazards and possible future exploration of methane hydrates as an energy source.
Lower doses of rFVIIa therapy are safe and effective for surgical interventions in patients with severe FXI deficiency and inhibitors
Authors: KENET G. , LUBETSKY A. , LUBOSHITZ J. , RAVID B. , TAMARIN I. , VARON D. , MARTINOWITZ U.
Published: May 2009

Summary.  Severe FXI deficiency is a rare injury‐related bleeding disorder. In patients with FXI inhibitors, surgeries may be treated using recombinant activated factor VII; however, treatment safety is a major concern and the best dosing regimen as well as mode of administration is still to be defined. We describe four patients with severe factor XI deficiency and inhibitors to FXI, undergoing eight (four major) surgical procedures treated with continuous infusion of rFVIIa. Following acute MI that evolved after surgery of our first patient, all other patients were treated with low‐dose bolus rFVIIa followed by low‐dose continuous infusion of rFVIIa. Haemostasis was successfully achieved and no further thrombotic complications occurred. To support our clinical results ex‐vivo thromboelastography studies were performed, demonstrating the differences of clot formation and lysis between patients with FXI deficiency and healthy controls and suggesting that low‐dose rFVIIa corrects coagulation similarly to high‐dose rFVIIa in FXI deficiency. Recombinant FVIIa at low doses may effectively induce haemostasis and seems to be a safe treatment mode in patients with FXI deficiency and inhibitors undergoing surgeries.
Very early mortality in patients starting antiretroviral treatment at primary health centres in rural Malawi
Authors: Zachariah Rony , Harries Katie , Moses Massaquoi , Manzi Marcel , Line Arnould , Mwagomba Beatrice , Harries Anthony D.
Published: May 2009

Objectves  To report on the cumulative proportion of deaths occurring within 3 months of starting antiretroviral treatment (ART) and to identify factors associated with such deaths, among adults at primary health centres in a rural district of Malawi.

Methods  Retrospective cohort study: from June 2006 to April 2008, deaths occurring over a 3‐month period were determined and risk factors examined.

Results  A total of 2316 adults (706 men and 1610 women; median age 35 years) were included in the analysis and followed up for a total of 1588 person‐years (PY); 277 (12%) people died, of whom 206 (74%) people died within 3 months of initiating ART (cumulative incidence: 13.0; 95% confidence interval: 11.3–14.8 per 100 PY of follow‐up). Significant risk factors associated with early deaths included male sex, WHO stage 4 disease, oesophageal or persistent oral candidiasis and unexplained presumed or measured weight loss >10%. One in every 3 patients who either died or was lost to follow up had unexplained weight loss >10%, and survival in this group was significantly different from patients without this condition.

Conclusions  Seven in 10 individuals initiating ART at primary health centres die early. Specific groups of patients are at higher risk of such mortality and should receive priority attention, care and support.
Performance‐based financing for better quality of services in Rwandan health centres: 3‐year experience
Authors: Rusa Louis , Ngirabega Jean de Dieu , Janssen Willy , Van Bastelaere Stefaan , Porignon Denis , Vandenbulcke Werner
Published: May 2009

In 2005, the Ministry of Health in Rwanda, with the support of the Belgian Technical Cooperation, launched a strategy of performance‐based financing (PBF) in a group of 74 health centres (HCs), covering 2‐m inhabitants. In 2006, PBF was extended to an additional group of 85 HCs, thus reaching 3.8‐m inhabitants. This study evaluates the effect of PBF on HC performance from 2005 to 2007. Composite indicators for measuring quantity and quality of services were developed and evaluated through monthly formative supervisions by qualified and well‐trained district supervisors. The strategy was based on a fixed fee per quality‐approved service. The entire budget spent on the implementation of PBF amounted to $0.25/cap/year, of which $0.20/cap/year for subsidies and an estimated $0.05/cap/year for administration, supervision and training. A positive effect on utilization rates was only seen for activities that were previously less well organized; in this case, growth monitoring services and institutional deliveries. The quality of services, defined as the compliance rate with national and international norms, rose considerably for all services in both groups. A sustained level of quality between 80% and 95% was reached within 18 months in the first group. A similar result was reached in the second group in 8 months.
Self‐harm and self‐poisoning in southern India: choice of poisoning agents and treatment
Authors: Bose Anuradha , Sandal Sejbaek Camilla , Suganthy Pearline , Raghava Venkata , Alex Reginald , Muliyil Jayaprakash , Konradsen Flemming
Published: May 2009

Objective  To record cases of suicide and attempted suicide among a population of 108 000 people living in a primarily rural area of southern India, with the aim of guiding policies and strategies to restrict access to poisonous compounds at community level.

Method  Community‐based surveillance over a period of 2 years.

Results and conclusion  The overall suicide rate was 71.4 per 100 000 population; the highest burden was among men. Most people died through hanging (81, 54%) and self‐poisoning (46, 31%). Of the 46 who died from self‐poisoning, 78.3% had taken pesticides and 19.7% had eaten poisonous plants. Eighty per cent of the self‐poisoning cases obtained the poisonous substance in or in close proximity to the home, highlighting the importance of safe storage in the domestic environment. Of the 110 fatal and non‐fatal self‐poisoning cases, 87 (57.5%) were taken for treatment; 50 (57.4%) went to government hospitals and 37 (42.5%) to private facilities. This indicates the importance of including the private sector in the efforts to improve case management. Furthermore, the fact that 31 (67%) of the self‐poisoning patients, who eventually died, were alive after 4 h provides an incentive to focus on improved case management and access to health services.
Integration of insecticide‐treated net distribution into routine immunization services in Malawi: a pilot study
Authors: Mathanga Don P. , Luman Elizabeth T. , Campbell Carl H. , Silwimba Chimwemwe , Malenga Grace
Published: May 2009

Objectives  To determine the feasibility of distributing insecticide‐treated nets (ITNs) through routine immunization services, to increase ownership and use of ITNs among high‐risk groups, whereas maintaining or improving timely completion of routine vaccinations.

Methods  Free ITNs were provided with timely completion of routine vaccinations in two intervention districts in southern Malawi for 15 months. Cross‐sectional baseline and follow‐up household surveys were conducted in the two intervention districts and one control district.

Results  Insecticide‐treated nets utilization among children aged 12–23 months roughly doubled in the two intervention districts and did not change in the control district. Timely vaccination coverage increased in all three districts. The percentage of children aged 12–23 months who were both fully vaccinated by 12 months and slept under an ITN the night prior to the interview increased from 10–14% at baseline to 40–44% at follow‐up in the intervention districts (P < 0.001), but did not change significantly in the control district.

Conclusions  This study is the first to evaluate the provision of free ITNs at completion of a child’s primary vaccination series, demonstrating that such a linkage is both feasible and can result in improved coverage with the combined services. Additional studies are needed to determine whether such a model is effective in other countries, and whether integration of other health services with immunization delivery could also be synergistic.
Factors influencing adherence to referral advice following pre‐referral treatment with artesunate suppositories in children in rural Tanzania
Authors: Simba Daudi O. , Warsame Marian , Kimbute Omari , Kakoko Deodatus , Petzold Max , Tomson Goran , Premji Zul , Gomes Melba
Published: May 2009

Objective WHO recommends artemisinin suppository formulations as pre‐referral treatment for children who are unable to take oral medication and cannot rapidly reach a facility for parenteral treatment. We investigated factors influencing caretakers’ adherence to referral advice following pre‐referral treatment of their children with rectal artesunate suppositories.

Methods The study was nested within an intervention study that involved pre‐referral treatment of all children who came to a community dispenser for treatment because they were unable to take oral medications because of repeated vomiting, lethargy, convulsions or altered consciousness. All patients who did not comply with referral advice were stratified by actions taken post‐referral: taking their children to a drug shop, a traditional healer, or not seeking further treatment, and added to a random selection of patients who complied with referral advice. Caretakers of the children were interviewed about their socio‐economic status (SES), knowledge about malaria, referral advice given and actions they took following pre‐referral treatment. Interview data for 587 caretakers were matched with symptoms of the children, the time of treatment, arrival at a health facility or other actions taken post–pre‐referral treatment.

Results The majority (93.5%) of caretakers reported being given referral advice by the community drug dispenser. The odds of adherence with this advice were three times greater for children with altered consciousness and/or convulsions than for children with other symptoms [odds ratio (OR) 3.47, 95% confidence interval (CI) 2.32–5.17,P < 0.001]. When questioned, caretakers who rememberedwhen(OR 2.19, 95% CI 1.48–3.23,P < 0.001) andwhy(OR 1.77, 95% CI 1.07–2.95,P = 0.026) they were advised to proceed to health facility – were more likely to follow referral advice. Cost did not influence adherence except within a catchment area of facilities that charged for services. In these areas, costs deterred adherence by four to five times for those who had previously paid for laboratory services (OR = 0.25, 95% CI: 0.09–0.67,P = 0.006) or consultation (OR 0.20, 95% CI: 0.06–0.61,P = 0.005) compared with those who had not.

Conclusion When given referral advice, caretakers of patients with life‐threatening symptoms adhere to referral advice more readily than other caretakers. Health service charges deter adherence.
Healthcare‐associated hepatitis C virus transmission among patients in an abdominal organ transplant center
Authors: Thompson N.D. , Hellinger W.C. , Kay R.S. , Cohen L. , Ragan P. , Voss R.A. , Bacalis L.P. , Xia G. , Keating M.R. , Dickson R.C. , Hughes C.B. , Williams I.T. , Perz J.F.
Published: May 2009

Background. De novo hepatitis C virus (HCV) infection among transplant patients is rarely recognized but can have severe consequences. We investigated the scope, source, and mode of HCV transmission within a transplant center after incident HCV infection was identified in 2 patients who had liver transplantation in late 2006.

Methods. Patients were interviewed, and transplant logs, medical records, and staff practices were reviewed to identify opportunities for HCV transmission. Infection via receipt of blood or organs was evaluated. Molecular epidemiology was used to determine the relatedness between persons with incident and chronic HCV infection.

Results. HCV from infected blood or organ donors was ruled out. Among the 308 patients who underwent transplant in 2006, no additional incident HCV infections were identified. Eighty‐five (28%) had pre‐transplant chronic HCV infection; 13 were considered possible HCV source patients based upon shared days on the inpatient unit, nursing assignment, or invasive procedures in common with incident HCV case‐patients. Viral isolates from 1 HCV source patient and 1 incident case‐patient were found to be highly related by quasispecies analysis, confirming patient‐to‐patient HCV transmission. Possible modes of transmission identified were the improper use of multidose vials, sharing of blood‐contaminated glucometers, and touch contamination.

Conclusion. Sporadic transmission or endemic levels of HCV transmission might be overlooked in a setting with high HCV prevalence, such as liver transplant units, where multiple, repeated opportunities for patient‐to‐patient HCV transmission can occur. Surveillance through pre‐ and post‐transplant screening is necessary to identify incident HCV infection in this setting. Constant, meticulous attention must be paid to maintaining aseptic technique and good infection control practices to eliminate HCV transmission opportunities.
A randomized, controlled trial of banding ligation plus drug therapy versus drug therapy alone in the prevention of esophageal variceal rebleeding
Authors: Lo Gin‐Ho , Chen Wen‐Chi , Chan Hoi‐Hung , Tsai Wei‐Lun , Hsu Ping‐I , Lin Chiun‐Ku , Chen Tai‐An , Lai Kwok‐Hung
Published: May 2009

Background & Aims:  Both medications with beta‐blockers and isosorbide‐5‐mononitrate and endoscopic variceal ligation have been proven plausible in the prevention of variceal rebleeding. However, the relative efficacy and safety of the combined treatment for preventing rebleeding remains unresolved.

Methods:  Patients with history of esophageal variceal bleeding were enrolled. Emergency ligation was performed in patients with acute variceal bleeding. After hemodynamic stability, eligible patients were randomized to either the Medication group, using nadolol plus isorsorbide‐5‐mononitrate, or the Combined group, receiving banding ligation in addition to medications. Patients in the two groups with rebleeding from esophageal varices were treated with band ligation. The end points were rebleeding from varices or death.

Results:  After a median follow up of 23 months, recurrent upper gastrointestinal bleeding developed in 51% in the Medication group and 38% in the Combined group (P = 0.21). Recurrent bleeding from esophageal varices occurred in 26 patients (43%) in the Medication group and in 16 patients (26%) in the Combined group (P = 0.07). Recurrent bleeding from gastroesophageal varices occurred in 48% of Medication group and 28% of Combined group (P = 0.05). The frequency of adverse effects and mortality rates were similar between both groups (P = 0.28).

Conclusions:  Combined ligation with medications was marginally more effective than medication alone in the prevention of gastroesophageal variceal rebleeding with similar adverse effects and mortality.
Efficacy of prepackaged, low residual test meals with 4L polyethylene glycol versus a clear liquid diet with 4L polyethylene glycol bowel preparation: A randomized trial
Authors: Park Dong Il , Park Seung Ha , Lee Sang Kil , Baek Yoo Hum , Han Dong Soo , Eun Chang Soo , Kim Won Ho , Byeon Jeong‐Sik , Yang Suk‐Kyun
Published: May 2009

Background and study aims:  A prepackaged low residue one‐day diet (breakfast, lunch and dinner) has been recently developed to improve patient tolerance for bowel preparation prior to colonoscopy. The aims of this study were to evaluate the efficacy and tolerability of bowel preparation protocols based on a low residue diet and 4L polyethylene glycol (PEG) solution, and to compare these new options with the traditional liquid diet and the PEG 4L lavage.

Methods:  A total of 214 patients (mean age: 54.1 years; 120 male, 94 female) from four university hospitals were included in the analysis. Patients were randomized to receive a clear liquid diet and the PEG 4L regimen (106 patients) or the low residue test meals and the PEG 4L regimen (TM‐PEG 4L, 108 patients). The colon cleansing efficacy of the different preparations was rated using the Ottawa bowel preparation scale.

Results:  No significant differences were observed between the treatment groups according to the Ottawa cleansing scale findings (PEG 4L: 2.97 vs TM‐PEG 4L: 2.46, P = 0.063). The overall tolerability was higher in the TM‐PEG 4L group than in the PEG 4L group (P = 0.036). No difference was found when the two groups were compared with regard to adverse events (P = 0.599).

Conclusions:  A prepackaged low residue one‐day diet provided cleansing efficacy similar to that of a clear liquid diet and offered the benefit of improved tolerability compared to the conventional PEG 4L regimen.
Reflux profile of Chinese gastroesophageal reflux disease patients with combined multichannel intraluminal impedance‐pH monitoring
Authors: Xiao Ying L , Lin Jin K , Cheung Ting K , Wong Nina Y H , Hung Ivan F N , Wong Benjamin C Y , Peng Sui , Wang An J , Chen Min H
Published: May 2009

Background and Aims:  To investigate the reflux profile of Chinese gastroesophageal reflux disease (GERD) patients with the aid of combined multichannel intraluminal impedance‐pH (MII‐pH) monitoring technique.

Methods:  Consecutive patients presented with GERD symptoms were enrolled to erosive esophagitis (EE) group, non‐erosive reflux disease (NERD) group and functional heartburn (FH) group after upper endoscopy, combined MII‐pH monitoring and rabeprazole test. Another 20 healthy controls (HC) were recruited.

Results:  Sixty‐four GERD patients (EE:20, NERD:22, FH:22, HC:20) were enrolled. There were more episodes of liquid reflux and proximal reflux in EE and NERD groups than that in FH and HC groups (P < 0.05). Patients in FH and HC groups had higher proportion of mixed reflux (P = 0.000). The percentage of acid reflux in EE and NERD was much higher, while there was a higher percentage of weakly acidic reflux in FH and HC (P = 0.000). No significant difference was found in MII‐pH parameters between groups with and without response to rabeprazole test except recumbent percentage time of esophageal pH value below 4 and episodes of proximal reflux.

Conclusion:  Erosive esophagitis and NERD patients had more liquid and proximal reflux episodes than FH patients and healthy controls. Acid and liquid reflux was predominant in the former two groups, while weakly acidic and mixed reflux was predominant in the latter two groups.
Open‐labeled pilot study of cysteine‐rich whey protein isolate supplementation for nonalcoholic steatohepatitis patients
Authors: Chitapanarux Taned , Tienboon Prasong , Pojchamarnwiputh Suwalee , Leelarungrayub Donrawee
Published: May 2009

Background and Aims:  Glutathione (GSH) depletion contributes to liver injury and development of steatohepatitis. Undenatured cysteine‐rich whey protein isolate has been clinically proven to raise GSH in several patient groups. The aim of this study was to evaluate the effect of oral supplementation with whey protein on patients with nonalcoholic steatohepatitis (NASH).

Methods:  In an open‐labeled clinical trial, 38 patients (18 male, 20 female; mean age 48 ± 14 years) with NASH confirmed by computed tomography measurements and liver biochemistries were given with a daily dose of 20 g whey protein isolate for 12 weeks.

Results:  A significant reduction in alanine aminotransferase (ALT) (64 ± 72 vs 46 ± 36, P = 0.016) and aspartate aminotransferase (AST) (45 ± 49 vs 33 ± 18, P = 0.047) were observed. Plasma glutathione and total antioxidant capacity increased significantly at the end of study (53 ± 11 vs 68 ± 11, P < 0.05 and 1.26 ± 0.10 vs 2.03 ± 0.10, P < 0.05). Liver attenuation index improved from −13.4 ± 11.1 to −9.7 ± 13.1 (P = 0.048). Hepatic macrovesicular steatosis decreased significantly after 12 weeks of supplementation (33.82 ± 12.82 vs 30.66 ± 15.96, P = 0.046). Whey protein isolate was well tolerated. No serious adverse events were observed.

Conclusions:  The results indicate that oral supplementation of cysteine‐rich whey protein isolate leads to improvements in liver biochemistries, increased plasma GSH, total antioxidant capacity and reduced hepatic macrovesicular steatosis in NASH patients. The results support the role of oxidative stress in the pathogenesis of this disease.
Disease pattern and seasonal variation among Japanese expatriate children in Thailand
Authors: Sakai Rie , Marui Eiji , Wongkhomthong Som‐Arch , Laobhripatr Suchart
Published: May 2009

Background:  Due to recent globalization, the number of Japanese expatriates including children has increased. The aim of the present study was to clarify the disease patterns and seasonal variation among Japanese children living in Thailand.

Methods:  Records of Japanese children seen at the outpatient clinic at Bangkok Hospital in 2005 (n = 1668) were analyzed and records of Thai children (n = 23 339) were also analyzed for comparison.

Results:  ‘Diseases of the respiratory system’ was the most frequent category in both groups (Japanese, 42.1%; Thai, 45.0 %,) followed by ‘factors influencing health status and contact with health services’ (Japanese, 12.7%; Thai, 14.9%), and ‘certain infectious and parasitic diseases’ (Japanese, 10.3%; Thai, 8.5%). The number of hospital visits by Japanese patients decreased in January, April, August and December and those by Thai patients in April and September. Identical drops in the number of visits for diseases of the respiratory system were also seen. A large number of patients visited the hospital for viral infections characterized by skin and mucous membrane lesions during the rainy season. The number of hospital visits for intestinal infection fluctuated during the rainy season.

Conclusion:  There were no marked differences between disease patterns of Japanese patients and Thai patients. Temporary visits back to Japan could account for sharp drops in total hospital visits and hospital visits for diseases of the respiratory system in January, April, August and December because these times of the year corresponded to extended school vacations. Preventive measures for viral infections characterized by skin and mucous membrane lesions should be promoted during the rainy season.
Pentaschistis (Poaceae) diversity in the Cape mediterranean region: habitat heterogeneity and climate stability
Authors: Galley C. , Linder H. P. , Zimmermann N. E.
Published: May 2009

Aim  To evaluate the role of habitat heterogeneity on species richness and turnover in the mega species‐rich Cape Floristic Region (Cape), the mediterranean region of southern Africa.

Location  The Cape and Drakensberg regions of southern Africa.

Methods  Bioclimatic data were used to estimate habitat amount and habitat heterogeneity in the Cape and Drakensberg regions; these data were then used to explain the patterns of species diversity in the Pentaschistis clade (Poaceae) in these two regions. Habitat variables were used to create ‘bioclimatic units’ to characterize 1′× 1′ cells in southern Africa and to describe the niches of species. Using these bioclimatic units, the niche and range sizes of species in the two regions were compared. A phylogram was used to test for age and lineage effects.

Results  Pentaschistis species diversity and turnover are higher in the Cape than the Drakensberg. There is no significant difference in the habitat amount and heterogeneity between the two regions. Species occupy the same range of estimated niche sizes, yet there are significantly more range‐restricted Pentaschistis species in the Cape.

Main conclusions  The roles of age‐ and lineage‐related effects are rejected; biodiversity differences lie in the regions. Current macrohabitat does not explain the differences in biodiversity between the two regions. The larger number of range‐restricted species in the Cape cannot be explained by dispersal mechanism or the occupation of range‐restricted habitats. Species of Pentaschistis and other Cape clades share characteristics associated with species from historically climatically stable areas, and palaeoclimatic and palaeontological evidence indicates the Cape climate has been more stable than the Drakensberg climate throughout the Pleistocene. We conclude that the corresponding lack of extinction might have allowed an accumulation of species in the Cape. Similar climatic and biological evidence for the south‐west Australian Floristic and Mediterranean regions indicate that the same mechanism might explain the high species richness of these mediterranean regions.
Short‐ and long‐term effects of endurance training in patients with mitochondrial myopathy
Authors: Jeppesen T. D. , Dunø M. , Schwartz M. , Krag T. , Rafiq J. , Wibrand F. , Vissing J.
Published: May 2009

Background and purpose:  It is unknown whether prolonged training is a safe treatment to alleviate exercise intolerance in patients with mitochondrial DNA (mtDNA) mutations.

Methods:  The effect of 3 and 12 months training and 3–12 months deconditioning was studied in four patients carrying different mtDNA mutations.

Results:  Three‐month moderate‐intensity training increased oxidative capacity by 23%, which was sustained after 6–12 months of low‐intensity training. Training and deconditioning did not induce adverse effects on clinical symptoms, muscle morphology and mtDNA mutation load in muscle.

Conclusion:  Long‐term training effectively improves exercise capacity in patients with mitochondrial myopathy, and appears to be safe.