bluuebunny/crossref_metadata_2025 huggingface dataset:
Three decades of heart transplantation in Scandinavia: long‐term follow‐up
Authors: Dellgren Göran , Geiran Odd , Lemström Karl , Gustafsson Finn , Eiskjaer Hans , Koul Bansi , Hagerman Inger , Selimovic Nedim ,   on behalf of the Nordic Thoracic Transplant Study Group
Published: October 2012

Aim

Heart transplantation (HTx) has become a standard treatment for patients with end‐stage heart disease. The aim of this study was to report the long‐term outcome after HTx in Scandinavia.

Methods and results

During the period, 1983–2009, 2333 HTxs were performed in 2293 patients (mean age 45 ± 16 years, range 0–70, 78% male). The main indications for HTx were non‐ischaemic cardiomyopathy (50%), ischaemic cardiomyopathy (34%), valvular cardiomyopathy (3%), congenital heart disease (7%), retransplantation (2%), and miscellaneous (4%). The registry consists of pre‐operative data from recipients and donors, data from pre‐operative procedures, and long‐term follow‐up data. Mean follow‐up was 7.8 ± 6.6 years (median 6.9, interquartile range 2.5–12.3, interval 0–27) and no patients were lost to follow‐up. Long‐term survival for HTx patients was 85, 76, 61, 43, and 30% at 1, 5, 10, 15, and 20 years of follow‐up, respectively. Ten‐year survival in patients bridged with mechanical circulatory support, in children, after retransplantation, and after concomitant other organ transplantation was 56, 74, 38, and 43%, respectively. Older patients (age >55 years) had a significantly worse survival (P < 0.001). Patients transplanted more recently had a significantly better survival (P < 0.001). In a multivariate Cox regression analysis, independent predictors of long‐term survival were recipient age (P < 0.001), donor age (P < 0.001), diagnosis (P = 0.001), and era of transplantation (P < 0.001).

Conclusions

HTx in Scandinavia proves to have a significantly better survival among patients transplanted in the last decade. HTxs from mechanical circulatory support, in children, after retransplantation, and with concomitant other organ transplantation were performed with acceptable results.
Feedback effects of aspherical supernova explosions on galaxies
Authors: Bekki Kenji , Shigeyama Toshikazu , Tsujimoto Takuji
Published: October 2012

We investigate how explosions of aspherical supernovae (A-SNe) can influence star formation histories and chemical evolution of dwarf galaxies by using a new chemodynamical model. We mainly present the numerical results of two comparative models so that the A-SN feedback effects on galaxies can be more clearly seen. SNe originating from stars with masses larger than 30 M⊙ are A-SNe in the ‘ASN’ model, whereas all SNe are spherical ones (S-SNe) in the ‘SSN’ model. Each S-SN and A-SN are assumed to release feedback energy of 1051 and 1052 erg, respectively, and chemical yields and feedback energy of A-SN ejecta depend on angles between the axis of symmetry and the ejection directions. We find that star formation can become at least by a factor of ∼3 lower in the ASN model in comparison with the SSN one owing to the more energetic feedback of A-SNe. As a result of this, chemical evolution can proceed very slowly in the ASN model. A-SN feedback effects can play a significant role in the formation of giant gaseous holes and energetic gaseous outflow and unique chemical abundances (e.g. high [Mg/Ca]). Based on these results, we provide a number of implications of the A-SN feedback effects on galaxy formation and evolution.
Purification, crystallization and preliminary X-ray crystallographic analysis of the ETS domain of human Ergp55 in complex with thecfospromoter DNA sequence
Authors: Gangwar Shanti P. , Meena Sita R. , Saxena Ajay K.
Published: October 2012

The Ergp55 protein belongs to the Ets family of transciption factors. The Ets transcription factors are involved in various developmental processes and the regulation of cancer metabolism. They contain a highly similar DNA-binding domain known as the ETS domain and have diverse functions in oncogenesis and physiology. The Ets transcription factors differ in their DNA-binding preference at the ETS site and the mechanisms by which they target genes are not clearly understood. To understand its DNA-binding mechanism, the ETS domain of Ergp55 was expressed and purified. The ETS domain was crystallized in the native form and in complex forms with DNA sequences from theE74andcfospromoters. An X-ray diffraction data set was collected from an ETS–cfosDNA complex crystal at a wavelength of 0.9725 Å on the BM14 synchrotron beamline at the ESRF, France. The ETS–cfosDNA complex crystal belonged to space groupC2221, with four molecules in the asymmetric unit. For structure analysis, initial phases for the ETS–cfosDNA complex were obtained by the molecular-replacement technique withPhaserin theCCP4 suite using the coordinates of Fli-1 protein (PDB entry 1fli) andcfosDNA (PDB entry 1bc7) as search models. Structure analysis of the ETS–cfosDNA complex may possibly explain the DNA-binding specificity and its mechanism of interaction with the ETS domain of Ergp55.
Cloning, purification and preliminary X-ray crystallographic analysis of the OmpA-like domain of peptidoglycan-associated lipoprotein fromAcinetobacter baumannii
Authors: Song Jung Hyun , Lee Woo Cheol , Park Jeong Soon , Kim Seung Il , Lee Je Chul , Cheong Chaejoon , Kim Hye-Yeon
Published: October 2012

Peptidoglycan-associated lipoprotein (Pal) is one component of the Tol–Pal system that is involved in maintaining the integrity and stability of the outer membrane. The C-terminal OmpA-like domain of Pal interacts noncovalently with peptidoglycan. In this study, the OmpA-like domain of Pal fromAcinetobacter baumanniiwas overexpressed inEscherichia colistrain BL21 (DE3), purified and crystallized using the vapour-diffusion method. A native crystal diffracted to 1.4 Å resolution and belonged to space groupP61orP65, with unit-cell parametersa=b= 72.58,c= 44.65 Å, a calculated Matthews coefficient of 2.64 Å3 Da−1and one molecule per asymmetric unit.
Cloning, purification and preliminary X-ray data analysis of the human ID2 homodimer
Authors: Wong Marie V. , Palasingam Paaventhan , Kolatkar Prasanna R.
Published: October 2012

The ID proteins are named for their role as inhibitors of DNA binding and differentiation. They contain a helix–loop–helix (HLH) domain but lack a basic DNA-binding domain. In complex with basic HLH (bHLH) transcription factors, gene expression is regulated by DNA-binding inactivation. Although the HLH domain is highly conserved and shares a similar topology, the IDs preferentially bind class I bHLH-group members such as E47 (TCF3) but not the class III bHLH member Myc. A structure of an ID protein could potentially shed light on its mechanism. Owing to their short half-livesin vivoand reportedin vitroinstability, this paper describes the strategies that went into expressing sufficient soluble and stable ID2 to finally obtain diffraction-quality crystals. A 2.1 Å resolution data set was collected from a crystal belonging to space groupP3121 with unit-cell parametersa=b= 51.622,c= 111.474 Å, α = β = 90, γ = 120° that was obtained by hanging-drop vapour diffusion in a precipitant solution consisting of 0.1 MMES pH 6.5, 2.0 Mpotassium acetate. The solvent content was consistent with the presence of one or two molecules in the asymmetric unit.
Crystallization and diffraction of an Isl1–Ldb1 complex
Authors: Gadd Morgan S. , Jacques David A. , Guss J. Mitchell , Matthews Jacqueline M.
Published: October 2012

A stable intramolecular complex comprising the LIM domains of the LIM-homeodomain protein Isl1 tethered to a peptide region of Ldb1 has been engineered, purified and crystallized. The orthorhombic crystals belonged to space groupP2221, with unit-cell parametersa= 57.2,b= 56.7,c= 179.8 Å, and diffracted to 3.10 Å resolution.
Crystallization, X-ray diffraction analysis and SIRAS phasing of human α-L-iduronidase
Authors: Maita Nobuo , Taniguchi Hisaaki , Sakuraba Hitoshi
Published: October 2012

Human lysosomal α-L-iduronidase, whose deficiency causes mucopolysaccharidosis type I, was crystallized using sodium/potassium tartrate and polyethylene glycol 3350 as a precipitant. Using synchrotron radiation, a native data set was collected from a single crystal at 100 K to 2.3 Å resolution. The crystal belonged to space groupR3 with unit-cell dimensions ofa=b= 259.22,c= 71.83 Å. To obtain the phase information, mercury-derivative crystals were prepared and a single-wavelength anomalous dispersion (SAD) data set was collected at the Hg peak wavelength. Phase calculation with the single isomorphous replacement with anomalous scattering (SIRAS) method successfully yielded an interpretable electron-density map.
Crystallization and X-ray diffraction studies of crustacean proliferating cell nuclear antigen
Authors: Carrasco-Miranda Jesus S. , Cardona-Felix Cesar S. , Lopez-Zavala Alonso A. , de-la-Re-Vega Enrique , De la Mora Eugenio , Rudiño-Piñera Enrique , Sotelo-Mundo Rogerio R. , Brieba Luis G.
Published: October 2012

Proliferating cell nuclear antigen (PCNA), a member of the sliding clamp family of proteins, interacts specifically with DNA replication and repair proteins through a small peptide motif called the PCNA-interacting protein or PIP box. PCNA is recognized as one of the key proteins involved in DNA metabolism. In the present study, the recombinant PCNA fromLitopenaeus vannamei(LvPCNA) was heterologously overexpressed and purified using metal ion-affinity chromatography. Crystals suitable for diffraction grew overnight using the hanging-drop vapour-diffusion method.LvPCNA crystals belong to space groupC2 with unit-cell parametersa= 144.6,b= 83.4,c= 74.3 Å, β = 117.6°. One data set was processed to 3 Å resolution, with an overallRmeasof 0.09 and a completeness of 93.3%. Initial phases were obtained by molecular replacement using a homology model ofLvPCNA as the search model. Refinement and structural analysis are underway. This report is the first successful crystallographic analysis of a marine crustacean decapod shrimp (L. vannamei) proliferating cell nuclear antigen.
Purification, crystallization, preliminary X-ray diffraction and molecular-replacement studies of catfish (Clarias magur) haemoglobin
Authors: Jaimohan S. M. , Naresh M. D. , Mandal A. B.
Published: October 2012

Haemoglobin is an interesting physiologically significant protein composed of specific functional prosthetic haem and globin moieties. In recent decades, there has been substantial interest in attempting to understand the structural basis and functional diversity of fish haemoglobins (Hbs). Towards this end, purification, crystallization, preliminary X-ray diffraction and molecular-replacement studies have been carried out onClarias magurHb. Crystals were grown by the hanging-drop vapour-diffusion method using PEG 2000 and NaCl as precipitants. The crystals belonged to the primitive monoclinic systemP2, with unit-cell parametersa= 98.35,b= 56.63,c= 112.88 Å, β = 100.22°; a complete data set was collected to a resolution of 2.4 Å. The Matthews coefficient of 2.42 Å3 Da−1for the crystal indicated the presence of two α2β2tetramers in the asymmetric unit.
Characterization, crystallization and preliminary X-ray diffraction analysis of an (S)-specific esterase (pfEstA) fromPseudomonas fluorescensKCTC 1767: enantioselectivity for potential industrial applications
Authors: Kim Seulgi , Duc Ngo Tri , Kim Kyeong Kyu , Kim T. Doohun
Published: October 2012

The structures and reaction mechanisms of enantioselective hydrolases, which can be used in industrial applications such as biotransformations, are largely unknown. Here, the X-ray crystallographic study of a novel (S)-specific esterase (pfEstA) fromPseudomonas fluorescensKCTC 1767, which can be used in the production of (S)-ketoprofen, is described. Multiple sequence alignments with other hydrolases revealed thatpfEstA contains a conserved Ser67 within the S-X-X-K motif as well as a highly conserved Tyr156. Recombinant protein containing an N-terminal His tag was expressed inEscherichia coli, purified to homogeneity and characterized using SDS–PAGE, MALDI-TOF MS and enantioselective analysis.pfEstA was crystallized using a solution consisting of 1 Msodium citrate, 0.1 MCHES pH 9.5, and X-ray diffraction data were collected to a resolution of 1.9 Å with anRmergeof 7.9%. The crystals ofpfEstA belonged to space groupP212121, with unit-cell parametersa= 65.31,b= 82.13,c = 100.41 Å, α = β = γ = 90°.
Expression, purification, crystallization and preliminary X-ray structure analysis ofVibrio choleraeuridine phosphorylase in complex with thymidine
Authors: Lashkov Alexander A. , Gabdulkhakov Azat G. , Prokofev Igor I. , Seregina Tatyana A. , Sotnichenko Sergey E. , Lyashenko Andrey V. , Shtil Alexander A. , Mironov Alexander S. , Betzel Christian , Mikhailov Al'bert M.
Published: October 2012

A high-resolution structure of the complex ofVibrio choleraeuridine phosphorylase (VchUPh) with its physiological ligand thymidine is important in order to determine the mechanism of the substrate specificity of the enzyme and for the rational design of pharmacological modulators. Here, the expression and purification ofVchUPh and the crystallization of its complex with thymidine are reported. Conditions for crystallization were determined with an automated Cartesian Dispensing System using The Classics, MbClass and MbClass II Suites crystallization kits. Crystals of theVchUPh–thymidine complex (of dimensions ∼200–350 µm) were grown by the sitting-drop vapour-diffusion method in ∼7 d at 291 K. The crystallization solution consisted of 1.5 µlVchUPh (15 mg ml−1), 1 µl 0.1 Mthymidine and 1.5 µl reservoir solution [15%(w/v) PEG 4000, 0.2 MMgCl2.6H2O in 0.1 MTris–HCl pH 8.5]. The crystals diffracted to 2.12 Å resolution and belonged to space groupP21(No. 4), with unit-cell parametersa = 91.80,b= 95.91,c= 91.89 Å, β = 119.96°. The Matthews coefficient was calculated as 2.18 Å3 Da−1; the corresponding solvent content was 43.74%.
Crystallization of uridine phosphorylase fromShewanella oneidensisMR-1 in the laboratory and under microgravity and preliminary X-ray diffraction analysis
Authors: Safonova Tatyana N. , Mordkovich Nadezhda N. , Polyakov Konstantin M. , Manuvera Valentin A. , Veiko Vladimir P. , Popov Vladimir O.
Published: October 2012

Uridine phosphorylase (UDP, EC 2.4.2.3), a key enzyme in the pyrimidine salvage pathway, catalyses the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate. The gene expression of UDP fromShewanella oneidensisMR-1 was performed in the recipient strainEscherichia coli. The UDP protein was crystallized on earth (in the free form and in complex with uridine as the substrate) by the hanging-drop vapour-diffusion method at 296 K and under microgravity conditions (in the free form) aboard the Russian Segment of the International Space Station by the capillary counter-diffusion method. The data sets were collected to a resolution of 1.9 Å from crystals of the free form grown on earth, 1.6 Å from crystals of the complex with uridine and 0.95 Å from crystals of the free form grown under microgravity. All crystals belong to the space groupP21and have similar unit-cell parameters. The crystal of uridine phosphorylase grown under microgravity diffracted to ultra-high resolution and gave high-quality X-ray diffraction data.
Crystallization and first data collection of the putative transfer protein TraN from the Gram-positive conjugative plasmid pIP501
Authors: Goessweiner-Mohr Nikolaus , Fercher Christian , Abajy Mohammad Yaser , Grohmann Elisabeth , Keller Walter
Published: October 2012

Conjugative plasmid transfer is the most important route for the spread of resistance and virulence genes among bacteria. Consequently, bacteria carrying conjugative plasmids are a substantial threat to human health, especially hospitalized patients. Whilst detailed information about the process has been obtained for Gram-negative type-4 secretion systems, little is known about the corresponding mechanisms in Gram-positive (G+) bacteria. The successful purification and crystallization of the putative transfer protein TraN from the G+ conjugative model plasmid pIP501 ofEnterococcus faecalisare presented. Native crystals diffracted to 1.8 Å resolution on a synchrotron beamline. The crystals belonged to space groupP21, with unit-cell parametersa= 32.88,b = 54.94,c= 57.71 Å, β = 91.89° and two molecules per asymmetric unit.
Drug resistance and IS6110‐RFLP patterns of Mycobacterium tuberculosis in patients with recurrent tuberculosis in northern Thailand
Authors: Sukkasem Supaporn , Yanai Hideki , Mahasirimongkol Surakameth , Yamada Norio , Rienthong Dhanida , Palittapongarnpim Prasit , Khusmith Srisin
Published: October 2012

The emergence of drug resistant Mycobacterium tuberculosis has become a global threat to tuberculosis (TB) prevention and control efforts. This study aimed to determine the drug resistance profiles and DNA fingerprints of M. tuberculosis strains isolated from patients with relapsed or retreatment pulmonary TB in Chiang Rai province in northern Thailand. Significant differences in multidrug resistance (MDR) (P = 0.025) and resistance to isoniazid (P = 0.025) and rifampin (P = 0.046) between first and second registrations of patients with retreatment TB were found. However, there were no significant differences in resistance to any drugs in patients with relapsed TB. The rate of MDR‐TB strains was 12.2% among new patients at first registration, 22.5% among patients with recurrence who had previously undergone treatment at second registration and 12.5% at third registration. Two retreatment patients whose initial treatment had failed had developed MDR‐TB with resistance to all TB drugs tested, including rifampin, isoniazid, streptomycin and ethambutol. IS6110‐RFLP analysis revealed that 66.7% (10/15 isolates) of MDR‐TB belonged to the Beijing family. In most cases, IS6110‐RFLP patterns of isolates from the same patients were identical in relapse and retreatment groups. However, some pairs of isolates from retreatment patients after treatment failure had non‐identical IS6110‐RFLP patterns. These results suggest that, after failure and default treatment, patients with retreatment tuberculosis have a significantly greater risk of MDR‐TB, isoniazid and rifampin resistance than do other patients.
Linking nutrition and sexual selection across life stages in a model butterfly system
Authors: Tigreros Natasha
Published: October 2012

Early nutrition plays an important role in determining adult fitness. Theory proposes that in organisms with complex life cycles, the fitness effects of larval nutritional constraints are mainly captured by two developmental traits: time and size at metamorphosis. However, recent evidence suggests that latent effects, which are independent of these developmental traits, must be included to fully understand how larval nutrition impacts fitness.

In this study, I used the cabbage butterfly (Pieris rapae) as a model system to investigate how larval nutrition influences male fitness through development time, adult size and latent effects. Specifically, I examined how variation in dietary nitrogen impacts male fitness by measuring a comprehensive suite of pre‐ and postcopulatory traits.

Results indicate a complex role for larval nutrition in determining adult fitness. Larval nutritional constraints influence adult fitness through three different pathways: development time, adult size and latent effects. Longer development times were associated with shorter adult life span and reduced male mating success. Body size was positively correlated with traits related to postcopulatory fitness, such as spermatophore size and protein content. Larval nitrogen availability, independent of the developmental traits, also affected traits associated with male mating success such as wing coloration and latency to first mating.

These results provide new insights into how larval nitrogen availability alters adult fitness by revealing novel links between larval dietary nitrogen and various adult fitness components.
Stress as a modifier of biodiversity effects on ecosystem processes?
Authors: Gessner Mark O. , Hines Jes
Published: October 2012

A limnephilid caddisfly larvae (Anomalocosmoecus sp.) removed from its case and an amphipod (Hyalella sp.) from Andean streams. Leaf litter of five different qualities was offered to these two detritivores in an experiment to test whether the stress‐gradient hypothesis from plant ecology might apply to stream invertebrate communities. Photo and copyright: Patricio Andino.

image

A limnephilid caddisfly larvae (Anomalocosmoecus sp.) removed from its case and an amphipod (Hyalella sp.) from Andean streams. Leaf litter of five different qualities was offered to these two detritivores in an experiment to test whether the stress‐gradient hypothesis from plant ecology might apply to stream invertebrate communities. Photo and copyright: Patricio Andino.

Fugère, V., Andino, P., Espinosa, R., Anthelme, F., Jacobsen, D. & Dangles, O. (2012) Testing the stress‐gradient hypothesis with aquatic detritivorous invertebrates: insights for biodiversity ecosystem functioning research. Journal of Animal Ecology, 81, 1259–1267.

Does stress, defined as a reduction in growth by external constraints, modify biodiversity effects on ecosystem functioning? That is, are diversity effects stronger under stressful, as opposed to favourable conditions? The study by Fugère et al. (2012) in this issue borrows the stress‐gradient hypothesis from plant ecology to explore this issue in an aquatic detritus‐detritivore system. Although they find weak support for their hypothesis, the study opens the door for future experimental and theoretical investigations into the role of stress in modifying the relationship between the diversity of animal communities and ecosystem processes.
Comparison of cardioprotective efficacy resulting from a combination of atorvastatin and ischaemic post‐conditioning in diabetic and non‐diabetic rats
Authors: Fan Ying , Yang Shusen , Zhang Xiukun , Cao Yang , Huang Yonglin
Published: October 2012

The aim of the present study was to investigate whether the combination of acute or chronic atorvastatin treatment with ischaemic post‐conditioning (IPost) exerts differential effects within the hearts of diabetic and non‐diabetic rats.

Diabetic and non‐diabetic rats were randomly assigned to one of six groups: (i) a non‐conditioned group; (ii) a group subjected to IPost; (iii) acute statin treatment (50 μmol/L atorvastatin during reperfusion) without IPost; (iv) acute statin treatment plus IPost; (v) chronic statin treatment (10 mg/kg atorvastatin per day for 2 weeks) without IPost; and (vi) chronic statin treatment plus IPost. The hearts from rats in each group were subjected to 30 min global ischaemia, followed by 120 min reperfusion. Infarct size, haemodynamics and Akt and endothelial nitric oxide synthase (eNOS) expression were examined.

In hearts from diabetic rats, IPost did not limit infarct size or recover contractile dysfunction. Acute atorvastatin treatment with IPost limited infarct size and recovered contractile dysfunction in hearts from both diabetic and non‐diabetic rats and further activated Akt and eNOS signalling pathways to enhance these protective effects in hearts from diabetic rats. Chronic statin treatment with IPost neither reduced infarct size nor increased recovery of myocardial dysfunction in hearts from both diabetic and non‐diabetic rats; this may be associated with inhibition of Akt and eNOS phosphorylation.

The combination of acute atorvastatin treatment with IPost had a greater protective effect within hearts from diabetic rats, but chronic statin treatment with IPost failed to protect against reperfusion injury in hearts from either diabetic or non‐diabetic rats. These findings will be important for the design of future clinical investigations.
Editorial: Trust and HRM: Current insights and future directions
Authors: Searle Rosalind H. , Dietz Graham
Published: October 2012

Over the last 20 years, HRM has been identified as one of the most influential organisational contexts in which to explore trust, and yet scholars have been slow to look systematically at both the systems and practices that underlie this assertion. Organisations make choices regarding both the design and implementation of HRM policies and practices, with research considering the impact on trust for both key single policy areas and bundles of policies. We outline the previous dominance on teleological approaches compared with a dearth of more deontological perspectives which would highlight moral and ethical considerations implicit in definitions of trustworthiness. We review the contribution of five new articles to further our understanding of trust and HRM and identify future research and practice agendas.
Annotated checklist and fisheries interactions of cetaceans in Togo, with evidence of Antarctic minke whale in the Gulf of Guinea
Authors: SEGNIAGBETO Gabriel H. , VAN WAEREBEEK Koen , BOWESSIDJAOU Joseph E. , KETOH Koffivi , KPATCHA Takouda K. , OKOUMASSOU Kotchikpa , AHOEDO Kossi
Published: October 2012

Based on strandings and captures, 9 cetacean species, including 6 odontocetes and 3 mysticetes, are documented (photos and specimens) in Togo's coastal waters (newly‐recorded species marked with an asterisk): Antarctic minke whale (Balaenoptera bonaerensis*), Bryde's whale (Balaenoptera brydei or B. edeni), humpback whale (Megaptera novaeangliae), sperm whale (Physeter macrocephalus), pygmy sperm whale (Kogia breviceps*), short‐finned pilot whale (Globicephala macrorhynchus*), pantropical spotted dolphin (Stenella attenuata*), common bottlenose dolphin (Tursiops truncatus) and common dolphin Delphinus sp. An anecdotal sighting record for killer whale (Orcinus orca) is considered reliable. The lack of Sousa teuszii records in Togo is consistent with its apparent contemporaneous absence in Ghana. The B. bonaerensis specimen, entangled in a purse seine set on small pelagics, is a first record for the Gulf of Guinea. The occurrence of this Southern Ocean species north of the equator underscores the severe gaps in our understanding of cetacean distribution off western Africa. The majority of artisanal fishermen operating in Togolese coastal waters are of Ghanaian origin and are thought to promote trade and consumption of cetacean bushmeat. Because captures are illegal, enforced with some success in the main fishing centers, covert landings of cetaceans are exceedingly difficult to monitor, quantify or sample. Concern is expressed about pollution of Togo's coastal waters with heavy metals due to phosphorite mining and export from the coastal basin near Hahotoé and Kpogamé.
Can we use a lower intravaginal dose of misoprostol in the medical management of miscarriage? A randomised controlled study
Authors: Petersen Scott G. , Perkins Anneliese , Gibbons Kristen , Bertolone Julia , Devenish‐Meares Paul , Cave Donald , Mahomed Kassam
Published: October 2012

Background

The optimal dose of misoprostol to be used in the medical management of miscarriage before 13 weeks has not been resolved.

Aim

To evaluate the effectiveness and side effect profile of two different dosages of misoprostol.

Methods

A randomised controlled, equivalence study comparing 400 vs 800 μg misoprostol per vaginum (PV) on an outpatient basis. The allocated dose was repeated the next day if clinically the products of conception had not been passed. Complete miscarriage was evaluated using two methods: ultrasound criteria on Day 7 and the need for surgical management (clinical criteria). Equivalence was demonstrated if the 95% confidence interval [CI] of the observed risk difference between the two doses for complete miscarriage lay between −15.0 and 15.0%. Differences in side effects and patient satisfaction were evaluated using patient‐completed questionnaires.

Results

One hundred and fifty‐eight women were allocated to receive 400 μg and 152 women to 800 μg misoprostol for the management of missed (91.3%) or incomplete (8.7%) miscarriage. The rate of induced complete miscarriage was equivalent using both ultrasound criteria (observed risk difference (ORD) −4.6%, 95% CI −12.8 to 3.7%; P = 0.313) and clinical criteria (ORD −5.6%, 95% CI −14.8 to 3.6%; P = 0.273). Following the 400 μg dose, the reported rate of fever/rigors was lower (ORD −15.6%, 95% CI −28.1 to −3.0%; P = 0.015), and more women reported their decision to undergo medical management as a good decision (ORD 15.2%, 95% CI 2.8 to 27.7%; P = 0.018).

Conclusion

Four hundred‐microgram misoprostol PV can be recommended for the medical management of miscarriage on an outpatient basis.
Utilisation of preconception care in women with pregestational diabetes  in Western Australia
Authors: Zhu Hongdong , Graham Dorothy , Teh Ru‐Wen , Hornbuckle Janet
Published: October 2012

This study investigated the level of awareness of the availability of preconception care in a tertiary obstetric hospital for women with type 1 and 2 diabetes, the willingness of these women to attend for preconception counselling and the barriers that may impact upon access to preconception care in Western Australia. The results show greater effort is needed to improve the awareness of women about the importance of preconception care and their willingness to attend the clinic. Access to consistent preconception care should be available for all women with diabetes. The counselling process should be individualised to accommodate different needs.
Novel insights into mechanisms of food allergy and allergic airway inflammation using experimental mouse models
Authors: Corazza N. , Kaufmann T.
Published: October 2012

Over the last decades, considerable efforts have been undertaken in the development of animal models mimicking the pathogenesis of allergic diseases occurring in humans. The mouse has rapidly emerged as the animal model of choice, due to considerations of handling and costs and, importantly, due to the availability of a large and increasing arsenal of genetically modified mouse strains and molecular tools facilitating the analysis of complex disease models. Here, we review latest developments in allergy research that have arisen from in vivo experimentation in the mouse, with a focus on models of food allergy and allergic asthma, which constitute major health problems with increasing incidence in industrialized countries. We highlight recent novel findings and controversies in the field, most of which were obtained through the use of gene‐deficient or germ‐free mice, and discuss new potential therapeutic approaches that have emerged from animal studies and that aim at attenuating allergic reactions in human patients.
Review article: faecal incontinence in children: epidemiology, pathophysiology, clinical evaluation and management
Authors: Rajindrajith S. , Devanarayana N. M. , Benninga M. A.
Published: October 2012

Background

Faecal incontinence (FI) in children is a significant gastrointestinal problem, with great personal and social impacts. It is characterised by recurrent loss of faecal matter into the underwear. Both functional and organic causes contribute to its aetiology with the former predominating.

Aim

To review the epidemiology, pathophysiology, clinical evaluation and management of functional faecal incontinence in children.

Methods

A PubMed search was conducted using search terms f(a)ecal incontinence, and encopresis. Articles on epidemiology, pathophysiology, clinical evaluation, investigation and management of functional FI in children were retrieved and assessed.

Results

Community prevalence of this distressing problem ranges from 0.8% to 7.8% globally. Male: female ratio varies from 3:1 to 6:1. The diagnosis of FI is often based on established clinical criteria. The majority (82%) have constipation associated functional FI. Biopsychosocial factors play a crucial role in the pathogenesis. Limited physiological testing of anorectal function is recommended in the diagnostic procedures, particularly in children with atypical symptoms and possible organic disorders. Management of FI needs a multidisciplinary approach which includes establishment of an effective doctor‐patient partnership, understanding the underlying mechanisms, pharmacotherapy and behavioural treatment. Approximately 15% of children with functional nonretentive faecal incontinence (FNRFI) had the same symptoms at the age of 18 years.

Conclusion

Significant therapeutic advances have been made for retentive faecal incontinence, but treatment options for functional nonretentive faecal incontinence are limited. Limited long‐term outcome data show that the majority outgrow faecal incontinence. A substantial proportion of children progress to adulthood with faecal incontinence.
Treatment of children with acute myeloid leukaemia who relapsed after allogeneic haematopoietic stem cell transplantation
Authors: Lee Jae Wook , Jang Pil‐Sang , Chung Nack‐Gyun , Cho Bin , Kim Hack‐Ki
Published: October 2012

Despite improvements in diagnosis and treatment, 30–40% of children with acute myeloid leukaemia (AML) experience relapse. For those who relapse after allogeneic haematopoietic stem cell transplantation (allo‐HSCT), the prognosis is particularly poor, with limited reported literature on these patients. We reviewed the clinical course of 49 children with AML (28 males, 21 females) who received allo‐HSCT between 1993 and 2011, and who had subsequently relapsed. Study endpoints included (i) complete remission (CR) rate after intensive chemotherapy, and prognostic factors for CR, (ii) disease‐free survival (DFS) and overall survival (OS) for patients who achieved CR and (iii) OS for recipients of intensive chemotherapy and prognostic factors for OS. Of the 36 patients who received intensive chemotherapy after post‐HSCT relapse, 26 (72%) achieved CR. For patients who achieved CR, 5‐year DFS and OS were 32·6 ± 10·2% and 44·4 ± 11·1%, respectively. For all recipients of intensive chemotherapy, 5‐year OS was 31·6 ± 8·7%. Cumulative incidence of treatment‐related death was 14·4%. All three recipients of second HSCT died. Amongst prognostic factors predicting improved survival, only disease status at HSCT (early first CR vs. others) proved significant in multivariate study (Hazard Ratio 2·42, 95% Confidence Interval 1·02–5·74, P = 0·045). Treatment with curative intent was able to salvage a minor but important subset of children with AML who relapsed post‐allogeneic transplant.
Mode of delivery, mutans streptococci colonization, and early childhood caries in three‐ to five‐year‐old Thai children
Authors: Pattanaporn K. , Saraithong P. , Khongkhunthian S. , Aleksejuniene J. , Laohapensang P. , Chhun N. , Chen Z. , Li Y.
Published: October 2012

Objective

To investigate whether mode of delivery is associated with mutans streptococci (MS) colonization and early childhood caries (ECC) in preschool Thai children.

Methods

Three hundred and fifty mothers and their 3‐ to 5‐year‐old children (184 born vaginally and 166 born by Caesarean section) participated in the study. Data included a dental examination, MS colonization assessed by the Dentocult® SM Strip Mutans method, and a questionnaire survey of family socio‐demographic information, as well as children's birth history, dietary habits, and oral health practices.

Results

Overall, ECC prevalence was 56% in 3‐year‐old and 78% in 5‐year‐old Thai children. Compared to children delivered by C‐section, vaginally born children experienced increased ECC prevalence (73.8% versus 59.6%; P = 0.009) and were more likely to have higher MS scores (OR = 1.8, 95% CI = 1.1–2.9), adjusting for mother's gestational age, MS score, feeding practice habits; child's age and tooth brushing habits. Children's MS scores were highly correlated with their mothers' MS scores (P < 0.001). Additionally, children's age, MS colonization, and mothers' prechewing feeding habits were the most significant risk indicators for ECC in Thai children.

Conclusion

Our findings suggest that mode of delivery is significantly correlated with MS colonization and caries outcomes in young Thai children. Future studies are needed to further understand the possible biological mechanisms linking mode of child delivery to the colonization of cariogenic microbiota and development of ECC.
Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life
Authors: Harb H. , van Tol E. A. F. , Heine H. , Braaksma M. , Gross G. , Overkamp K. , Hennen M. , Alrifai M. , Conrad M. L. , Renz H. , Garn H.
Published: October 2012

Background

Oral supplementation with probiotic bacteria can protect against the development of allergic and inflammatory diseases.

Objective

The aim of this study was to investigate potential immunomodulatory and allergy‐protective effects of processed Lactobacillus rhamnosus GG (LGG)‐derived supernatants early in life in neonatal mice.

Methods

In vitro, RAW264.7 mouse macrophages were stimulated with viable LGG, LGG‐derived supernatants, prepared from different growth phases, and different size fractions thereof, and pro‐ and anti‐inflammatory cytokine production was analysed. Supernatant fractions were also treated with protease, DNAse or carbohydrate‐digesting enzymes to define the nature of immunomodulatory components. In vivo, neonatal Balb/c mice were orally supplemented with differentially processed LGG supernatants. Starting at 4 weeks of age, a protocol of ovalbumin‐induced acute allergic airway inflammation was applied and protective effects of processed LGG supernatants were assessed.

Results

Incubation of RAW264.7 cells with LGG‐derived supernatants significantly increased TNFα and IL‐10 production. These effects were not restricted to a particular molecular size fraction. Treatment with protease, but not with DNAse or carbohydrate‐digesting enzymes, completely abolished the immunomodulatory activities. Incubation of TLR/NOD‐transfected cells with LGG‐derived supernatants revealed that recognition and signalling of bioactive components is mediated by TLR2 and NOD2. In vivo supplementation of newborn mice with processed LGG‐derived supernatants resulted in pronounced protective effects on the allergic inflammatory response as reflected by reduced eosinophil numbers, modified T helper cell cytokine production, significantly less lung inflammation and reduced goblet cell numbers in comparison with sham‐treated controls.

Conclusion

LGG‐derived supernatants exert immunomodulatory activities, and neonatal administration of specifically processed supernatants may provide an alternative to viable probiotics in reducing allergic inflammatory responses.
Cellular immune responses in multiple sclerosis patients treated with interferon-beta
Authors: Bustamante M F , Rio J , Castro Z , Sánchez A , Montalban X , Comabella M
Published: October 2012

We investigated cellular immune responses at baseline in peripheral blood mononuclear cells (PBMC) of patients with multiple sclerosis (MS) treated with interferon (IFN)-β and classified into responders and non-responders according to clinical response criteria. Levels for IFN-γ, interleukin (IL)-17A, IL-17F, IL-10 and IL-4 were determined in activated PBMC of 10 responders, 10 non-responders and 10 healthy controls by cytometric bead arrays. Cytokine levels in cell culture supernatants were similar between responders and non-responders, and comparable to those obtained in healthy controls. These findings do not support differential cellular immune responses in PBMC at baseline between IFN-β responders and non-responders.
An evaluation of early cardiometabolic risk factors in children and adolescents with Turner syndrome
Authors: O'Gorman Clodagh S. , Syme Catriona , Lang Jun , Bradley Timothy J. , Wells Greg D. , Hamilton Jill K.
Published: October 2012

Background and Objectives

Turner syndrome (TS) confers increased lifetime risk of type 2 diabetes mellitus and cardiovascular disease. We compared cardiometabolic risk factors and measures of subcutaneous, visceral adipose tissue and intra‐myocellular lipid between young TS girls and an age‐ and BMI‐standard deviation scores (SDS)‐matched healthy female cohort.

Patients and Methods

A cross‐sectional cohort study was conducted at the Hospital for Sick Children, Toronto. Nineteen TS and 17 control girls (13·7 ± 2·5 vs 12·7 ± 3·4 years of age, respectively, P = 0·30). Multiple‐sample oral glucose tolerance test with measurement of fasting insulin, LDL, HDL, triglycerides, adiponectin and highly sensitive C‐reactive protein (hsCRP) was performed. Subcutaneous adipose tissue, visceral adipose tissue intramyocellular lipid levels evaluated by magnetic resonance techniques. Insulin secretion (IS), sensitivity (Si) and the insulin secretion–sensitivity index (ISSI‐2) were calculated from oral glucose tolerance test data.

Results

Five TS and no controls had impaired fasting glucose or impaired glucose tolerance; none had type 2 diabetes mellitus. Insulin sensitivity and insulin secretion were similar between groups; ISSI‐2 was lower in TS (923·5 ± 307·3 vs 659·1 ± 387·3; P = 0·03). TS girls had higher blood pressure (82·5 ± 13·6 vs 73·5 ± 5·5 mmHg; P = 0·0146), waist circumference (76·0 ±11·8 vs 65·9 ± 9·7; P = 0·0087) and subcutaneous adipose tissue (135·6 ± 88·6 vs 69·3 ± 59·9; P = 0·01) than controls. Visceral adipose tissue, intramyocellular lipid levels and adiponectin were not different between groups. TS girls also had higher triglycerides (1·1 ± 0·6 vs 0·7 ± 0·3; P = 0·003), total cholesterol (4·4 ± 0·7 vs 3·9 ± 0·4; P = 0·02) and hsCRP (2·0 ± 1·9 vs 0·8 ± 0·3; P = 0·01).

Conclusions

TS girls exhibit more cardiometabolic risk factors and reduced beta cell function compared with age‐ and BMI‐SDS‐matched girls. Increased awareness of early risk of type 2 diabetes mellitus and hypertension in TS girls is needed.
Cytokines expression in saliva and peri‐implant crevicular fluid of patients with peri‐implant disease
Authors: Fonseca Fabio José Persegani Olivar , Junior Mario Moraes , Lourenço Eduardo José Veras , de Moraes Teles Daniel , Figueredo Carlos Marcelo
Published: October 2012

Objective

This study aimed to measure the levels of GM‐CSF, IL‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐7, IL‐8, IL‐10, IL‐12, IFN‐γ and TNF‐α in peri‐implant crevicular fluid (PICF) and saliva from patients with peri‐implant disease.

Methods

Twenty two total edentulous patients were divided into two groups: Mucositis (MU) patients with bone loss around the implants until the first thread and pocket depth ≤3 mm, and Peri‐implantitis (PI) patients with at least one implant with bone loss around two or more threads and pocket depth ≥4 mm. The clinical parameters evaluated were probing pocket depth, bleeding on probing, and percentage of plaque. PICF samples were collected from MU sites, and from shallow (SPI) and deep (DPI) sites in PI. Unstimulated whole and parotid duct saliva was collected from all patients. The cytokines were measured by a multiplexed immunoassay.

Results

PI patients had a higher percentage of plaque compared with MU (P = 0.02). MU sites had lower pocket depth compared to SPI (P = 0.001) and to DPI (P ≤ 0.001). In PICF, the levels of IL‐1β were significantly higher in SPI sites compared to MU (P = 0.03). In the saliva from parotid, IL‐8 and IL‐12 were significantly higher in patients with PI (P = 0.04).

Conclusion

Elevated levels of IL‐1β in PICF seem to be a characteristic trait of patients with peri‐implantitis. The parotid duct saliva showed a significant increase in expression of IL‐8, which might be related to a systemic response.
MPTP Animal Model of Parkinsonism: Dopamine Cell Death or Only Tyrosine Hydroxylase Impairment? – A Study Using PET Imaging, Autoradiography, and Immunohistochemistry in the Cat
Authors: Aznavour Nicolas , Cendres‐Bozzi Christophe , Lemoine Laetitia , Buda Colette , Sastre Jean‐Pierre , Mincheva Zoïa , Zimmer Luc , Lin Jian‐Sheng
Published: October 2012

Aims

1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is a neurotoxin widely used to produce experimental models of Parkinson's disease in laboratory animals. It is believed to cause a selective destruction of substantia nigra dopamine neurons, mainly based on a large reduction of tyrosine hydroxylase (TH), the catecholamine's synthesizing enzyme. Unlike Parkinson's disease in humans, however, all animal models are able to recover more or less rapidly from the MPTP induced Parkinsonian syndrome. This raises the question as whether MPTP causes a cell death with a decrease in dopamine transporter or a simple impairment of TH.

Methods

To respond to this question, we quantified in a cat model of Parkinson's disease (MPTP 5 mg/kg i.p. during 5 days) the dopamine transporter using positron emission tomography (PET) imaging and autoradiography of [11C]PE2I and compared the data with the TH‐immunoreactivity.

Results

We found no changes in [11C]PE2I PET binding either 5 or 26 days after MPTP treatment when compared to baseline levels. Similarly, there were no significant changes in [11C]PE2I autoradiographic binding in the cat brain one week after MPTP treatment. In sharp contrast, MPTP treated cats exhibited severe Parkinson‐like motor syndrome during the acute period with a marked decrease in TH‐immunoreactivity in the striatum.

Conclusion

These data suggest that MPTP toxicity impairs efficiently TH and that such an effect is not necessarily accompanied by significant reduction of dopamine transporter seen with in vitro or in vivo [11C]PE2I binding.
How protandry and protogyny affect female mating failure: a spatial population model
Authors: Larsen Elise , Calabrese Justin M. , Rhainds Marc , Fagan William F.
Published: October 2012

Population growth and persistence depend on the collective ability of individuals to find mates in both space and time. When individuals are reproductively mature for only a portion of a population's breeding season, reproductive asynchrony can cause mating failure and a temporal Allee effect, which is exacerbated by spatial constraints in isolated populations. However, the effect of phenological variation by sex (protandry, protogyny) in spatiotemporal mate finding is not well understood. Here, we examine the interacting roles of sex‐specific and population‐wide individual asynchrony on female matelessness in spatially isolated populations. By incorporating sex‐specific phenology into a two‐sex reaction‐diffusion system, we explore female matelessness as a function of phenology, movement behavior, and patch size. Although individual asynchrony may lead to female mating failure in small and isolated populations, we find that moderate protandry reduces female mating failure across a variety of scenarios. We go on to examine model behavior for a case study based on the bagworm, Thyridopteryx ephemeraeformisHaworth (Lepidoptera: Psychidae), where many populations exhibit pronounced protogyny. Overall, we find a consistent benefit of moderate protandry, which may mitigate female matelessness for many populations.