bluuebunny/crossref_metadata_2025 huggingface dataset:
RID1
, encoding a Cys2/His2-type zinc finger transcription factor, acts as a master switch from vegetative to floral development in rice
Authors: Wu Changyin , You Changjun , Li Caishun , Long Tuan , Chen Guoxing , Byrne Mary E. , Zhang Qifa
Published: August 2008

Transition from the vegetative phase to reproductive phase is a crucial process in the life cycle of higher plants. Although the molecular mechanisms of flowering regulation have been extensively characterized in a number of plant species, little is known regarding how the transition process initiates. Here, we show that the
Rice Indeterminate 1
(
RID1
) gene acts as the master switch for the transition from the vegetative to reproductive phase.
RID1
encodes a Cys-2/His-2-type zinc finger transcription factor that does not have an ortholog in
Arabidopsis spp.
A
RID1
knockout (
rid1
), mutated by T-DNA insertion, never headed after growing for >500 days under a range of growth conditions and is thus referred to as a never-flowering phenotype. This mutation-suppressed expression of the genes is known to be involved in flowering regulation, especially in the
Ehd1
/
Hd3a
pathway and a series of
RFT
homologs.
RID1
seems to be independent of the circadian clock. A model was proposed to place
RID1
in the molecular pathways of flowering regulation in rice, for which there are two indispensable elements. In the first,
RID1
is controlling the phase transition and initiation of floral induction. In the other, the
Hd3a
/
RFL1
/
FTL
complex acts as the immediate inducer of flowering. Loss of function in either element would cause never-flowering. Once the phase transition is induced with the activation of
RID1
, flowering signal is transduced and regulated through the various pathways and eventually integrated with
FT
-like proteins to induce flowering.
Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium
Authors: Furue Miho K. , Na Jie , Jackson Jamie P. , Okamoto Tetsuji , Jones Mark , Baker Duncan , Hata Ryu-Ichiro , Moore Harry D. , Sato J. Denry , Andrews Peter W.
Published: August 2008

A major limitation in developing applications for the use of human embryonic stem cells (HESCs) is our lack of knowledge of their responses to specific cues that control self-renewal, differentiation, and lineage selection. HESCs are most commonly maintained on inactivated mouse embryonic fibroblast feeders in medium supplemented with FCS, or proprietary replacements such as knockout serum-replacement together with FGF-2. These undefined culture conditions hamper analysis of the mechanisms that control HESC behavior. We have now developed a defined serum-free medium, hESF9, for the culture of HESCs on a type I-collagen substrate without feeders. In contrast to other reported media for the culture of HESCs, this medium has a lower osmolarity (292 mosmol/liter),
l
-ascorbic acid-2-phosphate (0.1 μg/ml), and heparin. Insulin, transferrin, albumin conjugated with oleic acid, and FGF-2 (10 ng/ml) were the only protein components. Further, we found that HESCs would proliferate in the absence of exogenous FGF-2 if heparin was also present. However, their growth was enhanced by the addition of FGF-2 up to 10 ng/ml although higher concentrations were deleterious in the presence of heparin.
Global alignment of multiple protein interaction networks with application to functional orthology detection
Authors: Singh Rohit , Xu Jinbo , Berger Bonnie
Published: August 2008

Protein–protein interactions (PPIs) and their networks play a central role in all biological processes. Akin to the complete sequencing of genomes and their comparative analysis, complete descriptions of interactomes and their comparative analysis is fundamental to a deeper understanding of biological processes. A first step in such an analysis is to align two or more PPI networks. Here, we introduce an algorithm, IsoRank, for global alignment of multiple PPI networks. The guiding intuition here is that a protein in one PPI network is a good match for a protein in another network if their respective sequences and neighborhood topologies are a good match. We encode this intuition as an eigenvalue problem in a manner analogous to Google's PageRank method. Using IsoRank, we compute a global alignment of the
Saccharomyces cerevisiae
,
Drosophila melanogaster
,
Caenorhabditis elegans
,
Mus musculus
, and
Homo sapiens
PPI networks. We demonstrate that incorporating PPI data in ortholog prediction results in improvements over existing sequence-only approaches and over predictions from local alignments of the yeast and fly networks. Previous methods have been effective at identifying conserved, localized network patterns across pairs of networks. This work takes the further step of performing a global alignment of multiple PPI networks. It simultaneously uses sequence similarity and network data and, unlike previous approaches, explicitly models the tradeoff inherent in combining them. We expect IsoRank—with its simultaneous handling of node similarity and network similarity—to be applicable across many scientific domains.
Taiwanese older adults’ perceptions of aging and communication with peers and young adults
Authors: Lin Mei-Chen , Zhang Yan Bing
Published: August 2008

This study examined interview accounts from thirty-one Taiwanese older adults about their inter- and intra-generational communication experiences, and perceptions of today’s young and older people. Thematic analysis showed that Taiwanese older adults tended to initiate conversation topics accommodative to young people’s lives such as their job and marriage, whereas conversation topics with their old-age peers centered on adjustment into senior years (e.g., health, exercise) and their children’s achievement. Analysis also revealed some of the Taiwanese older adults’ major perceptions of young people (e.g., less respectful towards elders) and their peers (e.g., losing status in the family). The discursive strategies used in constructing such perceptions (e.g., discourse on self exception, denial of self inclusion) demonstrated the ways in which they negotiated and managed their age identity in inter- and intra-generational communication. Results are discussed in light of Social Identity Theory, Communication Accommodation Theory, age identity, filial piety, and cultural change.
Mitigation on the minibus
Authors: Gibbons John
Published: August 2008

One well documented aspect of politeness is that speakers, when making requests, often try to avoid the appearance of imposing on the other person. There is some evidence that the degree of politeness is affected by socio-demographic variables such as age, sex and SES. This paper is a small scale study of variation in politeness usage in Hong Kong Cantonese. It uses a context, in which the interactive negotiation of a social relationship is very constrained, so that the effects of the socio-demographic variables can be clearly manifested. The findings indicate that it is possible that SES plays a small role in variation, and that women and young people are in general more polite. The study has implications for variation studies and politeness studies.
Cantonese as written standard?
Authors: Snow Don
Published: August 2008

“Standard language” status is a relative construct defined by a variety of attributes rather than by any single criteria. This paper uses the taxonomy of standard language attributes presented in Downes 1998 as a framework for examining the degree to which written Cantonese, particularly in Hong Kong, has developed attributes of a standard language. In particular, it is argued that written Cantonese has gained a degree of autonomy from Standard Written Chinese, that the Cantonese speech community has clear usage norms regarding how spoken Cantonese words should be represented in writing, that written Cantonese is functionally elaborated in the sense that users have little difficulty with lack of vocabulary for technical or academic concepts, that written Cantonese plays a growing social role in Hong Kong, and that its level of prestige is increasing. The paper concludes that while written Cantonese does not have all the attributes associated with standard languages, it has developed a significant number of these attributes to a significant degree, and that the growing role of written Cantonese is an important indicator of the degree to which Cantonese is taking on a regional standard role in China.
Cultural values and aging in Chinese television commercials
Authors: Zhang Yan Bing , Song Yi , Jensen Carver Leilani
Published: August 2008

This study examined commercials (N = 141) featuring older adult(s) shown on three Chinese TV stations (i.e., national, provincial, and local) in the fall of 2005 to uncover the dominant value themes, the major product categories, and the association between value themes and product categories. Content analysis results revealed that three dominant value themes (i.e., health/life, product effectiveness, and family) appeared frequently in the Chinese television commercials featuring older adults, in which some major product categories such as food/drink, food/health supplements, and medicine were promoted. Results also indicated that the value of health/life was presented frequently in commercials for medicine and food/health supplements and that the family value appeared frequently in food/drinks commercials. Altogether these results demonstrated the importance of health and a lack of emphasis of modern values in Chinese television commercials which feature older adults, indicating a mixed view of aging (i.e., passive and negative). Findings are discussed in the context of the Chinese culture, aging, and television advertising.
News discourse of teachers’ suicide
Authors: Siu Wanda Luen Wun
Published: August 2008

This research reported findings from discourse analysis and content analysis on media coverage about a specific educational crisis on teachers’ suicide in Hong Kong. Overall, findings revealed that there was a great difference in sources being used by newspapers of different political ideology. The official position did not guarantee smooth access to the mass media via sources. Press ideology interfered in this process and determined what kind and how frequent news sources were used. Specifically, it was shown how linguistic choices in news texts accomplished the goal of framing the conflict, demarcating those supporting the education reform from those opposing the reform.
uPAR promotes formation of the p130Cas–Crk complex to activate Rac through DOCK180
Authors: Smith Harvey W. , Marra Pierfrancesco , Marshall Christopher J.
Published: August 2008

The urokinase-type plasminogen activator receptor (uPAR) drives tumor cell membrane protrusion and motility through activation of Rac; however, the pathway leading from uPAR to Rac activation has not been described. In this study we identify DOCK180 as the guanine nucleotide exchange factor acting downstream of uPAR. We show that uPAR cooperates with integrin complexes containing β3 integrin to drive formation of the p130Cas–CrkII signaling complex and activation of Rac, resulting in a Rac-driven elongated-mesenchymal morphology, cell motility, and invasion. Our findings identify a signaling pathway underlying the morphological changes and increased cell motility associated with uPAR expression.
In vivo reconstitution of autophagy in Saccharomyces cerevisiae
Authors: Cao Yang , Cheong Heesun , Song Hui , Klionsky Daniel J.
Published: August 2008

Autophagy is a major intracellular degradative pathway that is involved in various human diseases. The role of autophagy, however, is complex; although the process is generally considered to be cytoprotective, it can also contribute to cellular dysfunction and disease progression. Much progress has been made in our understanding of autophagy, aided in large part by the identification of the autophagy-related (ATG) genes. Nonetheless, our understanding of the molecular mechanism remains limited. In this study, we generated a Saccharomyces cerevisiae multiple-knockout strain with 24 ATG genes deleted, and we used it to carry out an in vivo reconstitution of the autophagy pathway. We determined minimum requirements for different aspects of autophagy and studied the initial protein assembly steps at the phagophore assembly site. In vivo reconstitution enables the study of autophagy within the context of the complex regulatory networks that control this process, an analysis that is not possible with an in vitro system.
Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly of newly synthesized proteins
Authors: Medicherla Balasubrahmanyam , Goldberg Alfred L.
Published: August 2008

Accumulation of misfolded oxidant-damaged proteins is characteristic of many diseases and aging. To understand how cells handle postsynthetically damaged proteins, we studied in Saccharomyces cerevisiae the effects on overall protein degradation of shifting from 30 to 38°C, exposure to reactive oxygen species generators (paraquat or cadmium), or lack of superoxide dismutases. Degradation rates of long-lived proteins (i.e., most cell proteins) were not affected by these insults, even when there was widespread oxidative damage to proteins. However, exposure to 38°C, paraquat, cadmium, or deletion of SOD1 enhanced two- to threefold the degradation of newly synthesized proteins. By 1 h after synthesis, their degradation was not affected by these treatments. Degradation of these damaged cytosolic proteins requires the ubiquitin–proteasome pathway, including the E2s UBC4/UBC5, proteasomal subunit RPN10, and the CDC48–UfD1–NPL4 complex. In yeast lacking these components, the nondegraded polypeptides accumulate as aggregates. Thus, many cytosolic proteins proceed through a prolonged “fragile period” during which they are sensitive to degradation induced by superoxide radicals or increased temperatures.
Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum
Authors: Axe Elizabeth L. , Walker Simon A. , Manifava Maria , Chandra Priya , Roderick H. Llewelyn , Habermann Anja , Griffiths Gareth , Ktistakis Nicholas T.
Published: August 2008

Autophagy is the engulfment of cytosol and organelles by double-membrane vesicles termed autophagosomes. Autophagosome formation is known to require phosphatidylinositol 3-phosphate (PI(3)P) and occurs near the endoplasmic reticulum (ER), but the exact mechanisms are unknown. We show that double FYVE domain–containing protein 1, a PI(3)P-binding protein with unusual localization on ER and Golgi membranes, translocates in response to amino acid starvation to a punctate compartment partially colocalized with autophagosomal proteins. Translocation is dependent on Vps34 and beclin function. Other PI(3)P-binding probes targeted to the ER show the same starvation-induced translocation that is dependent on PI(3)P formation and recognition. Live imaging experiments show that this punctate compartment forms near Vps34-containing vesicles, is in dynamic equilibrium with the ER, and provides a membrane platform for accumulation of autophagosomal proteins, expansion of autophagosomal membranes, and emergence of fully formed autophagosomes. This PI(3)P-enriched compartment may be involved in autophagosome biogenesis. Its dynamic relationship with the ER is consistent with the idea that the ER may provide important components for autophagosome formation.
TGFβ induces SIK to negatively regulate type I receptor kinase signaling
Authors: Kowanetz Marcin , Lönn Peter , Vanlandewijck Michael , Kowanetz Katarzyna , Heldin Carl-Henrik , Moustakas Aristidis
Published: August 2008

Signal transduction by transforming growth factor β (TGFβ) coordinates physiological responses in diverse cell types. TGFβ signals via type I and type II receptor serine/threonine kinases and intracellular Smad proteins that regulate transcription. Strength and duration of TGFβ signaling is largely dependent on a negative-feedback program initiated during signal progression. We have identified an inducible gene target of TGFβ/Smad signaling, the salt-inducible kinase (SIK), which negatively regulates signaling together with Smad7. SIK and Smad7 form a complex and cooperate to down-regulate the activated type I receptor ALK5. We further show that both the kinase and ubiquitin-associated domain of SIK are required for proper ALK5 degradation, with ubiquitin functioning to enhance SIK-mediated receptor degradation. Loss of endogenous SIK results in enhanced gene responses of the fibrotic and cytostatic programs of TGFβ. We thus identify in SIK a negative regulator that controls TGFβ receptor turnover and physiological signaling.
SopB promotes phosphatidylinositol 3-phosphate formation on Salmonella vacuoles by recruiting Rab5 and Vps34
Authors: Mallo Gustavo V. , Espina Marianela , Smith Adam C. , Terebiznik Mauricio R. , Alemán Ainel , Finlay B. Brett , Rameh Lucia E. , Grinstein Sergio , Brumell John H.
Published: August 2008

Salmonella colonizes a vacuolar niche in host cells during infection. Maturation of the Salmonella-containing vacuole (SCV) involves the formation of phosphatidylinositol 3-phosphate (PI(3)P) on its outer leaflet. SopB, a bacterial virulence factor with phosphoinositide phosphatase activity, was proposed to generate PI(3)P by dephosphorylating PI(3,4)P2, PI(3,5)P2, and PI(3,4,5)P3. Here, we examine the mechanism of PI(3)P formation during Salmonella infection. SopB is required to form PI(3,4)P2/PI(3,4,5)P3 at invasion ruffles and PI(3)P on nascent SCVs. However, we uncouple these events experimentally and reveal that SopB does not dephosphorylate PI(3,4)P2/PI(3,4,5)P3 to produce PI(3)P. Instead, the phosphatase activity of SopB is required for Rab5 recruitment to the SCV. Vps34, a PI3-kinase that associates with active Rab5, is responsible for PI(3)P formation on SCVs. Therefore, SopB mediates PI(3)P production on the SCV indirectly through recruitment of Rab5 and its effector Vps34. These findings reveal a link between phosphoinositide phosphatase activity and the recruitment of Rab5 to phagosomes.
Three-Year Prospective Study to Improve the Management of Blood-Exposure Incidents
Authors: van Wijk Paul Th. L. , Pelk-Jongen Marianne , Wijkmans Clementine , Voss Andreas , Schneeberger Peter M.
Published: August 2008

Objective.

Throughout 2003-2005, all blood-exposure incidents registered by an expert counseling center in The Netherlands accessible by telephone 24 hours a day, 7 days a week, were analyzed to assess quality improvement in the center's management of such incidents. The expert center was established to handle blood-exposure incidents that occur both inside and outside of a hospital. Infection control practitioners carried out risk assessment, made the practical arrangements associated with managing incidents, and carried out treatment and follow-up, all in accordance with standardized procedures.

Design.

We analyzed the time it took for exposed individuals to report the incident, the time required to perform a human immunodeficiency virus (HIV) test for the source individual when needed, occurrence of injuries, hepatitis B (HBV) vaccination status of exposed individuals, and adherence to protocol at the expert center.

Results.

A mean of 465 incidents was registered during each year of the 3-year study period. Although 698 (50%) of 1,394 reported exposures took place in a hospital, 704 (50%) took place outside of a hospital, and 460 (33%) occurred at a time other than regular office hours. HIV tests for source individuals were performed increasingly quickly over the course of the 3-year study period because of earlier reporting and improvements in practical matters associated with performing and processing the tests. The percentage of healthcare workers employed outside a hospital who were vaccinated against HBV increased from 34% (52 of 152) to 70% (119 of 170) during the 3-year study period. Consequently, the administration of immunoglobulin and unnecessary laboratory testing were reduced. In assessing the quality of the expert center, flaws in the handling of incidents were identified in 148 (37%) of 396 incidents analyzed in 2003, compared with 38 (8%) of 461 incidents analyzed in 2005.

Conclusions.

The practical matters associated with management of blood-exposure incidents, such as timely reporting and administration of prophylaxis, should be optimized for incidents that occur at times other than regular office hours and outside of hospitals. The establishment of a 24-hour centralized counseling facility that was open 7 days a week to manage blood exposures resulted in significant improvements in incident management and better care.
The New York Yankees Cope with the Great Depression
Authors: Surdam David G.
Published: August 2008

The New York Yankees donated their financial records to the National Baseball Hall of Fame. These records provide a rare glimpse into the business of professional team sports. I use these records to examine how the Yankees' management reacted to the Great Depression. Since the team possessed both price-setting power over ticket prices andmonopsony power over player salaries, how did the team adjust ticket prices and salaries in response to the falling incomes of its customers and general deflation of the early 1930s? How did the team's response differ from other teams in Major League Baseball?
Seasonal shifts in the diet of lake zooplankton revealed by phospholipid fatty acid analysis
Authors: TAIPALE SAMI , KANKAALA PAULA , HÄMÄLÄINEN HEIKKI , JONES ROGER I.
Published: August 2008

1. We analysed the phospholipid fatty acid (PLFA) profiles of seston and of the dominant zooplankter, Daphnia longispina, through the open water period in a small, dystrophic lake to investigate seasonal variation in the diet of Daphnia. Phytoplankton, heterotrophic bacteria, green sulphur bacteria and methane‐oxidizing bacteria (MOB) were all present in the water column of the lake, and previous studies have indicated that vertically migrating Daphnia can exploit all these potential food sources.

2. For adult Daphnia, although there was some correspondence between the PLFA profile of Daphnia and the concurrent seston PLFA profile, strongest correlations were between the Daphnia PLFA profile and those of potential food sources determined 7 days earlier. This interval presumably reflects the time it takes for adult Daphnia to turn over their fatty acid pool.

3. A correlation between the concentration of polyunsaturated fatty acids (PUFAs) in the epi‐ and metalimnion and measured primary production indicated that, within the total PLFA fraction, PUFAs can be useful biomarkers for phytoplankton in food‐web studies. Algal PUFAs contributed appreciably to total PLFAs in adult Daphnia during spring and summer, but less so in autumn.

4.  Daphnia in the lake actually reached their highest biomass in autumn, when methanotrophic activity was also highest, and the highest magnitude of MOB‐specific PLFAs was recorded in both adult and juvenile Daphnia. A strong relationship existed between δ13C values of Daphnia reported previously and the proportion of MOB‐specific PLFAs in Daphnia. Autumnal mixing evidently stimulates bacterial oxidation of methane from the hypolimnion, and exploitation of the methanotrophic bacteria sustains a high Daphnia population late in the season.

5. Our results show that the PLFA composition of freshwater zooplankton like Daphnia corresponds rather well to that of their in situ diet of phytoplankton and bacteria, with a lag period of around 1 week in the case of adult animals. The PLFA profile of seston revealed the dominant available food sources, and relating these to the Daphnia PLFA profile provided insights into seasonal changes in Daphnia diet.
Drainage ditching at the catchment scale affects water quality and macrophyte occurrence in Swedish lakes
Authors: ECKE FRAUKE
Published: August 2008

1. We have limited knowledge of the effects of land use in general and of drainage ditching in particular on macrophyte communities in lakes. I quantified catchment land use, including drainage ditching, as well as water quality and the number of macrophyte species in 17 Swedish lakes in summer 2005.

2. Land use within 1 km of the studied lakes was analysed in a geographic information system. The following variables were included: areas of forests, mires, agricultural land and urbanization, length of drainage ditches (classified according to the use of the land they drained), and shortest distance from lake to an urban area. To extract and analyse general trends in the data sets, redundancy analysis was used.

3. Water quality was explained mainly by three land‐use related variables: the lengths of agricultural, forest and mire ditches. The length of agricultural ditches was positively correlated with lake water conductivity, total dissolved solids, Ca, N and total organic carbon (TOC). The lengths of forest and mire ditches were positively correlated with lake water characteristics, especially TOC.

4. The number of species representing different macrophyte life forms was explained by three environmental variables: conductivity, and lengths of forest and agricultural ditches. The numbers of isoetids, nymphaeids, elodeids and total obligate hydrophytes were negatively correlated with length of forest ditches. In contrast, the number of lemnids and helophytes was positively correlated with conductivity and length of agricultural ditches. Furthermore, the number of isoetids was exponentially related (negatively) to lengths of agricultural and forest ditches, indicating a threshold response to drainage ditch length.

5. The results suggest that effects on water quality and macrophyte communities result from drainage ditching in the lake catchments rather than from land use itself. Given the total area of drainage‐ditched land worldwide (millions of ha in Scandinavia alone), drainage ditching should be considered when evaluating environmental impacts on lake water quality and macrophyte occurrence and when determining reference conditions for catchment land use.
High‐resolution combined linkage physical map of short tandem repeat loci on human chromosome band Xq28 for indirect haemophilia A carrier detection
Authors: MACHADO F. B. , MEDINA‐ACOSTA E.
Published: August 2008

Summary.  Haemophilia A, the most common severe hereditary bleeding disorder in humans, is chiefly caused by mutations in the coagulation factor VIII F8 gene, which maps on chromosome band Xq28. Linkage analysis with F8 intragenic and/or closely located extragenic short tandem repeat (STR) elements is an effective method for indirect tracing of F8 pathogenic allelic variants in at‐risk families. STR profiling is currently limited to 14 markers, 11 of which are dinucleotide elements. The aim of this study was to define novel polymorphic STR loci for haemophilia A carrier screening. The combined linkage physical map was restricted to a 2.4‐Mb region on Xq28 that hosts 81 annotated genes, F8 inclusive. The inventory was in silico through comparative analyses with three X chromosome reference sequences, using microsatellite mining and validation computer software. Genetic distances for unmapped markers were interpolated on the Rutgers map of the human genome. The effort yielded 94 STR loci: 53 extragenic and 41 intragenic (14 STR elements map on the F8 gene; the other 27 on 19 further genes). The distribution per repeat period size was 61.7% di‐, 5.3% tri‐, 26.6% tetra‐ and 6.4% pentanucleotide loci. The success rate of validation of polymorphism for the new STR loci was 56.3%. For STR elements 0.78 Mb equidistant of the F8 gene, the interpolated downstream genetic length is 3.27 times the upstream genetic length. The inventory represents a 5.7‐fold increase in polymorphic STR loci useful in carrier detection. Genotyping with the upstream extragenic tetra‐ and pentanucleotide markers is thus apprized.
Retracted: Manuka honey vs. hydrogel – a prospective, open label, multicentre, randomised controlled trial to compare desloughing efficacy and healing outcomes in venous ulcers
Authors: Gethin Georgina , Cowman Seamus
Published: August 2008

Objective.  Comparison of desloughing efficacy after four weeks and healing outcomes after 12 weeks in sloughy venous leg ulcers treated with Manuka honey (Woundcare 18+) vs. standard hydrogel therapy (IntraSite Gel).

Background.  Expert opinion suggests that Manuka honey is effective as a desloughing agent but clinical evidence in the form of a randomised controlled trial is not available. There is a paucity of research which uses Manuka honey in venous ulcers.

Design.  Prospective, multicentre, open label randomised controlled trial.

Method.  Randomisation was via remote telephone. One hundred and eight patients with venous leg ulcers having ≥50% wound area covered in slough, not taking antibiotics or immunosuppressant therapy were recruited from vascular centres, acute and community care hospitals and leg ulcer clinics. The efficacy of WoundCare 18+ to deslough the wounds after four weeks and its impact on healing after 12 weeks when compared with IntraSite Gel control was determined. Treatment was applied weekly for four weeks and follow‐up was made at week 12.

Results.  At week 4, mean % reduction in slough was 67% WoundCare 18+ vs. 52·9% IntraSite Gel (p = 0·054). Mean wound area covered in slough reduced to 29% and 43%, respectively (p = 0·065). Median reduction in wound size was 34% vs. 13% (p = 0·001). At 12 weeks, 44% vs. 33% healed (p = 0·037). Wounds having >50% reduction in slough had greater probability of healing at week 12 (95% confidence interval 1·12, 9·7; risk ratio 3·3; p = 0·029). Infection developed in 6 of the WoundCare 18+ group vs. 12 in the IntraSite Gel group.

Conclusion.  The WoundCare 18+ group had increased incidence of healing, effective desloughing and a lower incidence of infection than the control. Manuka honey has therapeutic value and further research is required to examine its use in other wound aetiologies.

Relevance to clinical practice.  This study confirms that Manuka honey may be considered by clinicians for use in sloughy venous ulcers. Additionally, effective desloughing significantly improves healing outcomes.
Effect of iron or multiple micronutrient supplements on the prevalence of anaemia among anaemic young children of a malaria‐endemic area: a randomized double‐blind trial
Authors: Ouédraogo Hermann Z. , Dramaix‐Wilmet Michèle , Zeba Augustin N. , Hennart Philippe , Donnen Philippe
Published: August 2008

Objective  To assess the effect of supplementation with iron or multiple micronutrients (MM) on the prevalence of anaemia in a malaria‐endemic area.

Methods  A community‐based randomized double‐blind trial was conducted in rural Burkina Faso, including children aged 6–23 months with haemoglobin (Hb) concentrations of 70–109 g/l who were randomized into an iron group (Fe, n = 96), an iron and zinc group (IZ, n = 100) or an MM group (MM, n = 100), 5 days/week for 6 months. All children were provided with insecticide‐treated bednets; those who had a Plasmodium falciparum (PF) positive‐smear at baseline and/or at each monthly checking received antimalarial therapy.

Results  The mean (SD) endpoint Hb concentration was higher in the MM group [113.2 (13.6) g/l] than in the IZ group [106.3 (15.6) g/l] and the Fe group [107.1 (12.9) g/l] (P = 0.001). Children in the MM group were more likely to recover from anaemia than those in the Fe group [prevalence rate ratios, PRR (95% confidence interval, CI) = 1.62 (1.22–2.15), P < 0.001]. The IZ group did not differ from the Fe group [PRR (95% CI) = 0.94 (0.65–1.35), P = 0.72]. None of the interactions on the effect of supplementation of baseline age (0.13), or baseline height‐for‐age z‐score (P = 0.33), or incident PF parasitemia (P = 0.99), was significant.

Conclusion  In this malaria‐endemic area, in combination with malaria management, the MM supplement was more efficacious than the Fe supplement and the IZ supplement for reducing anaemia. Further investigation into limiting factors and amounts of micronutrients that would be more efficacious for reducing anaemia is recommended.
Drug regimens for visceral leishmaniasis in Mediterranean countries
Authors: Gradoni Luigi , Soteriadou Ketty , Louzir Hecmi , Dakkak Allal , Toz Seray Ozensoy , Jaffe Charles , Dedet Jean‐Pierre , Campino Lenea , Cañavate Carmen , Dujardin Jean‐Claude
Published: August 2008

Until the early 1990s, pentavalent antimony was the only documented first‐line drug employed for the treatment of zoonotic visceral leishmaniasis (VL) in the Mediterranean, with reported cure rates exceeding 95% in immunocompetent patients. The emergence of antimony resistance in other endemic settings and the increase in drug options have stimulated re‐evaluation of the current therapeutic approaches and outcomes in Mediterranean countries. A scientific consortium (‘LeishMed’ network) collected updated information from collaborating clinical health centres of 11 endemic countries of Southern Europe, Northern Africa and the Middle East. In contrast with the previous situation, VL is now treated differently in the region, basically through three approaches: (1) In Northern Africa and in part of the Middle East, pentavalent antimony is still the mainstay for therapy, with no alternative drug options for treating relapses; (2) In some European countries and Israel, both pentavalent antimony and lipid‐associated amphotericin B (AmB) formulations are used as first‐line drugs, although in different patients’ categories; (3) In other countries of Europe, mainly liposomal AmB is employed. Importantly, cure rates exhibited by different drugs, including antimonials in areas where they are still in routine use, are similarly high (≥95%) in immunocompetent patients. Our findings show that antimony resistance is not an emerging problem in the Mediterranean. A country’s wealth affects the treatment choice, which represents a balance between drug efficacy, toxicity and cost, and costs associated with patient’s care.
The effect of chronic variable stress on bowel habit and adrenal function in rats
Authors: Kim Yong S , Lee Moon Y , Choi Chang S , Sohn Young W , Park Byung R , Choi Myung‐Gyu , Nah Yong‐Ho , Choi Suck C
Published: August 2008

Background and Aim:  Increased colonic motility is a well‐known stress response and corticotropin releasing hormone plays an important role in this response, but sequential change of bowel habit and adrenal function during chronic stress has not been reported. The objective of this study was to evaluate the effect of chronic stress on bowel habit and adrenal function.

Methods:  Male Sprague‐Dawley rats were exposed to chronic variable stress (CVS) for 6 weeks. We measured daily the number and weight of pellets and weekly urinary corticosterone. After 6 weeks of experiment, visceromotor response (VMR) to colorectal distention (CRD), serum corticosterone and adrenal glands weight were measured.

Results:  The number and weight of pellets in CVS rats was greater than those of the control rats initially and decreased during the later period. However, CVS rats showed continuously exaggerated daily variation of pellet number than control rats to the end of experimental period. Urinary corticosterone was increased in CVS rat until the fifth week, but urine and serum corticosterone were not statistically different between groups at the sixth week. However, the relative weight of adrenal glands was higher in CVS rats at the sixth week. CVS rats showed exaggerated VMR to CRD than the control rats.

Conclusions:  The prolonged and variable stress to rats induced sustained bowel habit dysfunction and visceral hypersensitivity without adaptation. Chronic stress also increased adrenal activity from the early phase and finally caused adrenal hypertrophy with relatively decreased activity. But adrenal change was not parallel to bowel habit change and it remains to be seen whether adrenal dysfunction is directly related to bowel habit dysfunction.
Comparison of four current staging systems for Chinese patients with hepatocellular carcinoma undergoing curative resection: Okuda, CLIP, TNM and CUPI
Authors: Lu Wenping , Dong Jiahong , Huang Zhiqiang , Guo Deyu , Liu Yousheng , Shi Shuang
Published: August 2008

Background and Aim:  Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, there is no general consensus as to which staging system is the most reliable for predicting the survival of patients with HCC. The aims of this study were to compare commonly‐used staging systems in a cohort of Chinese HCC patients undergoing curative resection.

Methods:  From January 1991 to June 2002, 234 Chinese patients undergoing curative resection for HCC from one medical center were evaluated. All patients were classified by the Okuda, Cancer of the Liver Italian Program (CLIP), tumor node metastasis (TNM) (6th edition) and the Chinese University Prognostic Index (CUPI) staging systems. Survival curves were calculated using the Kaplan–Meier method and were examined using log‐rank testing. The overall predictive power for patient survival with each staging system was evaluated by the area under the receiver operating characteristic (ROC) curve.

Results:  The overall median survival of the entire cohort was 24.9 months (95% confidence interval (CI) 18.15–31.65 months) and the estimated survival rates at 1, 3, and 5 years were 69.66% ± 3.01%, 41.02% ± 3.31%, and 29.08% ± 3.55%, respectively. In our patient cohort, the log‐rank test demonstrated that the TNM and Okuda staging systems gave better results than the other staging systems in the prognosis stratification. The prognostic predictive powers of the TNM staging for survival, evaluated by ROC curve areas, was also superior.

Conclusions:  For HCC patients undergoing curative resection, the TNM staging system (6th edition) proved the best for prognostic stratification and prognosis prediction.
Biochemical and molecular characterization of hepatocyte‐like cells derived from human bone marrow mesenchymal stem cells on a novel three‐dimensional biocompatible nanofibrous scaffold
Authors: Kazemnejad Somaieh , Allameh Abdolamir , Soleimani Masoud , Gharehbaghian Ahmad , Mohammadi Yousef , Amirizadeh Naser , Jazayery Maryam
Published: August 2008

Background:  There is significant interest in using nanofibers in tissue engineering from stem cells. The transdifferentiation of mesenchymal stem cells into the hepatic lineage in a nanofibrous structure has not been reported. In this study, a three dimensional nanofibrous scaffold is introduced for differentiation of human bone marrow derived mesenchymal stem cells (hBMSCs) into hepatocytes.

Methods:  A scaffold composed of Poly (ε‐caprolactone), collagen and polyethersulfone was fabricated by the electrospinning technique. After characterization of isolated hBMSCs, the performance of the cells on the scaffold was evaluated by Scanning Electron Microscopy (SEM) and MTT assay. Cytological, molecular and biochemical markers were measured to confirm differentiation potential of hBMSCs into hepatocytes.

Results:  The isolated cells possessed the basic properties of mesenchymal stem cells (MSCs). Based on scanning electron microscope (SEM) analysis and MTT assay, it was shown that the cells adhere, penetrate and proliferate on the nanofibers. Cultured cells on the nanofibers differentiated into hepatocyte‐like cells and expressed hepatocyte specific markers such as albumin, α‐fetoprotein, cytokeratin‐18, cytokeratin‐19 and cytochrome P450 3A4 at mRNA levels. Appearance of a considerable number of albumin‐positive cells cultivated on the scaffold (47 ± 4%) as compared to the two‐dimensional culture system (28 ± 6%) indicates the supporting role of the scaffold. The efficiency of the cells to produce albumin, urea, transferrin, serum glutamic pyruvic transaminase and serum oxaloacetate aminotransferase in hepatocytes on the scaffold further attest to the functionality of the cells.

Conclusion:  The data presented in this study show that the engineered nanofibrous scaffold is a conductive matrix which supports and enhances MSC development into functional hepatocyte‐like cells.
Risks and clinical features of colorectal cancer complicating Crohn's disease in Japanese patients
Authors: Yano Yutaka , Matsui Toshiyuki , Uno Hiroyuki , Hirai Fumihito , Futami Kitaro , Iwashita Akinori
Published: August 2008

Background and Aim:  No reports on the relative risk of development of colorectal cancer (CRC) in Japanese patients with Crohn's disease (CD) have been published. The present study aimed to investigate the relative risk and the clinical features of CRC complicating CD among patients managed at Fukuoka University Chikushi Hospital, Fukuoka, Japan (a tertiary referral center for inflammatory bowel diseases).

Methods:  The clinical backgrounds were analyzed of 512 patients with CD who have been treated by our department during the last 20‐year period (1985–2005) (total 6212.6 person years at risk). The standardized incidence ratio (SIR) refers to the relative risk of CRC in the subjects as compared with that in a sex‐ and age‐matched healthy population.

Results:  There were six cases with CRC. The SIR was significantly higher (3.2‐fold higher; 95% confidence interval, 1.2–6.9 P < 0.05) in the CD group than in the healthy population. The significant risk factors identified were female sex, mixed small and large bowel type, observation period over 20 years, onset of CD at less than 25 years of age, presence of anal disease, and positive history of surgery. The prognosis for the six cases with CRC was very poor (five cases died within 1.5 years).

Conclusion:  The risk of CRC in longstanding CD in Japan was similar to that in Western countries. The necessity of surveillance in the management of CD would also need to be discussed in the near future, especially in CD patients with anal lesions or fistulae, and are particularly important in patients with a 20‐year or more history of CD.
Serum ghrelin levels in children with primary protein–energy malnutrition
Authors: Altinkaynak Sevin , Selimoglu Mukadder A. , Ertekin Vildan , Kilicarslan Buket
Published: August 2008

Background: Ghrelin, an appetite‐stimulating peptide, increases in cachectic conditions. It probably reflects peripheral nutritional status and influences nutrient intake and growth. The aim of the present study was to determine serum ghrelin levels in children with primary protein–energy malnutrition (PEM) and to find if any correlation exists between serum ghrelin levels and the clinical presentation of those patients.

Methods: Twenty‐eight children with primary PEM and 10 healthy children were included. Serum fasting ghrelin levels were measured using radioimmunoassay.

Results: Mean serum ghrelin level of healthy children and those with PEM were 107.7 ± 40.1 pg/mL and 141.6 ± 123.8 pg/mL, respectively (P < 0.001). Ghrelin levels were independent of age and sex (P > 0.05). Ghrelin was negatively correlated with body mass index in healthy children (P < 0.01), but not in those with PEM (P > 0.05). Mean serum ghrelin level of children with moderate malnutrition was higher than that of children with severe malnutrition (199.2 ± 154.1 pg/mL vs 98.4 ± 74.3 pg/mL, P < 0.05). Mean serum ghrelin levels of patients with kwashiorkor, marasmic kwashiorkor, and marasmus were 127.9 ± 97.8 pg/mL, 138.7 ± 95.8 pg/mL, and 162.3 ± 185.0 pg/mL, respectively (P > 0.05).

Conclusion: Serum ghrelin level is higher in patients with PEM, especially in those with marasmus, compared to healthy children. Although this observation suggests that ghrelin helps to fight malnutrition in children, it is obvious that further studies are needed to clarify the exact pathogenetic mechanism regarding this condition.
Clinical assessment of Mycoplasma pneumoniae‐associated hemophagocytic lymphohistiocytosis
Authors: Yoshiyama Megumi , Kounami Shinji , Nakayama Keiko , Aoyagi Noriyuki , Yoshikawa Norishige
Published: August 2008

Background: Mycoplasma pneumoniae has been reported to be an etiologic pathogen of infection‐associated hemophagocytic lymphohistiocytosis (HLH), but few case reports have been available to date.

Methods: The clinical features of four childhood cases of M. pneumoniae‐associated hemophagocytic lymphohistiocytosis (Mp‐HLH) were retrospectively assessed to obtain data that might be useful for early diagnosis and effective management. The previous English‐language literature pertaining to Mp‐HLH was also reviewed.

Results: The patients were two boys and two girls, aged between 1 and 11 years of age. One patient was demonstrated to have concurrent infection with rubella. All the patients had typical radiographic features of M. pneumoniae pneumonia, and one patient also had encephalopathy as a complication. All the children underwent bone marrow examination because of antibiotic‐refractory fever, mild hepatosplenomegaly, cytopenia, hyperferritinemia and elevated levels of urine β2‐microglobulin. Cytopenia and hepatosplenomegaly in the present patients were relatively mild as compared to those in cases of other infection‐associated HLH such as Epstein–Barr virus infection‐associated HLH. Treatment with corticosteroids resulted in prompt and complete resolution in two cases, and i.v. high‐dose gammaglobulin therapy achieved a complete response in another child. Spontaneous resolution under treatment with antibiotics alone was observed in one case.

Conclusion: Although Mp‐HLH is a rare complication of M. pneumoniae infection, it should always be considered in patients with antibiotic‐refractory M. pneumoniae infections with cytopenia. Mp‐HLH might be effectively treated by corticosteroids or high‐dose gammaglobulin. To clarify the diverse clinical manifestations of M. pneumoniae infections, immunological interactions between M. pneumoniae and the host immune system should be further investigated.
Management and outcome in prenatally diagnosed sacrococcygeal teratomas
Authors: Okada Tadao , Sasaki Fumiaki , Cho Kazutoshi , Honda Shouhei , Naito Satsuki , Hirokata Gentarou , Todo Satoru
Published: August 2008

Background: The aim of the present study was to retrospectively determine the clinical factors affecting the outcome after birth in prenatally diagnosed sacrococcygeal teratomas (SCT).

Methods: Six cases of prenatal SCT were identified from January 1985 until August 2005. A retrospective review of case‐notes and pathological reports was carried out. Clinical data during the perinatal period, operative findings, postoperative complications and follow up were evaluated in the patients with prenatally diagnosed SCT.

Results: SCT presented as type I in two neonates and type III in four between 22 and 33 weeks’ gestation. Fetal intervention was not performed for any fetus. Five of six were delivered by cesarean section and the other was delivered vaginally due to small tumor size. Patients were born at between 29 and 39 weeks’ gestation and weighed from 1840 to 3500 g. All patients with type III SCT presented with related diseases, including bilateral hydronephrosis, neurological deficit of the communicating peroneal nerve such as paralytic talipes equines, bladder or bowel dysfunction, high‐output cardiac failure, or fetal hydrops in one of a set of fraternal twins. A baby with high‐output cardiac failure and fetal hydrops underwent urgent cesarean section at 29 weeks’ gestation and died 8 days after birth despite intensive care due to multi‐organ failure. In five cases, surgery was successful with good outcomes maintained at follow‐up of between 8 months and 14 years.

Conclusions: Detailed ultrasound should be performed to rule out associated anomalies, and determine the presence or absence of hydrops in prenatally diagnosed SCT. Fetal hydrops, orthopedic impairment such as lower extremity weakness and swelling, and urinary incontinence are important clinical factors affecting the outcome after birth in prenatally diagnosed SCT. In particular, the present study indicated that the association of a fraternal twin and fetal hydrops makes it very difficult to treat SCT perinatally.