bluuebunny/crossref_metadata_2025 huggingface dataset:
Who Is Teaching Undergraduate Prosthodontics in US Dental Schools, 2007?
Authors: Hill Edward E. , Breeding Larry C.
Published: February 2009

Purpose: The shortage of full‐time dental school faculty along with a slow steady increase in student enrollment is not a new phenomenon. The purpose of this study was to determine who is teaching undergraduate prosthodontics in US dental schools—what percent are full‐time faculty; what percent are prosthodontists; and what percent are board‐certified prosthodontists—to allow schools to make a real‐time comparison of the composition of instructors they have teaching prosthodontics to the apparent status quo.

Materials and Methods: A short, ten‐question survey was sent via e‐mail to representatives at the 55 undergraduate US dental schools. A cover letter explained the nature of the study and requested participation and electronic return of the survey. Three weeks after the initial request, an aggressive follow‐up was conducted to schools that had not returned the survey. Answers were converted to percentages to compensate for differences between schools with many or few instructors. Schools were also grouped by location to see if regional differences exist.

Results: Thirty‐eight (69%) of the surveys were completed and returned. In general, the division between full‐time and part‐time instructors is about 50%. More removable prosthodontic instructors (60%) than fixed instructors (44%) are prosthodontists, and only a small percentage of the total (18% removable and 15% fixed) have completed board certification. The South and Midwest had the highest percentage of prosthodontists involved in teaching; the South had the highest percentage with specialty board certification.

Conclusion: This study indicated that only a few schools are fortunate enough to have sufficient full‐time, specialty‐trained faculty available for complete coverage of all undergraduate prosthodontic courses and clinics. The information presented serves as a baseline for future comparison to see if the percentage of full‐time and/or specialty‐certified prosthodontic faculty changes.
2. The Democratic Peace Myth: From Hiroshima to Baghdad
Authors: Fiala Andrew
Published: February 2009

Abstract

This paper examines the ideal of the democratic peace and the recent misuse of this ideal in the war on terrorism. It argues against the idea that aggressive military force can be employed to bring about the ideal of the democratic peace. By looking at John Stuart Mill's utilitarian justification of benevolent despotism for “barbarians,” it examines how idealism can lead to a defense of aggressive intervention. And it considers how idealistic zeal can lead to violations of just war principles, as in the case of Hiroshima. It concludes by arguing that Kant's deontological approach is better. Kant provides us with a reason to hope that as democracy spreads, peace will spread as well. But Kant also prohibits us from using force to actualize this ideal.
12. Transculture: A Broad Way Between Globalism and Multiculturalism
Authors: Epstein Mikhail
Published: February 2009

Abstract

This paper develops a concept of transculture as a model of cultural development that differs from both leveling globalism and isolating pluralism. While culture frees humans from the material dependencies of nature, it also creates new, symbolic dependencies—on customs, traditions, conventions, which a person receives as a member of a certain group and ethnos. Among the many freedoms proclaimed as rights of the individual, there emerges yet another freedom—from one's own culture, in which one was born and educated. Transculture is viewed as the next level of liberation, this time from the “prison house of language,” from unconscious predispositions and prejudices of the “native,” naturalized cultures. The case of the Japanese poet Araki Yasusada (1903–1972), a survivor of Hiroshima, demonstrates how transcultural creativity, though cast in the form of a literary hoax, can produce an internationally recognized achievement. Transculturalism is especially needed in world politics, where the factor of fixed cultural identity based on race, ethnos, religion, or ideological commitments turned out to be a source of conflict and violence. This paper argues that the categories of opposition and identity do not preclude the significance of the third category, which is difference. The differences complement each other and create a new interpersonal transcultural community to which we belong, not because we are similar but because we are different. The transcultural perspective opens a possibility for globalization not as homogenization but, rather, as further differentiation of cultures and their “dissemination” into transcultural individuals, liberating themselves from their dependence from their native cultures. The global society can be viewed as the space of diversity of free individuals rather than that of fixed groups and cultures. It is an alternative to the clash of civilizations and a hope for lasting peace.
Molecular Phylogeny of Parvilucifera prorocentri (Alveolata, Myzozoa): Insights into Perkinsid Character Evolution
Authors: HOPPENRATH MONA , LEANDER BRIAN S.
Published: February 2009

ABSTRACT. Perkinsids and colpodellids are lineages that diverged near the origins of dinoflagellates and apicomplexans, respectively, and provide compelling insights into the earliest stages of alveolate evolution. Perkinsids, including Perkinsus and Parvilucifera, are intracellular parasites of animals and dinoflagellates and possess traits also known in syndineans, dinokaryotes (mainly free living dinoflagellates), and colpodellids. An improved understanding of perkinsid biodiversity and phylogeny is expected to shed considerable light on the evolutionary origins of syndineans and dinokaryotes as well as the cellular identities of environmental sequences derived from marine and freshwater habitats. Accordingly, the small subunit (SSU) rDNA sequence from Parvilucifera prorocentri, a tube‐forming intracellular parasite of the marine benthic dinoflagellate Prorocentrum fukuyoi, was determined. Molecular phylogenetic analyses demonstrated, with very high statistical support, that P. prorocentri branched as a sister lineage to a divergent clade consisting of Parvilucifera infectans and Parvilucifera sinerae. The entire Parvilucifera clade was nested within a more inclusive and modestly supported clade consisting of Perkinsus and several environmental sequences. Because P. prorocentri possessed a novel combination of ultrastructural features known in Perkinsus, Parvilucifera, and/or syndineans (i.e. germ tubes, trichocysts, and a syndinean‐like nucleus), establishing the molecular phylogenetic position of this species enabled us to build a more comprehensive framework for understanding the earliest stages in the evolution of myzozoans.
Theileria gilberti n. sp. (Apicomplexa: Theileriidae) in the Gilbert's Potoroo (Potorous gilbertii)
Authors: LEE JEREMY Y. , RYAN UNA M. , JEFFERIES RYAN , MCINNES LINDA M. , FORSHAW DAVID , FRIEND J. ANTHONY , IRWIN PETER J.
Published: February 2009

ABSTRACT. The morphology and genetic characterisation of a new species of piroplasm identified in the blood of the Gilbert's potoroo (Potorous gilbertii) from the Two Peoples Bay Nature Reserve near Albany, Western Australia, is described from blood and tissue samples from 16 Gilbert's potoroos. Microscopy of blood showed these parasites are highly pleomorphic with a mean length of 1.8 μm and mean width of 0.85 μm. Phylogenetic analysis of 18S rRNA sequence data identified the piroplasm as a new species of Theileria that is closely related to other Australian marsupial piroplasm species. Based on biological and molecular data, it is proposed that the parasite from Gilbert's potoroo be given the name Theileria gilberti n. sp.
Nanofibrous substrates support colony formation and maintain stemness of human embryonic stem cells
Authors: Gauthaman Kalamegam , Venugopal Jayarama Reddy , Yee Fong Chui , Peh Gary Swee Lim , Ramakrishna Seeram , Bongso Ariff
Published: February 2009

Inadequate cell numbers in culture is one of the hurdles currently delaying the application of human embryonic stem cells (hESCs) for transplantation therapy. Nanofibrous scaffolds have been effectively used to expand and differentiate non‐colony forming multipotent mesenchymal stem cells (MSC) for the repair of tissues or organs. In the present study, we evaluated the influence of nanofibrous scaffolds for hESC proliferation, increase in colony formation, self‐renewal properties, undifferentiation and retention of ‘stemness’. Polycaprolactone/collagen (PCL/collagen) and PCL/gelatin nanofibrous scaffolds were fabricated using electrospinning technology. The hESCs were seeded on the nanofibrous scaffolds in the presence or absence of mitomycin‐C treated mouse embryonic fibroblasts (MEFs). The hESCs grown on both scaffolds in the presence of the MEFs produced an increase in cell growth of 47.58% (P≤ 0.006) and 40.18% (P≤ 0.005), respectively, over conventional controls of hESCs on MEFs alone. The hESC colonies were also larger in diameter on the scaffolds compared to controls (PCL/collagen, 156.25 ± 7 μM and PCL/gelatin, 135.42 ± 5 μM). Immunohistochemistry of the hESCs grown on the nanofibrous scaffolds with MEFs, demonstrated positive staining for the various stemness‐related markers (octamer 4 [OCT‐4], tumour rejection antigen‐1–60, GCTM‐2 and TG‐30), and semi‐quantitative RT‐PCR for the pluripotent stemness genomic markers (NANOG, SOX‐2, OCT‐4) showed that they were also highly expressed. Continued successful propagation of hESC colonies from nanofibrous scaffolds back to conventional culture on MEFs was also possible. Nanofibrous scaffolds support hESC expansion in an undifferentiated state with retention of stemness characteristics thus having tremendous potential in scaling up cell numbers for transplantation therapy.
Human cardiac fibroblasts express B‐type natriuretic peptide: fluvastatin ameliorates its up‐regulation by interleukin‐1α, tumour necrosis factor‐α and transforming growth factor‐β
Authors: Jarai Rudolf , Kaun Christoph , Weiss Thomas W. , Speidl Walter S. , Rychli Kathrin , Maurer Gerald , Huber Kurt , Wojta Johann
Published: February 2009

B‐type natriuretic peptide (BNP) is a cardiac hormone, which plays a major role in body fluid and cardiovascular homeostasis. Produced by cardiac ventricles, its expression is highly regulated by various mediators. Canine cardiac fibroblasts have been identified as a source of BNP. Cardiac fibroblasts are key regulators of myocardial structure and function. We treated cultured human adult cardiac fibroblasts (HACF) with 2000 U/ml tumour necrosis factor‐α (TNF‐α), 200 U/ml interleukin‐1α (IL‐1α) or 50 ng/ml transforming growth factor‐β (TGF‐β) in the presence or absence of 500 nM fluvastatin. N‐terminal pro‐BNP (Nt‐proBNP) concentration was determined by a competitive enzyme immunoassay. RealTime polymerase chain reaction (real‐time PCR) was performed to investigate changes in BNP mRNA expression. Nt‐proBNP peptide was present in the conditioned media of HACF and incubation with fluvastatin significantly reduced Nt‐proBNP peptide levels. Treatment of HACF with TNF‐α, IL‐1α or TGF‐β significantly increased Nt‐proBNP levels compared with untreated cells. This effect was completely abolished in the presence of fluvastatin. Real‐time PCR analysis confirmed these changes at the level of mRNA expression. Our data suggest that cardiac fibroblasts are a potential source of BNP in the human heart. Pro‐inflammatory cytokines, associated with ventricular dysfunction and cardiac fibrosis, seem to be major inducers of BNP production in cardiac fibroblasts. This effect can be reverted by a statin. Based on our data, we speculate that elevated plasma BNP levels might not only reflect increased myocardial stretch but also inflammatory and remodelling processes. A possible benefit of statin‐induced reduction in BNP production requires further studies.
Serum regulates adipogenesis of mesenchymal stem cells via MEK/ERK‐dependent PPARγ expression and phosphorylation
Authors: Wu Ling , Cai Xiaoxiao , Dong Hai , Jing Wei , Huang Yuanding , Yang Xingmei , Wu Yao , Lin Yunfeng
Published: February 2009

Mesenchymal stem cells (MSCs) provide us an excellent cellular model to uncover the molecular mechanisms underlying adipogenic differentiation of adult stem cells. PPARγ had been considered as an important molecular marker of cells undergoing adipogenic differentiation. Here, we demonstrated that expression and phosphorylation of PPARγ could be found in bone marrow–derived MSCs cultured in expansion medium without any adipogenic additives (dexamethasone, IBMX, insulin or indomethacin). Then, PPARγ was dephosphorylated in MSCs during the process of adipogenic differentiation. We then found that inhibition of MEK activation by specific inhibitor (PD98059) counteracted the PPARγ expression and phosphorylation. However, expression and phosphorylation of PPARγ did not present in MSCs cultured in medium with lower serum concentration. When these MSCs differentiated into adipocytes, no phosphorylation could be detected to accompany the expression of PPARγ. Moreover, exposure of MSCs to higher concentration of serum induced stronger PPARγ expression, and subsequently enhanced their adipogenesis. These data suggested that activation of the MEK/ERK signalling pathway by high serum concentration promoted PPARγ expression and phosphorylation, and subsequently enhanced adipogenic differentiation of MSCs.
Inhibition of LPS‐induced production of inflammatory factors in the macrophages by mono‐carbonyl analogues of curcumin
Authors: Liang Guang , Zhou Huiping , Wang Yi , Gurley Emily C. , Feng Biao , Chen Li , Xiao Jian , Yang Shulin , Li Xiaokun
Published: February 2009

Curcumin (diferuloylmethane) is an orange–yellow compound from turmeric (Curcuma longa), a spice found in curry powder. Traditionally known for its anti‐inflammatory effects, curcumin has established itself in the last two decades to be a potent immunomodulatory agent that can regulate the activation of a variety of immunocytes and the expression of inflammatory factors. Considering that the β‐diketone moiety of curcumin may result in its instability and poor metabolic property, we previously designed a series of mono‐carbonyl analogues of curcumin with enhanced stability by deleting this moiety. These compounds demonstrate improved pharmacokinetic profiles both in vitro and in vivo. In this study, we reported a total of 44 mono‐carbonyl analogues, which have been evaluated for the inhibitory activities against LPS‐induced TNF‐α and IL‐6 release in the macrophages. Based on the screening results of these analogues, five active compounds A01, A03, A13, B18 and C22 were investigated to inhibit TNF‐α and IL‐6 release in a dose‐dependent manner, three of which further demonstrated inhibitory effects on LPS‐induced TNF‐α, IL‐1β, IL‐6, MCP‐1, COX‐2, PGES, iNOS and p65 NF‐κB mRNA production. The results indicated that these mono‐carbonyl analogues may possess anti‐inflammatory activities similar to curcumin despite the absence of the β‐diketone. These mono‐carbonyl analogues may be a favourable alternative for the development of curcumin‐based anti‐inflammatory drugs both pharmacokinetically and pharmacologically. We further examined the biological properties of A13, the only hydrosoluble analogue when combined with hydrochloric acid. The results showed a dose‐dependent inhibition of LPS‐induced cytokine production. These data further indicated that compound A13 may be explored as a promising anti‐inflammatory molecule.
Potential for control of detrusor smooth muscle spontaneous rhythmic contraction by cyclooxygenase products released by interstitial cells of Cajal
Authors: Collins Clinton , Klausner Adam P. , Herrick Benjamin , Koo Harry P. , Miner Amy S. , Henderson Scott C. , Ratz Paul H.
Published: February 2009

Interstitial cells of Cajal (ICCs) have been identified as pacemaker cells in the upper urinary tract and urethra, but the role of ICCs in the bladder remains to be determined. We tested the hypotheses that ICCs express cyclooxygenase (COX), and that COX products (prostaglandins), are the cause of spontaneous rhythmic contraction (SRC) of isolated strips of rabbit bladder free of urothelium. SRC was abolished by 10 μM indomethacin and ibuprofen (non‐selective COX inhibitors). SRC was concentration‐dependently inhibited by selective COX‐1 (SC‐560 and FR‐122047) and COX‐2 inhibitors (NS‐398 and LM‐1685), and by SC‐51089, a selective antagonist for the PGE‐2 receptor (EP) and ICI‐192,605 and SQ‐29,548, selective antagonists for thromboxane receptors (TP). The partial agonist/antagonist of the PGF‐2α receptor (FP), AL‐8810, inhibited SRC by ∼50%. Maximum inhibition was ∼90% by SC‐51089, ∼80–85% by the COX inhibitors and ∼70% by TP receptor antagonists. In the presence of ibuprofen to abolish SRC, PGE‐2, sulprostone, misoprostol, PGF‐2α and U‐46619 (thromboxane mimetic) caused rhythmic contractions that mimicked SRC. Fluorescence immunohistochemistry coupled with confocal laser scanning microscopy revealed that c‐Kit and vimentin co‐localized to interstitial cells surrounding detrusor smooth muscle bundles, indicating the presence of extensive ICCs in rabbit bladder. Co‐localization of COX‐1 and vimentin, and COX‐2 and vimentin by ICCs supports the hypothesis that ICCs were the predominant cell type in rabbit bladder expressing both COX isoforms. These data together suggest that ICCs appear to be an important source of prostaglandins that likely play a role in regulation of SRC. Additional studies on prostaglandin‐dependent SRC may generate opportunities for the application of novel treatments for disorders leading to overactive bladder.
What is the biological basis of pattern formation of skin lesions?
Authors: Paus Ralf , Chuong C. M. , Dhouailly D. , Gilmore S. , Forest L. , Shelley W. B. , Stenn K. S. , Maini P. , Michon F. , Parimoo S. , Cadau S. , Demongeot J. , Zheng Y. , Paus R. , Happle R.
Published: February 2009

Abstract:  Pattern recognition is at the heart of clinical dermatology and dermatopathology. Yet, while every practitioner of the art of dermatological diagnosis recognizes the supreme value of diagnostic cues provided by defined patterns of ‘efflorescences’, few contemplate on the biological basis of pattern formation in and of skin lesions. Vice versa, developmental and theoretical biologists, who would be best prepared to study skin lesion patterns, are lamentably slow to discover this field as a uniquely instructive testing ground for probing theoretical concepts on pattern generation in the human system. As a result, we have at best scraped the surface of understanding the biological basis of pattern formation of skin lesions, and widely open questions dominate over definitive answer. As a symmetry‐breaking force, pattern formation represents one of the most fundamental principles that nature enlists for system organization. Thus, the peculiar and often characteristic arrangements that skin lesions display provide a unique opportunity to reflect upon – and to experimentally dissect – the powerful organizing principles at the crossroads of developmental, skin and theoretical biology, genetics, and clinical dermatology that underlie these – increasingly less enigmatic – phenomena. The current ‘Controversies’ feature offers a range of different perspectives on how pattern formation of skin lesions can be approached. With this, we hope to encourage more systematic interdisciplinary research efforts geared at unraveling the many unsolved, yet utterly fascinating mysteries of dermatological pattern formation. In short: never a dull pattern!
Reduced IL‐1Ra/IL‐1 ratio in ultraviolet B‐exposed skin of patients with polymorphic light eruption
Authors: Janssens A. S. , Pavel S. , Tensen C. P. , Teunissen M. B. M. , Out‐Luiting J. J. , Willemze R. , De Gruijl F. R.
Published: February 2009

Abstract:  Polymorphic light eruption (PLE) is a putative delayed‐type allergic reaction to (solar) ultraviolet (UV) exposure. Inadequate immune suppression after UVB‐induced sunburn appears to be associated with reduced trafficking of Langerhans cells (LCs) out of and neutrophils into the epidermis of patients sensitive to UVB provocation of PLE. Therefore, we investigated whether pro‐inflammatory and chemotactic cytokines are differentially expressed in UVB‐irradiated skin of UVB‐provocable PLE patients (n = 6) and age‐ and gender‐matched healthy controls (n = 6). Interstitial interleukin‐1α (IL‐1α), IL‐1β, IL‐1Ra, IL‐4, IL‐8, tumor necrosis factor‐α (TNF‐α), macrophage inflammatory protein 1‐α (MIP‐1α), MIP‐1β and monocyte chemotactic protein‐1 (MCP‐1) were measured in suction blister fluid raised 16 h after exposure to 0, three and six minimal erythemal UVB doses. In unirradiated skin, the IL‐1Ra levels were significantly lower in the PLE patients than in controls (P < 0.05). IL‐8 and TNF‐α levels increased strongly upon UVB irradiation in both groups. No differential shifts in cytokine profiles were found that could explain a reduced trafficking of Langerhans cells and neutrophils in PLE patients. Dose‐trend analyses showed that UVB irradiation caused significant increases in IL‐1α in both groups, and that the levels of IL‐1α and IL‐1β were on average twofold higher in the PLE group (P = 0.03 and P = 0.004, respectively.). Accordingly, the ratios of IL‐1Ra over IL‐1α and over IL‐1β were overall lower in the skin of PLE patients (P = 0.015 and P < 0.001, respectively.). This shift in cytokines in UVB‐irradiated skin of PLE patients reveals an amplified early pro‐inflammatory cytokine response, which may contribute to the allergic reaction to UVB radiation.
Augmentation of sebaceous lipogenesis by an ethanol extract of Grifola frondosa (Maitake mushroom) in hamsters in vivo and in vitro
Authors: Nagao Mie , Sato Takashi , Akimoto Noriko , Kato Yuya , Takahashi Masao , Ito Akira
Published: February 2009

Abstract:  Grifola frondosa (Maitake mushroom) is an edible and medicinal mushroom with versatile effects such as antitumor and immunomodulating actions. Here, we demonstrated that an ethanol extract of G. frondosa fruiting body (Maitake extract) augmented intracellular lipid droplet formation and the production of triacylglycerols (TG), a major component of sebum, along with the activation of diacylglycerol acyltransferase, a rate‐limiting enzyme of TG synthesis in cultured hamster sebocytes. The topical treatment of Maitake extract on the skin of hamster auricles augmented sebum accumulation in sebaceous glands and ducts. However, in comparison with the Maitake extract, another ethanol extract prepared from Agaricus blazei Murill showed less activity in sebaceous lipogenesis in hamsters in vivo and in vitro. These results provide novel evidence that Maitake extract augments sebaceous lipogenesis in hamsters in vivo and in vitro. Thus, Maitake extract is likely to be a unique agent leading to the remission of dry skin.
Riding Shotgun: A Dual Role for the Epidermal Growth Factor‐Cripto/FRL‐1/Cryptic Protein Cripto in Nodal Trafficking
Authors: Constam Daniel B.
Published: February 2009

Nodal is a secreted protein of the transforming growth factor β (TGFβ) family that activates Smad2 and Smad3 transcription factors through complexes of type I and type II activin receptors and glycosyl‐phosphatidylinositol‐anchored coreceptors of the epidermal growth factor‐like Cripto/FRL‐1/Cryptic family. During early embryogenesis, it stimulates the proliferation of pluripotent progenitor cells and specifies, in a dosage‐dependent manner, their subsequent allocation to distinct germ layers. Available evidence indicates that the signaling strength of Nodal is controlled at the level of endocytic uptake and turnover of activated receptor complexes in early endosomes, but insights into the underlying molecular mechanisms are still limited. In this review, I briefly survey literature on the trafficking of the related TGFβ receptors, and I discuss recent findings indicating that endocytosis of Nodal is coupled to proteolytic processing of its precursor at the cell surface and that the maturation and internalization of Nodal need to be guided by Cripto to stabilize endosomal signaling platforms.
Hutchinson‐Gilford progeria syndrome: oral and craniofacial phenotypes
Authors: Domingo DL , Trujillo MI , Council SE , Merideth MA , Gordon LB , Wu T , Introne WJ , Gahl WA , Hart TC
Published: February 2009

Objective:  Hutchinson‐Gilford progeria syndrome (HGPS) is a rare early‐onset accelerated senescence syndrome. In HGPS, a recently identified de novo dominant mutation of the lamin A gene (LMNA) produces abnormal lamin A, resulting in compromised nuclear membrane integrity. Clinical features include sclerotic skin, cardiovascular and bone abnormalities, and marked growth retardation. Craniofacial features include ‘bird‐like’ facies, alopecia, craniofacial disproportion, and dental crowding. Our prospective study describes dental, oral soft tissue, and craniofacial bone features in HGPS.

Methods:  Fifteen patients with confirmed p.G608G LMNA mutation (1–17 years, seven males, eight females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones, and dentition were identified.

Results:  Radiographic findings included hypodontia (n = 7), dysmorphic teeth (n = 5), steep mandibular angles (n = 11), and thin basal bone (n = 11). Soft tissue findings included ogival palatal arch (n = 8), median sagittal palatal fissure (n = 7), and ankyloglossia (n = 7). Calculated dental ages (9 months to 11 years 2 months) were significantly lower than chronological ages (1 year 6 months to 17 years 8 months) (P = 0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms.

Conclusion:  Novel oral‐craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS.
Pharmacoeconomic model of topical treatment options of mild to moderate psoriasis vulgaris in Germany
Authors: Augustin Matthias , Radtke Marc , Van Engen Anke , Ruedig Cornelia , Lapp Christina , Moehling Ulrich
Published: February 2009

Background: Psoriasis vulgaris is one of the most common dermatologic diseases in Germany with a prevalence of about 2%. Along with efficacy and safety, costs are an important criterion for selecting appropriate therapy for this chronic disease. The majority of the patients with mild to moderate psoriasis vulgaris can be successfully treated with topical therapy alone. The most important agents are vitamin D3 analogs and corticosteroids either as single agents or in a fixed combination (Daivobet®).

Methods: For the evaluation of the cost‐effectiveness of different topical psoriasis treatments, a Markov model was developed that compares a fixed combination treatment followed by calcipotriol with a morning/evening application of the individual agents, as well as a comparison with tacalcitol.

Results: The pharmacoeconomic evaluation showed a higher cost‐effectiveness of the fixed combination treatment compared to using single agents (morning/evening) and to the tacalcitol. Treatment with the fix combination is more effective and more economic. Additional sensitivity analyses demonstrated that the advantage remains even when assuming a maximum compliance for twice daily usage, and varying the effectiveness of the fixed combination by 10%.

Conclusions: The treatment of mild to moderate psoriasis with a fixed calcipotriol/betamethasone combination is a more cost‐effective treatment than a treatment with the single agents or tacalcitol monotherapy.
DLQI scores in patients with keloids and hypertrophic scars: a prospective case control study
Authors: Balci Didem Didar , Inandi Tacettin , Dogramaci Cigdem Asena , Celik Ebru
Published: February 2009

Background: Keloids and hypertrophic scars (HTS) can cause functional impairment and psychosocial burdens, both of which affects quality of life (QoL). Our aim was to compare Dermatology Life Quality Index (DLQI) scores in patients with keloids and HTS to those of psoriasis patients and normal controls.

Patients and Methods: Forty‐eight consecutive patients with keloids and HTS and 48 with psoriasis vulgaris attending our dermatology outpatient clinic, as well as 48 sex‐ and age‐matched healthy controls completed the DLQI.

Results: Total DLQI scores of patients with keloids and HTS (7.79 ± 5.10) and psoriasis (8.73 ± 5.63) were comparable and significantly higher than that of healthy controls (0.58 ± 0.77). No significant difference were found between patients with psoriasis and patients with keloids and HTS in terms of the total DLQI scores and the subscale scores (p > 0.05) except “treatment” (p < 0.05) sub‐scale scores which were higher in psoriasis.

Conclusions: The QoL of patients with keloids and HTS is impaired as much as that of those with psoriasis. The DLQI questionnaire is a reliable and valid instrument for assessing the QoL in patients with keloids and HTS.
Subcorneal pustulosis with combined lack of IgG/IgM and monoclonal gammopathy type IgA/Kappa
Authors: Rasch Astrid , Schimmer Melanie , Sander Christian A.
Published: February 2009

Subcorneal pustulosis (Sneddon‐Wilkinson disease) is a rare inflammatory neutrophilic dermatosis. While subcorneal pustulosis is often associated with an IgA gammopathy, the combined lack of IgG/IgM seen in our case is rare. An 83‐year‐old man with combined lack of IgG/IgM and monoclonal gammopathy type IgA/Kappa presented with subcorneal pustules. Intravenous immunoglobulin therapy led to complete regression and might be another therapeutic option.
Parental and perinatal factors affecting childhood anthropometry of very‐low‐birth‐weight premature infants: a population‐based survey
Authors: Makhoul Imad R , Awad Eman , Tamir Ada , Weintraub Zalman , Rotschild Avi , Bader David , Yurman Shmuel , Reich Dan , Bental Yoram , Jammalieh Jeryes , Smolkin Tatiana , Sujov Polo , Hochberg Ze'ev
Published: February 2009

Background: The perinatal–neonatal course of very‐low‐birth‐weight (VLBW) infants might affect their childhood growth. We evaluated the effect of parental anthropometry and perinatal and neonatal morbidity of VLBW neonates on their childhood growth.

Methods: We obtained parental anthropometry, height and weight at age 6–10.5 years of 334 children born as VLBW infants. Parental, perinatal and neonatal data of these children were tested for association with childhood anthropometry.

Results: (1) Maternal and paternal weight standard deviation score (SDS) and discharge weight (DW) SDS were associated with childhood weight SDS (R2= 0.111, p < 0.00001); (2) Maternal and paternal height SDS, corrected gestational age (GA) at discharge, maternal assisted reproduction and SGA status were associated with childhood height SDS (R2= 0.208, p < 0.00001); (3) paternal weight SDS, DW SDS and surfactant therapy were associated with childhood body mass index (BMI) SDS (R2= 0.096, p < 0.00001). 31.1% of VLBW infants had DW SDS < −1.88, and are to be considered small for gestational age (‘SGA’). One quarter of these infants did not catch up by age 6–10.5 years.

Conclusion: Childhood anthropometry of VLBW infants depends on parental anthropometry, postnatal respiratory morbidity and growth parameters at birth and at discharge. Almost one‐third of VLBW premature infants had growth restriction at discharge from neonatal intensive care unit (NICU), a quarter of whom did not catch up by age 6–10.5 years.
Left‐sided gastroschisis with meromelia of the limbs: A rare association
Authors: Punia Raj Pal Singh , Dhingra Neerja , Chopra Rajan , Mohan Harsh , Huria Anju
Published: February 2009

Gastroschisis is a malformation of the anterior abdominal wall that presents as herniation of abdominal contents through a paramedian abdominal defect, usually to the right side of the midline. The defect involves all the layers of the abdominal wall and there is no membranous covering. In newborns with isolated gastroschisis, the overall prognosis is very good. In rare cases, gastroschisis is associated with other congenital malformations, making the prognosis worse. We herein report a rare case of left‐sided gastroschisis associated with meromelia of the limbs.
Heart changes in 17‐day‐old fetuses of diabetic ICR (Institute of Cancer Research) mothers: Improvement with maternal immune stimulation
Authors: Claudio Gutierrez Juan , Prater Mary Renee , Hrubec Theresa C. , Smith Bonnie J. , Freeman Larry E. , Holladay Steven D.
Published: February 2009

Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non‐specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFNγ) has been associated with protection against birth malformations. Using a diabetic mouse model, late‐gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non‐diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFNγ. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment‐induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One‐way parametric and non‐parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P < 0.05). Maternal hyperglycemia altered morphology of the late‐gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFNγ protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear.
Critical periods for the teratogenicity of immune‐suppressant Leflunomide in mice
Authors: Fukushima Ryou , Kanamori Susumu , Hirashiba Masahiro , Hishikawa Atsuko , Muranaka Ri‐ichi , Kaneto Masako , Kitagawa Hiroshi
Published: February 2009

Leflunomide has inhibitory effects on dihydroorotate‐dehydrogenase activity and protein tyrosine kinase activity. In the present study, a single dose of 50 mg/kg Leflunomide was administered to pregnant mice on one of gestation days (GD)6–11. Characteristic external malformations were craniofacial defects following dosing on GD7, cleft palate on GD9, cleft palate and limb and tail deformities on GD10, and limb deformities on GD11. Skeletal examination revealed cervical to caudal vertebral malformations after treatment on GD7, GD8, GD9 or GD10. In the viscera, cardiovascular deformities were observed in the GD7 and GD9 Leflunomide‐treated groups. These results demonstrate that multiple malformations were seen in various organs and most of the malformations observed appeared to be developmental stage‐specific responses to Leflunomide treatment.
Ribonuclease H: the enzymes in eukaryotes
Authors: Cerritelli Susana M. , Crouch Robert J.
Published: February 2009

Ribonucleases H are enzymes that cleave the RNA of RNA/DNA hybrids that form during replication and repair and which could lead to DNA instability if they were not processed. There are two main types of RNase H, and at least one of them is present in most organisms. Eukaryotic RNases H are larger and more complex than their prokaryotic counterparts. Eukaryotic RNase H1 has acquired a hybrid binding domain that confers processivity and affinity for the substrate, whereas eukaryotic RNase H2 is composed of three different proteins: the catalytic subunit (2A), similar to the monomeric prokaryotic RNase HII, and two other subunits (2B and 2C) that have no prokaryotic counterparts and as yet unknown functions, but that are necessary for catalysis. In this minireview, we discuss some of the most recent findings on eukaryotic RNases H1 and H2, focusing on the structural data on complexes between human RNase H1 and RNA/DNA hybrids that had provided great detail of how the hybrid binding‐ and RNase H‐domains recognize and cleave the RNA strand of the hybrid substrates. We also describe the progress made in understanding the in vivo function of eukaryotic RNases H. Although prokayotes and some single‐cell eukaryotes do not require RNases H for viability, in higher eukaryotes RNases H are essential. Rnaseh1 null mice arrest development around E8.5 because RNase H1 is necessary during embryogenesis for mitochondrial DNA replication. Mutations in any of the three subunits of human RNase H2 cause Aicardi–Goutières syndrome, a human neurological disorder with devastating consequences.
Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription
Authors: Champoux James J. , Schultz Sharon J.
Published: February 2009

Retroviral reverse transcriptases possess both a DNA polymerase and an RNase H activity. The linkage with the DNA polymerase activity endows the retroviral RNases H with unique properties not found in the cellular counterparts. In addition to the typical endonuclease activity on a DNA/RNA hybrid, cleavage by the retroviral enzymes is also directed by both DNA 3′ recessed and RNA 5′ recessed ends, and by certain nucleotide sequence preferences in the vicinity of the cleavage site. This spectrum of specificities enables retroviral RNases H to carry out a series of cleavage reactions during reverse transcription that degrade the viral RNA genome after minus‐strand synthesis, precisely generate the primer for the initiation of plus strands, facilitate the initiation of plus‐strand synthesis and remove both plus‐ and minus‐strand primers after they have been extended.
Cobalamin uptake and reactivation occurs through specific protein interactions in the methionine synthase–methionine synthase reductase complex
Authors: Wolthers Kirsten R. , Scrutton Nigel S.
Published: February 2009

Human methionine synthase reductase (MSR), a diflavin enzyme, restores the activity of human methionine synthase through reductive methylation of methionine synthase (MS)‐bound cob(II)alamin. Recently, it was also reported that MSR enhances uptake of cobalamin by apo‐MS, a role associated with the MSR‐catalysed reduction of exogenous aquacob(III)alamin to cob(II)alamin [Yamada K, Gravel RA, TorayaT & Matthews RG (2006) Proc Natl Acad Sci USA103, 9476–9481]. Here, we report the expression and purification of human methionine synthase from Pichia pastoris. This has enabled us to assess the ability of human MSR and two other structurally related diflavin reductase enzymes (cytochrome P450 reductase and the reductase domain of neuronal nitric oxide synthase) to: (a) stimulate formation of holo‐MS from aquacob(III)alamin and the apo‐form of MS; and (b) reactivate the inert cob(II)alamin form of MS that accumulates during enzyme catalysis. Of the three diflavin reductases studied, cytochrome P450 reductase had the highest turnover rate (55.5 s−1) for aquacob(III)alamin reduction, and the reductase domain of neuronal nitric oxide synthase elicited the highest specificity (kcat/Km of 1.5 × 105 m−1·s−1) and MSR had the lowest Km (6.6 μm) for the cofactor. Despite the ability of all three enzymes to reduce aquacob(III)alamin, only MSR (the full‐length form or the isolated FMN domain) enhanced the uptake of cobalamin by apo‐MS. MSR was also the only diflavin reductase to reactivate the inert cob(II)alamin form of purified human MS (Kact of 107 nm) isolated from Pichia pastoris. Our work shows that reactivation of cob(II)alamin MS and incorporation of cobalamin into apo‐MS is enhanced through specific protein–protein interactions between the MSR FMN domain and MS.
Association between access block and time to parenteral opioid analgesia in renal colic: A pilot study
Authors: Chu Kevin , Brown Anthony
Published: February 2009

Objective:  To seek an association between access block and time to parenteral opioid analgesia (POA) in ED patients presenting with renal colic.

Methods:  Renal colic patients given POA were retrospectively identified over 3 months. Time of administration of POA was abstracted from patients' charts. Access block data, time of arrival and demographics were retrieved electronically. A logistic regression was used to seek an association between time to POA (dichotomized into <1 h and >1 h of arrival) with daily access block (proportion of patients requiring hospital admission in a 24 h period who have a total ED time >8 h, dichotomized at its median), time of administration of POA (00.00–07.59 hours [T1], 08.00–15.59 hours [T2], 16.00–23.59 hours [T3] ), age and sex.

Results:  Of 69 patients, 42 (60.1%, 95% CI 51–70%) received POA within 1 h. Access block occurred daily (median 28.8%, range 6.8–53.1%). Mean hourly ED attendance rates for all patients during T1, T2 and T3 were 4.0, 11.7 and 7.8 patients/h respectively. As predictors of time to POA (>1 h vs≤1 h), the adjusted OR for access block (≥29% vs <29%) was 1.0 (95% CI 0.4–2.9), T3 versus T2 was 5.0 (95% CI 1.4–17.7), T1 versus T2 was 1.0 (95% CI 0.3–23.8), age (≥47 years vs <47 years) was 0.8 (95% CI 0.3–2.3) and for sex (female vs male) was 0.4 (95% CI 0.1–1.6).

Conclusion:  Time to POA was related to time of administration, but not to access block. Access block might be too crude a measure to quantify ED overcrowding, and so its influence on time to POA may not be exhibited.
Procedural sedation in children in the emergency department: A PREDICT study
Authors: Borland Meredith , Esson Amanda , Babl Franz , Krieser David
Published: February 2009

Objective: To investigate current procedural sedation practice and compare clinical practice guidelines (CPG) for procedural sedation at Paediatric Research in Emergency Departments International Collaborative (PREDICT) sites. This will determine areas for improvement and provide baseline data for future multicentre studies.

Methods: A questionnaire of specialist emergency physicians regarding demographics, general procedural sedation practice and specific sedation agents given to children. CPG for general sedation and sedation agents were obtained for each site.

Results: Seventy‐five (71%) useable surveys returned from 105 potential respondents. Most commonly used agents were nitrous oxide (N2O) (75, 100%), ketamine (total 72, 96%; i.v. 59, 83% and i.m. 22, 31%) and midazolam (total 68, 91%; i.v. 52, 81%, oral 47, 73%, intranasal 26, 41% and i.m. 6, 9%). Sedation was used for therapeutic and diagnostic procedures. Forty‐three (57%) used formal sedation records and sedation checklists and thirty‐one (41%) respondents reported auditing sedations. Four sites ran staff education and competency programmes. Nine sites had general sedation CPG, eight for ketamine, nine for N2O, eight for midazolam (four parenteral, five oral and six intranasal) and three for fentanyl. No site had a guideline for propofol administration.

Conclusion: Procedural sedation in this research network commonly uses N2O, ketamine and midazolam for a wide range of procedures. Areas of improvement are the lack of guidelines for certain agents, documentation, staff competency training and auditing processes. Multicentre research could close gaps in terms of age cut‐offs, fasting times and optimal indications for various agents.
National Differences in Patient–Clinician Communication Regarding Hypoactive Sexual Desire Disorder
Authors: Goldstein Irwin , Lines Carol , Pyke Robert , Scheld Jan Stefan
Published: February 2009

Introduction

Despite greater awareness and openness about sexual problems among women, many patients remain reserved about discussing such problems with their doctor. Clinicians are often reluctant to ask about sexual dysfunction.

Aim

To learn how clinicians can communicate more effectively with patients who have hypoactive sexual desire disorder (HSDD) by exploring the language used by patients and clinicians in the United States, France, and Germany when describing the symptoms, causes, and correlates of HSDD.

Methods

Independently conducted face-to-face, semi-structured interview with 127 clinicians involved in the treatment of female sexual dysfunction (FSD) and 95 women with FSD who were screened for HSDD using a brief adaptation of the Sexual Interest and Desire Inventory-Female®.

Main Outcome Measure

Language used by clinicians and patients.

Results

Clinicians and patients found FSD a difficult subject to discuss. Recognition of the term HSDD was low, with “decrease in sexual desire” preferred. Distress, currently integral to the diagnosis of HSDD, was an unpopular term. It implied to participants a state of fear or anxiety and a degree of severity not reflected by their feelings about the condition. Key feelings conveyed by patients included low self-esteem, frustration, confusion, dissatisfaction/discontent, concern, anger, embarrassment, stress, depression, and a sense of being incomplete. Clinicians were frustrated by the lack of effective treatment options for HSDD, which contributed to reluctance in discussing sexual health with patients. Patients were increasingly motivated to seek treatment, with an “improvement in level of desire” identified as the most meaningful treatment outcome, rather than an increase in satisfying sexual events.

Conclusions

More carefully constructed definitions, based on understanding the common language between clinicians and patients, would improve doctor–patient communications and set common expectations for treatment of HSDD. Defining HSDD in simpler, non-psychiatric terms such as “decreased sexual desire” illustrates how HSDD can be translated into more patient-friendly language.
Dynamical constraints on the neutron star mass in EXO 0748-676
Authors: Muñoz-Darias T. , Casares J. , O'Brien K. , Steeghs D. , Martínez-Pais I. G. , Cornelisse R. , Charles P. A.
Published: February 2009

We present Very Large Telescope (VLT) intermediate resolution spectroscopy of UY Vol, the optical counterpart of the low mass X-ray binary (LMXB) X-ray burster EXO 0748-676. By using Doppler tomography we detect narrow components within the broad He iiλ4542, λ4686 and λ5412 emission lines. The phase, velocity and narrowness of these lines are consistent with their arising from the irradiated hemisphere of the donor star, as has been observed in a number of LMXBs. Under this assumption, we provide the first dynamical constraints on the stellar masses in this system. In particular, we measure K2 > Kem= 300 ± 10 km s-1. Using this value, we derive 1 M⊙≤M1≤ 2.4 M⊙ and 0.11 ≤q≤ 0.28. We find M1≥ 1.5 M⊙ for the case of a main sequence companion star. Our results are consistent with the presence of a massive neutron star as has been suggested by Özel (2006), although we cannot discard the canonical value of ∼1.4 M⊙.