bluuebunny/crossref_metadata_2025 huggingface dataset:
The Practice and Process of Delivering Integration through Strategic Planning
Authors: Jarzabkowski Paula , Balogun Julia
Published: July 2009

abstract

This paper explains how strategic planning is able to deliver strategic integration within organizations. While communication and participation within planning processes are perceived to have an integrative effect, we argue that these effects are unlikely to arise simply from bringing people together. Rather, we suggest that, given the varying interests of actors in different business units, integration will only arise from active negotiations and compromises between these actors. The paper is based upon a case of strategic planning in a multinational that was attempting to develop greater strategic integration across Europe. Drawing upon an activity theory framework, we examine how a common strategy emerges over time through modifications to the planning process and to different actors' roles within it. The findings are used to develop a process model that shows how different business unit characteristics of planning experience and relative power shape different experiences of communication and participation activities and different processes for achieving integration. The paper concludes with a discussion of how this process model contributes to the literature on strategic planning, political processes of strategy‐making, and strategy‐as‐practice.
The Failure of Political Argument: The Languages of Anti-Fascism and Anti-Totalitarianism in Post-September 11th Discourse
Authors: Shorten Richard
Published: July 2009

Terms like ‘Islamo-fascism’, the ‘anti-totalitarian’ case for war in Iraq and the description of religiously motivated political extremism as a ‘new totalitarianism’ were all remarkable features of the political discourse organised around the response to the events of 11 September 2001. They share in common the attempt to ground political commitments and allegiances in two morally charged political languages: anti-fascism and anti-totalitarianism. But why did they fail to connect with the public imagination? This article argues that they were not constructed for present purposes so much as appropriated. Yet their projected consumption by a broader public turned on the feasibility of effecting conceptual change to accommodate new meanings and applications. The failure, in this case, to meet the standards thereby required suggests that an important dimension of the response to September 11th is the failure of political argument. It is proposed that this has implications more broadly for the relation between political theory and political rhetoric.
Privatised Keynesianism: An Unacknowledged Policy Regime
Authors: Crouch Colin
Published: July 2009

There have now been two successive policy regimes since the Second World War that have temporarily succeeded in reconciling the uncertainties and instabilities of a capitalist economy with democracy's need for stability for people's lives and capitalism's own need for confident mass consumers. The first of these was the system of public demand management generally known as Keynesianism. The second was not, as has often been thought, a neo-liberal turn to pure markets, but a system of markets alongside extensive housing and other debt among low- and medium-income people linked to unregulated derivatives markets. It was a form of privatised Keynesianism. This combination reconciled capitalism's problem, but in a way that eventually proved unsustainable. After its collapse there is debate over what will succeed it. Most likely is an attempt to re-create it on a basis of corporate social responsibility.
Headlong into the Polanyian Dilemma: The Impact of Middle-Class Moral Panic on the British Government's Response to the Sub-prime Crisis
Authors: Watson Matthew
Published: July 2009

This article focuses on the discursive construction in Britain of a middle-class moral panic occasioned by the distress caused to self-styled ‘responsible mortgage borrowers’ by falling house prices. In the context of the move towards asset-based welfare the sub-prime crisis manifested itself most obviously in the popular consciousness as a threat to housing market wealth. The Labour government used the political space opened up by the narrative of middle-class moral panic in order to protect banks' balance sheets from the consequences of their own failed investments in mortgage-backed securities. The ensuing arrangements immunised banks from the implications of market self-regulation in the first-phase response to the sub-prime crisis while simultaneously allowing them to continue to impose the experience of market self-regulation on their customers. An increasingly asymmetric approach to banking regulation has arisen analogous to that which Karl Polanyi associated with the contradictory co-existence of market and non-market forms.
The other Side of the Coin: Reading the Politics of the 2008 Financial Tsunami
Authors: Preston Peter
Published: July 2009

In the spring of 2009, long months after the September 2008 financial tsunami had begun its destructive journey around the financial machineries of the global system, the governing party of the United Kingdom, one of two countries whose financial centres had precipitated all the trouble, is still in place, notwithstanding the almost audible sound of a population tapping its collective foot as it awaits an electoral opportunity to wreak a measure of revenge. But the electorate is condemned to wait upon the convenience of the government and administrative machineries that are responsible for the debacle. This seems unreasonable. One might ask how is this possible and what—speculatively—could happen to improve matters; that is, one can ask how the elite's insulating machineries might be reduced in order to bring them more routinely within the reach of the judgements of the electorate.
Genes for Psychosis and Creativity
Authors: Kéri Szabolcs
Published: July 2009

Why are genetic polymorphisms related to severe mental disorders retained in the gene pool of a population? A possible answer is that these genetic variations may have a positive impact on psychological functions. Here, I show that a biologically relevant polymorphism of the promoter region of the neuregulin 1 gene (SNP8NRG243177/rs6994992) is associated with creativity in people with high intellectual and academic performance. Intriguingly, the highest creative achievements and creative-thinking scores were found in people who carried the TIT genotype, which was previously shown to be related to psychosis risk and altered prefrontal activation.
Language That Puts You in Touch With Your Bodily Feelings
Authors: Foroni Francesco , Semin Gün R.
Published: July 2009

Observing and producing a smile activate the very same facial muscles. In Experiment 1, we predicted and found that verbal stimuli (action verbs) that refer to emotional expressions elicit the same facial muscle activity (facial electromyography) as visual stimuli do. These results are evidence that language referring to facial muscular activity is not amodal, as traditionally assumed, but is instead bodily grounded. These findings were extended in Experiment 2, in which subliminally presented verbal stimuli were shown to drive muscle activation and to shape judgments, but not when muscle activation was blocked. These experiments provide an important bridge between research on the neurobiological basis of language and related behavioral research. The implications of these findings for theories of language and other domains of cognitive psychology (e.g., priming) are discussed.
Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD)
Authors: Zhou J , Li PCK , Kumarasamy N , Boyd M , Chen YMA , Sirisanthana T , Sungkanuparph S , Oka S , Tau G , Phanuphak P , Saphonn V , Zhang FJ , Omar SFS , Lee CKC , Ditangco R , Merati TP , Lim PL , Choi JY , Law MG , Pujari S ,   on behalf of the TREAT Asia HIV Observational Database
Published: July 2009

Objective
The aim of the study was to examine the rates and predictors of treatment modification following combination antiretroviral therapy (cART) failure in Asian patients with HIV enrolled in the TREAT Asia HIV Observational Database (TAHOD).

Methods
Treatment failure (immunological, virological and clinical) was defined by World Health Organization criteria. Countries were categorized as high or low income by World Bank criteria.

Results
Among 2446 patients who initiated cART, 447 were documented to have developed treatment failure over 5697 person‐years (7.8 per 100 person‐years). A total of 253 patients changed at least one drug after failure (51.6 per 100 person‐years). There was no difference between patients from high‐ and low‐income countries [adjusted hazard ratio (HR) 1.02; P=0.891]. Advanced disease stage [Centers for Disease Control and Prevention (CDC) category C vs. A; adjusted HR 1.38, P=0.040], a lower CD4 count (≥51 cells/μL vs. ≤50 cells/μL; adjusted HR 0.61, P=0.022) and a higher HIV viral load (≥400 HIV‐1 RNA copies/mL vs. <400 copies/mL; adjusted HR 2.69, P<0.001) were associated with a higher rate of treatment modification after failure. Compared with patients from low‐income countries, patients from high‐income countries were more likely to change two or more drugs (67%vs. 49%; P=0.009) and to change to a protease‐inhibitor‐containing regimen (48%vs. 16%; P<0.001).

Conclusions
In a cohort of Asian patients with HIV infection, nearly half remained on the failing regimen in the first year following documented treatment failure. This deferred modification is likely to have negative implications for accumulation of drug resistance and response to second‐line treatment. There is a need to scale up the availability of second‐line regimens and virological monitoring in this region.
Promoting Leisure Physical Activity Participation among Adults with Intellectual Disabilities: Validation of Self‐Efficacy and Social Support Scales
Authors: Peterson Jana J. , Andrew Peterson N. , Lowe John B. , Nothwehr Faryle K.
Published: July 2009

Background  Many individuals with intellectual disabilities are not sufficiently active for availing health benefits. Little is known about correlates of physical activity among this population on which to build health promotion interventions.

Materials and Methods  We developed scales for measurement of self‐efficacy and social support for leisure physical activity among adults with intellectual disabilities. Study participants were 152 adults with mild to moderate intellectual disabilities.

Results  The scales demonstrated good internal consistency and fair to excellent test–re‐test reliability. Confirmatory factor analyses revealed good fit for each of the scales, supporting the hypothesized structure of each. Scales also correlated with self‐reported leisure physical activity, providing evidence of construct validity.

Conclusions  Studies of physical activity correlates are needed to formulate evidence‐based programmes to promote physical activity participation. This measure demonstrated good psychometric properties, and will be useful for examining social support and self‐efficacy for physical activity by adults with intellectual disabilities.
Karyotyping or rapid aneuploidy detection in prenatal diagnosis? The different views of users and providers of prenatal care
Authors: Boormans EMA , Birnie E , Bilardo CM , Oepkes D , Bonsel GJ , van Lith JMM
Published: July 2009

Developments in prenatal diagnosis raise the question which test strategy should be implemented. However, preferences of women and caregivers are underexposed. This study investigates what kind of prenatal test pregnant women and caregivers prefer and if differences between the groups exist, using self‐report questionnaires. Women preferred either karyotyping (50%) or rapid aneuploidy detection (43%). Caregivers opted for the latter (78%). A test targeted on Down syndrome was the least preferred in both groups. We recommend the use of individualised choice for genetic test in prenatal diagnosis, overcoming the existing differences in preferences between women and caregivers.
Obstetric interventions for babies born before 28 weeks of gestation in Europe: results of the MOSAIC study
Authors: Kollée LAA , Cuttini M , Delmas D , Papiernik E , den Ouden AL , Agostino R , Boerch K , Bréart G , Chabernaud J‐L , Draper ES , Gortner L , Künzel W , Maier RF , Mazela J , Milligan D , Van Reempts P , Weber T , Zeitlin J ,   the MOSAIC Research group
Published: July 2009

Objective  To describe obstetric intervention for extremely preterm births in ten European regions and assess its impact on mortality and short term morbidity.

Design  Prospective observational cohort study.

Setting  Ten regions from nine countries participating in the ‘Models of Organising Access to Intensive Care for Very Preterm Babies in Europe’ (MOSAIC) project.

Population  All births from 22 to 29 weeks of gestation (n = 4146) in 2003, excluding terminations of pregnancy.

Methods  Comparison of three obstetric interventions (antenatal corticosteroids, antenatal transfer and caesarean section for fetal indication) rates at 22–23, 24–25 and 26–27 weeks to that at 28–29 weeks and the association of the level of intervention with pregnancy outcome.

Main outcome measures  Use of antenatal corticosteroids, antenatal transfer and caesarean section by two‐week gestational age groups as well as a composite score of these three interventions. Outcomes included stillbirth, in‐hospital mortality and intraventricular haemorrhage (IVH) grades III and IV and/or periventricular leucomalacia (PVL) and bronchopulmonary dysplasia (BPD).

Results  There were large differences between regions in interventions for births at 22–23 and 24–25 weeks. Differences were most pronounced at 24–25 weeks; in some regions these babies received the same care as babies of 28–29 weeks, whereas elsewhere levels of intervention were distinctly lower. Before 26 weeks and especially at 24–25 weeks, there was an association between the composite intervention score and mortality. No association was observed at 26–27 weeks. For survivors at 24–25 weeks, the intervention score was associated with higher rates of BPD, but not with IVH or PVL.

Conclusions  There are large differences between European regions in obstetric practices at the lower limit of viability and these are related to outcome, especially at 24–25 weeks.
Changes in Doppler flow velocity waveforms and fetal size at 20 weeks gestation among cigarette smokers
Authors: Kho EM , North RA , Chan E , Stone PR , Dekker GA , McCowan LME ,   on behalf of the SCOPE consortium
Published: July 2009

Objectives  To compare umbilical and uterine artery Doppler waveforms and fetal size at 20 weeks between smokers and nonsmokers.

Design  Prospective cohort study.

Setting  Auckland, New Zealand and Adelaide, Australia.

Population  Nulliparous participants in the Screening for Pregnancy Endpoints (SCOPE) study.

Methods  Self‐reported smoking status was determined at 15 ± 1 weeks’ gestation. At the 20 ± 1 week anatomy scan, uterine and umbilical Doppler resistance indices (RI) and fetal measurements were compared between smokers and nonsmokers.

Main outcomes measures  Umbilical and mean uterine artery Doppler RI values, abnormal umbilical and uterine Doppler (RI > 90th centile) and fetal biometry.

Results  Among the 2459 women, 248 (10%) were smokers. Smokers had higher umbilical RI [0.75 (SD 0.06) versus 0.73 (0.06), P < 0.0001] and mean uterine RI [0.59 (0.09) versus 0.56 (0.10), P < 0.0001]. They were twice as likely to have an abnormal umbilical Doppler at 20 weeks compared with nonsmokers [n = 35 (14.6%) versus n = 156 (7.2%), OR 2.21, 95% CI 1.49–3.27]. This effect remained significant after adjusting for age, ethnicity, marital status, employment and BMI (adjusted OR 1.62, 95% CI 1.03–2.54). Smokers were more likely to have an abnormal mean uterine RI [n = 33 (13.7%) versus n = 198 (9.2%), OR 1.57, 95% CI 1.06–2.33], but this association was not significant after adjusting for confounders. Fetuses of women who smoked had a small reduction in femur length and estimated weight compared with nonsmokers.

Conclusions  At 20 weeks’ gestation, women who smoke have higher umbilical artery RI, a surrogate measure for an abnormal placental villous vascular tree. This may contribute to later fetal growth restriction among smokers. Further research is needed to explore the clinical significance of these findings.
GEOCHEMICAL AND ENGINEERING GEOLOGICAL PROPERTIES OF THE VOLCANIC TUFFS USED IN THE ETRUSCAN TOMBS OF NORCHIA (NORTHERN LATIUM, ITALY) AND A STUDY OF THE FACTORS RESPONSIBLE FOR THEIR RAPID SURFACE AND STRUCTURAL DECAY
Authors: CICCIOLI P. , CATTUTO C. , PLESCIA P. , VALENTINI V. , NEGROTTI R.
Published: July 2009

The geochemical and engineering geological properties of the tuffs used in the rock‐cut cliff tombs of the Etruscan necropolis of Norchia were investigated to evaluate their susceptibility to different weathering agents and confirm their origin. For the first time, materials were characterized by X‐ray powder diffraction (XRD), Fourier‐transform infrared spectroscopy (FT–IR), thermogravimetric analyses (TGA, DGA and DTG), scanning electron microscopy (SEM–EDS) and energy‐dispersive X‐ray fluorescence (ED–XRF), and their different origins confirmed. Tests of material properties indicate that both tuffs are poorly durable, but one of them is less susceptible to weathering. Although tombs made with the more resistant material show limited surface weathering, they undergo severe structural damage because of stress release and plant root infiltration. This, combined with the microclimatic conditions established inside river canyons, can trigger rock falls, leading ultimately to the complete destruction of these tombs.
Suicide among the elderly in mainland China
Authors: LI Xia , XIAO Zeping , XIAO Shifu
Published: July 2009

Suicide in mainland China shows unique demographic patterns with age: the over‐65 age group has the highest rate of completed suicide, reaching 44.3–200 per 100 000, which is four to five times higher than the Chinese general population. Rural suicide rates among the elderly are three to five times higher than the urban rates. The gender ratio of suicide in the elderly shows a reversal to those younger than 60 years of age in China. In addition, suicide methods and causes are different from those in Western countries. In the present paper, the profile of suicide among the elderly in China is delineated, including the prevalence, characteristics, underlying reasons and measures of preventing it.
What is ‘early onset dementia’?
Authors: MIYOSHI Koho
Published: July 2009

There are two types of dementia with early onset: (i) presenile dementias; and (ii) senile dementias with early onset. Most patients who develop dementia before 65 years of age have Alzheimer's disease (AD). The remainder are likely to have vascular dementia (VaD), frontotemporal dementia, head injury, alcohol intoxication, or metabolic disorder. Presenile dementias, caused by frontotemporal lobar degeneration, progressive supranuclear palsy, and corticobasal degeneration, usually occur in patients of presenile and are rarely seen in patients of senile age. Although the factors responsible for the accelarted onset of the illness are not fully known, genetic abnormalities appear to be important in some types of presenile dementia, such as frontotemporal dementia with parkinsonism linked to chromosome 17. Conversely, senile dementias such as sporadic AD and VaD commonly occur in patients of senile age. These disorders may also occur in patients of presenile age, although less frequently. Alzheimer's disease was originally classified as a ‘presenile dementia’. Since the 1980s, ‘senile dementia of Alzheimer type’ (SDAT) and ‘Alzheimer's disease’ have been considered to belong to the same pathological entity and both are now known as ‘dementia of Alzheimer's type (DAT)’ or merely ‘Alzheimer's disease’. Rapid progression of cognitive impairment with neuropsychological syndromes and neurological symptoms has been considered a characteristic of early onset AD. However, recently, neurological symptoms such as spastic paraparesis, seizures, and myoclonic convulsions have been reported to occur infrequently in early onset AD, although language problems and visuospatial dysfunctions are common. There are at least three dominant genes that have been identified in cases of familial Alzheimer's disease with early onset, namely the amyloid precursor gene (APP), and the genes encoding presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Therefore, genetic abnormalities are important factors contributing to the earlier onset of the illness. It is also important to investigate the pathophysiological mechanism in relation to genetic abnormalities, environmental factors, physical illnesses, and metabolic disturbances to understand the processes underlying the development of dementia with early onset.
Neuroimaging studies in patients with Charles Bonnet Syndrome
Authors: KAZUI Hiroaki , ISHII Ryouhei , YOSHIDA Tetsuhiko , IKEZAWA Koji , TAKAYA Masahiko , TOKUNAGA Hiromasa , TANAKA Toshihisa , TAKEDA Masatoshi
Published: July 2009

Charles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. Many psychiatrists have taken an interest in CBS because this syndrome could provide clues to the mechanisms underlying visual hallucinations. In the present paper, we review previous neuroimaging studies in patients with CBS and summarize the results of these studies. There could be a fundamental dysfunction in the primary and secondary visual cortices in some patients with CBS, and transient cortical activation occurs in the inferior lateral temporal cortex during the appearance of visual hallucinations in CBS patients. External visual stimuli are perceived in the retina and are transmitted to the primary visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to the secondary visual cortex (BA 18) and then to the visual association cortices (BA 19 and BA 37). In general, our perception of external visual stimuli normally has an inhibitory effect on the endogenous activation of the visual cortex. Visual loss due to certain conditions, of which eye pathology is the most commonly postulated in CBS patients, produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon). The results of previous neuroimaging studies suggest that the cortical release phenomenon hypothesis for the occurrence of visual hallucinations in patients with CBS is plausible. In addition, the results indicate that not only eye pathology, but also dysfunction in the primary and secondary visual cortices could result in deprivation of external visual stimuli.
Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan
Authors: NOZAWA Motohiro , ICHIMIYA Yosuke , NOZAWA Eiko , UTUMI Yushi , SUGIYAMA Hideki , MURAYAMA Norio , ISEKI Eizo , ARAI Heii
Published: July 2009

Background:  Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease.

Methods:  We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini‐mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated.

Results:  The Revised Hasegawa Dementia Scale and mini‐mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials.

Conclusions:  The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer‐term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day.
Hypoxia‐enhanced wound‐healing function of adipose‐derived stem cells: Increase in stem cell proliferation and up‐regulation of VEGF and bFGF
Authors: Lee Eun Young , Xia Ying , Kim Won‐Serk , Kim Myoung Hee , Kim Tae Hwan , Kim Kea Jeung , Park Byung‐Soon , Sung Jong‐Hyuk
Published: July 2009

Adipose‐derived stem cells (ADSCs) have been shown to induce wound‐healing effects. Because inflammation near the wound area induces oxygen deficiency, it is interesting to elucidate the effect of hypoxia on the function of ADSCs. In this work, we asked: (1) does hypoxia alter the wound‐healing function of ADSCs? and (2) what are the major factors responsible for the alteration in the wound‐healing function? Effect of hypoxia on the proliferation of ADSCs was first examined that hypoxia (2% O2) enhanced the proliferation of ADSCs in either the presence of serum or in the absence of serum. The conditioned medium of ADSCs harvested under hypoxia (hypoCM) significantly promoted collagen synthesis and the migration of human dermal fibroblasts, compared with that in normoxia (norCM). In the animal studies, hypoCM significantly reduced the wound area compared with norCM. Furthermore, mRNA and protein measurements showed that hypoxia up‐regulated growth factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Inhibition of VEGF and bFGF using neutralizing antibodies reversed the migration of the wounded human dermal fibroblasts and the healing of wounds in animal experiment. Collectively, these results suggest that hypoxia increases the proliferation of ADSCs and enhances the wound‐healing function of ADSCs, at least partly, by up‐regulating the secretion of VEGF and bFGF.
Extracorporeal shock‐wave therapy enhanced wound healing via increasing topical blood perfusion and tissue regeneration in a rat model of STZ‐induced diabetes
Authors: Kuo Yur‐Ren , Wang Chun‐Ting , Wang Feng‐Sheng , Chiang Yuan‐Cheng , Wang Ching‐Jen
Published: July 2009

Extracorporeal shock‐wave therapy (ESWT) has a significant positive effect in accelerating chronic wound healing. However, the bio‐mechanisms operating during ESWT of wounds remain unclear. This study investigated the effectiveness of ESWT in the enhancement of diabetic wound healing. A dorsal skin defect (area, 6 × 5 cm) in a streptozotocin‐induced diabetes rodent model was used. Fifty male Wistar rats were divided into five groups. Group I consisted of nondiabetic control; group II included diabetic control receiving no ESWT; group III included rats that underwent one session of ESWT (ESW‐1) on day 3 (800 impulses at 0.09 mJ/mm2) postwounding; group IV included rats that underwent two sessions of ESWT (ESW‐2) on days 3 and 7; and group V included rats that underwent three sessions of ESWT (ESW‐3) on days 3, 7, and 10. The wound healing was assessed clinically. Blood perfusion scan was performed with laser Doppler. The VEGF, eNOS, and PCNA were analyzed with immunohistochemical stain. The results revealed that the wound size was significantly reduced in the ESWT‐treated rats, especially in the ESW‐2 and ESW‐3 groups, as compared with the control (p<0.01). Blood perfusion was significantly increased after ESWT compared with the controls. Histological findings revealed a significant reduction in the topical pro‐inflammatory reaction in the ESWT group as compared with the control. In immunohistochemical stain, significant increases in VEGF, eNOS, and PCNA expressions were observed in the ESWT group, especially in the ESW‐2 and ESW‐3 groups, as compared with the control. In conclusion, treatment with an optimal session of ESWT significantly enhanced diabetic wound healing associated with increased neo‐angiogenesis and tissue regeneration, and topical anti‐inflammatory response.
Bone marrow mesenchymal stem cells undergo nemosis and induce keratinocyte wound healing utilizing the HGF/c‐Met/PI3K pathway
Authors: Peura Matti , Bizik Jozef , Salmenperä Pertteli , Noro Ariel , Korhonen Matti , Pätilä Tommi , Vento Antti , Vaheri Antti , Alitalo Riitta , Vuola Jyrki , Harjula Ari , Kankuri Esko
Published: July 2009

We previously showed cell–cell contacts of human dermal fibroblasts to induce expression of the hepatocyte growth factor/scatter factor (HGF) in a process designated as nemosis. Now we report on nemosis initiation in bone marrow mesenchymal stem cells (BMSCs). Because BMSCs are being used increasingly in cell transplantation therapy we aimed to demonstrate a functional effect and benefit of BMSC nemosis for wound healing. Nemotic and monolayer cells were used to stimulate HaCaT keratinocyte migration in a scratch‐wound healing assay. Both indicators of nemosis, HGF production and cyclooxygenase‐2 expression, were induced in BMSC spheroids. When compared with a similar amount of cells as monolayer, nemotic cells induced keratinocyte in vitro scratch‐wound healing in a concentration‐dependent manner. The HGF receptor, c‐Met, was rapidly phosphorylated in the nemosis‐stimulated keratinocytes. Nemosis‐induced in vitro scratch‐wound healing was inhibited by an HGF‐neutralizing antibody as well as the small molecule c‐Met inhibitor, SU11274. HGF‐induced in vitro scratch‐wound healing was inhibited by PI3K inhibitors, wortmannin and LY294002, while LY303511, an inactive structural analogue of LY294002, had no effect. Inhibitors of the mitogen‐activated protein kinases MEK/ERK1/2 (PD98059 and U0126), and p38 (SB203580) attenuated HGF‐induced keratinocyte in vitro scratch‐wound healing. We conclude that nemosis of BMSCs can induce keratinocyte in vitro scratch‐wound healing, and that in this effect signaling via HGF/c‐Met is involved.
Determinants of wound healing in bone marrow‐impregnated collagen matrix treatment: Impact of microcirculatory response to surgical debridement
Authors: Ichioka Shigeru , Yokogawa Hideki , Sekiya Naomi , Kouraba Sachio , Minamimura Ai , Ohura Norihiko , Hasegawa Hiromi , Nakatsuka Takashi
Published: July 2009

Although previous reports have suggested the efficacy of autologous bone marrow‐impregnated collagen matrix experimentally and clinically, we occasionally encounter difficult wounds that fail to respond to the treatment. The current study retrospectively investigated the factors that affect clinical outcomes based on the hypothesis that periwound microcirculation may play a significant role. Fifty‐three patients with chronic wounds received surgical debridement, followed by application of an autologous bone marrow‐impregnated collagen matrix. The periwound transcutaneous oxygen tension (TcPO2) was evaluated (n=39). The patients were retrospectively divided into successful and unsuccessful subgroups. Successful treatment was defined as wound closure by spontaneous healing or skin graft. The TcPO2 of the unsuccessful subgroup significantly decreased after debridement while that of the successful subgroup increased. Among various parameters, the TcPO2 at 4 days after debridement showed the strongest association with the success of the treatment. As reference data, we collected the information of the patients (n=22) who received standard wound care, and they showed the same trend wherein the TcPO2 of the unsuccessful subgroup markedly decreased after debridement. Reactivity of the wound microcirculation to increased wound perfusion in response to the surgical debridement might be a key determinant for successful wound healing.
Activation of latent transforming growth factor‐β1 by nitric oxide in macrophages: Role of soluble guanylate cyclase and MAP kinases
Authors: Metukuri Mallikarjuna Reddy , Namas Rajaie , Gladstone Chase , Clermont Thierry , Jefferson Bahiyya , Barclay Derek , Hermus Linda , Billiar Timothy R. , Zamora Ruben , Vodovotz Yoram
Published: July 2009

The inducible nitric oxide (NO) synthase and the cytokine transforming growth factor‐β1 (TGF‐β1), both central modulators of wound healing, interact reciprocally: TGF‐β1 generally suppresses iNOS expression, while NO can induce and activate latent TGF‐β1. We have shown that chemical NO activates recombinant human latent TGF‐β1 by S‐nitrosation of the latency‐associated peptide (LAP), a cleaved portion of pro‐TGF‐β1 that maintains TGF‐β1 in a biologically‐inactive state. We hypothesized that cell‐associated TGF‐β1 could be activated by NO via known NO‐inducible signaling pathways (soluble guanylate cyclase [sGC] and mitogen‐activated protein [MAP] kinases). Treatment of mouse RAW 264.7 macrophage‐like cells with the NO donor S‐nitroso‐N‐acetyl‐D,L‐penicillamine (SNAP) led to a dose‐ and time‐dependent increase in cell‐associated active and latent TGF‐β1, as assessed by quantitative immunocytochemistry for active TGF‐β1 vs. LAP and partially validated by western blot analysis. Treatment with the sGC inhibitor 1,H‐[1,2,4]oxadiazole[4,3‐a]quinoxalon‐1‐one (ODQ) reduced both active and latent TGF‐β1 dose‐dependently. SNAP, in the presence or absence of ODQ or the MAP kinase inhibitors, did not affect steady‐state TGF‐β1 mRNA levels. Treatment with inhibitors specific for JNK1/2, ERK1/2, and p38 MAP kinases suppressed SNAP‐induced active and latent TGF‐β1. Treatment with the cell‐permeable cGMP analog 8‐Br‐cGMP increased both active and latent TGF‐β1. However, TGF‐β1 activation induced by 8‐Br‐cGMP was not blocked by MAP kinase inhibitors. Our findings suggest that NO activates latent TGF‐β1 via activation of sGC and generation of cGMP and separately via MAP kinase activation, and may shed insight into the mechanisms by which both cGMP production and MAP kinase activation enhance wound healing.
Mammalian Diaphanous (mDia) may be involved in the signal transduction of sphingosine‐1‐phosphate on developing actin stress fiber of human fibroblasts
Authors: Syuto Tomoko , Abe Masatoshi , Yokoyama Yoko , Ishikawa Osamu
Published: July 2009

Sphingosine 1‐phosphate (S1P) is a biologically active lipid mediator with many pivotal roles in the regulation of cell growth, migration, differentiation, and apoptosis. However, signal transduction mediated by S1P in human fibroblasts is still unclear. We investigated signal transduction by S1P in human fibroblasts using collagen matrix contraction in order to explore whether or not S1P could be applied for the treatment of skin wound healing. We found that S1P promoted floating collagen matrices' contraction, for the in vitro model of initial phase wound contraction, in which some kinds of G protein, such as Giα, Rac 1, and Rho, were involved. However, Rho‐associated coiled‐coil forming kinase (ROCK) was partially involved in S1P‐promoting floating collagen matrices contraction. Mammalian Diaphanous (mDia) as well as ROCK have been identified to be putative downstream target molecules of Rho. In mDia‐silenced cells, the ROCK inhibitor suppressed actin stress fiber formation regardless of the presence or absence of S1P. Our results indicate that mDia as well as ROCK may be situated downstream of Giα, Rac1, and Rho to induce actin stress fiber development by human fibroblasts stimulated with SIP.
Relationship between lymphangiogenesis and exudates during the wound‐healing process of mouse skin full‐thickness wound
Authors: Shimamura Kimi , Nakatani Toshio , Ueda Aiko , Sugama Junko , Okuwa Mayumi
Published: July 2009

We considered the relationship among exudate, wound area, angiogenesis, lymphangiogenesis, and reepithelialization during wound healing. Full‐thickness wounds were made on the dorsum of mice. The weight of exudate absorbed into the dressing as well as the wound area was determined daily. Sections of the wounds were stained with anti‐LYVE‐1 and CD31 antibodies. Indian ink was injected into the wound for observing the movement of the exudate on days 3, 5, and 7 after wounding. New epithelium completely covered the wound on day 11. The quantity of exudate peaked on day 1, and then rapidly decreased until it was undetectable on day 11. Most of the Indian ink injected into the wound was retained within the wound and did not flow into the surrounding tissue. New blood vessels showed a uniform distribution in the granulation tissue on day 5. New lymphatics appeared in the granulation tissue approximately 2 days later than the blood vessels and they were distributed toward the center of the granulation tissue on day 11. Thus, reduction of exudate from the wound appears to be related to blood vessels, not lymphatics. However, increasing lymphatics may play a role in the late phase of the wound‐healing process.
Advanced glycoxidation products and impaired diabetic wound healing
Authors: Peppa Melpomeni , Stavroulakis Panagiotis , Raptis Sotirios A.
Published: July 2009

Impaired wound healing is an important diabetic complication associated with increased morbidity and mortality. It appears to be the net result of micro‐ and macrovascular disease. Diabetic neuropathy and the resulting loss of protective sensation (LOPS) has been recognized as one of the major causes for delayed healing in diabetic foot ulcer patients. In addition, hyperglycemia and a number of hyperglycemia‐related factors have been linked to impaired diabetic wound healing, including advanced glycation end products (AGE). A large body of evidence from in vitro and in vivo studies and also data from studies using anti‐AGE agents, indicate that AGE may play a role in the pathogenesis of impaired diabetic wound healing. AGE affect the wound healing process either directly by their interference with a variety of components involved or indirectly through their association with diabetic neuropathy and/or angiopathy. However, further studies need to be performed, mostly clinical studies, to evaluate the exact role of AGE in the impaired diabetic wound healing, suggesting new therapeutic approaches.
Clinical Review and Epidemiology of Headache Disorders in US Service Members: With Emphasis on Post‐traumatic Headache
Authors: Neely Edward T. , Midgette Lynn A. , Scher Ann I.
Published: July 2009

Migraine or headache is a common problem in the active duty population, in the recently deployed service members, and is a cardinal symptom of traumatic brain injury. While there is increasing appreciation of the clinical burden of post‐traumatic headache (PTHA) in the military traumatic brain injury population, there remain significant research gaps related to the epidemiology of PTHA, including lack of understanding of natural history, whether there are predisposing factors that predict the development or prognosis of headache post trauma and, most basically, the features that distinguish PTHA from other forms of chronic headache. Although diagnostic criteria for PTHA are included in the International Classification of Headache Disorders, 2nd edition, revised, these criteria are somewhat arbitrary and were not empirically defined. This lack of precision about the PTHA phenotype limits the rigor of observational studies of PTH but does not appear to significantly hamper treatment, provided the treatment involves a multi‐modality approach.
A new strategy to improve the cost‐effectiveness of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis testing of blood donations in sub‐Saharan Africa: a pilot study in Burkina Faso
Authors: Kania Dramane , Sangaré Lassana , Sakandé Jean , Koanda Abdoulaye , Nébié Yacouba Kompingnin , Zerbo Oumarou , Combasséré Alain Wilfried , Guissou Innocent Pierre , Rouet François
Published: July 2009

BACKGROUND: In Africa where blood‐borne agents are highly prevalent, cheaper and feasible alternative strategies for blood donations testing are specifically required.

STUDY DESIGN AND METHODS: From May to August 2002, 500 blood donations from Burkina Faso were tested for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV), syphilis, and hepatitis C virus (HCV) according to two distinct strategies. The first strategy was a conventional simultaneous screening of these four blood‐borne infectious agents on each blood donation by using single‐marker assays. The second strategy was a sequential screening starting by HBsAg. HBsAg‐nonreactive blood donations were then further tested for HIV. If nonreactive, they were further tested for syphilis. If nonreactive, they were finally assessed for HCV antibodies. The accuracy and cost‐effectiveness of the two strategies were compared.

RESULTS: By using the simultaneous strategy, the seroprevalences of HBsAg, HIV, syphilis, and HCV among blood donors in Ouagadougou were estimated to be 19.2, 9.8, 1.6, and 5.2%. No significant difference of HIV, syphilis, and HCV prevalence rates was observed by using the sequential strategy (9.2, 1.9, and 4.7%, respectively). Whatever the strategy used, 157 blood donations (31.4%) were found to be reactive for at least one transfusion‐transmissible agent and were thus discarded. The sequential strategy allowed a cost decrease of €908.6, compared to the simultaneous strategy. Given that approximately there are 50,000 blood donations annually in Burkina Faso, the money savings reached potentially €90,860.

CONCLUSIONS: In resource‐limited settings, the implementation of a sequential strategy appears as a pragmatic solution to promote safe blood supply and ensure sustainability of the system.
Age‐related donor return patterns among first‐time blood donors in the United States
Authors: Notari IV Edward P. , Zou Shimian , Fang Chyang T. , Eder Anne F. , Benjamin Richard J. , Dodd Roger Y.
Published: July 2009

BACKGROUND: Committed repeat donors are vital to the continued success of blood collections, yet the effect of age of first‐time (FT) donation on return behavior is poorly described. Sixteen‐year‐old donors are increasingly allowed to donate and have the highest rates of adverse events, which negatively impacts return behavior.

STUDY DESIGN AND METHODS: Annual cohorts of allogeneic FT donors from 2005 and 2006 were selected within the American Red Cross system and followed for 25 and 13 months, respectively. Return and total yield rates among different age groups were compared.

RESULTS: A total of 2.3 million FT donors from 2005 and 2006 gave 4.2 million donations during the study. Sixteen‐ to 19‐year old FT donors made up 41% of the FT donor base in 2005 and 16‐, 17‐, 18‐, and 19‐year‐olds, respectively, had initial return rates of 62, 52, 35, and 28% and yield rates of 2.0, 1.76, 1.51, and 1.41 over 13 months. Multivariate analysis of FT yield rates shows that younger (16 and 17 years) and older (50+ years) donors, males, blood group O donors, and those without any initial adverse reaction are most likely to return. Increasing severity of donor adverse reactions correlated with a reduction in yield and return rates.

CONCLUSION: FT 16‐year‐old donors had the highest return and yield rates despite the negative impact of increased adverse event rates. Donation at young age is critical to building a cadre of committed repeat donors but donor reactions must be addressed to ensure the donors' well‐being and to sustain return behavior.
Mini buffy coat photopheresis for children and critically ill patients with extracorporeal photopheresis contraindications
Authors: Hackstein Holger , Misterek Joachim , Nockher Angelika , Reiter Alfred , Bein Gregor , Woessmann Willi
Published: July 2009

BACKGROUND: Conventional extracorporeal photopheresis (ECP) has proven efficacy for the treatment of several diseases but is limited to patients with sufficient body weight. A novel simplified mini buffy coat ECP technique that allows treatment of small children and patients with apheresis contraindications has been developed.

STUDY DESIGN AND METHODS: White blood cell (WBC)‐rich buffy coat fractions were prepared from 5 to 8 mL/kg whole blood in a closed system, diluted, and ultraviolet A (UVA)‐irradiated after addition of 8‐methoxypsoralen (8‐MOP). Apoptosis and cell death were analyzed by annexin V and 7‐aminoactinomycin staining. Lymphocyte proliferation was measured after CD3/CD28 and phytohemagglutinin (PHA) stimulation. Autologous residual blood and UVA‐irradiated buffy coat were returned to the patients. Fifty‐six mini buffy coat ECP procedures were applied to three children with acute steroid‐refractory skin graft‐versus‐host disease and apheresis contraindications.

RESULTS: Mean whole blood and buffy coat volumes were 166 (±61.8) and 8 (±1.6) mL, respectively, and resulted in a hematocrit of 2.2% (±0.4) after saline dilution (median ± SD). UVA irradiation of 8‐MOP buffy coat preparations resulted in significant induction of WBC apoptosis at 48‐72 hours (p ≤ 0.006). WBC proliferation was significantly inhibited both after CD3/CD28 stimulation and after PHA stimulation when compared to controls (p ≤ 0.001). No clinical or laboratory side effects were observed during mini ECP procedures and the three patients responded to the therapy.

CONCLUSION: Mini buffy coat ECP induces apoptosis and lymphocyte proliferation inhibition, both of which occur after standard ECP. This study proposes that mini buffy coat ECP be used as a simple and inexpensive alternative to classical ECP in children and adult patients with apheresis contraindications.
Risk for malaria in United States donors deferred for travel to malaria‐endemic areas
Authors: Spencer Bryan , Steele Whitney , Custer Brian , Kleinman Steven , Cable Ritchard , Wilkinson Susan , Wright David
Published: July 2009

BACKGROUND: Deferral for travel to malaria‐endemic areas excludes many blood donors in the United States. Most transfusion‐transmitted malaria is associated with lengthy residence in malaria‐endemic areas rather than routine travel. This study compares the impact of existing deferral requirements to the risk that a presenting donor with malaria travel history harbors malaria parasites under current and hypothetical alternate regulations.

STUDY DESIGN AND METHODS: Deferred donors from six blood centers were sampled to estimate a national cohort of donors deferred annually for malaria travel to different geographic regions. Risk for malaria infection after travel to each region and distribution of incubation periods for each malaria species were estimated for US travelers. Region‐specific travel risks were used to estimate the risk that a presenting blood donor with malaria travel might asymptomatically harbor malaria parasites at different intervals after return to the United States.

RESULTS: Travel to Africa presents risk for malaria infection greater than 1000 times that of travel to malaria‐endemic parts of Mexico, yet Mexico accounts for more than 10 times as many deferred donors. Shortening the deferral period from 12 to 3 months for travelers to Mexico increases the risk of collecting a contaminated unit by only 1 unit per 57 years (sensitivity analysis, 1 every 29‐114 years), at annual gain of more than 56,000 donations.

CONCLUSION: This study provides the first systematic appraisal of the US requirements for donor qualification regarding travel to malarial areas. Consideration should be given to relaxing the guidelines for travel to very‐low‐risk areas such as Mexico.