bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical features of healthcare‐associated pneumonia (HCAP) in a Japanese community hospital: Comparisons among nursing home‐acquired pneumonia (NHAP), HCAP other than NHAP, and community‐acquired pneumonia
Authors: UMEKI KENJI , TOKIMATSU ISSEI , YASUDA CHIE , IWATA ATSUKO , YOSHIOKA DAISUKE , ISHII HIROSHI , SHIRAI RYO , KISHI KENJI , HIRAMATSU KAZUFUMI , MATSUMOTO BUNROKU , KADOTA JUN‐ICHI
Published: May 2011

Background and objective:  More than 100 000 Japanese die of pneumonia every year. The number of people residing in nursing homes is increasing with the ageing of the population. In 2005, the American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) published important guidelines for the management of healthcare‐associated pneumonia (HCAP). In Japan, however, the optimum strategy for management of HCAP is still unclear. The purpose of this study was to clarify the clinical features of patients with HCAP.

Methods:  Patients (n = 202) who were consecutively admitted with a diagnosis of acute pneumonia between October 2007 and September 2009 were retrospectively evaluated. Using the ATS/IDSA guidelines, patients were divided into three groups: a community‐acquired pneumonia (CAP) group (n = 123), a nursing home‐acquired pneumonia (NHAP) group (n = 46) and a HCAP other than NHAP (O‐HCAP) group (n = 33). These groups were then compared with respect to laboratory data, microbiological findings and mortality.

Results:  Thirty‐day mortality in the NHAP group (10.9%) tended to be higher than that in the CAP group (3.3%) or the O‐HCAP group (0%). The pathogens most frequently identified were Streptococcus pneumoniae and Haemophilus influenzae in the CAP group, methicillin‐resistant Staphylococcus aureus and Klebsiella pneumoniae in the NHAP group, and S. pneumoniae and K. pneumoniae in the O‐HCAP group.

Conclusions:  The NHAP group was clinically different from the O‐HCAP group, based on bacteriological examination and mortality rates. In order to accurately diagnose, and formulate optimum treatment strategies for Japanese patients, the categories of HCAP, as specified in the ATS/IDSA guidelines, should not be applied directly either to patients with NHAP or those with O‐HCAP.
Reversibility of impaired nasal mucociliary clearance in smokers following a smoking cessation programme
Authors: CIPULO RAMOS ERCY MARA , DE TOLEDO ALESSANDRA CHOQUETA , XAVIER RAFAELLA FAGUNDES , FOSCO LUCIANA CRISTINA , VIEIRA RODOLFO PAULA , RAMOS DIONEI , JARDIM JOSÉ ROBERTO
Published: May 2011

Background and objective:  Smoking cessation (SC) is recognized as reducing tobacco‐associated mortality and morbidity. The effect of SC on nasal mucociliary clearance (MC) in smokers was evaluated during a 180‐day period.

Methods:  Thirty‐three current smokers enrolled in a SC intervention programme were evaluated after they had stopped smoking. Smoking history, Fagerström's test, lung function, exhaled carbon monoxide (eCO), carboxyhaemoglobin (COHb) and nasal MC as assessed by the saccharin transit time (STT) test were evaluated. All parameters were also measured at baseline in 33 matched non‐smokers.

Results:  Smokers (mean age 49 ± 12 years, mean pack‐year index 44 ± 25) were enrolled in a SC intervention and 27% (n = 9) abstained for 180 days, 30% (n = 11) for 120 days, 49.5% (n = 15) for 90 days or 60 days, 62.7% (n = 19) for 30 days and 75.9% (n = 23) for 15 days. A moderate degree of nicotine dependence, higher education levels and less use of bupropion were associated with the capacity to stop smoking (P < 0.05). The STT was prolonged in smokers compared with non‐smokers (P = 0.002) and dysfunction of MC was present at baseline both in smokers who had abstained and those who had not abstained for 180 days. eCO and COHb were also significantly increased in smokers compared with non‐smokers. STT values decreased to within the normal range on day 15 after SC (P < 0.01), and remained in the normal range until the end of the study period. Similarly, eCO values were reduced from the seventh day after SC.

Conclusions:  A SC programme contributed to improvement in MC among smokers from the 15th day after cessation of smoking, and these beneficial effects persisted for 180 days.
Did central Australian megafaunal extinction coincide with abrupt ecosystem collapse or gradual climate change?
Authors: Murphy Brett P. , Williamson Grant J. , Bowman David M. J. S.
Published: May 2011

Aim  In central Australia, the giant flightless bird Genyornis newtoni disappeared about 45–50 thousand years ago (ka). It has been reported that coincident with this extinction the carbon isotopic composition of preserved eggshells of the extant emu (Dromaius novaehollandiae) shows an abrupt dietary shift from tropical grasses (C4 photosynthesis) to temperate grasses and/or woody browse (C3 photosynthesis). This abrupt shift has been interpreted as signalling ‘ecosystem collapse’ due to landscape burning by humans. We evaluate an alternative interpretation, that the shift in diet was not abrupt, but gradual, and caused by the weakening of the Australian monsoon.

Location  Lake Eyre, central Australia.

Methods  We re‐analysed a large, published dataset of emu diet δ13C (inferred from δ13C of preserved eggshells) spanning the last 140,000 years, using time‐series analysis. Using Akaike's information criterion, we compared two contrasting models: (1) there was an abrupt shift in δ13C coincident with the extinction of Genyornis, assumed 47.5 ka; and (2) there was a gradual shift in δ13C, correlated with reconstructed water level in Lake Eyre, a proxy for monsoon intensity.

Results  There was little evidence of an abrupt shift in emu diet δ13C about 45–50 ka, but δ13C appeared to steadily decrease between about 80 and 30 ka. Indeed, the model representing a correlation between δ13C and lake level was more than seven times more likely than the model representing an abrupt shift at 47.5 ka.

Main conclusions  The emu eggshell isotopic record from Lake Eyre does not support the hypothesis that landscape burning by humans transformed a savanna−grassland mosaic into the modern desert scrub, contributing to the extinction of Genyornis. While our findings cast strong doubt on the foremost line of evidence that landscape burning by humans caused the megafaunal extinctions, and suggest that central Australia was becoming increasingly arid in the Late Pleistocene, the relative roles of hunting by humans and climate change in the megafaunal extinctions remain unresolved.
Climatic history and dispersal ability explain the relative importance of turnover and nestedness components of beta diversity
Authors: Dobrovolski Ricardo , Melo Adriano S. , Cassemiro Fernanda A. S. , Diniz‐Filho José Alexandre Felizola
Published: May 2011

Aim  We tested whether the geographic variation in the proportion of beta diversity attributed to nestedness or turnover components was explained by the effect of past glaciation events. Specifically, we tested the hypothesis that most of the beta diversity in regions retaining ice until recent periods was due to nestedness. Additionally, we tested whether the variation was influenced by thermal tolerance and the dispersal ability of species.

Location  This study analysed data from the New World.

Methods  We used presence/absence data for amphibians, birds and mammals of the New World. We calculated beta diversity among each 1°× 1° cell and the adjacent cells using the Sorensen dissimilarity index that expresses the total beta diversity. Furthermore, we partitioned it into turnover and nestedness components. The relative importance of the two latter components was expressed as the proportion of total beta diversity explained by nestedness (βratio). We calculated the correlation between βratio and the time each cell was free of ice since the last glaciation (cell age). To control the effects of spatial autocorrelation, we calculated geographically effective degrees of freedom.

Results  The proportion of beta diversity attributed to nestedness was negatively correlated with cell age. Moreover, this effect was stronger for amphibians than mammals, and stronger for mammals than birds.

Main conclusions  Our results are in accordance with the hypothesis that the nestedness component of beta diversity is more important in areas affected by glaciations until recent time. The beta diversity in high latitudes is the result of past extinctions and recent recolonization, which result in higher levels of nestedness. This process is more evident for vertebrates with lower dispersal ability and lower temperature tolerance.
Effect of the global financial crisis on accounting convergence
Authors: Mala Rajni , Chand Parmod
Published: May 2011

Fair value accounting (FVA) is threatening the convergence of accounting practices around the world. It has been regarded as one of the contributing factors of the recent financial crisis. Given that International Financial Reporting Standards (IFRS) have embraced FVA, this financial crisis raises concerns about their suitability for financial reporting across the world. This study explores important implications of the global financial crisis for financial reporting, in particular seeking to identify whether the trend towards convergence has been impeded by inherent problems in the IFRS. Contrary to our expectations, analyses show that the financial crisis has made the case for global convergence of accounting standards more compelling than before. The majority of countries intending to converge in the near future have not been affected by the global financial crisis and are committed to adopt IFRS as planned. The analyses also show that the International Accounting Standards Board (IASB) has been facing pressure from the financial institutions, regulators, policy‐makers and finance ministers to review its rules on FVA. Consequently, the IASB has been undertaking measures to improve the reporting requirements in the light of the financial crisis.
Ethics and prevention of overweight and obesity: an inventory
Authors: ten Have M. , de Beaufort I. D. , Teixeira P. J. , Mackenbach J. P. , van der Heide A.
Published: May 2011

Efforts to counter the rise in overweight and obesity, such as taxes on certain foods and beverages, limits to commercial advertising, a ban on chocolate drink at schools or compulsory physical exercise for obese employees, sometimes raise questions about what is considered ethically acceptable. There are obvious ethical incentives to these initiatives, such as improving individual and public health, enabling informed choice and diminishing societal costs. Whereas we consider these positive arguments to put considerable effort in the prevention of overweight indisputable, we focus on potential ethical objections against such an effort. Our intention is to structure the ethical issues that may occur in programmes to prevent overweight and/or obesity in order to encourage further debate. We selected 60 recently reported interventions or policy proposals targeting overweight or obesity and systematically evaluated their ethically relevant aspects. Our evaluation was completed by discussing them in two expert meetings. We found that currently proposed interventions or policies to prevent overweight or obesity may (next to the benefits they strive for) include the following potentially problematic aspects: effects on physical health are uncertain or unfavourable; there are negative psychosocial consequences including uncertainty, fears and concerns, blaming and stigmatization and unjust discrimination; inequalities are aggravated; inadequate information is distributed; the social and cultural value of eating is disregarded; people's privacy is disrespected; the complexity of responsibilities regarding overweight is disregarded; and interventions infringe upon personal freedom regarding lifestyle choices and raising children, regarding freedom of private enterprise or regarding policy choices by schools and other organizations. The obvious ethical incentives to combat the overweight epidemic do not necessarily override the potential ethical constraints, and further debate is needed. An ethical framework to support decision makers in balancing potential ethical problems against the need to do something would be helpful. Developing programmes that are sound from an ethical point of view is not only valuable from a moral perspective, but may also contribute to preventing overweight and obesity, as societal objections to a programme may hamper its effectiveness.
MONTHLY GDP FORECASTING USING BRIDGE MODELS: APPLICATION FOR THE FRENCH ECONOMY
Authors: Barhoumi Karim , Darné Olivier , Ferrara Laurent , Pluyaud Bertrand
Published: May 2011

This paper presents a model to predict French gross domestic product (GDP) quarterly growth rate. The model is designed to be used on a monthly basis by integrating monthly economic information through bridge models, for both supply and demand sides, allowing thus economic interpretations. For each GDP component, bridge equations are specified by using a general‐to‐specific approach implemented in an automated way by Hoover and Perez and improved by Krolzig and Hendry. This approach allows to select explanatory variables among a large data set of hard and soft data. A rolling forecast study is carried out to assess the forecasting performance in the prediction of aggregated GDP, by taking publication lags into account in order to run pseudo real‐time forecasts. It turns out that the model outperforms benchmark models. The results show that changing the set of equations over the quarter is superior to keeping the same equations over time. In addition, GDP growth seems to be more precisely predicted from a supply‐side approach rather than a demand‐side approach.
The education of new Chinese immigrant children in Hong Kong: challenges and opportunities
Authors: ZHANG KAILI CHEN , TING CYNTHIA LAW MAN
Published: May 2011

In describing the current status of the education of new Chinese immigrant children (NCIC) in Hong Kong and to provide data useful for designing new policies, this article highlights the region's rise of new Chinese immigrants and the characteristics of the NCIC. Challenges to improve access to and equity in education in Hong Kong, overall quality of education for the NCIC and future possibilities are discussed. Implications from other countries are also included.
Perceptions of the barriers to effective inclusion in one primary school: voices of teachers and teaching assistants
Authors: GLAZZARD JONATHAN
Published: May 2011

This study examined the barriers to inclusion in one primary school in the north of England. Qualitative data were collected from teachers and teaching assistants through the use of a focus group. The evidence suggested that practices within the school were varied and ranged from highly inclusive to highly exclusive. Some teachers worked in good faith to develop effective inclusion for learners with special educational needs. Conversely, other teachers displayed negative attitudes towards these pupils and this impacted negatively on the school's commitment to inclusion. Lack of funding, resources and training were identified as key barriers to inclusion. Parental resistance to inclusion was also evident within the context of this school and there was a strong feeling that the inclusion agenda was problematic in the context of the standards agenda. Despite these issues there was a strong sense that practitioners should be willing to commit to the principles of inclusive education and the study considers some ways in which schools can advance their practice in this respect. Within this study the term ‘practitioner’ is used to represent teachers and teaching assistants.
‘Yes, but . . .’: rhetoric, reality and resistance in teaching assistants' experiences of inclusive education
Authors: MACKENZIE SUZANNE
Published: May 2011

This research examines the role of teaching assistants (TAs) working with children with special educational needs (SEN) in an increasingly complex and diverse context. The role of the TA has been given more attention recently, partly due to the increased focus on their effectiveness within an inclusive education system in a time of workforce reform. The research takes a life history approach to examining the experiences of TAs within inclusive contexts and focuses upon how their backgrounds impact upon their role within the classroom, as well as how their experiences demonstrate ambiguity, tension and contradictions. Rather than a focus on pupil and institutional outcomes, the article analyses the tensions between the policy and institutional frameworks of inclusion and how TAs experience this. TAs' contradictions, tensions, resistance and also pleasures within their work are explored from their own perspectives. The personal interpretations, understandings and day‐to‐day implementation of inclusion are the focus.
The role of education in the treatment of offenders
Authors: JOVANIĆ GORAN
Published: May 2011

This article considers an aspect of inclusive education that has received relatively limited exposure: the challenges involved in meeting the educational needs of offenders in prisons. It does this by taking the example of Serbia, where recent changes in legislation have ensured the educational rights of inmates. It then looks at possible ways in which more inclusive approaches to the education of inmates in prison might be developed in Serbia by illustrating some successful initiatives from the United States and other countries. The article points to the need for flexibility and a focus on the achievement of quality changes in behaviour, self‐image and relationships with other inmates, as well as literacy and vocational training. It goes on to argue that such innovations in prison education are a requirement to enable prisoners to be prepared for reintegration into society on their release.
Do Natural Barriers Affect the Relationship Between Trade Openness and Growth?*
Authors: Henry Michael , Kneller Richard , Milner Chris , Girma Sourafel
Published: May 2011

This article investigates whether there are threshold effects in the relationship between openness and productivity growth that are fashioned by a country's natural barriers, using a cross‐country growth model. Alternative methods of modelling thresholds are explored. An endogenous threshold model is shown to be preferable to the use of interaction effects. The results identify critical levels of natural barriers which affect how greater openness or liberalization impacts on productivity growth. We find that only countries with higher natural barriers receive growth benefits from trade liberalization.
On the Price Elasticity of Demand for Patents*
Authors: Rassenfosse Gaetan de , Potterie Bruno van Pottelsberghe de la
Published: May 2011

This paper provides an analysis of the impact of patent fees on the demand for patents. It presents a dataset of fees since 1980 at the European (EPO), the US and the Japanese patent offices. Descriptive statistics show that fees have severely decreased at the EPO over the 1990s, converging towards the level of fees in the US and Japan. The estimation of dynamic panel data models suggests that the price elasticity of demand for patents is about −0.30. These results suggest that the laxity of fee policy at the EPO has significantly contributed to the rising propensity to patent.
Trade Timing, Price Volatility and Serial Correlation
Authors: Wang Ming‐Chang , Zu Lon‐Ping
Published: May 2011

This study sets up a multiple‐period, competitive rational expectations model to facilitate an examination into how informed traders time their trading on private information so as to maximise their expected utility. We find that, in equilibrium, informed traders may elect to trade late on their information, a result which contradicts other competitive rational expectations models in which it is generally assumed that informed traders will trade immediately upon receiving private information. Our results imply that price volatility will increase and price changes may display positive serial correlation. This phenomenon helps to explain the excess volatility puzzle of asset prices and medium‐term continuations (momentum).
Cutaneous lumbosacral Herpes Simplex virus among patients hospitalized for an advanced disease
Authors: Toutous‐Trellu L. , Vantieghem K.M. , Terumalai K. , Herrmann F.R. , Piguet V. , Kaiser L. , Vuagnat H. , Zulian G.
Published: May 2011

Background  Cutaneous Herpes simplex virus (HSV) infections are regularly observed in lumbosacral areas, and many are refractory to appropriate initial diagnosis and management.

Objective  We aimed to evaluate the incidence of lumbosacral HSV among advanced disease patients, to estimate their survival index from HSV onset, and to describe their clinical and virological characteristics.

Methods  A prospective, descriptive study was conducted in a palliative and continuous care centre, collecting patients with suspected cutaneous HSV lesions in the lumbosacral area.

Results  From 2008 to 2010, 24 patients were included: 19 had HSV‐2 confirmed by at least one laboratory test. Incidence of HSV‐2 was 2.67% (1.73–4.33%, 95% CI). No age, gender or survival differences were observed compared to the global population in the centre. Most lesions were detected early as vesicles (14/24) or small ulcers. Sensitivity was good for all diagnostic methods (62.5% for immunofluorescence and 79.2% for culture and/or PCR). Outcome was favourable under classical antiherpetic drugs and topical antiseptic dressing.

Conclusions  Cutaneous lumbosacral HSV remains uncommon in patients hospitalized with advanced diseases. Most of these patients suffer from pressure ulcers or other dermatitis; we advocate increased attention of this diagnosis to avoid skin complications and added pain.
Isotretinoin has no negative effect on attention, executive function and mood
Authors: Ergun T. , Seckin D. , Ozaydin N. , Bakar Ö. , Comert A. , Atsu N. , Demircay Z. , Yoney H. , Zaimoglu S.
Published: May 2011

Background  According to some animal data, impairments in learning and memory are seen with isotretinoin. Isotretinoin has been shown to affect human brain metabolism, but the data on human neural functions is lacking.

Objectives  To evaluate whether isotretinoin treatment affects cognitive functions, causes depression and anxiety or alters anger level and anger expression.

Methods  Neuropsychological tests of attention and executive functions, behavioural tests measuring anger and depression and measures assessing acne severity were applied to 63 severe and/or resistant acne patients from four medical centres including one primary care institute and three university hospitals at the beginning, at the end of first month, third month and at end of treatment with isotretinoin.

Results  From a total of 63 patients, 15 missed the final visit and 48 were evaluated. Overall, 11 (six women, five men) and five (all women) patients reported anger and depression, respectively, during treatment. Eleven of these 16 patients improved spontaneously. No detrimental effects of isotretinoin treatment on either executive functions or mood were found. Several executive functions and control of anger trait were found to be improved. Clearing of acne was obtained in 94.6% of patients.

Limitations  Improvement of several measures may be related to learning effect of repeated testing. Investigating brain functions is a complex process and various methods can be used.

Conclusion  The test battery used in this study, which is commonly used to evaluate mental status both in adults and children, did not show any negative effect of isotretinoin on executive functional parameters in acne patients.
Narrow‐band UVB irradiation stimulates the migration and functional development of vitiligo‐IgG antibodies‐treated pigment cells
Authors: Wu C.‐S. , Lan C.‐C.E. , Yu H.‐S.
Published: May 2011

Background  The pathogenesis of vitiligo remains unclear. Most authorities favoured the autoimmune cause for the strong associations of vitiligo with multiple autoimmune diseases and the presence of autoantibodies in vitiligo patients. Narrow‐band UVB (NBUVB) irradiation has been considered to be an effective treatment for vitiligo with simple treatment procedure and decreased accumulated ultraviolet exposure doses.

Objectives  The aim this study was to investigate the effects of NBUVB irradiation on normal IgG antibodies (N‐IgG) or vitiligo IgG antibodies (V‐IgG)‐treated NCCmelan5 cells in terms of proliferation, migration and melanin formation.

Methods  Cultured NCCmelan5 cells were treated with (i) NBUVB irradiation alone, (ii) N‐IgG or V‐IgG alone, and (iii) combination of N‐IgG or V‐IgG with NBUVB irradiation. The proliferation of NCCmelan5 cells were evaluated using BrdU incorporation assay. Western blotting was used to determine the expressions of phosphorylated p125FAK (pp125FAK) and tyrosinase in NCCmelan5 cells. The locomotion of NCCmelan5 cells was assessed using time‐lapse assay and in vitro wound scratch assay.

Results  Neither N‐IgG nor V‐IgG significantly affected the proliferation of NCCmelan5 cells. The migration, melanin formation and tyrosinase expression in NCCmelan5 cells were decreased by V‐IgG. NBUVB irradiation increased the proliferation of V‐IgG treated NCCmelan5 cells. In addition, NBUVB irradiation enhanced the mobility of V‐IgG‐treated NCCmelan5 cells via upregulation of pp125FAK. The melanogenesis and tyrosinase expression in V‐IgG‐treated NCCmelan5 cells were promoted using NBUVB irradiation.

Conclusions  Our study demonstrated that the deleterious effects of V‐IgG in the pathogenesis of vitiligo might be overcome by NBUVB irradiation.
Effects of metoprolol therapy on cardiac gap junction remodelling and conduction in human chronic atrial fibrillation
Authors: Dhein S , Rothe S , Busch A , Rojas Gomez DM , Boldt A , Reutemann A , Seidel T , Salameh A , Pfannmüller B , Rastan A , Kostelka M , Mohr FW
Published: May 2011

BACKGROUND AND PURPOSE We investigated the influence of metoprolol on gap junction proteins connexin43 (Cx43) and connexin40 (Cx40) in atrial tissue from patients with/without atrial fibrillation (AF).

EXPERIMENTAL APPROACH Left atrial tissue samples from 160 patients with AF or sinus rhythm (SR) with or without metoprolol (mean daily dose: 65.2 ± 9.1 mg·day−1) were analysed for Cx43 and Cx40 by Western blot and immunohistology. Transverse and longitudinal conduction velocities were determined by 64 multi‐electrode mapping.

KEY RESULTS Both Cx43 and Cx40 expression were significantly increased in patients with AF versus SR. Cx43‐expression in AF was significantly higher in patients receiving metoprolol, while Cx40 expression was unaffected by metoprolol treatment. In AF, the ratio of lateral/polar expression of Cx43 and Cx40 was enhanced due to increased expression at the sides of the cells (lateral) and a loss at the cell poles. This AF‐induced increase in lateral/polar expression of Cx43, but not of Cx40, was significantly antagonized by metoprolol treatment. Functionally, in AF patients, transverse conduction velocity in atrial samples was significantly enhanced and this change was also significantly antagonized by metoprolol.

CONCLUSIONS AND IMPLICATIONS AF induced enhanced lateral expression of Cx43 and Cx40 together with enhanced transverse conduction velocity in left atrial tissue. Alterations in localization of Cx43 and conduction changes were both antagonized by metoprolol, showing that pharmacological modulation of gap junction remodelling seems, in principle, possible. This finding may open new approaches to the development of anti‐arrythmic drugs.
Paeoniflorin suppresses the expression of intercellular adhesion molecule‐1 (ICAM‐1) in endotoxin‐treated human monocytic cells
Authors: Jin Lei , Zhang Li‐Min , Xie Ke‐Qiang , Ye Yang , Feng Linyin
Published: May 2011

BACKGROUND AND PURPOSE Paeoniflorin (PF) has ameliorative effects on learning and memory impairment and cerebral ischaemia in rats and has protective effects against the degeneration of dopaminergic neurons in substantia nigra. The neuroprotective effects of PF are most probably derived from its anti‐inflammatory property. Abnormally high levels of intercellular adhesion molecule‐1 (ICAM‐1) have been found to be associated with a wide range of inflammatory and immune responses. Here we studied whether PF regulates the levels of ICAM‐1 elevated in LPS‐activated differentiated human monocytic U937 cells and TNF‐α‐stimulated human umbilical vein endothelial cells (HUVECs).

EXPERIMENTAL APPROACH mRNA levels were evaluated by RT‐PCR. Protein levels were evaluated by Western blot analysis. An immunofluorescence technique was used to estimate NF‐κB translocation, and NF‐κB binding to nuclear DNA was determined by EMSA.

KEY RESULTS PF inhibited ICAM‐1 expression elevated in LPS‐induced U937 cells and TNF‐α‐stimulated HUVECs. Although previous reports showed that PF's action is mediated by activating adenosine A1 receptors, application of a selective adenosine A1 receptor antagonist did not change the inhibitory effect of PF in our experiments. To elucidate the underlying mechanisms of the effect of PF, we studied its effect on signalling pathways upstream of ICAM‐1 expression. PF suppressed the activation of the NF‐κB pathway, which regulates the expression of ICAM‐1. The TLR4 and MAPK pathways were shown not to be involved in the effects of PF in these cells.

CONCLUSIONS AND IMPLICATIONS PF inhibits ICAM‐1 expression in LPS‐treated U937 cells and TNF‐α‐stimulated HUVECs by suppressing the activation of the NF‐κB pathway.
5α‐Reduced glucocorticoids exhibit dissociated anti‐inflammatory and metabolic effects
Authors: Yang C , Nixon M , Kenyon CJ , Livingstone DEW , Duffin R , Rossi AG , Walker BR , Andrew R
Published: May 2011

BACKGROUND AND PURPOSE Dissociating anti‐inflammatory efficacy from the metabolic side effects of glucocorticoids is an attractive therapeutic goal. 5α‐Tetrahydro‐corticosterone (5αTHB), produced from corticosterone by 5α‐reductases, activates glucocorticoid receptors. This study compares the effects of 5αTHB on inflammation and metabolism in vitro and in vivo.

METHODS Suppression of cytokine release by 5αTHB and corticosterone were studied following LPS activation of mouse bone marrow derived macrophages. In vivo the efficacy of these steroids to dysregulate metabolic homeostasis and modulate immune suppression and the responses to thioglycollate‐induced peritonitis in C57BL/6 mice were studied following acute injection (1.5–15 mg) and chronic infusion (50 µg·day−1, 14 days).

RESULTS In macrophages, 5αTHB increased secretion of IL‐10 similarly to corticosterone (180%, 340%; data are % vehicle, treated with 5αTHB and corticosterone, respectively) and suppressed LPS‐induced secretion of TNF‐α (21.9%, 74.2%) and IL‐6 (16.4%, 69.4%). In mice with thioglycollate‐induced peritonitis, both 5αTHB and corticosterone reduced the numbers of neutrophils (58.6%, 49.9%) and inflammatory monocytes (69.5%, 96.4%), and also suppressed MCP‐1 (48.7%, 80.9%) and IL‐6 (53.5%, 86.7%) in peritoneal exudate. In mice chronically infused with 5αTHB and corticosterone LPS‐induced production of TNF‐α from whole blood was suppressed to the same degree (63.2%, 37.2%). However, in contrast to corticosterone, 5αTHB did not induce body weight loss, increase blood pressure or induce hyperinsulinaemia.

CONCLUSIONS 5αTHB has anti‐inflammatory effects in vitro and in vivo. At doses with equivalent anti‐inflammatory efficacy to corticosterone, 5αTHB did not induce metabolic toxicity and thus may be a prototype for a safer anti‐inflammatory drug.
Prognostic value of 18F‐FDG PET for hepatocellular carcinoma patients treated with sorafenib
Authors: Lee Jae Hoon , Park Jun Yong , Kim Do Young , Ahn Sang Hoon , Han Kwang‐Hyub , Seo Hyo Jung , Lee Jong Doo , Choi Hye Jin
Published: May 2011

Background: Sorafenib (Nexavar) is an orally active multikinase inhibitor that is approved for the treatment of hepatocellular carcinoma (HCC). In this study, we used 18F‐2‐fluoro‐2‐deoxyglucose (18F‐FDG) with positron emission tomography (PET) to predict the treatment outcome of sorafenib in patients with advanced HCC.

Materials and methods: A total of 29 patients with HCC were included. Baseline 18F‐FDG PET scans were performed a median of 14 days before sorafenib treatment. Sorafenib was administered orally at a dose of 400 mg twice daily. For statistical analysis, the standardized uptake value (SUV) of the most hypermetabolic lesion was obtained and assigned as the SUVmax for each patient.

Results: Among 29 patients, one patient achieved partial remission and 14 patients showed stable disease. The overall survival (OS) and progression free survival (PFS) were 5.1 months [95% confidence interval (CI): 0.0–12.0] and 3.8 months (95% CI: 1.4–6.2). The multivariate analysis of OS showed that four indices, Eastern Cooperative Oncology Group performance status, α‐fetoprotein (AFP) concentration, portal vein thrombosis and SUVmax were significant prognostic factors (P=0.030, P=0.024, P=0.020 and P=0.015 respectively). AFP concentration and SUVmax were independent prognostic factors for PFS, too (P=0.003 and P=0.026 respectively). When the patients were divided into two groups: low SUVmax (n=10; <5.00) and high SUVmax (n=19;≥5.00), the low SUV group showed significantly longer OS and PFS (P=0.023 and P=0.042 respectively).

Conclusion: Our study showed that the degree of FDG uptake is an independent prognostic factor in patients with HCC who undergo sorafenib treatment.
Cholesterol: recapitulation of its active role during liver regeneration
Authors: Delgado‐Coello Blanca , Briones‐Orta Marco A. , Macías‐Silva Marina , Mas‐Oliva Jaime
Published: May 2011

Liver regeneration is a compensatory hyperplasia produced by several stimuli that promotes proliferation in order to provide recovery of the liver mass and architecture. This process involves complex signalling cascades that receive feedback from autocrine and paracrine pathways, recognized by parenchymal as well as non‐parenchymal cells. Nowadays the dynamic role of lipids in biological processes is widely recognized; however, a systematic analysis of their importance during liver regeneration is still missing. Therefore, in this review we address the role of lipids including the bioactive ones such as sphingolipids, but with special emphasis on cholesterol. Cholesterol is not only considered as a structural component but also as a relevant lipid involved in the control of the intermediate metabolism of different liver cell types such as hepatocytes, hepatic stellate cells and Kupffer cells. Cholesterol plays a significant role at the level of specific membrane domains, as well as modulating the expression of sterol‐dependent proteins. Moreover, several enzymes related to the catabolism of cholesterol and whose activity is down regulated are related to the protection of liver tissue from toxicity during the process of regeneration. This review puts in perspective the necessity to study and understand the basic mechanisms involving lipids during the process of liver regeneration. On the other hand, the knowledge acquired in this area in the past years, can be considered invaluable in order to provide further insights into processes such as general organogenesis and several liver‐related pathologies, including steatosis and fibrosis.
Inflammation in epilepsy: Clinical observations
Authors: Aronica Eleonora , Crino Peter B.
Published: May 2011

Over the past decade, an increasing number of observations indicate that activation of inflammatory processes occurs in variety of focal epilepsies. Understanding the feature and consequences of neuroinflammation, including the contribution to development and perpetuation of seizures, as well as to mood or cognitive dysfunction, is a major requisite for delineating its role in epilepsy. The present article discusses the most recent observations supporting the involvement of the inflammatory response in human focal epilepsy. It also evaluates emerging evidence concerning the possibility to identify epilepsy‐associated inflammatory biomarkers in cerebrospinal fluid and serum, as well as the potential application of neuroimaging approaches to study the inflammatory reactions in chronic epilepsy patients in vivo, aiming to improve the recognition of appropriate patient populations who might benefit from antiinflammatory or immunomodulatory therapies.
Molecular cascades that mediate the influence of inflammation on epilepsy
Authors: Friedman Alon , Dingledine Ray
Published: May 2011

Experimental evidence strongly indicates a significant role for inflammatory and immune mediators in initiation of seizures and epileptogenesis. Here we will summarize data supporting the involvement of IL‐1β, TNF‐α and toll‐like receptor 4 in seizure generation and the process of epileptogenesis. The physiological homeostasis and control over brain immune response depends on the integrity of the blood‐brain barrier, transforming growth factor (TGF)‐β signaling and leukocyte migration. To what extent targeting the immune system is successful in preventing epileptogenesis, and which signaling pathway should be beleaguered is still under intensive research.
Antiepileptic drugs and the immune system
Authors: Beghi Ettore , Shorvon Simon
Published: May 2011

Data on the effects of antiepileptic drugs on the immune system are frequently inconsistent and sometimes conflicting because the effects of drugs cannot be separated from those of seizures, first‐generation drugs have been most intensively investigated, the patient’s genetic background, the mechanism of action and the pharmacokinetic profile of AEDs and the concurrent use of immunosuppressant drugs may act as confounders. Valproate, carbamazepine, phenytoin, vigabatrin, levetiracetam, and diazepam have been found to modulate the immune system activity by affecting humoral and cellular immunity. AEDs are associated with pharmacokinetic interactions (most frequently occurring with carbamazepine, phenytoin, phenobarbital and valproate). Hepatic metabolism is the primary site of interaction for both AEDs and immunotherapies (ACTH, dexamethasone, hydrocortisone, methylprednisolone, cyclophosphamide, methotrexate, rituximab), which entail induction or inhibition of drug effects. However, the clinical importance of these drug interactions is still far from defined. An important adverse effect of the action of AEDs on the immune system is antiepileptic hypersensitivity syndrome (AHS), a life‐threatening, idiosyncratic cutaneous reaction to aromatic AEDs resulting in end organ damage. Phenytoin, carbamazepine, phenobarbital, lamotrigine, oxcarbazepine, felbamate, and zonisamide have been implicated. The pathogenic mechanisms of AHS are incompletely understood.
How we treat: transfusion medicine support of obstetric services
Authors: Goodnough Lawrence T. , Daniels Kay , Wong Amy E. , Viele Maurene , Fontaine Magali F. , Butwick Alexander J.
Published: May 2011

BACKGROUND: Obstetric services depend on the transfusion service (TS) to provide diagnostic testing and blood component therapy for clinical care pathways.

STUDY DESIGN AND METHODS: We describe three quality improvement (QI) initiatives implemented to improve TS support of obstetric services.

RESULTS: We implemented a pathway for patients requiring an ABO/Rh order for every admission to obstetric services, along with reconciliation of the daily hospital birth manifest and TS umbilical cord log to identify every woman eligible for RhIG. After assessment over 6 months, 21 (1%) of 2041 women lacked an admission ABO/Rh; all subsequently had ABO/Rh determinations. Umbilical cords were missing for eight (0.4%) mothers; four were D− and received RhIG. We developed algorithms for diagnostic blood ordering for patients deemed at “low,”“moderate,” or “high” risk of blood transfusion. A 27% reduction in total diagnostic test volumes and 24% reduction in charges was documented after compared to before implementation. We analyzed the impact of our massive transfusion protocol (MTP) on blood inventory management for 31 (0.25%) women undergoing 12,945 deliveries, representing 11% of 286 MTPs for all clinical services over a 32‐month interval. O− uncrossmatched red blood cells (RBCs) represented 103 (24%) of 421 RBC units issued. Wastage rates of RBCs, plasma, and platelets ordered and issued in the MTPs were 0.7, 16, and 3%, respectively.

CONCLUSION: QI initiatives for RhIG prophylaxis, diagnostic blood test ordering, and MTP improve TS support of obstetric services.
Intravascular Ultrasound Guided Percutaneous Coronary Intervention: A Practical Approach
Authors: LEE CHI‐HANG
Published: May 2011

Percutaneous coronary intervention (PCI) with stent implantation has become the predominant revascularization therapy for coronary artery disease. However, stent thrombosis and instent restenosis remain 2 major complications. Limitations of stand‐alone angiographic guidance play a significant role in the pathogenesis of these complications. Intravascular ultrasound (IVUS) guidance intuitively offers the best chance of optimizing the acute procedural outcomes, which translates to lower incidences of thrombosis and restenosis. This article aims to provide a practical approach on preintervention and postintervention lesion assessment by IVUS. Emphases of this article are on correct interpretation and application of the various vascular parameters obtained during IVUS imaging. Although consensus on some areas is lacking, the most commonly agreed IVUS concepts and criteria are presented. Limitations of the IVUS‐guided PCI on routine clinical practice are also addressed. A summary of the randomized study comparing IVUS‐ versus angiographic‐guided PCI, together with a critical appraisal of the data, are also presented. The roles of IVUS in PCI are likely to undergo revolutionary change in the era of plaque characterization and drug‐eluting stents. (J Interven Cardiol 2012;25:86–94)
Are People Successful at Learning Sequences of Actions on a Perceptual Matching Task?
Authors: Yakushijin Reiko , Jacobs Robert A.
Published: May 2011

We report the results of an experiment in which human subjects were trained to perform a perceptual matching task. Subjects were asked to manipulate comparison objects until they matched target objects using the fewest manipulations possible. An unusual feature of the experimental task is that efficient performance requires an understanding of the hidden or latent causal structure governing the relationships between actions and perceptual outcomes. We use two benchmarks to evaluate the quality of subjects’ learning. One benchmark is based on optimal performance as calculated by a dynamic programming procedure. The other is based on an adaptive computational agent that uses a reinforcement‐learning method known as Q‐learning to learn to perform the task. Our analyses suggest that subjects were successful learners. In particular, they learned to perform the perceptual matching task in a near‐optimal manner (i.e., using a small number of manipulations) at the end of training. Subjects were able to achieve near‐optimal performance because they learned, at least partially, the causal structure underlying the task. In addition, subjects’ performances were broadly consistent with those of model‐based reinforcement‐learning agents that built and used internal models of how their actions influenced the external environment. We hypothesize that people will achieve near‐optimal performances on tasks requiring sequences of action—especially sensorimotor tasks with underlying latent causal structures—when they can detect the effects of their actions on the environment, and when they can represent and reason about these effects using an internal mental model.
Cesarean section after induction of labor compared with expectant management: no added risk from gestational week 39
Authors: RASMUSSEN OLE BREDAHL , RASMUSSEN STEEN
Published: May 2011

Objective. To compare induction of labor and expectant management by gestational week with regard to the need for cesarean section (CS) in labor. Design. Cohort study. Setting. National study based on the Danish Birth Registry. Population. Aggregated data from 230 528 deliveries from 2004 until mid‐year 2009. Women with cesarean section before labor, previous cesarean, preterm birth, breech presentation, multiple pregnancy and specified medical illnesses in pregnancy were excluded. Methods. We compared by gestational week nulliparous and parous women who were either induced or had expectant management until later spontaneous or induced labor. For each of five comparisons, we conducted multivariable logistic regression analysis, controlling for body mass index, age, smoking in pregnancy and use of epidural analgesia during labor. Main Outcome Measure. Rate of CS in labor. Results. From gestational week 39 and thereafter, there was no difference with regard to CS rates in labor among nulliparous and parous women when comparing women with induced labor and those women who waited for a later labor, either induced or spontaneous. The odds ratios (with confidence intervals) for CS in labor in nulliparous women were 0.99 (0.84–1.17), 1.16 (1.04–1.30), 1.04 (0.94–1.15), 1.00 (0.92–1.10) and 0.97 (0.88–1.07) for weeks 37–41, respectively. For parous women the corresponding figures were 1.72 (1.35–2.20), 1.27 (1.04–1.55), 1.15 (0.95–1.39), 1.18 (0.99–1.40) and 1.07 (0.87–1.32), respectively. Conclusions. Induction of labor provides a sound tool when counseling a woman either going past term or presenting with a problem, even if it is not a severe medical illness.
Deep pelvic endometriosis negatively affects ovarian reserve and the number of oocytes retrieved for in vitro fertilization
Authors: PAPALEO ENRICO , OTTOLINA JESSICA , VIGANÒ PAOLA , BRIGANTE CLAUDIO , MARSIGLIO ELENA , DE MICHELE FRANCESCA , CANDIANI MASSIMO
Published: May 2011

Objective. Endometriosis‐associated infertility results in reduced ovarian response, fewer oocytes available for fertilization, compromised oocyte quality and higher miscarriage rates. A consistent proportion of women with endometriosis require in vitro fertilization. We sought to clarify the impact of deep infiltrating pelvic disease on antral follicle count and ovarian response to follicle‐stimulating hormone (FSH) stimulation in patients with severe endometriosis. Design. Retrospective cohort study. Setting. University hospital. Population. Patients with severe endometriosis (stages III–IV; n=51) were divided into two groups regarding localization of endometriosis during surgical staging: ovarian (n=27) and both ovarian and deep infiltrating disease (n=24). Methods. A total of 73 long‐protocol ovulation induction cycles with recombinant FSH for an intracytoplasmic sperm injection program were given. On day 3 of the cycle, measurements of FSH and luteinizing hormone and an ultrasound evaluation of antral follicle count were performed. Main Outcome Measures. Number of oocytes collected at ovum pick up, number of mature oocytes, number of embryos transferred and clinical pregnancy rate. Results. Ovarian reserve in terms of antral follicle count was damaged in both groups but, if adjusted for age, it was significantly lower in the ovarian and pelvic infiltrating group compared with patients having only ovarian endometriosis. Pelvic deep infiltrating disease significantly impacted on the number of oocytes collected at pick up when adjusted for age. Conclusions. Deep infiltrating pelvic disease can negatively affect ovarian reserve in terms of antral follicle count and number of oocytes retrieved. Mechanisms underlying this phenomenon need to be elucidated.