bluuebunny/crossref_metadata_2025 huggingface dataset:
Unravelling the cardiovascular effects induced by α‐terpineol: A role for the nitric oxide–cGMP pathway
Authors: Ribeiro Thaís P , Porto Dayanne L , Menezes Camilla P , Antunes Alessandra A , Silva Darízy F , De Sousa Damião P , Nakao Lia S , Braga Valdir A , Medeiros Isac A
Published: March 2010

1. α‐Terpineol is a monoterpene found in the essential oils of several aromatic plant species. In the present study, we investigated the mechanisms underlying the cardiovascular changes induced by α‐terpineol in rats.

2. In normotensive rats, administration of α‐terpineol (1, 5, 10, 20 and 30 mg/kg, i.v.) produced a dose‐dependent hypotension (−10 ± 3, −20 ± 8, −39 ± 16, −52 ± 21 and −57 ± 23 mmHg, respectively;n = 5) followed by tachycardia. The hypotensive responses to 1, 5, 10, 20 and 30 mg/kg, i.v., α‐terpineol were significantly attenuated following the administration ofNG‐nitro‐l‐arginine methyl ester (l‐NAME; 20 mg/kg, i.v.; −2 ± 1, −5 ± 2, −7 ± 3, −22 ± 9 and −22 ± 10 mmHg, respectively;P < 0.05;n = 5).

3. In 10 μmol/L phenylephrine (PE)‐precontracted mesenteric artery rings, α‐terpineol (10−12to 10−5 mol/L) caused a concentration‐dependent relaxation (maximum relaxation 61 ± 6%;n = 7). After removal of the endothelium, the vasorelaxation elicited by α‐terpineol was attenuated (maximum relaxation 20 ± 1%;P < 0.05;n = 7). In addition, vasorelaxation induced by α‐terpineol in rings pretreated with 100 or 300 μmol/Ll‐NAME, 30 μmol/L hydroxocobalamin or 10 μmol/L 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one was attenuated (maximum relaxation 18 ± 3, 23 ± 3, 24 ± 7 and 21 ± 1%, respectively;n = 6;P < 0.05).

4. Furthermore, in a rabbit aortic endothelial cell line, 10−6, 10−5and 10−4 mol/L α‐terpineol induced concentration‐dependent increases in nitric oxide (NO) levels (12 ± 6, 18 ± 9 and 34 ± 12%Δ fluorescence, respectively;n = 3).

5. In conclusion, using combined functional and biochemical approaches in the present study, we were able to demonstrate that α‐terpineol‐induced hypotension and vasorelaxation are mediated, at least in part, by the endothelium, most likely via NO release and activation of the NO–cGMP pathway.
Role of 5‐HT2B receptors in cardiomyocyte apoptosis in noradrenaline‐induced cardiomyopathy in rats
Authors: Bai Chong‐Feng , Liu Jin‐Cheng , Zhao Rong , Cao Wei , Liu Shui‐Bin , Zhang Xiao‐Nan , Guo Hong‐Ju , Yang Qi , Yi Ding‐Hua , Zhao Ming‐Gao
Published: March 2010

1. Serotonin (5‐hydroxytryptamine; 5‐HT) plays important roles in the development of cardiac hypertrophy via activation of 5‐HT receptors. The aim of the present study was to investigate the role of 5‐HT2B receptors in the development of cardiomyocyte apoptosis and hypertrophy associated with noradrenaline (NA) overload.

2. Cardiac hypertrophy was induced in rats by intraperitoneal injection of 1.5 mg/kg NA for 4 weeks. Starting from Day 15, 5‐HT2B receptor antagonist SB 204741 (i.p., 0.5 or 2 mg/kg) or SDZ SER 082 (i.p., 1 mg/kg) was injected twice daily for another 14 days. Whole‐cell patch‐clamp techniques were used to record ionic currents in freshly isolated ventricular cardiomyocytes. Western blot and terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling (TUNEL) assays were used to assess myocardial apoptosis.

3. Expression of 5‐HT2B receptors was enhanced in the hypertrophic left ventricle induced by NE overload in vivo. The 5‐HT2B receptor antagonist SB 204741 partially reversed cardiac hypertrophy induced by NE overload (P < 0.05) and decreased L‐type calcium currents in ventricular cardiomyocytes (P < 0.05). In addition, SB 204741 notably attenuated myocardial apoptosis, as evidenced by downregulation of Bax and caspase 3 (P < 0.05) and upregulation of the anti‐apoptotic Bcl‐2 protein (P < 0.05).

4. In conclusion, the data suggest an involvement of 5‐HT2B receptors in the generation of apoptotic events associated with cardiac remodelling during increased adrenergic stimulation.
Sitagliptin augments angiotensin II‐induced renal vasoconstriction in kidneys from rats with metabolic syndrome
Authors: Tofovic David S , Bilan Victor P , Jackson Edwin K
Published: March 2010

1. Dipeptidyl peptidase (DPP) IV inhibitors enhance renovascular responses to angiotensin (Ang) II in spontaneously hypertensive rats (SHR), but not Wistar‐Kyoto rats. Because DPPIV inhibitors are often used in metabolic syndrome, it is important to determine whether DPPIV inhibition in this setting enhances renovascular responses to AngII.

2. Six‐week‐old Lean‐ZSF1 rats (harbouring SHR genes, but without metabolic syndrome;n = 11) and Obese‐ZSF1 rats (harbouring SHR genes and expressing metabolic syndrome;n = 10) were provided food and waterad libitum, and metabolic parameters and renovascular responses to AngII were assessed when the animals were 7 and 8 weeks of age, respectively.

3. At 7 weeks of age, compared with Lean‐ZSF1, Obese‐ZSF1 demonstrated significant (P < 0.05) increases in bodyweight (262 ± 8vs310 ± 13 g), plasma glucose (112 ± 4vs153 ± 9 mg/dL), haemoglobin A1c (4.7 ± 0.1vs5.8 ± 0.4%), urinary glucose excretion (0.021 ± 0.003vs6.70 ± 1.80 g/kg bodyweight per 24 h) and urinary protein excretion (100 ± 7vs313 ± 77 mg/kg bodyweight per 24 h). Mean blood pressure was high (133 ± 7 mmHg) in both strains.

4. At 8 weeks of age, kidneys were isolated and perfused. In Lean‐ZSF1 rats, renovascular responses (i.e. changes in perfusion pressure) to physiological levels of AngII (0.1 nmol/L) were 3.4 ± 1.3 and 18.2 ± 5.9 mmHg in untreated (n = 5) and 1 μmol/L sitagliptin‐treated (n = 6) kidneys, respectively. In Obese‐ZSF1 rats, renovascular responses to AngII were 5.5 ± 1.3 and 17.8 ± 8.2 mmHg in untreated (n = 4) and sitagliptin‐treated (n = 6) kidneys, respectively. Analysis of variance revealed a significant (P = 0.0367) effect of sitagliptin on renovascular responses to AngII that was independent of strain.

5. In conclusion, sitagliptin enhances renovascular responses to AngII in rats harbouring SHR genes and this effect persists in rats with diabetic nephropathy and metabolic syndrome.
Increasing health‐care options: The perspectives of parents who use complementary and alternative medicines
Authors: O'Keefe Maree , Coat Suzette
Published: March 2010

Aim:  To explore the relationship between conventional medicine and complementary and alternative medicine (CAM) with parents who use CAM, and to consider factors that may contribute to parent non‐disclosure of CAM usage to their doctor.

Methods:  Thirty‐three parents participated in one of seven focus groups. Transcripts were analysed using an iterative process of theme identification and testing against transcript data.

Results:  The participants believed they should trust their instincts as parents in caring for their child. It was important also to the participants that they understood why their child was ill, and a range of theories of health and illness were discussed. The use of CAM was attractive as it offered more options in health care than just relying on conventional medicine alone. The use of additional therapies was seen as a means to increase the likelihood that something would work. Many of the participants described bad experiences with doctors when they discussed CAM use previously so they had become more circumspect in mentioning it. The participants were most satisfied with medical care for their child when they felt the doctor respected their point of view and listened to them.

Conclusions:  Doctors caring for children and their families should expect that many parents are using CAM to increase health‐care options. Enquires about CAM usage should be made in a non‐judgemental and encouraging manner so parents feel comfortable in providing an honest answer. Advice to parents about CAM may need to be backed up with evidence to address differing parent understanding of illness.
The natural history and osteodystrophy of mucolipidosis types II and III
Authors: David‐Vizcarra Grace , Briody Julie , Ault Jenny , Fietz Michael , Fletcher Janice , Savarirayan Ravi , Wilson Meredith , McGill Jim , Edwards Matthew , Munns Craig , Alcausin Melanie , Cathey Sara , Sillence David
Published: March 2010

Aim:  To assess the natural history and impact of the secondary bone disease observed in patients with mucolipidosis (ML) II and III.

Methods:  Affected children and adults were ascertained from clinical genetics units around Australia and New Zealand. Diagnoses were confirmed by the National Referral Laboratory in Adelaide. The study encompassed all patients ascertained between 1975 and 2005. Data focussing on biochemical parameters at diagnosis, and longitudinal radiographic findings were sought for each patient. Where feasible, patients underwent clinical review and examination. Examinations included skeletal survey, bone densitometry, and measurement of serum and urine markers of bone metabolism. In a subset of patients, functional assessment using the Pediatric Evaluation and Disability Inventory (PEDI) and molecular analysis of GNPTAB were performed.

Results:  Twenty‐five patients with mucolipidosis were ascertained over a 30‐year period. Morbidity and functional outcomes on living patients were described. Serum calcium and phosphate were normal. All, but one patient, had normal alkaline phosphatase. Serum osteocalcin and urine deoxypyridinoline/creatinine were elevated. Two radiological patterns were observed (i) transient neonatal hyperparathyroidism in infants with ML II and (ii) progressive osteodystrophy in patients with ML intermediate and ML III. Molecular analyses of GNPTAB in nine subjects are reported.

Conclusion:  ML is characterised by a progressive bone and mineral disorder which we describe as the ‘osteodystrophy of mucolipidosis’. The clinical and radiographic features of this osteodystrophy are consistent with a syndrome of ‘pseudohyperparathyroidism’. Much of the progressive skeletal and joint pathology is attributable to this bone disorder.
Nomogram to predict seminal vesicle invasion using the status of cancer at the base of the prostate on systematic biopsy
Authors: Ohori Makoto , Kattan Michael W , Yu Changhong , Matsumoto Kazumasa , Satoh Takefumi , Ishii Junichiro , Miyakawa Ayako , Irie Akira , Iwamura Masatsugu , Tachibana Masaaki
Published: March 2010

Objective:  The aim of this study was to predict seminal vesicle invasion (SVI) by developing a new nomogram based on clinical features including the status of cancer at the base of the prostate on systematic biopsy.

Methods:  We studied the 466 patients with T1–3N0M0 prostate cancer who were treated with radical prostatectomy at three institutions. Preoperative clinical variables were correlated with the presence or absence of SVI with an area under the curve (AUC) of receiver–operator characteristics analysis. A nomogram was developed to predict SVI based on logistic regression analysis.

Results:  A total of 81 patients (17%) had SVI. Cancer was present in a biopsy core from the base of the prostate in 209 patients, of whom 32.5% had SVI, compared with only 5% of the 257 patients without cancer at the base of the prostate (P < 0.005). On multivariate analysis, serum prostate‐specific antigen, biopsy Gleason score, clinical T stage, and presence or absence of cancer in a biopsy core at the base of the prostate were significant predictors of SVI (P < 0.005 for all). The AUC of a standard model including clinical stage, Gleason score, and prostate‐specific antigen was 0.83, which was significantly enhanced by including the presence of cancer at the base of the prostate (none, unilateral or bilateral lobes) (AUC 0.87, P= 0.023). Based on the logistic analysis, we developed the nomogram to predict SVI. The calibration plots appeared to be excellent.

Conclusion:  The information of presence or absence of cancer at the base from prostate biopsy and the resulting nomogram allow an accurate prediction of SVI in patients undergoing radical prostatectomy for prostate cancer.
Benign pathological findings in 303 Chinese patients undergoing surgery for presumed localized renal cell carcinoma
Authors: Xiong Yong‐Hong , Zhang Zhi‐Ling , Li Yong‐Hong , Liu Zhuo‐Wei , Hou Guo‐Liang , Liu Qing , Yun Jing‐Ping , Zhang Xue‐Qi , Zhou Fang‐Jian
Published: March 2010

Objective:  To analyze the incidence of benign lesions in Chinese patients undergoing nephrectomies for renal masses identified as localized renal cell carcinoma (RCC) in preoperative imaging.

Methods:  Between 1999 and 2007, 303 patients (112 female, 191 male) with presumed localized RCC underwent nephrectomy (234 radical nephrectomies and 69 partial nephrectomies). Preoperative computed tomography images and pathological findings were reviewed and analyzed.

Results:  Pathological examinations revealed 31 (10.2%) benign lesions in the 303 patients. Among these 31 benign lesions, 15 (5.0%) were angiomyolipomas (AML) and only four (1.3%) were oncocytomas. Significantly, 20 (17.9%) of the 112 female patients had benign lesions compared with 11 (5.8%; P = 0.001) male patients. Benign renal lesions were found in five (25.0%) of the 20 patients with renal masses smaller than 2 cm, 13 (13.0%) of the 100 patients with renal masses 2–4 cm in size and 13 (7.1%) of the 183 patients with renal masses larger than 4 cm.

Conclusions:  Patients in the present study population show a low incidence of benign renal lesions, approximately half of them being AML. Female patients and patients with renal masses smaller than 4 cm are more likely to have benign renal lesions.
Gender differences in prevalence of the metabolic syndrome in Gulf Cooperation Council Countries: a systematic review
Authors: Mabry R. M. , Reeves M. M. , Eakin E. G. , Owen N.
Published: March 2010

Diabet. Med. 27, 593–597 (2010)

Aims  To systematically review studies documenting the prevalence of the metabolic syndrome among men and women in Member States of the Gulf Cooperative Council (GCC; Bahrain, Kuwait, Oman, Qatar, Saudi Arabia and the United Arab Emirates)—countries in which obesity, Type 2 diabetes and related metabolic and cardiovascular diseases are highly prevalent.

Methods  A search was conducted on PubMed and CINAHL using the term ‘metabolic syndrome’ and the country name of each GCC Member State. The search was limited to studies published in the English language. The metabolic syndrome was defined according to the Third Adult Treatment Panel (ATPIII) of the National Cholesterol Education Program (NCEP) and/or International Diabetes Federation (IDF) definitions. The methodological quality of each study was evaluated based on four criteria: a national‐level population sample; equal gender representation; robustness of the sample size; an explicit sampling methodology.

Results  PubMed, CINAHL and reference list searches identified nine relevant studies. Only four were considered high quality and found that, for men, the prevalence of the metabolic syndrome ranged from 20.7% to 37.2% (ATPIII definition) and from 29.6% to 36.2% (IDF definition); and, for women, from 32.1% to 42.7% (ATPIII definition) and from 36.1% to 45.9% (IDF definition).

Conclusions  Overall, the prevalence of the metabolic syndrome in the GCC states is some 10–15% higher than in most developed countries, with generally higher prevalence rates for women. Preventive strategies will require identifying socio‐demographic and environmental correlates (particularly those influencing women) and addressing modifiable risk behaviours, including lack of physical activity, prolonged sitting time and dietary intake.
Southern Ocean iron fertilization by baleen whales and Antarctic krill
Authors: Nicol Stephen , Bowie Andrew , Jarman Simon , Lannuzel Delphine , Meiners Klaus M , Van Der Merwe Pier
Published: March 2010

Iron is the limiting micronutrient in the Southern Ocean and experiments have demonstrated that addition of soluble iron to surface waters results in phytoplankton blooms, particularly by large diatoms. Antarctic krill (Euphausia superba) eat diatoms and recycle iron in surface waters when feeding. Baleen whales eat krill, and, historically, defecation by baleen whales could have been a major mechanism for recycling iron, if whale faeces contain significant quantities of iron. We analysed the iron content in 27 samples of faeces from four species of baleen whale. Faecal iron content (145.9 ± 133.7 mg kg−1) is approximately ten million times that of Antarctic seawater, suggesting that it could act as a fertilizer. Furthermore, we analysed the iron content of seven krill species and of muscle tissue of two species of baleen whales; all samples had high iron levels. Using these figures, together with recent estimates of the range and biomass of krill, we calculate that the Antarctic krill population contains ∼24% of the total iron in the surface waters in its range. Thus, krill can act as a long‐term reservoir of iron in Antarctic surface waters, by storing the iron in their body tissue. Pre‐exploitation populations of whales and krill must have stored larger quantities of iron and would have also recycled more iron in surface waters, enhancing overall ocean productivity through a positive feedback loop. Thus, allowing the great whales to recover might actually increase Southern Ocean productivity through enhancing iron levels in the surface layer.
Are ‘digital natives’ really digitally competent?—A study on Chinese teenagers
Authors: Li Yan , Ranieri Maria
Published: March 2010

Literature review has found that despite the considerable attention focused on ‘digital natives’, few studies have carefully investigated the characteristics of this group. The purpose of this study is to contribute to the debate on digital natives by providing a ‘piece of evidence’ on the digital competence status of a group of Chinese teenagers (ninth grade students) randomly selected from the Jiangdong District in Ningbo City, Zhejiang Province. An Instant Digital Competence Assessment (iDCA) tool, developed by a research group from the University of Florence, was adopted as the measurement tool for the study. Quantitative research was employed and the research design for the study was descriptive in nature. Data analysis results found that the majority of the participating ninth grade students (n = 317) had personal computers (PCs) and the Internet available at home and the average period of time owing a PC was about 5 years. The iDCA results indicated that (1) participants' overall performance in the iDCA was just ‘pass’ rather than ‘good’ or ‘excellent’, which might imply that digital natives in China are not necessarily digitally competent; (2) there were big disparities among participants as regards their digital competence; (3) participants' digital competence differed depending on their schools and their ages; (4) participants' digital competence was not significantly influenced by such factors as having a PC or not, having the Internet or not at home, frequency of computers and Internet use. On the basis of the findings, the study concluded by highlighting the role of education in improving teenagers' digital competence and by recommending the development of well‐designed teaching and learning materials for the Chinese K‐12 school system.
Improving teaching and learning of computer programming through the use of the Second Life virtual world
Authors: Esteves Micaela , Fonseca Benjamim , Morgado Leonel , Martins Paulo
Published: March 2010

The emergence of new technologies such as three‐dimensional virtual worlds brings new opportunities for teaching and learning. We conducted an action research approach to the analysis of how teaching and learning of computer programming at the university level could be developed within the Second Life virtual world. Results support the notion that it is possible to use this environment for better effectiveness in the learning of programming. The main results are the identification of problems hampering the teacher's intervention in this virtual world and the detection of solutions for those problems that were found effective to the success in using this environment for teaching/learning computer programming.
Trigger videos on the Web: Impact of audiovisual design
Authors: Verleur Ria , Heuvelman Ard , Verhagen Pløn W.
Published: March 2010

Audiovisual design might impact emotional responses, as studies from the 1970s and 1980s on movie and television content show. Given today's abundant presence of web‐based videos, this study investigates whether audiovisual design will impact web‐video content in a similar way. The study is motivated by the potential influence of video‐evoked emotional responses to related activities in a web‐based learning environment. To examine this, a video scene was designed that follows the concept of an educational trigger video. A trigger video aims to evoking affective responses in viewers with respect to a social problem situation. An experiment was conducted that explored whether the manipulation of two audiovisual design variables—shot length and camera height—of a web trigger video affects how the problem situation and the characters are perceived. The results showed that audiovisual design did impact these video‐related tasks.
Managing Ontong Java: Social institutions for production and governance of atoll resources in Solomon Islands
Authors: Bayliss‐Smith Tim , Gough Katherine V. , Christensen Andreas Egelund , Kristensen Søren Pilgaard
Published: March 2010

This paper explores the changing nature of social institutions and organizations for resource management on Ontong Java and their central role in maintaining livelihoods. Using detailed field data for three time periods, 1970–72, 1986 and 2006–07, and drawing on earlier secondary data, a longitudinal analysis of changes in governance and livelihoods is undertaken. Increased exploitation of marine resources has widened the resource base and increased people's access to goods and services. Following the ban in 2005 on the bêche‐de‐mer trade, however, livelihoods have reverted to being more subsistence oriented. For almost two decades after 1978, a communal organization, the Area Council, succeeded in regulating exploitation of the atoll's marine resources to ensure sustainable use, but in the 1990s it collapsed. In addition there was a paralysis of institutions that had once settled land disputes. This failure of atoll governance is a greater threat to future ‘sustainability’ than the usual processes that are invoked for atolls and small islands generally. As the Solomon Islands state is also failing, we argue that local institutions and organizations have a vital role to play in managing access to resources and the future of livelihoods on Ontong Java atoll.
Public Goods and Tax Competition in a Two‐Sided Market
Authors: KOTSOGIANNIS CHRISTOS , SERFES KONSTANTINOS
Published: March 2010

A rather neglected issue in the tax competition literature is the dependence of equilibrium outcomes on the presence of firms and shoppers (two‐sided markets). Making use of a model of vertical and horizontal differentiation, within which jurisdictions compete by providing public goods and levying taxes in order to attract firms and shoppers, this paper characterizes the noncooperative equilibrium. It also evaluates the welfare implications for the jurisdictions of a popular policy of tax coordination: The imposition of a minimum tax. It is shown that the interaction of the two markets affects the intensity of tax competition and the degree of optimal vertical differentiation chosen by the competing jurisdictions. Though the noncooperative equilibrium is, as it is typically the case, inefficient such inefficiency is mitigated by the strength of the interaction in the two markets. A minimum tax policy is shown to be effective when the strength of the interaction is weak and ineffective when it is strong.
Bayesian Equilibrium in a Public Good Economy
Authors: HON‐SNIR SHLOMIT , SHITOVITZ BENYAMIN , SPIEGEL MENAHEM
Published: March 2010

This paper studies the provision of a public good via voluntary contributions in an economy with uncertainty and differential information. Consumers differ in their private information regarding their future endowment as well as in their preferences. Each consumer selects her consumption ex ante, i.e., before knowing the state of nature. Contributions to the provision of the public good are determined ex post, i.e., when the state of nature is realized. Assuming that some normality conditions hold, a Bayesian equilibrium exists. Further, equilibrium is unique, regardless of the number of consumers, when either (1) the information partitions of consumers can be ranked from the finest to the coarsest, or (2) there are only two types of consumers.
Italian validation of INQoL, a quality of life questionnaire for adults with muscle diseases
Authors: Sansone V. A. , Panzeri M. , Montanari M. , Apolone G. , Gandossini S. , Rose M. R. , Politano L. , Solimene C. , Siciliano G. , Volpi L. , Angelini C. , Palmieri A. , Toscano A. , Musumeci O. , Mongini T. , Vercelli L. , Massa R. , Panico M. B. , Grandi M. , Meola G.
Published: March 2010

Background and purpose:  A quality of life (QoL) questionnaire for neuromuscular diseases was recently constructed and validated in the United Kingdom in a sample of adult patients with a variety of muscle disorders. Preliminary results suggested it could be a more relevant and practical measure of QoL in muscle diseases than generic health measures of QoL. The purpose of our work was: (i) To validate INQoL in Italy on a larger sample of adult patients with muscle diseases (ii) to compare INQoL to SF‐36.

Methods:  We have translated into Italian and applied language adaptations to the original UK INQoL version. We studied 1092 patients with different muscle disorders and performed (i) test–retest reliability (n = 80); (ii) psychometric (n = 345), known‐group (n = 1092), external criterion (n = 70), and concurrent validity with SF‐36 (n = 183).

Results:  We have translated and formally validated the Italian version of INQoL confirming and extending results obtained in the United Kingdom. In addition to good results in terms of reliability, known‐group and criterion validity, a comparison with the SF‐36 scales showed a stronger association between INQoL total index and SF‐36 physical (r = −0.72) than mental (r = −0.38) summary health indexes. When considering comparable domains of INQoL and SF‐36 with respect to an objective measure of muscle strength assessment (MMRC), regression analysis showed a stronger correlation using INQoL rather than SF‐36 scores.

Conclusions:  INQoL is recommended to assess QoL in muscle diseases because of its ability to capture physical limitations that are specifically relevant to the muscle condition.
Active Support, Participation and Depression
Authors: Stancliffe Roger J. , McVilly Keith R. , Radler Gary , Mountford Louise , Tomaszewski Paul
Published: March 2010

Background  Staff training in Active Support is designed to enable direct support staff to increase the engagement and participation of people with intellectual disabilities in a range of daily activities.

Method  Residents (n = 41) and staff of nine group homes participated. The effectiveness of Active Support was evaluated with a pre‐test:post‐test design, using a number of standardized assessments and other questionnaires, with group home staff as informants. These assessments were conducted before Active Support training and an average of 6.5 months later.

Results  Following implementation of Active Support residents experienced significant increases in domestic participation and adaptive behaviour. There were significant decreases in internalized challenging behaviour, overall challenging behaviour and depression. There was no significant pre–post change in other forms of challenging behaviour.

Conclusions  Our findings confirm and extend previous Active Support research showing that implementation of Active Support is followed by increased resident participation in activities. The significant improvements in adaptive behaviour, challenging behaviour and depression are of particular interest as the present study is among the first to report such effects. The study’s limitations are discussed.
Positive Experiences of Mothers and Fathers of Children with Autism
Authors: Kayfitz Adam D. , Gragg Marcia N. , Robert Orr R.
Published: March 2010

Background  The present study examined the positive experiences of parents raising school‐aged children with autism within the context of parenting stress.

Materials and Methods  Participants included 23 mother/father pairs raising children with autism (ages 5 to 11 years, M = 7.39). Parents completed measures of parenting stress and positive experiences of raising their children.

Results  Consistent with previous research in a pre‐school aged population of children with autism, mothers reported significantly more positive experiences than did fathers. Mothers’ and fathers’ reports of their positive experiences were negatively related to their reports of parenting stress. Fathers’, but not mothers’, positive experiences were negatively related to their partners’ reports of parenting stress.

Conclusion  Findings are discussed within a positive psychology framework suggesting that a focus on positive experiences may buffer against negative well‐being.
Participation in Sports by People with Intellectual Disabilities in England: A Brief Report
Authors: Robertson Janet , Emerson Eric
Published: March 2010

Background  Participation in sports has been linked to a range of physical, social and mental health benefits. Little is known about the extent to which people with intellectual disabilities take part in sports. This study looks at participation in sports and factors associated with participation by people with intellectual disabilities in England.

Method  Data on participation in sports and measures of personal characteristics, living situation, social participation, and socioeconomic status associated with participation were analysed based on a sample of 2784 people with intellectual disabilities in England.

Results  Overall, 41% of participants had taken part in sports in the past month, nearly all of whom had enjoyed it. Of those who did not take part, 34% said they would like to. Participation in sport was associated with some personal characteristics but not with support needs, and was also associated with indicators of socioeconomic status.

Conclusions  Targeting interventions to increase participation in sports by people with intellectual disabilities may make a significant contribution to improving their health and well‐being.
Is the human population a large‐scale indicator of the species richness of ground beetles?
Authors: Barbosa A. M. , Fontaneto D. , Marini L. , Pautasso M.
Published: March 2010

Empirical evidence has often shown a large‐scale positive co‐occurrence of biodiversity‐rich and densely populated regions. This biogeographical pattern has important implications for conservation biology. Previous studies have supported two of the potential mechanisms behind this pattern: the distributions of biodiversity and of human beings tend to match climatic patterns, and human beings have settled in regions of higher habitat heterogeneity or they may have increased it. There has been little testing and evidence for an artefactual explanation: more populated regions may show more species only because of a more thorough sampling. Using a new country‐wide dataset, we tested whether the human population density correlates with the species richness of ground beetles in Italy's regions, provinces and 10 × 10 km (UTM) grid cells. As expected, the observed and estimated (Chao index) number of species increases significantly with increasing human population density for regions, while there is no significant variation for provinces. But this is not the case when controlling for sampling effort. Variations in observed and estimated species richness are primarily associated with the available number of records, which is in turn well correlated with human population size. These results were confirmed for endemic and widespread species richness. At the UTM level, when controlling for sampling effort and area, there was a significant positive correlation between the total/widespread species richness and variation in the human population size, while the correlation was negative for endemic species. We found no significant role of habitat heterogeneity in the above relationships. The available distributional data of Carabidae in Italy suggest (1) that the species richness of bio‐indicators may not be a reliable measure for regional biological assessment; (2) that some broad‐scale human population–biodiversity correlations can be artefactual.
Biomarkers of aging in Drosophila
Authors: Jacobson Jake , Lambert Adrian J. , Portero‐Otín Manuel , Pamplona Reinald , Magwere Tapiwanashe , Miwa Satomi , Driege Yasmine , Brand Martin D. , Partridge Linda
Published: March 2010

Low environmental temperature and dietary restriction (DR) extend lifespan in diverse organisms. In the fruit fly Drosophila, switching flies between temperatures alters the rate at which mortality subsequently increases with age but does not reverse mortality rate. In contrast, DR acts acutely to lower mortality risk; flies switched between control feeding and DR show a rapid reversal of mortality rate. Dietary restriction thus does not slow accumulation of aging‐related damage. Molecular species that track the effects of temperatures on mortality but are unaltered with switches in diet are therefore potential biomarkers of aging‐related damage. However, molecular species that switch upon instigation or withdrawal of DR are thus potential biomarkers of mechanisms underlying risk of mortality, but not of aging‐related damage. Using this approach, we assessed several commonly used biomarkers of aging‐related damage. Accumulation of fluorescent advanced glycation end products (AGEs) correlated strongly with mortality rate of flies at different temperatures but was independent of diet. Hence, fluorescent AGEs are biomarkers of aging‐related damage in flies. In contrast, five oxidized and glycated protein adducts accumulated with age, but were reversible with both temperature and diet, and are therefore not markers either of acute risk of dying or of aging‐related damage. Our approach provides a powerful method for identification of biomarkers of aging.
Evaluating Non‐Uniform Residual Stress by the Hole‐Drilling Method with Concentric and Eccentric Holes. Part I. Definition and Validation of the Influence Functions
Authors: Beghini M. , Bertini L. , Mori L. F.
Published: March 2010

Abstract:  Residual stresses play a fundamental role in predicting the resistance of several structural components, in particular when operating under alternating loads or in aggressive environments. Among the measurement techniques, the hole‐drilling method is unrivalled in terms of cost and flexibility. The currently available data reduction techniques do not account for some important parameters, in particular the hole eccentricity, and can be directly used only with certain rosettes or require the partial holes to be drilled at fixed depths. This paper presents a general approach for interpreting hole‐drilling measurements that includes the hole eccentricity and several other geometric and material parameters. The method is based on analytical influence functions relating the measured relieved strains to the residual stress by means of integral equations. By elaborating the results of accurate finite‐element simulations, continuous analytical influence functions are produced, which can be used to reduce the error in the reconstructed residual stress. We focus on the definition of the influence functions, their evaluation and assessment.
OFFSHORING AND PRODUCTIVITY: A MICRO‐DATA ANALYSIS
Authors: Tang Jianmin , Do Livramento Henrique
Published: March 2010

Offshoring has become increasingly important for businesses, especially manufacturing firms, to compete in domestic and international markets. This paper empirically studies the association between offshoring, productivity, and plant characteristics by focusing on the geographical dimension of plants' business activities. Using data from Statistics Canada's Survey of Innovation 2005 and Annual Surveys of Manufacturers, we show that material offshoring is strongly associated with firms' outward‐oriented business activities (including foreign operation, investing in foreign M&E, and exporting), even after controlling for geographic advantages and industry‐ and plant‐specific effects. For R&D offshoring, we find that it is mainly associated with investment in foreign M&E. In addition, this paper shows that material offshoring is positively associated with productivity and that the association is significantly larger for material offshoring to Asia Pacific countries than for material offshoring to the U.S. and other locations.
Upregulation of indoleamine 2,3‐dioxygenase in hepatocyte during acute hepatitis caused by hepatitis B virus‐specific cytotoxic T lymphocytes in vivo
Authors: Iwamoto Naoki , Ito Hiroyasu , Ando Kazuki , Ishikawa Tetsuya , Hara Akira , Taguchi Ayako , Saito Kuniaki , Takemura Masao , Imawari Michio , Moriwaki Hisataka , Seishima Mitsuru
Published: March 2010

Background/Aims: Indoleamine‐2,3‐dioxygenase (IDO) is a tryptophan‐catabolizing enzyme inducing suppression of T‐cell function and immune tolerance. In hepatitis B virus (HBV) transgenic (Tg) mice, the adoptive transfer of HBV‐specific cytotoxic T lymphocytes (CTL) causes a necroinflammatory liver disease that is histologically similar to acute viral hepatitis in man. The present study aimed to determine IDO expression in the liver and hepatocytes during an acute hepatitis model.

Methods: Serum l‐kynurenine (l‐Kyn) concentration in HBV Tg mice administered with HBV‐specific CTL was measured over time, together with serum levels of alanine aminotransferase (ALT). Furthermore, we examined the expression of IDO in the total liver and isolated hepatocytes of HBV Tg mice after CTL injection using immunohistochemical analysis and reverse‐transcription polymerase chain reaction (PCR).

Results: In HBV Tg mice, HBV‐specific CTL induced, over the course of several days, a chronic increase in serum l‐Kyn levels, which was associated with a sustained enhancement of liver IDO activity. In particular, IDO expression was enhanced in the liver parenchymal cells (hepatocytes) after HBV‐specific CTL injection both in immunohistochemical analysis and in reverse‐transcription PCR. Moreover, murine recombinant interferon‐γ (IFN‐γ) directly increased the IDO expression in primary hepatocytes in vitro.

Conclusions: Cytotoxic T lymphocytes transduction results in the upregulation of IDO, which might downregulate T‐cell responsiveness. Our findings provide evidence that hepatocyte itself expresses IDO and increases levels of l‐Kyn in the blood in acute lethal hepatitis of mice. These data indicate that HBV infection facilitates the induction of IDO in response to proinflammatory cytokines, particularly IFN‐γ.
The anti‐inflammatory effect of celecoxib does not prevent liver fibrosis in bile duct‐ligated rats
Authors: Yu Jun , Hui Alex Y. , Chu Eagle S. H. , Go Minnie Y. Y. , Cheung Kin F. , Wu Chung W. , Chan Henry L. Y. , Sung Joseph J. Y.
Published: March 2010

Background/Aims:Celecoxib was used in the treatment of inflammation in patients with cirrhosis. However, data on the progression of liver fibrosis after treatment by celecoxib are not available. This study aims to elucidate the effects of celecoxib on cholestatic liver fibrosis in rats.

Methods:Rats underwent bile duct ligation (BDL) for 1 or 2 weeks to induce hepatic fibrosis. Celecoxib was introduced on day 1 after operation. The effects of celecoxib were assessed by comparison of the severity of hepatic fibrosis.

Results:Infiltration of inflammatory cells and proliferation of bile ducts was seen after 1 week of BDL and fibrosis was induced after 2 weeks. Reduced alanine aminotransferase (ALT) levels and blunted expression of inflammatory factors [tumour necrosis factor‐α, interleukin (IL)‐1β and IL‐6] were seen in the liver of BDL‐treated rats that received celecoxib at week 1. Although celecoxib was sufficient in suppressing the cyclo‐oxygenase (COX)‐2 expression in the control organ (kidney), it failed to suppress the enhanced hepatic COX‐2 expression. At week 2, celecoxib did not alter the ALT level, the severity of fibrosis and hepatic collagen contents. This was associated with unchanged α‐smooth muscle actin protein expression and tissue inhibitor of metalloproteinase‐2 (TIMP‐2), matrix metalloproteinase (MMP)‐2 and MMP‐9 mRNA expressions in the liver. Celecoxib had no effect on the BDL‐dependent increase in bilirubin levels at any time point.

Conclusions:The present study provides morphological and molecular biological evidences for the role of celecoxib in cholestatic liver fibrosis. Celecoxib protects against hepatic inflammation in the early stage of BDL rats, but does not have an effect on liver fibrosis.
Targeting vascular endothelial growth factor with the monoclonal antibody bevacizumab inhibits human hepatocellular carcinoma cells growing in an orthotopic mouse model
Authors: Finn Richard S. , Bentley Greg , Britten Carolyn D. , Amado Rafael , Busuttil Ronald W.
Published: March 2010

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related death worldwide. Liver resection or transplantation is curative for a subset of patients with localized disease, but treatments for advanced disease are generally toxic and ineffective. Aberrant expression of the vascular endothelial growth factor (VEGF) has been implicated in the progression of HCC and represents a valid target for anticancer therapy. Bevacizumab, a humanized anti‐VEGF monoclonal antibody, is currently being evaluated in the treatment of HCC. In addition, other novel anti‐angiogenesis agents are being developed in HCC.

Aim: This study examines the effect of bevacizumab in a newly characterized orthotopic model of the disease using the human HCC cell line, Hep 3B, and provides preclinical evidence that an anti‐angiogenic approach holds promise in HCC.

Results: Administration of bevacizumab 5 mg/kg intraperitoneal twice a week significantly decreased microvessel density in tumours, decreased human serum α‐fetoprotein measurements and prolonged the time to progression for treatment mice compared with control mice.

Conclusions: Our findings suggest that targeting VEGF with bevacizumab may be an effective approach to the treatment of HCC and further study of other novel anti‐angiogenic agents in HCC is warranted.
The knockdown of endogenous replication factor C4 decreases the growth and enhances the chemosensitivity of hepatocellular carcinoma cells
Authors: Arai Masaaki , Kondoh Nobuo , Imazeki Nobuo , Hada Akiyuki , Hatsuse Kazuo , Matsubara Osamu , Yamamoto Mikio
Published: March 2010

Aims:To identify differentially expressed genes and thereby detect potential molecular targets for future therapies directed against hepatocellular carcinoma (HCC).

Methods:To isolate differentially expressed genes between HCC and adjacent non‐cancerous liver tissues, cDNA microarray and quantitative reverse transcriptase polymerase chain reaction analyses were performed. Gene knockdown experiments in HepG2 cells were also performed using small interfering RNAs (siRNAs). Proteins were detected by immunostaining, and cell proliferation was analysed using the MTT/WST‐8 assay. Apoptosis and cell cycle analyses were performed using flow cytometry.

Results:After an intensive screening for differentially expressed genes in HCC tissues, we isolated 23 upregulated genes in these lesions. Among these, we focused on the replication factor C4 (RFC4) gene. The expression of endogenousRFC4proteins in HepG2 cells was found to be significantly reduced byRFC4‐specific siRNA. This inhibition ofRFC4expression correlated with a decrease in cellular proliferation, increased levels of apoptosis and a sensitizing of the cells to the DNA‐damaging chemotherapeutic agents, doxorubicin and camptothecin.

Conclusion:The replication factor C4 gene may be a novel target for developing cancer therapeutics, which can enhance the antitumour activity of chemotherapeutic agents that induce DNA damage.
Activated protein C prevents hepatic ischaemia–reperfusion injury in rats
Authors: Kuriyama Naohisa , Isaji Shuji , Hamada Takashi , Kishiwada Masashi , Ohsawa Ichiro , Usui Masanobu , Sakurai Hiroyuki , Tabata Masami , Suzuki Koji , Uemoto Shinji
Published: March 2010

Background: Hepatic ischaemia–reperfusion injury (IRI) is a serious complication of liver surgery, especially extended hepatectomy and liver transplantation. Activated protein C (APC), a potent anticoagulant serine protease, has been shown to have cell‐protective properties by virtue of its anti‐inflammatory and anti‐apoptotic activities.

Methods: The present study was designed to examine the cytoprotective effects of APC in a 60‐min warm‐IRI rat model.

Results: Following a single intravenous injection of APC before reperfusion, APC exerted cytoprotective effects 4 h after reperfusion, as evidenced by: (i) decreased levels of transaminase and improved histological findings of IRI, (ii) reduced infiltration and activation of neutrophils, macrophages and T cells, (iii) reduced expression of tumour necrosis factor‐α, (iv) reduced expression of P‐selectin and intracellular adhesion molecule‐1, (v) inhibited coagulation and attenuated sinusoidal endothelial cell injury, (vi) improved hepatic microcirculation and (vii) decreased transferase‐mediated dUTP nick end‐labelling‐positive cells. These effects of APC were observed 4 h but not 24 h after reperfusion. However, multiple injections of APC after reperfusion significantly decreased the levels of transaminase and the activity of myeloperoxidase, and improved histological findings of IRI 24 h after reperfusion.

Conclusion: These results suggest that APC is a promising therapeutic option for hepatic warm‐IRI; however, multiple injections of APC are necessary to maintain its cell‐protective action over the long term.
Morbidity and mortality after liver resection for benign and malignant hepatobiliary lesions
Authors: Erdogan Deha , Busch Olivier R. C. , Gouma Dirk J. , Van Gulik Thomas M.
Published: March 2010

Aim: Although most partial liver resections are performed for malignant lesions, an increasing contingent of benign lesions is also considered for surgery. The aim was to assess post‐operative morbidity and mortality after liver resection for benign hepatobiliary lesions in comparison with outcome after resection of malignant lesions.

Methods: A total of 286 liver resections were undertaken between January 1992 and December 2004. After exclusion of resection for bile duct tumours or hepatocellular carcinoma, 205 partial liver resections were retrospectively analysed.

Results: Patients with benign lesions comprised 34% of the group (n=70). Benign lesions mainly consisted of focal nodular hyperplasia (n=12; 17%) and liver haemangiomas (11; 15.7%). The malignant lesions consisted of colorectal tumour metastases (n=121; 89%). Patients with benign lesions predominantly underwent minor liver resections (66 vs. 47%; P=0.013). The overall post‐operative morbidity occurred in 31% (64/205). Major morbidity occurred in 16% (22/135) in the malignant group compared with 9% (6/70) in the benign group (P=0.099). No differences were seen in major post‐operative morbidity in the earlier period compared with the later period (14 vs. 14.3%, P=0.950). In multivariate analysis, only presence of comorbidity (P=0.017), prolonged surgical procedure (P=0.021) and surgical irradicality (P=0.039) maintained significance as independent risk factors for major morbidity.

Conclusion: Limited liver resections for the treatment of a wide range of benign hepatobiliary lesions are associated with low morbidity and no mortality. However, the indications must be assessed with care. The presence of comorbidity, prolonged surgical time and incomplete resections were associated with major morbidity.