bluuebunny/crossref_metadata_2025 huggingface dataset:
What's new: innovative concepts in inflammatory bowel disease
Authors: Sandborn W. J.
Published: March 2006

Inflammatory bowel disease (IBD) has been the subject of recent intense research and development. A greater insight into the basic pathological mechanisms of ulcerative colitis (UC) and Crohn's disease (CD) has resulted in the emergence of more sophisticated and effective management options. Additionally, established therapies are attracting renewed interest with novel dosage regimens and new formulations offering improved efficacy whilst maintaining an excellent tolerance profile.

High dose 5‐aminosalicylic acid (5‐ASA) has been a focus for investigation in recent clinical trials. The ASCEND study, which compared a 4.8 g/day dose with a 2.4 g/day dose, demonstrated that high dose mesalazine was significantly superior in achieving treatment success and symptom control, whilst maintaining a comparable tolerance and safety profile. The development of biotechnology agents targeted against tumour necrosis factor (TNF) provides promise of new treatment options in both CD and UC. The efficacy of CDP571, adalimumab and certolizumab have been investigated in CD, and infliximab, which is currently approved as an agent in inflammatory and fistulizing CD, has also been recently investigated in UC. Investigational pipeline molecules such as natalizumab, MLN‐02, an anti‐interleukin 12 antibody and sargramostim, have also shown encouraging results from early studies and are now undergoing evaluation in large clinical trials.
Inflammatory bowel disease: the view of the surgeon
Authors: Hancock L. , Windsor A. C. , Mortensen N. J.
Published: March 2006

Despite advances in medical therapy, surgery is required in approximately 30–40% of patients with ulcerative colitis (UC) and 70–80% of patients with Crohn's disease (CD) at some point during their lifetime. For patients with UC, surgery may be curative, whereas recurrence of CD following surgery is common due to the potentially pan‐enteric distribution of the disease. As a result, the indications and surgical management of the disease may be quite different. For UC, the surgeon is involved in the identification of new cases, management of severe disease, recognition of dysplasia and restorative proctocolectomy. Most of the advances in surgery for UC have been in novel techniques relating to the ileal pouch–anal anastomosis, which can now be performed safely for UC with a 10% pouch failure rate long term. For CD, the surgeon is involved in the management of small bowel and ileo‐colonic disease, Crohn's colitis and perianal disease. Advances in the surgical management of CD include strictureplasty for extensive small bowel disease, laparoscopic ileo‐caecal resection and a combined medical and surgical approach to perianal disease. For both CD and UC close liaison between the gastroenterologist and colorectal surgeon is essential.
New lessons: classic treatments, expanding options in ulcerative colitis
Authors: Hanauer S. B.
Published: March 2006

Ulcerative colitis (UC) of moderate severity is a common presentation in gastroenterological practice and a number of treatment options exist to rapidly and effectively induce remission. This review highlights how novel formulations and dosing regimens can ensure treatment success at a greater convenience for the patient with no increased risk of adverse effects. 5‐aminosalicyclic acid (5‐ASA) is well tolerated with a low incidence of adverse effects, and has a significant role in the management of UC. Different formulations of oral 5‐ASA are now available and allow targeted treatment to inflammatory areas of the small bowel and ascending colon. 5‐ASA is often initiated at a low dose for patients with mild to moderately active UC and with increasing doses for those who fail or have a poor response. 5‐ASA at high doses is increasingly being used as induction therapy for active UC, particularly in patients with recurrent and/or extensive disease. The recent ASCEND studies show that an induction dose of 5‐ASA of 4.8 g daily in patients with moderate UC is significantly more effective and resolves symptoms faster compared with a daily dose of 2.4 g. The evidence provided by the ASCEND studies support the rationale for a ‘top‐down’ dosing strategy for UC where more potent therapies are introduced at an earlier stage of moderately severe disease.
New thinking: theory vs practice. A case study illustrating evidence‐based therapeutic decision making
Authors: Travis S. P. L.
Published: March 2006

Evidence‐based medicine (EBM) plays a key role for decision making in clinical practice. Clinicians are encouraged to adhere to treatment guidelines based on high quality clinical trials, systematic reviews and meta‐analyses, that are the focus of the Cochrane Collaboration. EBM is not, however, a panacea for medical decision making. The results of randomized clinical trials apply to populations of patients, and the challenge is to translate the results to individuals. Individual patients require different thought processes because presentation and response vary, and external factors (e.g. patient preference) influence the choice of treatment. The application of EBM demands clinical judgement. The case of a 28 year old scientist who presented with typical features of moderate ulcerative colitis, illustrates the dilemma. At each stage of his illness the treatment options based on EBM were discussed, including high dose 5‐aminosalicyclic acid with or without topical therapy, corticosteroids, infliximab, immunomodulation, complementary therapy and surgery. Ultimately, therapeutic decisions depended on the patient's circumstances, preferences and response. Decisions should avoid circular motion caused by the illusion of progress and always consider the direction of travel.
Degradation in insulin sensitivity with increasing severity of the metabolic syndrome in obese postmenopausal women
Authors: Karelis A. D. , Henry J.‐F. , St‐Pierre D. H. , Prud'homme D. , Rabasa‐Lhoret R.
Published: March 2006

Aim:  We investigated the relationship between insulin sensitivity and the graded increase in the number of features of the metabolic syndrome in a cross‐sectional sample of obese postmenopausal women. We hypothesized that insulin sensitivity would deteriorate with an increased number of metabolic syndrome phenotypes.

Methods:  Insulin sensitivity was measured in 75 obese postmenopausal women (age: 57.3 ± 5.3 years; BMI: 32.8 ± 4.5 kg/m2) by using both the hyperinsulinaemic–euglycaemic clamp and the homeostasis model assessment (HOMA‐IR). Features of the metabolic syndrome included visceral fat (>130 cm2), HDL‐cholesterol (<1.29 mmol/l), fasting triglycerides (≥1.7 mmol/l), blood pressure (≥130/≥85 mmHg) and fasting glucose (≥6.1 mmol/l). Participants were classified into three categories based on the presence of metabolic syndrome phenotypes: 0–1 vs. 2 vs. ≥3 features of the metabolic syndrome.

Results:  We found that insulin sensitivity decreased in a graded fashion (12.19 ± 3.2 vs. 11.80 ± 2.3 vs. 9.29 ± 2.6 mg/min/FFM) and HOMA‐IR increased in a similar manner (2.95 ± 1.1 vs. 3.28 ± 1.3 vs. 4.65 ± 2.2), as the number of features of the metabolic syndrome increased from 0–1 to ≥3. When insulin sensitivity was statistically adjusted for visceral fat (as measured by computed tomography) and plasma triglycerides, the differences among groups were abolished.

Conclusions:  These findings suggest that a decreased insulin sensitivity is associated with increased features of the metabolic syndrome in obese postmenopausal women and that visceral fat as well as plasma triglyceride accumulation might be potential mediators of this relationship.
Effect of fat distribution on endothelial‐dependent and endothelial‐independent vasodilatation in healthy humans
Authors: Williams I. L. , Chowienczyk P. J. , Wheatcroft S. B. , Patel A. , Sherwood R. , Momin A. , Shah A. M. , Kearney M. T.
Published: March 2006

Aim:  The present study aims to explore the relationship between inflammatory cytokines, plasma lipids, insulin, blood pressure (BP), total adiposity/markers of fat distribution and endothelial function in healthy people across a wide range of body fatness.

Methods:  Seventy‐three healthy people (44 women; age range: 24–64 years) with body mass index (BMI) range of 18.6–73.1 kg/m2 were recruited. All participants underwent assessment of conduit artery endothelial‐dependent vasodilatation by using flow‐mediated vasodilatation (FMD) of the brachial artery and endothelial‐independent vasodilatation to sublingual GTN. They had blood taken for measurement of plasma markers of glucose homeostasis (fasting insulin and glucose), systemic inflammation (interleukin‐6 (IL‐6), C‐reactive protein (CRP) and tumour necrosis factor‐α receptor 2 (TNF‐α R2)) and lipids (low‐density lipoprotein (LDL), high‐density lipoprotein (HDL) and triglycerides). Morphometric assessment (waist circumference, BMI and waist‐to‐hip ratio (WHR)) and systolic and diastolic arterial pressure were also measured.

Results:  Markers of total body fat/fat distribution (waist circumference, BMI and WHR), inflammation (IL‐6, CRP and TNF‐α R2), metabolism (fasting insulin, HDL, LDL and triglycerides) and BP (systolic and diastolic) correlated with FMD. Among these measurements, WHR was the only independent predictor of FMD (r2 = 0.30; p = 0.0001).

Conclusions:  WHR is an important marker of endothelial dysfunction in healthy people across a wide range of body fatness.
Phenotypic variations between a fat‐preferring strain and a macronutrient non‐preferring strain of mouse
Authors: South T. , Huang X.‐F.
Published: March 2006

Aim: This study aims to establish a model that will allow the comparison of the phenotypic variations between a fat‐preferring strain and a macronutrient non‐preferring strain of mouse.

Methods: Five strains (AKR, A/J, ARC, C57Bl/6 and BALB/c) were fed a two‐choice diet (high‐fat/low‐carbohydrate and low‐fat/high‐carbohydrate) for 30 days. Following completion of the 30‐day feeding period, the brains of the fat‐preferring and macronutrient non‐preferring mice were removed for the analysis of the expression of the genes – agouti‐related peptide (AgRP) and pro‐opiomelanocortin (POMC).

Results: Upon completion of the experiment, it was found that the C57Bl/6 strain was the strongest fat preferrer consuming 72% of their calories from the high‐fat diet, whereas the BALB/c was found to have no macronutrient preference. Usingin situhybridization techniques, no significant differences in the expression of POMC were found between the two strains. It was, however, showed that the BALB/c mice had a 33.7% higher expression level of AgRP than the C57Bl/6 mice.

Conclusions: The lower expression level of AgRP in the C57Bl/6 mice may be suggestive of a defensive response to their chronic preferential consumption of the high‐fat diet. However, the wide variety of neuroregulatory signals involved in macronutrient preference along with the possibility of the occurrence of post‐transcriptional effects suggests further biological analyses need to be performed using this model.
Energy expenditure, body composition and insulin response to glucose in male twins discordant for the Trp64Arg polymorphism of the β3‐adrenergic receptor gene
Authors: Højlund K. , Christiansen C. , Bjørnsbo K. S. , Poulsen P. , Bathum L. , Henriksen J. E. , Lammert O. , Beck‐Nielsen H.
Published: March 2006

Aim:  The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the β3‐adrenergic receptor (β3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role.

Methods:  In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual‐energy X‐ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry.

Results:  Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild‐type co‐twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post‐prandial energy expenditure.

Conclusions:  In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the β3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.
Insulin stimulates arterial neointima formation in normal rats after balloon injury
Authors: Foster E. , Zhang S. , Kahn A. M.
Published: March 2006

Aim:  Insulin resistance in patients is associated with increased atherosclerosis and arterial restenosis. It is thought that the concomitant hyperinsulinaemia exacerbates vascular disease because resistance to insulin‐induced glucose disposal is associated with resistance to certain effects of insulin which inhibit, but with no resistance to other effects which promote, neointimal hyperplasia. We sought to determine the net effect of hyperinsulinaemia on neointimal hyperplasia in normal animals.

Methods:  Rats were infused with or without insulin for 16 days and the carotid artery injured by balloon catheter on day 2.

Results:  Steady‐state serum insulin concentrations were 0.56 ± 0.04 and 1.25 ± 0.05 nm for control and hyperinsulinaemic rats respectively (p < 0.01). Systolic blood pressures, weights and serum glucose levels were not affected by hyperinsulinaemia. Fourteen days after injury, the neointima‐to‐media area ratio was 0.72 ± 0.07 and 1.39 ± 0.15 for control and hyperinsulinaemic rats respectively (p < 0.05). Media area was unaffected by hyperinsulinaemia.

Conclusions:  The effects of hyperinsulinaemia which promote neointimal hyperplasia after balloon injury of rat carotid artery predominate over the effects which inhibit it even in normal animals.
Insulin resistance – a common link between type 2 diabetes and cardiovascular disease
Authors: Lebovitz Harold E.
Published: March 2006

Evidence suggests that diabetes and cardiovascular disease (CVD) may share an underlying cause(s), a theory known as the ‘common soil’ hypothesis. Insulin resistance is central both to the progression from normal glucose tolerance to type 2 diabetes and to a constellation of cardiovascular risk factors known as the metabolic syndrome. These risk factors include visceral obesity and dyslipidaemia characterized by low levels of high‐density lipoprotein cholesterol, hypertriglyceridaemia and raised small dense low‐density lipoprotein particle levels. Changes in adipose tissue mass and metabolism may link insulin resistance and visceral obesity, a condition that is common in type 2 diabetes. Furthermore, weight reduction, increased physical activity, metformin and acarbose have been shown to reduce the development of type 2 diabetes in genetically predisposed subjects and may decrease the high cardiovascular risk of patients with diabetes. Some fatty acid derivatives can affect energy metabolism by activating peroxisome proliferator‐activated receptors (PPARs), nuclear receptors that play a key role in energy homeostasis. These receptors represent an ideal therapeutic target for reducing cardiovascular risk, because they are involved in the regulation of both insulin action and lipid metabolism. In addition to lifestyle changes, PPARγ agonists such as thiazolidinediones are frequently beneficial and have been shown to ameliorate insulin resistance, while activation of PPARα (e.g. by fibrates) can lead to improvements in free fatty acid oxidation and lipid profile, and a reduction in cardiovascular events. The development of agents with both PPARα and PPARγ activity promises added benefits with amelioration of insulin resistance, delayed progression to and of type 2 diabetes and a reduction of CVD.
Statistica data analytica est et aliter*
Authors: Gower J. C.
Published: March 2006

This paper comprises general comments on some current statistical issues, inspired in part by some papers that have been published in Statistica Neerlandica. Occasional glimpses of the future are hazarded.
Re‐examining 50‐year‐old OLS estimates of the Klein–Goldberger model
Authors: McCullough B. D. , Renfro Charles G. , Stokes Houston H.
Published: March 2006

This paper examines the ordinary least squares estimates of the Klein–Goldberger model by Fox (Journal of Political Economy, 64, 1956, 128). Because Klein and Goldberger published the data set with the model, it is possible to re‐examine Fox's results years later, and investigate the accuracy with which these estimates were calculated. The examination reported in this paper was conducted by making independent estimates using three different modern econometric software packages. This examination reveals that the Fox estimates for a number of the equations of this model are replicable, to the two or three digits reported by Fox. Fox's results for other equations cannot be replicated. Not all the reasons for this lack of replicability can be determined, but in several cases the computational methods used by Fox and his assistants have been found to be faulty by modern computational standards.
Models and methods for economic policy: 60 years of evolution at CPB*
Authors: Don F. J. H. , Verbruggen J. P.
Published: March 2006

What is now known in English as the Netherlands Bureau for Economic Policy Analysis (CPB) has been involved in econometric model building since its foundation in 1945. During the 60 years of developing and using the models reviewed in this article, CPB's model building has evolved significantly. Over this period, a shift of emphasis can be observed from econometrics and empiricism to economic theory. New questions from policymakers and new features in the national economy have guided research, while new developments in econometrics and economic theory were taken on board wherever they helped to improve the quality and scope of the analysis. Although considerable progress has been achieved in several spheres, even the most sophisticated and up‐to‐date models continue to be riddled with some longstanding limitations and weaknesses.
Proliferation and apoptosis of hippocampal granule cells require local oestrogen synthesis
Authors: Fester L. , Ribeiro‐Gouveia V. , Prange‐Kiel J. , Von Schassen C. , Böttner M. , Jarry H. , Rune G. M.
Published: March 2006

Ovarian oestrogens have been demonstrated to influence neurogenesis in the dentate gyrus. As considerable amounts of oestrogens are synthesized in hippocampal neurones, we focused on the role of hippocampus‐derived estradiol on proliferation and apoptosis of granule cells in vitro. We used hippocampal dispersion cultures, which allowed for cultivation of the cells under steroid‐ and serum‐free conditions and monitoring of oestrogen synthesis. To address the influence of hippocampus‐derived estradiol on neurogenesis, we inhibited oestrogen synthesis by treatment of hippocampal cell cultures with letrozole, a specific aromatase inhibitor. Alternatively, we used siRNA against steroidogenic acute regulatory protein (StAR). The number of proliferative cells decreased whereas the number of apoptotic cells increased dose‐dependently, in response to reduced estradiol release into the medium after treatment with letrozole. This also held true for siRNA against StAR transfected cell cultures. Application of estradiol to the medium had no effect on proliferation and apoptosis whereas the anti‐proliferative and pro‐apoptotic effects of StAR knock‐down and letrozole treatment were restored by treatment of the cultures with estradiol. Our findings suggest that neurogenesis and apoptosis in the hippocampus require a defined range of estradiol concentrations that is physiologically provided by hippocampal cells but not by gonads.
Are Physician Reimbursement Strategies Associated with Processes of Care and Patient Satisfaction for Patients with Diabetes in Managed Care?
Authors: Ettner Susan L. , Thompson Theodore J. , Stevens Mark R. , Mangione Carol M. , Kim Catherine , Neil Steers W. , Goewey Jennifer , Brown Arleen F. , Chung Richard S. , Venkat Narayan K. M. ,   the TRIAD Study Group
Published: March 2006

Objective. To examine associations between physician reimbursement incentives and diabetes care processes and explore potential confounding with physician organizational model.

Data Sources. Primary data collected during 2000–2001 in 10 managed care plans.

Study Design. Multilevel logistic regressions were used to estimate associations between reimbursement incentives and process measures, including the receipt of dilated eye exams, foot exams, influenza immunizations, advice to take aspirin, and assessments of glycemic control, proteinuria, and lipid profile. Reimbursement measures included the proportions of compensation received from salary, capitation, fee‐for‐service (FFS), and performance‐based payment; the performance‐based payment criteria used; and interactions of these criteria with the strength of the performance‐based payment incentive.

Data Collection. Patient, provider group, and health plan surveys and medical record reviews were conducted for 6,194 patients with diabetes.

Principal Findings. Without controlling for physician organizational model, care processes were better when physician compensation was based primarily on direct salary rather than FFS reimbursement (four of seven processes were better, with relative risks ranging from 1.13 to 1.23) or capitation (six were better, with relative risks from 1.06 to 1.36); and when quality/satisfaction scores influenced physician compensation (three were better, with relative risks from 1.17 to 1.26). However, these associations were substantially confounded by organizational model.

Conclusions. Physician reimbursement strategies are associated with diabetes care processes, although their independent contributions are difficult to assess, due to high correlation with physician organizational model. Regardless of causality, a group's use of quality/satisfaction scores to determine physician compensation may indicate delivery of high‐quality diabetes care.
Practice Characteristics Associated with Patient‐Specific Receipt of Dental Diagnostic Radiographs
Authors: Gilbert Gregg H. , Weems Richard A. , Litaker Mark S. , Shelton Brent J.
Published: March 2006

Objective. To quantify the role of practice characteristics in patient‐specific receipt of dental diagnostic radiographic services.

Data Source/Study Setting. Florida Dental Care Study (FDCS).

Study Design. The FDCS was a 48‐month prospective observational cohort study of community‐dwelling adults. Participants' dentists were asked to complete a questionnaire about their practice characteristics.

Data Collection/Extraction Methods. In‐person interviews and clinical examinations were conducted at baseline, 24, and 48 months, with 6‐monthly telephone interviews in between. A single multivariate (four radiographic service outcomes) multivariable (multiple explanatory covariates) logistic regression was used to model service receipts.

Principal Findings. These practice characteristics were significantly associated with patient‐specific receipt of radiographic services: number of different practices attended during follow‐up; dentist's rating of how busy the practice was; typical waiting time for a new patient examination; practice size; percentage of patients that the dentist reported as interested in details about the condition of their mouths; percentage of African American patients in the practice; percentage of patients in the practice who do not have dental insurance; and dentist's agreement with a statement regarding whether patients should be dismissed from the practice. Effects had differential magnitudes and directions of effect, depending upon radiograph type.

Conclusions. Practice characteristics were significantly associated with patient‐specific receipt of services. These effects were independent of patient‐specific disease level and patient‐specific sociodemographic characteristics, suggesting that practitioners do influence receipt of these diagnostic services. These findings are consistent with the conclusion that practitioners act in response to a mix of patients' interests, economic self‐interests, and their own treatment preferences.
Familial Pseudo‐Wolff‐Parkinson‐White Syndrome
Authors: STERNICK EDUARDO BACK , OLIVA ANTONIO , MAGALHÃES LUIZ P. , GERKEN LUIZ M. , HONG KUI , SANTANA OTO , BRUGADA PEDRO , BRUGADA JOSEP , BRUGADA RAMON
Published: March 2006

Introduction: PRKAG2 plays a role in regulating metabolic pathways, and mutations in this gene are associated with familial ventricular preexcitation, hypertrophic cardiomyopathy, and atrioventricular conduction disturbances. Clinico‐pathologic and experimental data suggest the hypothesis of a glycogen storage disease.

Objective: To report a unique pattern of clinical features observed in individuals with a mutant PRKAG2 from two unrelated families.

Methods and Results: We studied two large families and found a total of 20 affected individuals showing a combination of sinus bradycardia, short PR interval, RBBB, intra and infrahisian conduction disturbances often requiring a pacemaker, and atrial tachyarrhythmias. Three individuals died suddenly at a young age. No patient had the Wolff‐Parkinson‐White (WPW) syndrome, and only two patients (10%) had myocardial hypertrophy. We performed screening of the exons and exon‐intron boundaries of PRKAG2. Genetic analysis revealed a missense mutation (Arg302Gln) in the affected individuals from both families. This mutation had been described before and has been associated with the familial form of the WPW syndrome and with a high prevalence of left ventricular hypertrophy.

Conclusion: PRKAG2 mutations are responsible for a diverse phenotype and not only the familial form of the WPW syndrome. Familial occurrence of right bundle branch block, sinus bradycardia, and short PR interval should raise suspicion of a mutant PRKAG2 gene.
Technological and policy options for sustainable agricultural intensification in eastern Uganda
Authors: Woelcke Johannes
Published: March 2006

This article presents a bio‐economic household model, which has been developed to assess the potential impacts of agricultural intensification efforts on economic and ecological indicators in eastern Uganda. A study region in the Lake Victoria Crescent was selected with comparative advantages for intensive agricultural production: high agricultural potential, high market access, and high population density. However, current production is characterized by low input–output systems revealing a discrepancy between development opportunities and actual development outcomes. Based on a farmer participatory research approach, production methods were introduced in the study region aimed at fostering sustainable agricultural development. Data from two community surveys, two comprehensive household and plot level surveys, and farm‐trial data were used to develop and calibrate bio‐economic models for four representative household types. Model scenarios reveal that farm households in eastern Uganda would not pursue sustainable intensification under current socio‐economic conditions. The market environment has to be improved substantially, i.e., transaction and transportation costs have to be reduced, innovative credit schemes for smallholders have to be introduced, and alternative forms of labor acquisition have to be promoted, to provide sufficient economic incentives for the adoption of environmentally sound production methods. In addition, agricultural service provision needs to be reformed and more agricultural research is needed for new and better‐targeted technologies.
Policies for sustainable development in the hillside areas of Honduras: a quantitative livelihoods approach
Authors: Jansen Hans G. P. , Pender John , Damon Amy , Wielemaker Willem , Schipper Rob
Published: March 2006

In this article, we use data for 376 households, 1,066 parcels, and 2,143 plots located in 95 villages in the hillside areas in Honduras to generate information needed by decision makers to assess the needs and opportunities for public investments, and design policies that stimulate natural resource conservation. We develop a quantitative livelihood approach, using factor and cluster analysis to group households based on the use of their main assets. This resulted in seven household categories that pursue similar livelihood strategies. We use a multinomial logit model to show that livelihood strategies are determined by comparative advantages as reflected by a combination of biophysical and socioeconomic variables. While 92% of the rural hillsides population in Honduras lives on US$1.00/capita/day or less, households that follow a livelihood strategy based on basic grain farming are the poorest because they often live in isolated areas with relatively poor agro‐ecological and socioeconomic conditions. Opportunities for off‐farm work tend to be limited in these areas and household strategies that combine on‐farm work with off‐farm work earn higher incomes. Per capita incomes can be increased by improving road infrastructure, widening access to land, policies that reduce household size and dependency ratios, and adoption of sustainable land management technologies that restore soil fertility. We used probit models to show that the latter can be promoted by agricultural extension programs and land redistribution. Investments in physical assets should be directed toward households that pursue livelihood strategies based on off‐farm employment or coffee production, while agricultural training programs are best focused on livestock producers.
Tenure security, resource poverty, public programs, and household plot‐level conservation investments in the highlands of northern Ethiopia
Authors: Hagos Fitsum , Holden Stein
Published: March 2006

Land degradation poses a serious problem for the livelihoods of rural producers. Furthermore, there is rarely enough private investment taking place to commensurate the scale of the problem. This article examines the role of tenure insecurity, resource poverty, risk and time preferences, and community‐led land conservation on differentiated patterns of household investment in land conservation in northern Ethiopia. We control for biophysical, household characteristics, market access conditions, and village level factors. Investments in soil bunds and stone terraces are specifically studied so as to capture the link between these various factors and the durability of conservation investments. We introduce the distinction between the determinants of the decision to invest and how much to invest in conservation. Regression results show that publicly led conservation programs seem to significantly stimulate private investment. A host of plot‐level variables and household perceptions of returns on conservation investments, expressed in terms of perceived improvements in land quality and increased crop yields, were found to be critical to the decision to invest and intensify soil conservation. The evidence on the significance of households' attitudes toward risk aversion suggests the important role of risk and the household's risk‐bearing capacity in the decision to intensify conservation measures. At the same time, tenure security indicators and households' resource endowments (resource poverty) had weaker effects in increasing willingness to invest and the level of investment made. The policy implications of these results point to the importance of agricultural research and extension efforts that target technologies which reduce household risk and poverty while enabling sustainable investments in conservation measures by individual households.
Sustainable agricultural intensification in forest frontier areas
Authors: Maertens Miet , Zeller Manfred , Birner Regina
Published: March 2006

The Lore Lindu region in Indonesia—as in many forest frontier areas in Southeast Asia—has experienced rapid deforestation due to agricultural expansion in the uplands, at the forest margins. This has resulted in aggravated problems of erosion and water availability, threatening agricultural productivity growth. At the same time, technical progress is promoting agricultural intensification in the lowlands. In this article, we examine how improved technologies for paddy rice cultivation in the lowlands have affected agricultural expansion and deforestation in the uplands. The question of a “forest‐saving” or “forest‐clearing” effect related to technical innovation is important from a sustainable development perspective and remains a controversial issue in the literature. We address this question for the Lore Lindu region with an empirical model in which expansion in the lowlands and the uplands is estimated simultaneously. We use data from an extensive village survey conducted in the region, combined with GIS data. To guide the empirical analysis, we develop a theoretical framework based on a Chayanov‐type agricultural household model. The model analyzes farmers' land allocation decisions, taking into account the lowland–upland dichotomy in the agricultural sector. The empirical findings, corroborated by the analytically derived results, show how technical progress for lowland production affects land use at the forest margins and how these effects depend on the factor‐intensity of the technology. The findings imply specific rural development policies for sustainable agricultural intensification in forest frontier areas.
Improved compliance and self‐care in patients with periodontitis – a randomized control trial
Authors: Jönsson B , Lindberg P , Oscarson N , Öhrn K
Published: March 2006

Abstract:  The present study was a randomized control trial to test an intervention emanating from the Client Self‐care Commitment Model (CSCCM), to encourage patients to increase their responsibility for their oral self‐care. Materials and methods: A total of 75 individuals were re‐examined 1–2 years after their initial therapy at the Department of Periodontology, Uppsala County Council, Sweden. Patients who exhibited insufficient compliance, 37 individuals, were included in a randomized single‐blind control trial to test an intervention based on the CSCCM. Patients were examined at baseline and 3 months after hygiene treatment. Results: The results demonstrated that patients in the intervention (IV) group increased their interdental cleaning and reduced their plaque index significantly compared with the control group. The former also reduced the number of periodontal pockets >4 mm significantly from baseline until after the hygiene treatment. The majority of the individuals in the IV group reported that the written commitment had influenced on their oral self‐care habits in a positive direction. Conclusions: The CSCCM enhanced the client participation in the treatment process and improved the compliance and oral self‐care behaviours. In addition, the model contributed to a reduction in periodontal pockets.
Development of a stain shade guide to aid the measurement of extrinsic dental stain
Authors: Gadhia K , Shah R , Swaminathan D , Wetton S , Moran J
Published: March 2006

Abstract:  Background: Accurate and reproducible assessment of extrinsic staining is pivotal to determining efficacy of some tooth whitening oral hygiene products. The aim of this study was: (1) to produce a stain shade guide to aid the in vitro and in vivo stain assessment (2) to assess intra‐ and inter‐examiner reproducibility of stain assessment using the stain shade guide. Method: Using chlorhexidine and tea, perspex and acrylic teeth specimens were stained. The amount of staining on the perspex was measured with a spectrophotometer and the values obtained were assigned to the stained acrylic teeth, which were made into a stain guide. Using clinical photographs and a group of 10 volunteers, stain area and intensity were assessed using the stain guide and the recognized Lobene stain index by two examiners. The degree of intra‐ and inter‐examiner reproducibility for these measurements were assessed using Cohen's kappa statistics. Results: For both the clinical examination and use of photographs, intra‐examiner reproducibility for stain intensity was improved when using the stain guide compared with the Lobene Index. Similarly, when assessing inter‐examiner reproducibility, stain intensity kappa values were greater using the stain guide (κ = 0.82) compared with the Lobene Index (κ = 0.57). Conclusion: The findings of this study would suggest that the use of the stain guide could be of importance in the assessment of extrinsic dental stain.
Learning priorities and attitudes towards computer‐assisted learning of general medical practitioners, general dental practitioners and dental hygienists
Authors: Al‐Wahadni A , Elnasser Z , Azab M , Owais AI
Published: March 2006

Objectives: The objectives of this survey were to assess the attitudes and learning priorities of general medical practitioners (GMPs), general dental practitioners (GDPs), and dental hygienists (DHs) working at Jordan University of Science and Technology (JUST), Irbid, Jordan in relation to post‐graduate education, to gather information on their attitudes and skills in using computers and computer‐assisted learning (CAL) and to see whether the material in this form is acceptable to participate as a means of teaching. Methods: Data for this study was gathered via a questionnaire distributed to 63 health professionals including GMPs, general dental practitioners and DHs (mean age 24.79 ± 2.69 years) working at JUST. Results: Of the 63 participants, 80% of the participants have home computers, 38% have office computers at work and only 25% have both home and office computers. Approximately 53% of the participants had their first CAL experience at home. Seventy‐three of the participants indicated that connection to Internet is necessary for their work. Seventy‐one of the participants were interested in the possibility of using CAL to further improve and increase their medical knowledge. The most important topic for doctors was ‘learning about new techniques which may supersede those in current use’, for DHs it was ‘improve knowledge or skill in radiology’, and for dentists it was ‘reinforcement of well established techniques commonly used in dental practice’. Conclusions: It is necessary for practicing health care professionals to update themselves by taking continuous education courses after graduation more conveniently via CAL methods.
Interaction between catalytically inactive calpain and calpastatin
Authors: Averna Monica , Stifanese Roberto , De Tullio Roberta , Defranchi Enrico , Salamino Franca , Melloni Edon , Pontremoli Sandro
Published: March 2006

Conformational changes in the calpain molecule following interaction with natural ligands can be monitored by the binding of a specific monoclonal antibody directed against the catalytic domain of the protease. None of these conformational states showed catalytic activity and probably represent intermediate forms preceding the active enzyme state. In its native inactive conformation, calpain shows very low affinity for this monoclonal antibody, whereas, on binding to the ligands Ca2+, substrate or calpastatin, the affinity increases up to 10‐fold, with calpastatin being the most effective. This methodology was also used to show that calpain undergoes similar conformational changes in intact cells exposed to stimuli that induce either a rise in intracellular [Ca2+] or extensive diffusion of calpastatin into the cytosol without affecting Ca2+ homeostasis. The fact that the changes in the calpain state are also observed under the latter conditions indicates that calpastatin availability in the cytosol is the triggering event for calpain–calpastatin interaction, which is presumably involved in the control of the extent of calpain activation through translocation to specific sites of action.
Identification of ERRα as a specific partner of PGC‐1α for the activation of PDK4 gene expression in muscle
Authors: Araki Makoto , Motojima Kiyoto
Published: March 2006

Pyruvate dehydrogenase kinase 4 (PDK4) is a key regulatory enzyme involved in switching the energy source from glucose to fatty acids in response to physiological conditions. Transcription of the PDK4 gene is activated by fasting or by the administration of a PPARα ligand in a tissue‐specific manner. Here, we show that the two mechanisms are independent, and that ERRα is directly involved in PPARα‐independent transcriptional activation of the PDK4 gene with PGC‐1α as a specific partner. This conclusion is based on the following evidence. First, detailed mutation analyses of the cloned PDK4 gene promoter sequence identified a possible ERRα‐binding motif as the PGC‐1α responsive element. Second, overexpression of ERRα by cotransfection enhanced, and the knockout of it by shRNAs diminished, PGC‐1α‐dependent activation. Third, specific binding of ERRα to the identified PGC‐1α responsive sequence was confirmed by the electrophoresis mobility shift assay. Finally, cell‐type‐specific responsiveness to PGC‐1α was observed and this could be explained by differences in the expression levels of ERRα, however, ectopic expression of ERRα in poorly responsive cells did not restore PGC‐1α responsiveness, indicating that ERRα is necessary, but not sufficient for the response.
The protein shuffle
Authors: Park Chin‐Ju , Choi Byong‐Seok
Published: March 2006

Xeroderma pigmentosum (XP) is an inherited disease in which cells from patients exhibit defects in nucleotide excision repair (NER). XP proteins A–G are crucial in the processes of DNA damage recognition and incision, and patients with XP can carry mutations in any of the genes that specify these proteins. In mammalian cells, NER is a dynamic process in which a variety of proteins interact with one another, via modular domains, to carry out their functions. XP proteins are key players in several steps of the NER process, including DNA strand discrimination (XPA, in complex with replication protein A), repair complex formation (XPC, in complex with hHR23B; XPF, in complex with ERCC1) and repair factor recruitment (transcription factor IIH, in complex with XPG). Through these protein–protein interactions, various types of bulky DNA adducts can be recognized and repaired. Communication between the NER system and other cellular pathways is also achieved by selected binding of the various structural domains. Here, we summarize recent studies on the domain structures of human NER components and the regulatory networks that utilize these proteins. Data provided by these studies have helped to illuminate the complex molecular interactions among NER factors in the context of DNA repair.
Dual role of Nbs1 in the ataxia telangiectasia mutated‐dependent DNA damage response
Authors: Lee Joo‐Hyeon , Lim Dae‐Sik
Published: March 2006

The Nbs1 protein associates with Mre11 and Rad50 proteins to form the Mre11–Rad50–Nbs1 complex, which plays an important role in the intracellular signaling pathway activated in response to DNA damage. Mutations in the genes for each of these three components of the Mre11–Rad50–Nbs1 complex result in human diseases characterized by genomic instability. Insight into the functions of Nbs1 in the DNA damage response mediated by the protein kinase, ataxia telangiectasia mutated, has been provided by recent studies. Nbs1 acts both as a downstream target of ataxia telangiectasia mutated in the S‐phase checkpoint of the cell cycle as well as an upstream modulator or activator of ataxia telangiectasia mutated in the DNA damage response.
Roles of base excision repair subpathways in correcting oxidized abasic sites in DNA
Authors: Sung Jung‐Suk , Demple Bruce
Published: March 2006

Base excision DNA repair (BER) is fundamentally important in handling diverse lesions produced as a result of the intrinsic instability of DNA or by various endogenous and exogenous reactive species. Defects in the BER process have been associated with cancer susceptibility and neurodegenerative disorders. BER funnels diverse base lesions into a common intermediate, apurinic/apyrimidinic (AP) sites. The repair of AP sites is initiated by the major human AP endonuclease, Ape1, or by AP lyase activities associated with some DNA glycosylases. Subsequent steps follow either of two distinct BER subpathways distinguished by repair DNA synthesis of either a single nucleotide (short‐patch BER) or multiple nucleotides (long‐patch BER). As the major repair mode for regular AP sites, the short‐patch BER pathway removes the incised AP lesion, a 5′‐deoxyribose‐5‐phosphate moiety, and replaces a single nucleotide using DNA polymerase (Polβ). However, short‐patch BER may have difficulty handling some types of lesions, as shown for the C1′‐oxidized abasic residue, 2‐deoxyribonolactone (dL). Recent work indicates that dL is processed efficiently by Ape1, but that short‐patch BER is derailed by the formation of stable covalent crosslinks between Ape1‐incised dL and Polβ. The long‐patch BER subpathway effectively removes dL and thereby prevents the formation of DNA–protein crosslinks. In coping with dL, the cellular choice of BER subpathway may either completely repair the lesion, or complicate the repair process by forming a protein–DNA crosslink.
SOX10, in combination with Sp1, regulates the endothelin receptor type B gene in human melanocyte lineage cells
Authors: Yokoyama Satoru , Takeda Kazuhisa , Shibahara Shigeki
Published: March 2006

Waardenburg syndrome (WS) is an auditory–pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. WS type 4 (WS4), a subtype of WS, is characterized by the presence of the aganglionic megacolon and is associated with mutations in the gene encoding either endothelin 3, endothelin receptor type B (EDNRB), or Sry‐box 10 (SOX10). Here, we provide evidence that SOX10 regulates the expression of EDNRB gene in human melanocyte‐lineage cells, as judged by RNA interference and chromatin immunoprecipitation analyses. Human melanocytes preferentially express the EDNRB transcripts derived from the conventional EDNRB promoter. SOX10 transactivates the EDNRB promoter through the cis‐acting elements, the two CA‐rich sequences and the GC box. Moreover, a transcription factor Sp1 enhances the degree of the SOX10‐mediated transactivation of the EDNRB promoter through these cis‐acting elements. Furthermore, we have shown that the EDNRB promoter is heavily methylated in HeLa human cervical cancer cells, lacking EDNRB expression, but not in melanocytes and HMV‐II melanoma cells. The expression of EDNRB became detectable in HeLa cells after treatment with a demethylating reagent, 5′‐aza‐2′‐deoxycytidine, which was further enhanced in the transformed cells over‐expressing SOX10. We therefore suggest that SOX10, alone or in combination with Sp1, regulates transcription of the EDNRB gene, thereby ensuring appropriate expression level of EDNRB in human melanocytes.