bluuebunny/crossref_metadata_2025 huggingface dataset:
Current Genetic Epidemiology of -Thalassemias and Structural Hemoglobin Variants in the Lazio Region (Central Italy) Following Recent Migration Movements
Authors: Amato Antonio , Cappabianca Maria Pia , Colosimo Alessia , Perri Maria , Grisanti Paola , Zaghis Ivo , Ponzini Donatella , Lerone Maria
Published: October 2010

The aim of this study was to describe the changing pattern of mutational spectrum of -thalassemia (-thal) in the Lazio region (Central Italy), as consequence of recent demographic variations. From 1994 until present, 256 immigrant subjects with hemoglobin disorders (including 191 heterozygotes and 65 homozygotes or compound heterozygotes) coming from 44 different foreign countries, have been molecularly characterized. 14 -globin gene mutations were identified and their frequencies reflect different ethnic origins: 8 of these mutations account for 76.97% of all molecular defects, while 6 of them are much rare, representing less than 2% of the total. These data differ, both in type and percentage, from the mutational spectrum detected in the native population in 1995. Since a few defects are prevalent in each country, a proper strategy for the identification of mutations in immigrant individuals relies on the prior knowledge of their frequency in native ethnic group.
Simulation of Surface Ozone Pollution in the Central Gulf Coast Region Using WRF/Chem Model: Sensitivity to PBL and Land Surface Physics
Authors: Yerramilli Anjaneyulu , Challa Venkata Srinivas , Dodla Venkata Bhaskar Rao , Dasari Hari Prasad , Young John H. , Patrick Chuck , Baham Julius M. , Hughes Robert L. , Hardy Mark G. , Swanier Shelton J.
Published: October 2010

The fully coupled WRF/Chem (Weather Research and Forecasting/Chemistry) model is used to simulate air quality in the Mississippi Gulf coastal region at a high resolution (4 km) for a moderately severe summer ozone episode between 18 CST 7 and 18 CST 10 June 2006. The model sensitivity is studied for meteorological and gaseous criteria pollutants (O3, NO2) using three Planetary Boundary Layer (PBL) and four land surface model (LSM) schemes and comparison of model results with monitoring station observations. Results indicated that a few combinations of PBL and LSMs could reasonably produce realistic meteorological fields and that the combination of Yonsei University (YSU) PBL and NOAH LSM provides best predictions for winds, temperature, humidity and mixed layer depth in the study region for the period of study. The diurnal range in ozone concentration is better estimated by the YSU PBL in association with either 5‐layer or NOAH land surface model. The model seems to underestimate the ozone concentrations in the study domain because of underestimation of temperatures and overestimation of winds. The underestimation of NO2 by model suggests the necessity of examining the emission data in respect of its accurate representation at model resolution. Quantitative analysis for most monitoring stations indicates that the combination of YSU PBL with NOAH LSM provides the best results for various chemical species with minimum BIAS, RMSE, and high correlation values.
Space-Based FPGA Radio Receiver Design, Debug, and Development of a Radiation-Tolerant Computing System
Authors: Baker Zachary K. , Dunham Mark E. , Morgan Keith , Pigue Michael , Stettler Matthew , Graham Paul , Schmierer Eric N. , Power John
Published: October 2010

Los Alamos has recently completed the latest in a series of Reconfigurable Software Radios, which incorporates several key innovations in both hardware design and algorithms. Due to our focus on satellite applications, each design must extract the best size, weight, and power performance possible from the ensemble of Commodity Off-the-Shelf (COTS) parts available at the time of design. A large component of our work lies in determining if a given part will survive in space and how it will fail under various space radiation conditions. Using two Xilinx Virtex 4 FPGAs, we have achieved 1 TeraOps/second signal processing on a 1920 Megabit/second datastream. This processing capability enables very advanced algorithms such as our wideband RF compression scheme to operate at the source, allowing bandwidth-constrained applications to deliver previously unattainable performance. This paper will discuss the design of the payload, making electronics survivable in the radiation of space, and techniques for debug.
Applications of BMI or BSI: Differences and Revisions According to Age and Height
Authors: Schult Otto W. B. , Feinendegen Ludwig E. , Zaum Stephan , Shreeve Walton W. , Pierson Richard N.
Published: October 2010

Validation of body-mass relationships requires a careful statistical analysis of data of normal weight individuals. BMI (ratio between body mass and square of body height) and BSI values (ratio between mass and cube of body height) have been calculated for 99 persons with ages between 1 day and 76 years. These BMI or BSI values have been used for least squares fits yielding mean BMI or BSI values, their variances (providing precision), and average deviations of individual BMI/BSI values from the BMI/BSI means. The latter allows limits to over- and underweight. For adults we found mean values of BSI of 12.36 and confirmed 21.7 for the mean BMI; but the BSI was 1.4 times more precise than the BMI. For children shorter than 1.3 m and younger than 8 years we found the BMI average of 15.9 and over-/underweight limits of 17.4/14.4 being significantly smaller than and incompatible with the recommended BMI values.
Cytoplasmic and Nuclear STAT3 in GH-Stimulated Fibroblasts of Children with Idiopathic Short Stature
Authors: Martínez Pinto Jonathan , Salazar Teresa , Ocaranza Paula , Fuentes Ariel , Román Rossana , Cassorla Fernando
Published: October 2010

Background: STAT5, which plays an important role in GH signal transduction, has been studied extensively in children with growth retardation, but there is scarce information regarding STAT3. Aim: We determined total and phosphorylated STAT3 after GH stimulation in fibroblasts from children with idiopathic short stature (ISS) and control children with normal stature. Subjects and Methods: We studied 15 prepubertal children (age 7.6 ± 0.4 years) with short stature (height –2.8 ± 0.2 SDS), decreased growth velocity (10 ng/ml to the clonidine stimulation test and decreased serum IGF-I concentrations (<–1 SDS), and 19 control children with normal stature (age 6.7 ± 0.3 years). We determined the levels of total and phosphorylated STAT3 in the cytoplasmic and nuclear fractions of fibroblast cultures obtained from a skin biopsy, stimulated with GH (200 ng/ml) for 15–60 min. Results: We observed a reduction in nuclear pSTAT3 levels and a lower nuclear/cytoplasmic STAT3 phosphorylated ratio in 3 patients from the study group compared to the control children. Conclusion: These results suggest that some children with ISS may exhibit a reduction in the nuclear content of their phosphorylated STAT3.
Circulating MicroRNA-208b and MicroRNA-499 Reflect Myocardial Damage in Cardiovascular Disease
Authors: Corsten Maarten F. , Dennert Robert , Jochems Sylvia , Kuznetsova Tatiana , Devaux Yvan , Hofstra Leon , Wagner Daniel R. , Staessen Jan A. , Heymans Stephane , Schroen Blanche
Published: October 2010

Background—

Small RNA molecules, called microRNAs, freely circulate in human plasma and correlate with varying pathologies. In this study, we explored their diagnostic potential in a selection of prevalent cardiovascular disorders.

Methods and Results—

MicroRNAs were isolated from plasmas from well-characterized patients with varying degrees of cardiac damage: (1) acute myocardial infarction, (2) viral myocarditis, (3) diastolic dysfunction, and (4) acute heart failure. Plasma levels of selected microRNAs, including heart-associated (miR-1, -133a, -208b, and -499), fibrosis-associated (miR-21 and miR-29b), and leukocyte-associated (miR-146, -155, and -223) candidates, were subsequently assessed using real-time polymerase chain reaction. Strikingly, in plasma from acute myocardial infarction patients, cardiac myocyte–associated miR-208b and -499 were highly elevated, 1600-fold (
P
<0.005) and 100-fold (
P
<0.0005), respectively, as compared with control subjects. Receiver operating characteristic curve analysis revealed an area under the curve of 0.94 (
P
<10
−10
) for miR-208b and 0.92 (
P
<10
−9
) for miR-499. Both microRNAs correlated with plasma troponin T, indicating release of microRNAs from injured cardiomyocytes. In viral myocarditis, we observed a milder but significant elevation of these microRNAs, 30-fold and 6-fold, respectively. Plasma levels of leukocyte-expressed microRNAs were not significantly increased in acute myocardial infarction or viral myocarditis patients, despite elevated white blood cell counts. In patients with acute heart failure, only miR-499 was significantly elevated (2-fold), whereas no significant changes in microRNAs studied could be observed in diastolic dysfunction. Remarkably, plasma microRNA levels were not affected by a wide range of clinical confounders, including age, sex, body mass index, kidney function, systolic blood pressure, and white blood cell count.

Conclusions—

Cardiac damage initiates the detectable release of cardiomyocyte-specific microRNAs-208b and -499 into the circulation.
Candidate Genes and Mechanisms for 2-Methoxyestradiol–Mediated Vasoprotection
Authors: Barchiesi Federica , Lucchinetti Eliana , Zaugg Michael , Ogunshola Omolara O. , Wright Matthew , Meyer Markus , Rosselli Marinella , Schaufelberger Sara , Gillespie Delbert G. , Jackson Edwin K. , Dubey Raghvendra K.
Published: October 2010

2-Methoxyestradiol (2-ME; estradiol metabolite) inhibits vascular smooth muscle cell (VSMC) growth and protects against atherosclerosis and vascular injury; however, the mechanisms by which 2-ME induces these actions remain obscure. To assess the impact of 2-ME on biochemical pathways regulating VSMC biology, we used high-density oligonucleotide microarrays to identify differentially expressed genes in cultured human female aortic VSMCs treated with 2-ME acutely (4 hours) or long term (30 hours). Both single gene analysis and Gene Set Enrichment Analysis revealed 2-ME–induced downregulation of genes involved in mitotic spindle assembly and function in VSMCs. Also, Gene Set Enrichment Analysis identified effects of 2-ME on genes regulating cell-cycle progression, cell migration/adhesion, vasorelaxation, inflammation, and cholesterol metabolism. Transcriptional changes were associated with changes in protein expression, including inhibition of cyclin D1, cyclin B1, cyclin-dependent kinase 6, cyclin-dependent kinase 4, tubulin polymerization, cholesterol and steroid synthesis, and upregulation of cyclooxygenase 2 and matrix metalloproteinase 1. Microarray data suggested that 2-ME may activate peroxisome proliferator-activated receptors (PPARs) in VSMCs, and 2-ME has structural similarities with rosiglitazone (PPARγ agonist). However, our finding of weak activation and lack of binding of 2-ME to PPARs suggests that 2-ME may modulate PPAR-associated genes via indirect mechanisms, potentially involving cyclooxygenase 2. Indeed, the antimitogenic effects of 2-ME at concentrations that do not inhibit tubulin polymerization were blocked by the PPAR antagonist GW9662 and the cyclooxygenase 2 inhibitor NS398. Finally, we demonstrated that 2-ME inhibited hypoxia-inducible factor 1α. Identification of candidate genes that are positively or negatively regulated by 2-ME provides important leads to investigate and better understand the mechanisms by which 2-ME induces its vasoprotective actions.
Violent Youth Culture in Northern Ireland: Young Men, Violence, and the Challenges of Peacebuilding
Authors: Harland Ken
Published: October 2010

This article discusses violent male youth culture in Northern Ireland within the context of a society emerging from a prolonged period of political violence toward peacebuilding. Specifically, the article focuses on the findings from a qualitative study carried out by the Centre for Young Men’s Studies with 130 marginalized young men aged 13 to 16 from 20 different communities across Northern Ireland addressing themes of violence, conflict, and safety. Despite a changing context of peacebuilding, findings reveal that violence and paramilitary influence continue to perpetuate a male youth subculture epitomized by sectarianism and increasing racist attitudes. Underpinning this is an enduring cycle of suspicion, fear, and distrust of others and a confused state of mind that leaves these young men “stuck” somewhere between the ceasefire mentality of paramilitaries and the ambiguous messages of peacebuilding. This article concludes by stating the need for more realistic ways to engage and integrate marginalized young men into their communities.
Interweaving Youth Development, Community Development, and Social Change Through Youth Organizing
Authors: Christens Brian D. , Dolan Tom
Published: October 2010

Community organizing groups that have built coalitions for local change over the past few decades are now involving young people as leaders in efforts to improve quality of life. The current study explores a particularly effective youth organizing initiative through review of organizational documents and collection and analysis of qualitative data. The study finds that this model for youth organizing is effective at producing impacts at multiple levels because it weaves together youth development, community development, and social change into a unified organizing cycle. The initiative encourages participants by promoting psychological empowerment, leadership development, and sociopolitical development. Simultaneously, youth organizing produces community-level impacts, including new program implementation, policy change, and institution building. Social changes include intergenerational and multicultural collaboration in the exercise of power. This interplay between youth development, community development, and social change is discussed in relation to the growing field of youth organizing and other efforts to engage youth in civil society.
Psychiatric Disorder, Comorbidity, and Suicidal Behavior in Juvenile Justice Youth
Authors: Wasserman Gail A. , McReynolds Larkin S. , Schwalbe Craig S. , Keating Joseph M. , Jones Shane A.
Published: October 2010

Results of collaborations with juvenile justice agencies nationwide were examined to provide generalizable estimates of psychiatric disorder and suicidality among justice system youth. Diagnostic assessments were aggregated from 57 sites ( N = 9,819) from an automated computer-assisted self-interview (Voice Diagnostic Interview Schedule for Children). Disorder was predicted from setting type (system intake, detention, corrections), adjusting for demographic and offense characteristics, and for cross-site variability within settings. Race by comorbid disorder interactions were examined in predicting substance use disorder (SUD). White youth, repeat offenders, and those with further justice system penetration reported higher rates of most disorders; girls reported higher rates of internalizing conditions only. Although presence of another disorder increased SUD for most groups, SUD was high in American Indians regardless of either affective disorder or recent suicide attempt. Findings highlight (a) varying mental health needs across settings, (b) prior justice contact relating strongly to need, (c) girls’ elevated rates of internalizing disorder, and (d) racial/ethnic differences in diagnostic profiles.
Iopromide-induced encephalopathy following coronary angioplasty
Authors: Kocabay Gonenc , Karabay Can Yucel
Published: October 2010

Non-ionic agents have pharmacological side effects, such as seizure, alteration of cerebral function, confusion, short-term memory loss, mental aberrations and ophthalmoplegia.

In this report, we present two cases that developed contrast-induced encephalopathy following coronary angioplasty by the non-ionic contrast agent, iopromide (Ultravist® ). As a result, we concluded that iopromide-induced encephalopathy may occur during angioplasty in patients with no particular predispositions. In addition to that, contrast-induced encephalopathy should be considered as a new-onset neurological disorder.
The relationship between objectively and subjectively measured activity levels in people with chronic low back pain
Authors: van Weering MGH , Vollenbroek-Hutten MMR , Hermens HJ
Published: October 2010

Objective: To compare self-report measures of daily activities with objective activity data to determine whether patients with chronic lower back pain report their activity levels as accurately as controls do.

Design: A cross-sectional study was performed in patients and controls.

Setting: The study was carried out in the daily environment of the subjects.

Subjects: Thirty-two chronic lower back pain patients with symptoms more than three months and 20 healthy controls from the Netherlands, aged 18–65 years.

Main measures: A tri-axial accelerometer was worn for five weekdays and the Baecke Physical Activity Questionnaire was filled in. Pearson’s correlation was calculated to get insight in the awareness of patients and controls. Comparisons of the relationship between the objective and subjective scores of each individual patient with those of the group of controls were used to allocate each patient into subgroups: overestimators, underestimators and aware patients. Physical and psychological characteristics of these groups were explored.

Results: Patients showed weak correlations between the objective and subjective scores of physical activity and appear to have problems in estimating their activity levels ( r = −0.27), in contrast to controls who showed strong correlations between the objective and subjective scores ( r = 0.66). Comparison of the individual relationships of patients with those of controls showed that 44% of the patients were not aware of their activity level. There were relatively more underestimators (30%) than overestimators (14%). Physical characteristics between the three groups tended to be different.

Conclusions: Patient self-reports about their activity level are relatively inaccurate when compared to objective measurements.
Higher-intensity treadmill walking during rehabilitation after stroke in feasible and not detrimental to walking pattern or quality: a pilot randomized trial
Authors: Kuys Suzanne S , Brauer Sandra G , Ada Louise
Published: October 2010

Objective: To determine whether higher-intensity treadmill walking during rehabilitation in those newly able to walk after stroke is feasible, is detrimental to walking or is beneficial.

Design: A single-blind, randomized trial.

Setting: Two rehabilitation units.

Participants: Thirty people with first stroke.

Interventions: Experimental group received 30 minutes of higher-intensity treadmill walking, three times per week for six weeks, in addition to usual physiotherapy. Control group received usual physiotherapy only.

Main outcome measures: Feasibility was measured by examining compliance and adverse events. Detriment to walking was measured by examining pattern and quality. Benefit to walking was measured as capacity using six-minute walk test and speed, at baseline (Week 0), immediately after (Week 6) and at three months (Week 18).

Results: Overall compliance was 89%, with no adverse events reported. There was no between-group difference in walking pattern and quality. By Week 6, the experimental group improved walking capacity by 62 m (95% confidence interval (CI) 10 to 114), comfortable walking speed by 0.18 m/s (95% CI 0.07 to 0.29) and fast walking speed by 0.18 m/s (95% CI 0.03 to 0.35) more than the control group. By Week 18, the experimental group was still walking 0.26 m/s (95% CI 0.12 to 0.41) faster than the control group.

Conclusions: Higher-intensity treadmill walking during rehabilitation after stroke is feasible and not detrimental to walking pattern and quality in those newly able to walk. 94 participants are required to detect a between-group difference of 75 m on six-minute walk test (α 0.05, β 0.90) in future trials.

Trial registration: ACTRN12607000412437
Land degradation versus fire: A spiral process?
Authors: Bajocco Sofia , Salvati Luca , Ricotta Carlo
Published: October 2010

Originally associated to arid regions, vulnerability to land degradation (LD) has rapidly spread in temperate areas, such as the Mediterranean basin. In this region LD increased in the last years due to worsening climate conditions, land-cover changes, soil erosion and anthropogenic pressures. Increasing land vulnerability is mutually linked with an increasing risk of disturbance propagation: the spatio-temporal distribution of areas with different degrees of LD determines different dynamic patterns of the disturbance; in turn, LD is strongly affected by the disturbance occurrence regime, which alters the status quality of a given territory. These considerations invite a comparison between vulnerability to LD and fire occurrence, since historically, in the Mediterranean areas, fire represents one of the main disturbance sources, which is mostly human-induced and with a strong seasonality pattern. Under certain conditions, LD may create conducive conditions for fire to thrive that in turn if repeated may alter the quality status of a landscape, setting the interested area into a LD-fire feedback dynamic. The aim of this paper is to analyse the relationship between fire incidence and LD and their potential feedbacks in Sardinia during two reference periods, 1990 and 2000. Results indicated that in areas already affected by high LD vulnerability there is a sort of LD-fire spiralling connection that can be seen as a ‘mutual early-warning system’ with strong implications on fire prevention strategies and landscape quality status monitoring.
A Clinical Study of ADHD Symptoms With Relation to Symptoms of Learning Disorders in Schoolchildren in Bogota, Colombia
Authors: Talero-Gutierrez Claudia , Van Meerbeke Alberto Velez , Reyes Rodrigo González
Published: October 2010

Objective: To investigate possible relationships between symptoms of ADHD and of learning disorder (LD) in a population geographically, culturally, and linguistically distinct from previous studies. Method: The authors evaluated a cross section of 834 Colombian schoolchildren for childhood neurological pathologies on the basis of a medical examination and performance with reference to the Diagnostic and Statistical Manual (4th ed.) attention checklist, the General and Differential Aptitudes Battery, and the Visual–Motor Integration (VMI) test. Results: Of the total sample, 382 were classified as “ADHD only,” 54 as “LD only,” and 75 as “ADHD + LD.” A total of 459 had low VMI scores. ADHD, LD, and low VMI were significantly interrelated. Among the children with ADHD, the attention deficit subtype tended to have more learning problems than the hyperactive subtype, who showed no major deficiencies in their learning ability. Conclusions: This study provides additional evidence demonstrating a relationship between LD and ADHD, particularly with respect to verbal reasoning, visual–auditory memory, and VMI.
Using Self-Monitoring to Increase Attending to Task and Academic Accuracy in Children With Autism
Authors: Holifield Cassandra , Goodman Janet , Hazelkorn Michael , Heflin L. Juane
Published: October 2010

This study was conducted to investigate the effectiveness of a self-monitoring procedure on increasing attending to task and academic accuracy in two elementary students with autism in their self-contained classroom. A multiple baseline across participants in two academic subject areas was used to assess the effectiveness of the intervention. Both students were taught to self-monitor in language arts and mathematics with measures of attending to task and academic accuracy being collected simultaneously. Results are interpreted to conclude that the self-monitoring procedure was effective for both students and resulted in immediate increases in attending to task and academic accuracy even though results in academic accuracy were variable. Social validity was documented by the increase in two behaviors relevant for student success (attending to task and academic accuracy) and greater student independence.
Internet intervention for increasing physical activity in persons with multiple sclerosis
Authors: Motl Robert W , Dlugonski Deirdre , Wójcicki Thomas R , McAuley Edward , Mohr David C
Published: October 2010

Background:Physical activity has been associated with improvements in walking mobility and quality of life in persons with multiple sclerosis (MS), and yet this population is largely sedentary and inactive compared with the general population.

Objectives:We conducted a pilot, randomized controlled trial (RCT) for examining the effect of an Internet intervention based on social cognitive theory (SCT) for favorably increasing physical activity among persons with MS. We further examined variables from SCT as possible mediators of the Internet intervention.

Methods:We randomly allocated 54 persons with MS into either an Internet intervention condition or a waitlist control condition. The participants completed measures of physical activity, self-efficacy, outcome expectations, functional limitations, and goal setting before and after the 12-week period.

Results:The intervention group reported a statistically significant ( p = 0.01) and large increase in physical activity over time ( d = 0.72), whereas the control group had a small ( d = 0.04) and non-significant change in physical activity ( p = 0.71). The intervention group further reported a statistically significant ( p = 0.001) and large increase in goal setting over time ( d = 0.97), whereas the control group had a small ( d = −0.13) and non-significant change ( p = 0.17). The change in goal setting over time mediated the effect of the Internet intervention on physical activity behavior.

Conclusions:This pilot study sets the stage for a subsequent RCT that includes a larger sample of persons with MS, longer intervention period along with a follow-up, objective measure of physical activity, and secondary outcomes of walking mobility and QOL.
The making and breaking of relationships: Organizational and clinical questions in providing services for looked after children?
Authors: Simmonds John
Published: October 2010

The mental health of children in public care has received considerable attention in recent years. There are significant differences in the prevalence rates compared to children living at home and not in public care and these are added to by other adverse lifestyle issues. Considerable attention has been focused on the importance of stable and secure placements supported by access to a range of services including education, health and mental health. Identifying and classifying mental health needs proves to be challenging as the child’s genetic inheritance, pre- and post-birth experiences, including maltreatment, interact with the uncertainty and delays commonly associated with child protection processes, action in the legal system and the difficulty in establishing secure and permanent placements. Clinical need is also related to the age of the child and the reasons they came into care and the length of time they remain. A case illustrating many of these issues, publicly reported in the court’s judgement, is used as the basis for exploring the complexity for the identified child in understanding and making sense of their experiences as placement plans are made for them. These are used to explore the difficulties in establishing clinical protocols such as those recently published in the USA. Particular emphasis is given to the issues faced by children and their carers in establishing new family relationships which address the child’s inheritance from their family of origin especially where these are traumatic and conflicted in origin.
Review: Inequalities in healthcare provision for people with severe mental illness
Authors: Lawrence David , Kisely Stephen
Published: October 2010

There are many factors that contribute to the poor physical health of people with severe mental illness (SMI), including lifestyle factors and medication side effects. However, there is increasing evidence that disparities in healthcare provision contribute to poor physical health outcomes. These inequalities have been attributed to a combination of factors including systemic issues, such as the separation of mental health services from other medical services, healthcare provider issues including the pervasive stigma associated with mental illness, and consequences of mental illness and side effects of its treatment. A number of solutions have been proposed. To tackle systemic barriers to healthcare provision integrated care models could be employed including co-location of physical and mental health services or the use of case managers or other staff to undertake a co-ordination or liaison role between services. The health care sector could be targeted for programmes aimed at reducing the stigma of mental illness. The cognitive deficits and other consequences of SMI could be addressed through the provision of healthcare skills training to people with SMI or by the use of peer supporters. Population health and health promotion approaches could be developed and targeted at this population, by integrating health promotion activities across domains of interest. To date there have only been small-scale trials to evaluate these ideas suggesting that a range of models may have benefit. More work is needed to build the evidence base in this area.
Review article: Antithrombotic therapy in patients with diabetes mellitus and coronary artery disease
Authors: Ferreiro José Luis , Cequier Ángel R , Angiolillo Dominick J
Published: October 2010

Currently approved antiplatelet treatment strategies have proved successful for reducing cardiovascular adverse events in patients with CAD. However, despite the use of recommended antiplatelet treatment strategies, the presence of DM has been consistently associated with a negative impact on outcomes and a high rate of adverse cardiovascular events continue to occur in patients with DM. The elevated prevalence of low response to standard oral antiplatelet agents contribute to these impaired outcomes. Thus, the search for more potent antiplatelet treatment strategies is warranted in high-risk patients, such as those with DM. The present manuscript provides an overview on the current status of knowledge on currently available antiplatelet agents, focusing on the benefits and limitations of these therapies in DM patients, and evaluating the potential role of new antithrombotic agents and treatment strategies currently under development to overcome these limitations.
Nevirapine-Associated Toxicity in Clinical Practice in Buenos Aires, Argentina
Authors: Bottaro Edgardo Gabriel , Huberman Mara Judith , Iannella María del Carmen , Vesperoni Fernando Adrián , Scapellato Pablo Gustavo , Errea Sylvia , Antonelli Leslie , Cassetti Lidia Isabel
Published: October 2010

Objectives: To determine the incidence and risk factors for nevirapine (NVP)-associated toxicity in a cohort of HIV-infected people in Buenos Aires, Argentina. Design: Retrospective study. Methods: HIV-infected adults who received NVP-based highly active antiretroviral therapy (HAART) at least for 2 weeks between May 1997 and March 2008 were included in this study. We analyzed patients’ age, gender, HIV transmission route, HIV disease stage, pregnancy, alcohol intake, adverse events, coinfection with hepatitis B or C virus, time until toxicity, and withdrawal rates. Results: A total of 1110 patients (631 men) were included. Rash was the most frequently observed adverse event; it was more frequent in women. The incidence of severe rash and hepatotoxicity was similar in women and men. Female sex was the only variable significantly associated with mild-to-moderate rash. High CD4 count, pregnancy, and chronic hepatitis were not associated with NVP-related toxicity. An undetectable viral load at the time of starting NVPtreatment resulted in a lower risk of NVP-related rash.
Social networks, social capital and chronic illness self-management: a realist review
Authors: Vassilev Ivaylo , Rogers Anne , Sanders Caroline , Kennedy Anne , Blickem Christian , Protheroe Joanne , Bower Peter , Kirk Sue , Chew-Graham Carolyn , Morris Rebecca
Published: October 2010

Background: Existing literature on the design of interventions and health policy about self-management have tended to focus on individual-centred definitions of self-care and there is growing recognition of the need to extend consideration beyond individual factors, which determine self-care, to examine wider influences such as the health service, the family and the wider social context.

Aims: To explore the theoretical and empirical links between social networks, social capital and the self-care practices associated with chronic illness work and management in the context of people’s everyday lives.

Method: A realist review method was used to search and appraise relevant quantitative and qualitative literature.

Findings: The review findings indicate that social networks play an important part in the management of long-term conditions. We found that social networks tend to be defined narrowly and are primarily used as a way of acknowledging the significance of context. There is insufficient discussion in the literature of the specific types of networks that support or undermine self-care as well as an understanding of the processes involved. This necessitates shifting the emphasis of self-care towards community and network-centred approaches, which may also prove more appropriate for engaging people in socially and economically deprived contexts.
The 1-Year Mortality of Patients Treated in a Hip Fracture Program for Elders
Authors: Schnell Scott , Friedman Susan M. , Mendelson Daniel A. , Bingham Karilee W. , Kates Stephen L.
Published: October 2010

Comanagement of geriatric hip fracture patients with standardized protocols has been shown to improve short-term outcomes after surgery. A standardized, patient-centered, comanaged Hip Fracture Program for Elders is examined for 1-year mortality. Patients ≥60 years of age who were treated in the Hip Fracture Program for Elders were comanaged by orthopaedic surgeons and geriatricians. Data including age, place of origin, procedure, length of stay, 1-year mortality, Charlson score, and activities of daily living (ADLs) were retrospectively collected. A total of 758 patients ≥60 years of age with hip fractures between April 15, 2005, and March 1, 2009, were included. Their data were analyzed, and the Social Security Death Index and the hospital data system were searched for mortality data. Seventy-eight percent were female, with a mean age of 84.8 years. The mean Charlson score was 3. Fifty percent were admitted from an institutional setting. The overall 1-year mortality was 21.2%. Age (odds ratio [OR] = 1.03, 95% confidence interval [CI] = 1.00-1.05; P = .02), male gender (OR = 1.55, 95% CI = 1.01-2.36; P = .04), low Parker mobility score (OR = 2.94, 95% CI = 1.31-6.57; P = .01), and a Charlson score of 4 or greater (OR = 2.15, 95% CI = 1.30-3.55; P = .002) were predictive of 1-year mortality. ADL dependence was a borderline predictor, as was medium Parker mobility score. Prefracture residence and moderate comorbidity (Charlson score of 2-3) were not independently predictive of mortality at 1 year after adjusting for other characteristics. A comprehensive comanaged hip fracture program for elders not only improves the short-term outcomes but also demonstrates a low 1-year mortality rate, particularly in patients from nursing facilities.
Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations
Authors: Talbot Jhimmy , Magno Luiz Alexandre V , Santana Cinthia VN , Sousa Sandra MB , Melo Paulo RS , Correa Ronan X , Di Pietro Giuliano , Rios-Santos Fabrício
Published: October 2010

Background

N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on theNAT2gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization ofNAT2SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five commonNAT2SNPs (G191A,C481T,G590A,A803Gand G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution ofNAT2polymorphism is different among these three ethnic groups.

Results

Overall, there were no statistically significant differences in the distribution ofNAT2polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies ofG590Awere significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block betweenG590AandA803Gwas verified exclusively among Amerindians.

Conclusions

Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in theNAT2gene and also offer new insights for the investigation of possible newNAT2gene-environment effects in admixed populations.
Genomic organization and evolution of the Atlantic salmon hemoglobin repertoire
Authors: Quinn Nicole L , Boroevich Keith A , Lubieniecki Krzysztof P , Chow William , Davidson Evelyn A , Phillips Ruth B , Koop Ben F , Davidson William S
Published: October 2010

Background

The genomes of salmonids are considered pseudo-tetraploid undergoing reversion to a stable diploid state. Given the genome duplication and extensive biological data available for salmonids, they are excellent model organisms for studying comparative genomics, evolutionary processes, fates of duplicated genes and the genetic and physiological processes associated with complex behavioral phenotypes. The evolution of the tetrapod hemoglobin genes is well studied; however, little is known about the genomic organization and evolution of teleost hemoglobin genes, particularly those of salmonids. The Atlantic salmon serves as a representative salmonid species for genomics studies. Given the well documented role of hemoglobin in adaptation to varied environmental conditions as well as its use as a model protein for evolutionary analyses, an understanding of the genomic structure and organization of the Atlantic salmon α and β hemoglobin genes is of great interest.

Results

We identified four bacterial artificial chromosomes (BACs) comprising two hemoglobin gene clusters spanning the entire α and β hemoglobin gene repertoire of the Atlantic salmon genome. Their chromosomal locations were established using fluorescence in situ hybridization (FISH) analysis and linkage mapping, demonstrating that the two clusters are located on separate chromosomes. The BACs were sequenced and assembled into scaffolds, which were annotated for putatively functional and pseudogenized hemoglobin-like genes. This revealed that the tail-to-tail organization and alternating pattern of the α and β hemoglobin genes are well conserved in both clusters, as well as that the Atlantic salmon genome houses substantially more hemoglobin genes, including non-Bohr β globin genes, than the genomes of other teleosts that have been sequenced.

Conclusions

We suggest that the most parsimonious evolutionary path leading to the present organization of the Atlantic salmon hemoglobin genes involves the loss of a single hemoglobin gene cluster after the whole genome duplication (WGD) at the base of the teleost radiation but prior to the salmonid-specific WGD, which then produced the duplicated copies seen today. We also propose that the relatively high number of hemoglobin genes as well as the presence of non-Bohr β hemoglobin genes may be due to the dynamic life history of salmon and the diverse environmental conditions that the species encounters.

Data deposition: BACs S0155C07 and S0079J05 (fps135): GenBank GQ898924; BACs S0055H05 and S0014B03 (fps1046): GenBank GQ898925
Instability of chromosome number and DNA methylation variation induced by hybridization and amphidiploid formation between Raphanus sativus L. and Brassica alboglabraBailey
Authors: Li Xuanli , Guo Weiwei , Wang Bing , Li Xiangsong , Chen Honggao , Wei Lihua , Wang Yanjie , Wu Jiangsheng , Long Hong
Published: October 2010

Background

Distant hybridization can result genome duplication and allopolyploid formation which may play a significant role in the origin and evolution of many plant species. It is unclear how the two or more divergent genomes coordinate in one nucleus with a single parental cytoplasm within allopolyploids. We used cytological and molecular methods to investigate the genetic and epigenetic instabilities associated with the process of distant hybridization and allopolyploid formation, measuring changes in chromosome number and DNA methylation across multiple generations.

Results

F1 plants from intergeneric hybridization between Raphanus sativus L. (2n = 18, RR) and Brassica alboglabra Bailey (2n = 18, CC) were obtained by hand crosses and subsequent embryo rescue. Random amplification of polymorphic DNA (RAPD) markers were used to identify the F1 hybrid plants. The RAPD data indicated that the hybrids produced specific bands similar to those of parents and new bands that were not present in either parent. Chromosome number variation of somatic cells from allotetraploids in the F4 to F10 generations showed that intensive genetic changes occurred in the early generations of distant hybridization, leading to the formation of mixopolyploids with different chromosome numbers. DNA methylation variation was revealed using MSAP (methylation-sensitive amplification polymorphism), which showed that cytosine methylation patterns changed markedly in the process of hybridization and amphidiploid formation. Differences in cytosine methylation levels demonstrated an epigenetic instability of the allopolyploid of Raphanobrassica between the genetically stable and unstable generations.

Conclusions

Our results showed that chromosome instability occurred in the early generations of allopolyploidy and then the plants were reverted to largely euploidy in later generations. During this process, DNA methylation changed markedly. These results suggest that, epigenetic mechanisms play an important role in intergeneric distant hybridization, probably by maintaining a genetic balance through the modification of existing genetic materials.
Polymorphisms of XRCC4 are involved in reduced colorectal cancer risk in Chinese schizophrenia patients
Authors: Wang Yang , Wang Lei , Li Xingwang , Liu Baocheng , Zhao Qingzhu , Chen Peng , Wang Ti , Li Tao , Ji Jue , Yang Fengping , Wang Quan , Wang Jinfen , Xiao Yanzeng , Xu Yifeng , Feng Guoyin , Peng Zhihai , He Lin , He Guang
Published: October 2010

Background

Genetic factors related to the regulation of apoptosis in schizophrenia patients may be involved in a reduced vulnerability to cancer. XRCC4 is one of the potential candidate genes associated with schizophrenia which might induce colorectal cancer resistance.

Methods

To examine the genetic association between colorectal cancer and schizophrenia, we analyzed five SNPs (rs6452526, rs2662238, rs963248, rs35268, rs2386275) covering ~205.7 kb in the region of XRCC4.

Results

We observed that two of the five genetic polymorphisms showed statistically significant differences between 312 colorectal cancer subjects without schizophrenia and 270 schizophrenia subjects (rs6452536, p = 0.004, OR 0.61, 95% CI 0.44-0.86; rs35268, p = 0.028, OR 1.54, 95% CI 1.05-2.26). Moreover, the haplotype which combined all five markers was the most significant, giving a globalp= 0.0005.

Conclusions

Our data firstly indicate that XRCC4 may be a potential protective gene towards schizophrenia, conferring reduced susceptibility to colorectal cancer in the Han Chinese population.
Residential self-selection bias in the estimation of built environment effects on physical activity between adolescence and young adulthood
Authors: Boone-Heinonen Janne , Guilkey David K , Evenson Kelly R , Gordon-Larsen Penny
Published: October 2010

Background

Built environment research is dominated by cross-sectional designs, which are particularly vulnerable to residential self-selection bias resulting from health-related attitudes, neighborhood preferences, or other unmeasured characteristics related to both neighborhood choice and health-related outcomes.

Methods

We used cohort data from the National Longitudinal Study of Adolescent Health (United States; Wave I, 1994-95; Wave III, 2001-02; n = 12,701) and a time-varying geographic information system. Longitudinal relationships between moderate to vigorous physical activity (MVPA) bouts and built and socioeconomic environment measures (landcover diversity, pay and public physical activity facilities per 10,000 population, street connectivity, median household income, and crime rate) from adolescence to young adulthood were estimated using random effects models (biased by unmeasured confounders) and fixed effects models (within-person estimator, which adjusts for unmeasured confounders that are stable over time).

Results

Random effects models yielded null associations except for negative crime-MVPA associations [coefficient (95% CI): -0.056 (-0.083, -0.029) in males, -0.061 (-0.090, -0.033) in females]. After controlling for measured and time invariant unmeasured characteristics using within-person estimators, MVPA was higher with greater physical activity pay facilities in males [coefficient (95% CI): 0.024 (0.006, 0.042)], and lower with higher crime rates in males [coefficient (95% CI): -0.107 (-0.140, -0.075)] and females [coefficient (95% CI): -0.046 (-0.083, -0.009)]. Other associations were null or in the counter-intuitive direction.

Conclusions

Comparison of within-person estimates to estimates unadjusted for unmeasured characteristics suggest that residential self-selection can bias associations toward the null, as opposed to its typical characterization as a positive confounder. Differential environment-MVPA associations by residential relocation suggest that studies examining changes following residential relocation may be vulnerable to selection bias. The authors discuss complexities of adjusting for residential self-selection and residential relocation, particularly during the adolescent to young adult transition.