bluuebunny/crossref_metadata_2025 huggingface dataset:
Transgender Identities and Gender Variance in Vocational Psychology
Authors: O'Neil Maya Elin , McWhirter Ellen Hawley , Cerezo Alison
Published: February 2008

Effective practices for career counseling with gender variant individuals have yet to be identified for reasons that may include perceptions that the population is too small to warrant in-depth research, lack of funding for such efforts, and practitioners' lack of training and experience with transgender concerns. In this article, we describe the status of research and practice with respect to gender variant individuals. Definitions and terminology, vocational and workplace concerns, and vignettes of vocational and work-related situations that career counseling professionals may encounter when working with gender variant individuals are presented. Recommendations for practice, social advocacy, and future research are provided.
Hysteria and neurasthenia in pre-1914 British medical discourse and in histories of shell-shock
Authors: Loughran Tracey
Published: February 2008

Histories of shell-shock have argued that the diagnosis was subdivided into the categories hysteria and neurasthenia, and that the differential distribution and treatment of these diagnoses was shaped by class and gender expectations. These arguments depend on the presentation of hysteria and neurasthenia as opposed constructs in British medical discourse before 1914. An analysis of the framing of these diagnoses in British medical discourse c.1910—1914 demonstrates that hysteria and neurasthenia, although undergoing redefinition in these years, were closely connected through the designation of both as functional diseases, and the role attributed to heredity in each. Before the war these diagnoses were perceived as indicators of national decline. Continuity, as well as change, is evident in medical responses to shell-shock.
Palaeohydrological changes and human-impact history over the last millennium recorded at Lake Joux in the Jura Mountains, Switzerland
Authors: Magny M. , Gauthier E. , Vannière B. , Peyron O.
Published: February 2008

On the basis of sediment and pollen analyses of a radiocarbon-dated sediment sequence from Lake Joux in the Swiss Jura Mountains (west-central Europe), this paper presents a high-resolution record of lake-level and vegetation changes for the last millennium. The lake-level record makes it possible to determine that low-stands of the water-table dominated at c. AD 1200—1400, and from 1720 onward, with interruptions by short-lived rise events at c. AD 1340 and 1840. Highstands prevailed at c. AD 1100, and around AD 1450, 1550 and 1700. The comparison of the Joux lake-level record with a solar irradiance record based on cosmogenic nucleides supports the hypothesis of a major solar forcing of climate variations in west-central Europe over the last millennium. In agreement with other palaeohydrological records established in Western Europe and in the central North Atlantic Ocean, the Joux lake-level record suggests that, on a multicentennial scale, the period of the `Little Ice Age' coincided in the European mid-latitudes with wetter climatic conditions, and probably with an increase in summer precipitation. Variations in the hydrological cycle appear to have been associated with changes in the general atmospheric circulation pattern, probably coupled with variations in oceanic circulation and solar activity. The Joux record also points to changes in water resources expected to result from ongoing global warming. Finally, despite the severe climatic conditions which prevail in the Joux Valley, the human impact history at Lake Joux over the last millennium seems to reflect political choices and economic context more than climatic changes.
Development of Child Abuse Scale
Authors: Malik Farah D. , Shah Ashiq A.
Published: February 2008

The aim of the study was to develop a reliable self report measure to identify maltreatment among children—across a broad range of parental abusive and neglecting behaviours towards children— that could be used to evaluate different levels and types of abuse and neglect, that is, physical abuse, emotional abuse, physical neglect, emotional neglect and sexual abuse among children of the age ranging from 8–12 years with specific reference to Pakistani cultural context. This indigenous measure comprised 34 items indicative of parental abusive and neglecting behaviours towards children, and was further organised into four categories of abuse and neglect: physical abuse, emotional abuse, physical neglect and emotional care/neglect (low score on which was indicative of emotional neglect). A sample of 200 children (100 boys and 100 girls) taken from six different cities of Punjab indicated the measure to have a highly significant internal consistency measured by coefficient alpha for the total scale and its four sub-scales. Construct validity was determined with the help of Principal Component Factor Analysis that resulted in four-factor solution. Finally, the self report measure termed as Child Abuse Scale (CAS) comprised 34 items pertaining to four major categories of abuse and neglect, and these were labelled accordingly. The reasons for the exclusion of fifth category of sexual abuse have been discussed with special reference to Pakistani cultural and social set up.
Promoting Health and Well-being in Lives of People Living with HIV and AIDS
Authors: Biswas Urmi Nanda
Published: February 2008

The highly effective pharmaceutical polytherapies for the treatment of HIV (Human immunodeficiency virus) and AIDS (Acquired immune deficiency syndrome) have practically reduced HIV and AIDS to a chronic condition like any other chronic illness. People living with HIV and AIDS can now have an almost normal life expectancy; the challenge for them is to live a physically and mentally healthy life. These challenges involve avoiding and managing opportunistic infections physically on one hand and taking care of their mental health needs and promoting and sustaining psycho-social well-being on the other hand. Although a torrent of research has studied the psychosocial correlates of slower disease progression and psycho-social well-being among people living with HIV and AIDS, very few sustained approaches have been made to understand and isolate the contribution of different psycho-bio-behavioural parameters for the psycho-immuno-enhancement in people living with HIV and AIDS. Systematic search in different electronic databases as well as different relevant psychological and AIDS care journals have been done to assimilate and review the research studying the effect of different psycho-social, bio-behavioural interventions through randomised control trials on the health promotion, well-being and disease progression parameters in people living with HIV and AIDS. The article makes an attempt to synchronise and consolidate these research efforts, discussing the role of cognitive behavioural stress management, exercise, spiritual practices, hypnosis, relaxation and guided imagery, social support for the psycho-immuno-enhancement in lives of people living with HIV and AIDS, and suggests a comprehensive three-tier intervention model, consisting of intervention at individual, dyadic and community levels, for psychological and immunological improvement in lives of people living with HIV and AIDS.
Facilitating conversations across time: Using simulations in living history training
Authors: Seig Mary Theresa
Published: February 2008

This article describes the use of a simulation as a crucial part of a larger training program at a living history museum. The simulation provided an experiential, emotional base from which museum staff could re-envision their interactions with visitors and effect cultural and organizational change from within those interactions.
Ethnic Disparities in Special Education Labeling Among Children With Attention-Deficit/Hyperactivity Disorder
Authors: Mandell David S. , Davis Jasmine K. , Bevans Katherine , Guevara James P.
Published: February 2008

The authors examined disparities in special education labeling among children diagnosed with attention-deficit/hyperactivity disorder (ADHD) by merging calendar year 2002 special education records and Medicaid mental health claims for 4,852 children who had been diagnosed with ADHD in Philadelphia, Pennsylvania. Thirty-eight percent were receiving special education services. In adjusted analyses, Black children were less likely than White children to receive these services (odds ratio [O.R.] = 0.78); among the children in special education, Black children were more likely to have the emotional disturbance (ED) label (O.R. = 1.40). There was a significant interaction between ethnicity and receipt of behavioral health and rehabilitation services (BHRS): White children with BHRS were more likely to be in special education than were White children without BHRS or Black children. Among the children in special education, White children with BHRS and Black children were more likely than White children without BHRS to be labeled ED. The results indicate ethnic disparities in special education labeling among children with similar clinical profiles and that mental health and education services are substituted for each other differently based on ethnicity. Possible reasons include undertreatment of ADHD, differential interpretation of associated behaviors, and differences in parents' ability to advocate for children's educational and mental health needs.
Mother and Adolescent Reports of Interparental Discord Among Parents of Adolescents With and Without Attention-Deficit/Hyperactivity Disorder
Authors: Wymbs Brian T. , Pelham William E. , Molina Brooke S. G. , Gnagy Elizabeth M.
Published: February 2008

Evidence is scarce regarding the prevalence of interparental discord in families of adolescents with attention-deficit/hyperactivity disorder (ADHD). Using data collected from adolescents with childhood ADHD and comorbid oppositional defiant disorder (ODD; n = 46) or conduct disorder (CD; n = 23), with childhood ADHD only ( n = 26), and without ADHD ( n = 88) and their mothers, maternal and adolescent reports of interparental discord were compared. Adolescents with ADHD + CD reported witnessing more frequent and unresolved interparental conflict than adolescents without ADHD and with ADHD only. Adolescents with ADHD + CD also indicated more frequent conflict than adolescents with ADHD + ODD. However, differences in conflict resolution were nonsignificant when household income was covaried, and maternal ratings of interparental discord did not differ across groups. Findings highlight the potential utility of adolescents with ADHD as informants of interparental relationship quality.
Relationship Processes in Youth Psychotherapy
Authors: Karver Marc , Shirk Stephen , Handelsman Jessica B. , Fields Sherecce , Crisp Heather , Gudmundsen Gretchen , McMakin Dana
Published: February 2008

This study explores hypothesized associations among therapist engagement strategies, therapeutic alliance, client involvement, and treatment outcome in a randomized clinical trial comparing cognitive behavioral psychotherapy and nondirective supportive psychotherapy for adolescents with depressive symptoms who have attempted suicide. Ratings from audiotapes and self-report of the first four sessions for 23 adolescent clients were used. It was expected that therapeutic relationship variables would be equally important in both treatments. However, preliminary evidence appeared to be emerging only for therapeutic alliance and client involvement being related to treatment outcome in the cognitive behavioral treatment. Therapist lapse behaviors were found to predict alliance across both treatments. On the other hand, there was some preliminary evidence for different therapist behaviors to be related to the therapeutic alliance in each treatment. Results suggest that there may be variation in effective relationship factors, depending on the specific therapeutic approach.
Patterns of Clinical Functioning Over Time for Young People Served in a System of Care
Authors: Anderson Jeffrey A. , Wright Eric R. , Kelley Ken , Kooreman Harold
Published: February 2008

Few studies have examined the longitudinal impact that systems of care (SOCs) have on the clinical functioning of young people. This study investigated patterns of clinical improvement over time in an SOC and explored the degree to which demographic characteristics and referral source affected those patterns. Data were gathered at the time of enrollment in the SOC and collected at 6-month intervals, up to 36 months. Clinical change was assessed with three measurement tools, using hierarchical linear modeling to examine change patterns longitudinally. Results indicated that there were several clinical differences at the time of enrollment that were associated with specific demographic characteristics or referral source. Findings also indicated that clinically and statistically significant improvements occurred over time, with little regard to participants' demographic characteristics or source of referral. These findings lend support to the potential of SOCs to improve youth outcomes and suggest that such improvements appear regardless of individual-level differences among participants.
Cardiac Oxidative Stress Is Elevated at the Onset of Dilated Cardiomyopathy in Streptozotocin-Diabetic Rats
Authors: Crespo María J. , Zalacaín Joaquin , Dunbar Donald C. , Cruz Nildris , Arocho Lucy
Published: February 2008

The association between nitric oxide synthase (eNOS and iNOS) status, oxidative stress, and cardiac function was evaluated in streptozotocin (STZ)-diabetic rats to understand the etiology of diabetic cardiomyopathy. Cardiac function was determined by echocardiography. eNOS and iNOS status and superoxide production were assessed by immunohistochemistry and chemiluminescence, respectively. In STZ-diabetic rats, stroke volume, cardiac output, and left ventricular ejection fraction were significantly lower than in controls (CT, P < .05), whereas left ventricular end-systolic volume was higher. Cardiac NOS activity increased from 161 ± 18 cpm/mg tissue in CT rats to 286 ± 20 cpm/mg tissue ( P < .001) in STZ-diabetic rats. Furthermore, superoxide production and cardiac eNOS and iNOS levels were higher in STZ-diabetic rats than in CT rats ( P < .05). An increased activation of cardiac eNOS and iNOS is observed concomitantly with decreased cardiac function. Thus, increased oxidative stress in the heart may be implicated in the development of dilated cardiomyopathy in STZ-diabetic rats.
Aspirin Resistance: Biological and Clinical Implications
Authors: Tseeng Stephanie , Arora Rohit
Published: February 2008

Cardiovascular events are the leading causes of mortality and morbidity in the United States. This development has prompted the rise of aspirin therapy in the prevention of atherothrombotic events. However, not all patients benefit to the same extent from aspirin therapy and many continue experiencing atherothrombotic complications. Researchers have labeled this phenomenon aspirin resistance, and despite drawing much attention from both researchers and lay people the cause remains unknown. Much needs to be clarified and standardized regarding the phenomenon of aspirin resistance, including the prevalence, definition, appropriate measurement methods, mechanisms, and, most important, linking low response to aspirin with worsened clinical outcomes.
Choosing Objectives for a Distance Learning Behavioral Intervention in Autism Curriculum
Authors: Sulzer-Azaroff Beth , Fleming Richard , Tupa Megan , Bass Robert , Hamad Charles
Published: February 2008

The national need for individuals trained in applied behavior analysis (ABA) helped persuade the U.S. Department of Education to fund the development of a four-course, undergraduate-level curriculum on the topic. In this article, the authors report the results and application of a four-phase Delphi survey procedure designed to identify the most critical topics to cover in the curriculum. Thirty-four specialists in behavioral intervention participated and identified 74 items, 36 of which eventually emerged as strongly recommended, 27 as recommended and 11 as not recommended. This information was used to select topics and practices to cover in the courses. Other ABA scholars, researchers, and practitioners may find this information useful in designing instructional programs for adults.
Communicative Behavior in the Natural Environment
Authors: Meadan Hedda , Halle James , Ostrosky Michaelene M. , DeStefano Lizanne
Published: February 2008

Many individuals with developmental disabilities show delays in the development of sophisticated communication skills. Listeners often misunderstand their unconventional means of communication, and breakdowns occur. A communication repair is a second attempt to communicate a message when a breakdown is encountered. Qualitative methods were employed to assess and describe the communication repairs used by two young children with autism spectrum disorders who had limited expressive language. During natural observations, only one of the two participating children was observed to repair his initial requests. The results suggest that in contrast to the emphasis in the literature that development is the primary determinant of repair behavior, variables in the children's social and physical environment influenced their communication repair behavior. Implications for practice and research are described.
The needs of parents of hospitalized children in Australia
Authors: Shields Linda , Young Jeanine , McCann Damhnat
Published: February 2008

The aim of this study was to compare the perceptions of needs held by parents of hospitalized children with those held by the staff caring for them. Family-centred care is a central tenet of paediatrics and should encompass all aspects of the child and family's experience of hospitalization. Important to this are the needs of parents when their children are hospitalized. A widely used and validated tool was used with a convenience sample in paediatric facilities in a children's hospital in Australia. Some differences were found between parents and staff for scores for perceived importance of the 51 needs included in the questionnaire, and whether or not they were being met satisfactorily during children's hospital admission, although there were no consistent patterns. Parents declared themselves more independent than the staff perceived them to be. These findings facilitate improvements in communication between parents and staff and can be included in education programmes for both.
Diaphragmatic injuries: challenges in the diagnosis and management
Authors: Petrone Patrizio , Leppäniemi Ari , Inaba Kenji , Søreide Kjetil , Asensio Juan A
Published: February 2008

Establishing the clinical diagnosis of diaphragmatic injuries (DI) can be challenging for the trauma surgeon, as it is often clinically occult. Accurate diagnosis is critical however as a missed DI may result in grave sequelae due to herniation and strangulation of displaced intra-abdominal organs. The etiology of DI includes the following mechanisms: blunt, penetrating, and iatrogenic. Vital information about the mechanism of injury should be obtained from the emergency medical personnel. Left-sided hemidiaphragmatic injuries are considerably more common than right-sided injuries. Patients with right-sided hemidiaphragm rupture have higher pre-hospital mortality resulting from the greater impacting force require to produce a right-sided DI, associated with significant vascular injury. The diagnosis of a DI by imaging studies presents a challenge, as evidenced by the large number of investigative procedures employed to establish the diagnosis. Minimally invasive technology in the form of laparoscopy and thoracoscopy is in the trauma surgeon's diagnostic and therapeutic armamentarium. The surgical care of DI can be classified according to the phase of clinical presentation, into injuries requiring management in their acute phase versus those in their chronic phase. The patient's survival depends on the severity of their associated injuries, but if DI is not diagnosed promptly a missed injury can be associated with a high morbidity and mortality.
Integrating Research, Policy, and Practice in School-Based Physical Activity Prevention Programming: The School Health Action, Planning, and Evaluation System (SHAPES) Physical Activity Module
Authors: Leatherdale Scott T. , Manske Steve , Wong Suzy L. , Cameron Roy
Published: February 2008

The School Health Action, Planning, and Evaluation System (SHAPES) is a data collection and feedback system designed to support population-based intervention planning, evaluation, and field research related to youth. The Physical Activity Module of SHAPES consists of: (a) a machine readable questionnaire to collect physical activity data from all students (grades 6 to 12) in a school, (b) a school administrator questionnaire to assess school policies, programs, and resources related to physical activity, and (c) a school-specific feedback report documenting student behavior and school programs and policies. This SHAPES module provides schools with feedback that enables them to take stock of patterns of activity and obesity within their school, recognize what is (and what is not) in place to support physical activity, and how to plan and evaluate their own prevention efforts. SHAPES enables researchers and stakeholders to identify what interventions work, in what contexts, with what students.
Systematic Direct Observation of Time on Task as a Measure of Student Engagement
Authors: Spanjers Deanna M. , Burns Matthew K. , Wagner Angela R.
Published: February 2008

This study examines the relationship between systematic direct observation (SDO) of time on task (TOT) and student engagement as measured by a self-report task-specific measure. The research questions guiding the study are (a) what is the relationship between SDO of TOT and a self-report measure of student effort, and (b) what is the relationship between TOT and reading comprehension? An exploratory analysis compares the engagement among three levels of passage difficulty. Small partial correlations are found between TOT and self-reported engagement among 125 third and fourth graders ( r = −.15 and r = .30, respectively). Nonsignificant partial correlations between TOT and reading comprehension are also found. Exploratory multivariate analyses of the three variables show significant results for both third and fourth grade, but subsequent univariate analyses find a significant effect only for comprehension. Thus, these data suggest the need for additional research regarding the assessment of TOT with SDO.
A PAI-1 (SERPINE1) polymorphism predicts osteonecrosis in children with acute lymphoblastic leukemia: a report from the Children's Oncology Group
Authors: French Deborah , Hamilton Leo H. , Mattano Leonard A. , Sather Harland N. , Devidas Meenakshi , Nachman James B. , Relling Mary V.
Published: February 2008

As glucocorticoid use increased in acute lymphoblastic leukemia, osteonecrosis became an increasingly frequent complication. Besides increased age, host risk factors are poorly defined. We tested whether 12 polymorphisms were associated with osteonecrosis among patients 10 years and older treated on the CCG1882 protocol. Candidate genes (TYMS, MTHFR, ABCB1, BGLAP, ACP5, LRP5, ESR1, PAI-1, VDR, PTH, and PTHR) were chosen based on putative mechanisms underlying osteonecrosis risk. All children received dexamethasone, with doses varying by treatment arm. A PAI-1 polymorphism (rs6092) was associated with risk of osteonecrosis in univariate (P = .002; odds ratio = 2.79) and multivariate (P = .002; odds ratio = 2.89) analyses (adjusting for gender, age, and treatment arm). Overall, 21 of 78 (26.9%) children with PAI-1 GA/AA genotypes, versus 25 of 214 (11.7%) children with GG genotype, developed osteonecrosis. PAI-1 polymorphisms and PAI-1 serum levels have previously been associated with thrombosis. We conclude that PAI-1 genetic variation may contribute to risk of osteonecrosis.
Radiologic and nuclear events: contingency planning for hematologists/oncologists
Authors: Weinstock David M. , Case Cullen , Bader Judith L. , Chao Nelson J. , Coleman C. Norman , Hatchett Richard J. , Weisdorf Daniel J. , Confer Dennis L.
Published: February 2008

Untoward events involving radioactive material, either accidental or intentional, are potentially devastating. Hematologists and oncologists are uniquely suited to help manage radiation victims, as myelosuppression is a frequent complication of radiation exposure. In the aftermath of a large event, such as a nuclear detonation, there may be a national call for surge capacity that involves hematologists/oncologists across the country in the disaster response. In preparation, the National Marrow Donor Program and American Society for Blood and Marrow Transplantation have established the Radiation Injury Treatment Network (RITN), a voluntary consortium of transplant centers, donor centers, and umbilical cord blood banks. RITN is partnered with the Office of the Assistant Secretary for Preparedness and Response in the United States Department of Health and Human Services to develop treatment guidelines, educate healthcare professionals, coordinate situation response, and provide comprehensive evaluation and care for radiation injury victims. We outline the current plans for event response and describe scenarios, including catastrophic events that would require extensive support from hematologists/oncologists across the country. In addition, we highlight important reference resources and discuss current efforts to develop medical countermeasures against radiation toxicity. Practitioners and institutions across the country are encouraged to become involved and participate in the planning.
SPIKE – a database, visualization and analysis tool of cellular signaling pathways
Authors: Elkon Ran , Vesterman Rita , Amit Nira , Ulitsky Igor , Zohar Idan , Weisz Mali , Mass Gilad , Orlev Nir , Sternberg Giora , Blekhman Ran , Assa Jackie , Shiloh Yosef , Shamir Ron
Published: February 2008

Background

Biological signaling pathways that govern cellular physiology form an intricate web of tightly regulated interlocking processes. Data on these regulatory networks are accumulating at an unprecedented pace. The assimilation, visualization and interpretation of these data have become a major challenge in biological research, and once met, will greatly boost our ability to understand cell functioning on a systems level.

Results

To cope with this challenge, we are developing the SPIKE knowledge-base of signaling pathways. SPIKE contains three main software components: 1) A database (DB) of biological signaling pathways. Carefully curated information from the literature and data from large public sources constitute distinct tiers of the DB. 2) A visualization package that allows interactive graphic representations of regulatory interactions stored in the DB and superposition of functional genomic and proteomic data on the maps. 3) An algorithmic inference engine that analyzes the networks for novel functional interplays between network components.

SPIKE is designed and implemented as a community tool and therefore provides a user-friendly interface that allows registered users to upload data to SPIKE DB. Our vision is that the DB will be populated by a distributed and highly collaborative effort undertaken by multiple groups in the research community, where each group contributes data in its field of expertise.

Conclusion

The integrated capabilities of SPIKE make it a powerful platform for the analysis of signaling networks and the integration of knowledge on such networks withomicsdata.
Quantitative Single-letter Sequencing: a method for simultaneously monitoring numerous known allelic variants in single DNA samples
Authors: Monsion Baptiste , Duborjal Hervé , Blanc Stéphane
Published: February 2008

Background

Pathogens such as fungi, bacteria and especially viruses, are highly variable even within an individual host, intensifying the difficulty of distinguishing and accurately quantifying numerous allelic variants co-existing in a single nucleic acid sample. The majority of currently available techniques are based on real-time PCR or primer extension and often require multiplexing adjustments that impose a practical limitation of the number of alleles that can be monitored simultaneously at a single locus.

Results

Here, we describe a novel method that allows the simultaneous quantification of numerous allelic variants in a single reaction tube and without multiplexing. Quantitative Single-letter Sequencing (QSS) begins with a single PCR amplification step using a pair of primers flanking the polymorphic region of interest. Next, PCR products are submitted to single-letter sequencing with a fluorescently-labelled primer located upstream of the polymorphic region. The resulting monochromatic electropherogram shows numerous specific diagnostic peaks, attributable to specific variants, signifying their presence/absence in the DNA sample. Moreover, peak fluorescence can be quantified and used to estimate the frequency of the corresponding variant in the DNA population.

Using engineered allelic markers in the genome of Cauliflower mosaic virus, we reliably monitored six different viral genotypes in DNA extracted from infected plants. Evaluation of the intrinsic variance of this method, as applied to both artificial plasmid DNA mixes and viral genome populations, demonstrates that QSS is a robust and reliable method of detection and quantification for variants with a relative frequency of between 0.05 and 1.

Conclusion

This simple method is easily transferable to many other biological systems and questions, including those involving high throughput analysis, and can be performed in any laboratory since it does not require specialized equipment.
Role of sulphated polysaccharides from Sargassum Wightii in Cyclosporine A-induced oxidative liver injury in rats
Authors: Josephine Anthony , Nithya Kalaiselvam , Amudha Ganapathy , Veena Coothan Kandaswamy , Preetha Sreenivasan P , Varalakshmi Palaninathan
Published: February 2008

Background

Seaweeds or marine algae have long been made up a key part of the Asian diet, and as an antioxidant, sulphated polysaccharides have piqued the interest of many researchers as one of the ocean's greatest treasures. The present investigation suggests the therapeutic potential of sulphated polysaccharides from marine brown algae "Sargassum wightii" in Cyclosporine A (CsA)- induced liver injury. CsA is a potent immunosuppressive agent used in the field of organ transplantations and various autoimmune disorders. However, hepatotoxicity due to CsA remains to be one of the major clinical challenges.

Methods

The effect of sulphated polysaccharides on CsA-induced hepatotoxicity was studied in adult male albino rats of Wistar strain, and the animals were randomized into four groups with six rats in each. Group I served as vehicle control. Group II rats were given CsA at a dosage of 25 mg/kg body weight, orally for 21 days. Group III rats were given sulphated polysaccharides at a dosage of 5 mg/kg body weight, subcutaneously for 21 days. Group IV rats were given sulphated polysaccharides simultaneously along with CsA, as mentioned in Group II for 21 days.

Results

CsA provoked hepatotoxicity was evident from the decreased activities of hepatic marker enzymes. A significant rise in the level of oxidants, along with a striking decline in both the enzymic and non-enzymic antioxidants, marks the severity of oxidative stress in CsA-induced rats. This in turn led to enhanced levels of lipid peroxidation, 8-hydroxy-2-deoxy guanosine and protein carbonyls, along with a decrease in ATPase activities and alterations in lipid profile. Histopathological changes also strongly support the above aberrations. However, concomitant treatment with sulphated polysaccharides restored the above deformities to near control and prevented the morphological alterations significantly.

Conclusion

Thus, the present study highlights that sulphated polysaccharides can act therapeutically against CsA-induced hepatotoxicity.

Key Words

Cyclosporine A; hepatic markers; antioxidants; hyperlipidemia; macromolecules; sulphated polysaccharides.
K-rasmutations in sinonasal cancers in relation to wood dust exposure
Authors: Bornholdt Jette , Hansen Johnni , Steiniche Torben , Dictor Michael , Antonsen Annemarie , Wolff Henrik , Schlünssen Vivi , Holmila Reetta , Luce Danièle , Vogel Ulla , Husgafvel-Pursiainen Kirsti , Wallin Håkan
Published: February 2008

Background

Cancer in the sinonasal tract is rare, but persons who have been occupationally exposed to wood dust have a substantially increased risk. It has been estimated that approximately 3.6 million workers are exposed to inhalable wood dust in EU. In previous small studies of this cancer, ras mutations were suggested to be related to wood dust exposure, but these studies were too limited to detect statistically significant associations.

Methods

We examined 174 cases of sinonasal cancer diagnosed in Denmark in the period from 1991 to 2001. To ensure uniformity, all histological diagnoses were carefully reviewed pathologically before inclusion. Paraffin embedded tumour samples from 58 adenocarcinomas, 109 squamous cell carcinomas and 7 other carcinomas were analysed for K-ras codon 12, 13 and 61 point mutations by restriction fragment length polymorphisms and direct sequencing. Information on occupational exposure to wood dust and to potential confounders was obtained from telephone interviews and from registry data.

Results

Among the patients in this study, exposure to wood dust was associated with a 21-fold increased risk of having an adenocarcinoma than a squamous cell carcinoma compared to unexposed [OR = 21.0, CI = 8.0–55.0]. K-ras was mutated in 13% of the adenocarcinomas (seven patients) and in 1% of squamous cell carcinomas (one patient). Of these eight mutations, five mutations were located in the codon 12. The exact sequence change of remaining three could not be identified unambiguously. Among the five identified mutations, the G→A transition was the most common, and it was present in tumour tissue from two wood dust exposed adenocarcinoma patients and one patient with unknown exposure. Previously published studies of sinonasal cancer also identify the GGT → GAT transition as the most common and often related to wood dust exposure.

Conclusion

Patients exposed to wood dust seemed more likely to develop adenocarcinoma compared to squamous cell carcinomas. K-ras mutations were detected in 13% of adenocarcinomas. In this study and previously published studies of sinonasal cancer the found K-ras mutations, were almost exclusively G → A transitions. In conclusion, our study, based on a large representative collection of human SNC tumours, indicates that K-ras mutations are relatively infrequent, and most commonly occur in adenocarcinomas. Wood dust exposure alone was not found to be explanatory for the G→A mutations, but combination of exposure to tobacco, wood dust, and possibly other occupational agents may be a more likely explanation. Overall, the study suggests a limited role for K-ras mutations in development of sinonasal cancer.
Safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine in elderly Chinese subjects
Authors: Li Rongcheng , Fang Hanhua , Li Yanping , Liu Youping , Pellegrini Michele , Podda Audino
Published: February 2008

Background

The safety and immunogenicity of an MF59™-adjuvanted subunit influenza vaccine (Sub/MF59™; FLUAD®, Novartis Vaccines) was evaluated among elderly Chinese subjects (≥ 60 years of age). After a preliminary Phase I, open-label study (n = 25) to assess safety 1–14 days post-vaccination, a comparative observer-blind, randomised, controlled clinical trial (n = 600) was performed to assess safety and immunogenicity versus a non-adjuvanted subunit influenza vaccine (Subunit; Agrippal®, Novartis Vaccines). Subjects were randomised (2:1) to receive Sub/MF59™ or Subunit.

Results

Both vaccines were well tolerated, with no vaccine-related serious adverse events reported during the Phase I trial. During the observer-blind study, local and systemic reactions were generally similar for both vaccines 1–22 days post-vaccination; however, injection-site induration was more frequent among the Subunit group (P < 0.05), and mild pain at the injection site and fever were more frequent among Sub/MF59™ recipients (P ≤ 0.005). Both vaccines induced a significant (P < 0.001) increase in geometric mean titres (GMTs) for the three strains tested, versus baseline; GMTs against A/H1N1, A/H3N2 and B were significantly higher in the Sub/MF59™ group (P = 0.034, P < 0.001 and P = 0.005, respectively). GMT ratios against A/H1N1, A/H3N2 and B were also significantly higher in the Sub/MF59™ group (P = 0.038, P < 0.001 and P = 0.006, respectively). Similarly, the percentage of subjects achieving seroprotection or seroconversion on Day 22 was greater for Sub/MF59™ recipients, reaching significance for A/H3N2 (P < 0.001).

Conclusion

MF59™-adjuvanted subunit influenza vaccine is well tolerated by elderly Chinese subjects and induces a higher level of immunogenicity than a non-adjuvanted subunit influenza vaccine in this population that is at high risk of influenza-related complications.

Clinical trial registry

http://www.clinicaltrials.gov, NCT00310648
Effect of medial arch-heel support in inserts on reducing ankle eversion: a biomechanics study
Authors: Fong Daniel TP , Lam Mak-Ham , Lao Miko LM , Chan Chad WN , Yung Patrick SH , Fung Kwai-Yau , Lui Pauline PY , Chan Kai-Ming
Published: February 2008

Background

Excessive pronation (or eversion) at ankle joint in heel-toe running correlated with lower extremity overuse injuries. Orthotics and inserts are often prescribed to limit the pronation range to tackle the problem. Previous studies revealed that the effect is product-specific. This study investigated the effect of medial arch-heel support in inserts on reducing ankle eversion in standing, walking and running.

Methods

Thirteen pronators and 13 normal subjects participated in standing, walking and running trials in each of the following conditions: (1) barefoot, and shod condition with insert with (2) no, (3) low, (4) medium, and (5) high medial arch-heel support. Motions were captured and processed by an eight-camera motion capture system. Maximum ankle eversion was calculated by incorporating the raw coordinates of 15 anatomical positions to a self-compiled Matlab program with kinematics equations. Analysis of variance with repeated measures with post-hoc Tukey pairwise comparisons was performed on the data among the five walking conditions and the five running conditions separately.

Results

Results showed that the inserts with medial arch-heel support were effective in dynamics trials but not static trials. In walking, they successfully reduced the maximum eversion by 2.1 degrees in normal subjects and by 2.5–3.0 degrees in pronators. In running, the insert with low medial arch support significantly reduced maximum eversion angle by 3.6 and 3.1 degrees in normal subjects and pronators respectively.

Conclusion

Medial arch-heel support in inserts is effective in reducing ankle eversion in walking and running, but not in standing. In walking, there is a trend to bring the over-pronated feet of the pronators back to the normal eversion range. In running, it shows an effect to restore normal eversion range in 84% of the pronators.
Lack of CCR5 on dendritic cells promotes a proinflammatory environment in submandibular glands of the NOD mouse
Authors: Wildenberg Manon E , van Helden-Meeuwsen Cornelia G , van de Merwe Joop P , Moreno Christophe , Drexhage Hemmo A , Versnel Marjan A
Published: February 2008

Sjögren’s syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary glands. In the NOD mouse, a model for this disease, the development of lymphocytic infiltrates in the salivary glands is preceded by an accumulation of dendritic cells (DC). Given the key importance of DC in regulating the immune response, we characterized the DC isolated from NOD salivary glands. These DC lacked membrane expression of CCR5, whereas DC from control salivary glands did express this molecule. The lack of expression was present already prior to the onset of lymphocytic infiltration, indicating that this was not the result of ongoing inflammation. DC from other sources in the NOD mouse also showed a decrease in CCR5 expression. The lack of CCR5 expression in the NOD salivary gland was accompanied by an increase in inflammatory chemokines. Furthermore, DC from CCR5−/− animals or DC treated with a CCR5 antagonist showed increased secretion of IL-12. Interestingly, in Sjögren’s syndrome patients, CCR5 expression on circulating monocytes was decreased and correlated to increased levels of IL-12. These data indicate that CCR5 has regulatory properties and that the lack of CCR5 in NOD DC contributes to the proinflammatory environment in the salivary glands.
Review of Phase II Trial Designs Used in Studies of Molecular Targeted Agents: Outcomes and Predictors of Success in Phase III
Authors: El-Maraghi Robert H. , Eisenhauer Elizabeth A.
Published: February 2008

Purpose

Because the appropriate design and end points for phase II evaluation of targeted anticancer agents are unclear, we undertook a review of recent reports of phase II trials of targeted agents to determine the types of designs used, the planned end points, the outcomes, and the relationship between trial outcomes and regulatory approval.

Methods

We retrieved reports of single-agent phase II trials in six solid tumors for 19 targeted drugs. For each, we abstracted data regarding planned design and actual results. Response rates were examined for any relationship to eventual success of the agents, as determined by US Food and Drug Administration approval for at least one indication.

Results

Eighty-nine trials were identified. Objective response was the primary or coprimary end point in the majority of trials (61 of 89 trials). Fourteen reports were of randomized studies generally evaluating different doses of agents, not as controlled experiments. Enrichment for target expression was uncommon. Objective responses were seen in 38 trials; in 19 trials, response rates were more than 10%, and in eight, they were more than 20%. Agents with high response rates tended to have high nonprogression rates; renal cell carcinoma was the exception to this. Higher overall response rates were predictive of regulatory approval in the tumor types reviewed (P = .005).

Conclusion

In practice, phase II design for targeted agents is similar to that for cytotoxics. Objective response seems to be a useful end point for screening new targeted agents because, in our review, its observation predicted for eventual success. Improvements in design are recommended, as is more frequent inclusion of biological questions as part of phase II trials.
Lenalidomide for the Treatment of B-Cell Malignancies
Authors: Chanan-Khan Asher A. , Cheson Bruce D.
Published: February 2008

Lenalidomide is a novel anticancer agent that has made a major impact in the treatment of patients with B-cell malignancies. A more potent analog of thalidomide, lenalidomide was developed to enhance immunomodulatory properties with improved safety profile. Its antitumor activity seems mediated through modulation of both the cytokine and cellular tumor cell microenvironment. Preclinical as well as clinical observations demonstrate that lenalidomide downregulates production of various critical prosurvival cytokines in the tumor microenvironment while concurrently promoting activation of T- and natural killer (NK) cell-mediated antitumor response. Early clinical investigations noted its efficacy in relapsed and/or refractory multiple myeloma patients. Subsequently, larger randomized studies confirmed the clinical benefit of lenalidomide when added to dexamethasone compared with dexamethasone alone in previously treated myeloma patients resulting in its recent approval by the US Food and Drug Administration. Consequently, the role of lenalidomide in other B-cell malignancies has been investigated, with impressive results in chronic lymphocytic leukemia and non-Hodgkin's lymphoma. This review summarizes the data from various clinical investigations and highlights the impact of lenalidomide in the management of patients with B-cell malignancies.
Estrogen Receptor, Progesterone Receptor, HER-2, and Response to Postmastectomy Radiotherapy in High-Risk Breast Cancer: The Danish Breast Cancer Cooperative Group
Authors: Kyndi Marianne , Sørensen Flemming B. , Knudsen Helle , Overgaard Marie , Nielsen Hanne Melgaard , Overgaard Jens
Published: February 2008

Purpose

To examine the importance of estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER-2), and constructed subtypes in a large study randomly assigning patients to receive or not receive postmastectomy radiotherapy (PMRT).

Patients and Methods

The present analysis included 1,000 of the 3,083 high-risk breast cancer patients randomly assigned to PMRT in the Danish Breast Cancer Cooperative Group (DBCG) protocol 82 trials b and c. Tissue microarray sections were stained for ER, PgR, and HER-2. Median follow-up time for patients alive was 17 years. End points were locoregional recurrence as isolated first event, distant metastases, and overall survival. For statistical analyses four subgroups were constructed from hormonal receptors (Rec). Rec+ was defined as ER+ and/or PgR+. Rec–as both ER–and PgR–. The four subgroups were Rec+/HER-2–, Rec+/HER-2+, Rec–/HER-2–(triple negative), and Rec–/HER-2+.

Results

A significantly improved overall survival after PMRT was seen only among patients characterized by good prognostic markers such as hormonal receptor–positive and HER-2− patients (including the two Rec+ subtypes). No significant overall survival improvement after PMRT was found among patients with an a priori poor prognosis, the hormonal receptor–negative and HER-2+ patients, and in particular the Rec–/HER-2+ subtype. Furthermore, comparing hazard ratios and 95% CIs, significantly smaller improvements in locoregional recurrence control after PMRT were found for ER–and PgR–tumors compared with the ER+ and PgR+ tumors (P = .003 and .04, respectively), and for the triple-negative (P = .02), and the Rec–/HER-2+ subtypes (P = .003) compared with the Rec+/HER-2–subtype.

Conclusion

Hormonal receptor status, HER-2, and the constructed subtypes may be predictive of locoregional recurrence and survival after postmastectomy radiotherapy.
Lu Xun and Modernism/Postmodernism
Authors: Gu Ming Dong
Published: February 2008

Although Lu Xun (1881–1936) produced all his literary works in a period that coincided with the heyday of Western modernism (1910–30), scholars both inside and outside China have made few attempts to study them in the international context of the modernist movement. Because of Lu Xun's concern with the fate of the Chinese nation and his professed intention to be its spiritual physician, critical opinion holds that his writings are primarily political and cultural in thematics and realistic in formal representation. The scholarly consensus that he is a master of critical realism remains unchanged. However, Lu Xun's vision of literature and his writing techniques also draw on features common to symbolism, surrealism, supernatural realism, grotesque realism, magic realism, and other experimental forms. Since these are modernist, even postmodern, features, it would be of great interest to explore Lu Xun's relationship to the modernist movement that swept the West in the early twentieth century and the extent to which his writings anticipated postmodernism. I argue that his work should be viewed as a contribution to the international modernist movement from a non-Western, Third World country. Indeed, no history of international modernism is complete if it does not incorporate the incipient modernism that Lu Xun pioneered independently of the West.