bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consenting of the vulnerable: the informed consent procedure in advanced cancer patients in Mexico
Authors: Verástegui Emma L 
Published: December 2006

Abstract

Background
A topic of great concern in bioethics is the medical research conducted in poor countries sponsored by wealthy nations. Western drug companies increasingly view Latin America as a proper place for clinical research trials. The region combines a large population, modern medical facilities, and low per capita incomes. Participants from developing countries may have little or non alternative means of treatment other than that offered through clinical trials. Therefore, the provision of a valid informed consent is important.

Methods
To gain insight about some aspects of the informed consent procedure in a major cancer centre in Mexico, we conducted a three-step evaluation process: 1) a ten point multiple choice survey questionnaires, was used to explore some aspects of the patients' experiences during the informed consent process, 2) researchers' knowledge about specific aspects of the informed consent was evaluated in this study using survey questionnaires; and 3) the comprehensibility, readability and number of pages of the consent forms were analysed. The socioeconomic and educational level of the patients, were also considered. Results were reported using a numerical scale.

Results
Thirty five patients, 20 doctors, and 10 individuals working at the hospital agreed to participate in the study. Eighty three percent of the patients in the study were classified as living in poverty; education level was poor or non existent, and 31% of the patients were illiterate. The consent forms were difficult to understand according to 49% of the patients, most doctors agreed that the forms were not comprehensible to the patients. The average length of the IC documents analysed was 14 pages, and the readability average score was equivalent to 8TH Grade.

Conclusion
The results presented in this work describe some relevant characteristics of the population seen at public health care institutions in Mexico. Poverty, limited or no education, and the complexity of the information provided to the patients may question the validity of the informed consent procedure in this group of patients.
Relationship of hypoxia-inducible factor 1α and p21WAF1/CIP1 expression to cell apoptosis and clinical outcome in patients with gastric cancer
Authors: Mizokami Ken , Kakeji Yoshihiro , Oda Shinya , Maehara Yoshihiko 
Published: December 2006

AbstractBackgroundHypoxia-inducible factor-1α (HIF-1α) plays an essential role in oxygen homeostasis. The expression of HIF-1α-inducible genes is associated with tumor progression. p21 mediates cell cycle arrest and is one of the downstream genes targeted by HIF-1.Patients and methodsWe examined the relationship between HIF-1α and p21 expression, apoptosis and tumor progression using tissue specimens obtained surgically from 126 patients with gastric cancer.ResultsImmunohistochemical analysis indicated that loss of p21 expression correlated positively with patient age and tumor size. Lymph node metastasis was significantly more frequent in tumors with loss of p21 expression (P = 0.022). HIF-1α-positive/p21-negative tumors had a lower apoptotic index than any other tumor samples, and patients with HIF-1α-positive/p21-negative tumors also had a significantly poorer prognosis than the other patient populations.ConclusionThese results suggest that loss of HIF-1α-dependent p21 expression results in decreased apoptosis, increased cell survival and more aggressive tumors.
Pathways to health: a framework for health-focused research and practice
Authors: Fleischer Nancy L , Weber Ann M , Gruber Susan , Arambula Karina Z , Mascarenhas Maya , Frasure Jessica A , Wang Constance , Syme S Leonard 
Published: December 2006

AbstractPublic health research and practice is faced with three problems: 1) a focus on disease instead of health, 2) consideration of risk factor/disease relationships one at a time, and 3) attention to individuals with limited regard for the communities in which they live. We propose a framework for health-focused research and practice. This framework encompasses individual and community pathways to health while incorporating the dynamics of context and overall population vulnerability and resilience. Individual pathways to health may differ, but commonalities will exist. By understanding these commonalities, communities can work to support health-promoting pathways in addition to removing barriers. The perspective afforded by viewing health as a dynamic process instead of as a collection of risk factors and diseases expands the number of approaches to improving health globally. Using this approach, multidisciplinary research teams working with active community participants have the potential to reshape health and intervention sciences.
Exploring existing and deliberated community perspectives of newborn screening: informing the development of state and national policy standards in newborn screening and the use of dried blood spots
Authors: Muchamore Ian , Morphett Luke , Barlow-Stewart Kristine 
Published: December 2006

AbstractObjectiveSince the 1960s newborn screening (NBS) for several rare and serious disorders has been in place across Australia. Testing of a simple blood spot now enables the early detection of over 30 conditions. Policies across Australian states have diverged in some aspects of NBS, especially in the retention and further use of dried blood spots collected as part of the screening and attempts are underway to bring some further national consistency. Whilst this has initiated debate amongst health professionals and policy makers there is limited empirical evidence of wider community attitudes to such issues.MethodsThis research has explored the range and depth of views held by the wider community in New South Wales through moderated small group discussions. It has also assessed the range and depth of responses where the groups are reconvened after being given further information.ResultsThe findings suggest that there is limited community awareness of the public health importance of NBS and especially that resulting biological samples are stored. Members of the wider community presented with opportunities to consider current procedures and policies appear reassured and to have high levels of trust. However there are clearly some groups who have concerns with the storage of dried blood spot specimens and perceive that these may be abused.Policy implications and conclusionThe findings will inform health professionals and policy makers as to the perceived benefits and future challenges NBS raises for the wider community. The findings have implications for improving current communications about NBS, maintaining public confidence and the development of state and national initiatives in genetic health.
Characterization of Cold Sensitivity and Thermal Preference Using an Operant Orofacial Assay
Authors: Rossi Heather L , Vierck Charles J , Caudle Robert M , Neubert John K 
Published: December 2006

Background A hallmark of many orofacial pain disorders is cold sensitivity, but relative to heat-related pain, mechanisms of cold perception and the development of cold allodynia are not clearly understood. Molecular mediators of cold sensation such as TRPM8 have been recently identified and characterized using in vitro studies. In this study we characterized operant behavior with respect to individually presented cold stimuli (24, 10, 2, and −4°C) and in a thermal preference task where rats chose between −4 and 48°C stimulation. We also evaluated the effects of menthol, a TRPM8 agonist, on operant responses to cold stimulation (24, 10, and −4°C). Male and female rats were trained to drink sweetened milk while pressing their shaved faces against a thermode. This presents a conflict paradigm between milk reward and thermal stimulation. Results We demonstrated that the cold stimulus response function was modest compared to heat. There was a significant effect of temperature on facial (stimulus) contacts, the ratio of licking contacts to stimulus contacts, and the stimulus duration/contact ratio. Males and females differed only in their facial contacts at 10°C. In the preference task, males preferred 48°C to −4°C, despite the fact that 48°C and −4°C were equally painful as based on their reward/stimulus and duration/contact ratios. We were able to induce hypersensitivity to cold using menthol at 10°C, but not at 24 or −4°C. Conclusion Our results indicate a strong role for an affective component in processing of cold stimuli, more so than for heat, which is in concordance with human psychophysical findings. The induction of allodynia with menthol provides a model for cold allodynia. This study provides the basis for future studies involving orofacial pain and analgesics, and is translatable to the human experience.
Differential expression of type X collagen in a mechanically active 3-D chondrocyte culture system: a quantitative study
Authors: Yang Xu , Vezeridis Peter S , Nicholas Brian , Crisco Joseph J , Moore Douglas C , Chen Qian 
Published: December 2006

Abstract

Objective
Mechanical loading of cartilage influences chondrocyte metabolism and gene expression. The gene encoding type X collagen is expressed specifically by hypertrophic chondrocytes and up regulated during osteoarthritis. In this study we tested the hypothesis that the mechanical microenvironment resulting from higher levels of local strain in a three dimensional cell culture construct would lead to an increase in the expression of type X collagen mRNA by chondrocytes in those areas.

Methods
Hypertrophic chondrocytes were isolated from embryonic chick sterna and seeded onto rectangular Gelfoam sponges. Seeded sponges were subjected to various levels of cyclic uniaxial tensile strains at 1 Hz with the computer-controlled Bio-Stretch system. Strain distribution across the sponge was quantified by digital image analysis. After mechanical loading, sponges were cut and the end and center regions were separated according to construct strain distribution. Total RNA was extracted from the cells harvested from these regions, and real-time quantitative RT-PCR was performed to quantify mRNA levels for type X collagen and a housing-keeping gene 18S RNA.

Results
Chondrocytes distributed in high (9%) local strain areas produced more than two times type X collagen mRNA compared to the those under no load conditions, while chondrocytes located in low (2.5%) local strain areas had no appreciable difference in type X collagen mRNA production in comparison to non-loaded samples. Increasing local strains above 2.5%, either in the center or end regions of the sponge, resulted in increased expression of Col X mRNA by chondrocytes in that region.

Conclusion
These findings suggest that the threshold of chondrocyte sensitivity to inducing type X collagen mRNA production is more than 2.5% local strain, and that increased local strains above the threshold results in an increase of Col X mRNA expression. Such quantitative analysis has important implications for our understanding of mechanosensitivity of cartilage and mechanical regulation of chondrocyte gene expression.
Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons
Authors: Hoe Hyang-Sook , Freeman Jacob , Rebeck G William 
Published: December 2006

Abstract
Apolipoprotein E (apoE) receptors act as signaling molecules in neurons, altering phosphorylation of numerous proteins after extracellular ligand binding and affecting neurite outgrowth, synapse formation, and neuronal migration. Since apoE is important in the pathogenesis of Alzheimer's disease (AD), we tested whether apoE treatment of neurons affected molecules important to phosphorylation of tau, such as GSK 3β, P35, and CDK5, and the phosphorylation of tau itself. Treatment of primary neurons with 2 uM apoE (or an apoE-derived peptide) decreased levels of phospho-GSK 3β, P35 and CDK5, and decreased levels of phosphorylated forms of tau. A lower concentration of apoE (100 nM) had no effect on these molecules. The alteration of tau phosphorylation by apoE was blocked by an inhibitor of the low-density lipoprotein receptor family, demonstrating the effects were due to receptor interactions. These results demonstrate that apoE affects several downstream signaling cascades in neurons: decreased tau kinases phosphorylation and inhibition of tau phosphorylation at Thr171 and Ser202/Thr205 epitopes. We conclude that apoE can alter levels of tau kinases and phospho-tau epitopes, potentially affecting tau neuropathological changes seen in AD brains.
Distinct regulation of autoreactive CD4 T cell expansion by interleukin-4 under conditions of lymphopenia
Authors: Hill Natasha J , Stotland Aleksandr B , Sarvetnick Nora E 
Published: December 2006

AbstractIL-4 is protective against Type 1 diabetes in the NOD mouse. IL-4 promotes T cell survival in vitro, but little is known about the effect of IL-4 on clonal expansion in vivo. Here, we show that IL-4 only enhances the expansion of autoreactive CD4 T cells during lymphopenia and that neither the presence of islet IL-4 nor IL-4 deficiency affects T cell expansion significantly under conditions of immunosufficiency. The accumulation of proliferating cells induced by IL-4 in a lymphopenic host is inhibited incrementally by increasing the number of bystander cells and is prevented by cell numbers well below that of unmanipulated NOD mice. The ability of IL-4 to promote autoreactive CD4 T cell expansion is therefore sensitive to the degree of host immunodeficiency. Paradoxically, IL-4 receptor-deficient, autoreactive CD4 T cells proliferate more extensively than wild-type T cells in immunodeficient hosts, suggesting that the growth-promoting effect of islet IL-4 acts indirectly. These results suggest that IL-4-mediated protection against autoimmunity and diabetes may be outweighed during immunodeficiency by a pathogenic, IL-4-induced expansion of autoreactive T cells.
The Learning and Perceptions of Teacher Researchers and Facilitators in a Literacy-Focused, Teacher-Research Course: A Content Analysis of System, Learner, and Spheres of Influence
Authors: Massey Dixie , Duffy Ann 
Published: December 2006

The purpose of this research was to add to the knowledge base of teacher research in literacy education by focusing on the inquiry processes and learning of literacy teacher researchers from their perspectives. We accomplished this goal through presenting the voices of the teacher researchers, providing individual and collective voices and perspectives that are sometimes missing in discussions of literacy teacher-research inquiries. Using qualitative content analysis methodologies, our results indicated that these educators learned about themselves as system members, learners, and change agents within varying spheres of influence. We provide discussion and implications for research and practice, including conducting teacher research beyond the support of a university community and the constraints that teacher researchers face in this current political climate. It has been like putting a spotlight on the classroom to see where we are going, and where we have been.
Adipose Tissue-Derived Factors: Impact on Health and Disease
Authors: Trujillo Maria E. , Scherer Philipp E. 
Published: December 2006

The endocrine functions of the adipose organ are widely studied at this stage. The adipose organ, and in particular adipocytes, communicate with almost all other organs. Although some adipose tissue pads assume the functions as distinct “miniorgans,” adipocytes can also be present in smaller numbers interspersed with other cell types. Although fat pads have the potential to have a significant systemic impact, adipocytes may also affect neighboring tissues through paracrine interactions. These local or systemic effects are mediated through lipid and protein factors. The protein factors are commonly referred to as adipokines. Their expression and posttranslational modifications can undergo dramatic changes under different metabolic conditions.Due to the fact that none of the mutations that affect adipose tissue trigger embryonic lethality, the study of adipose tissue physiology lends itself to genetic analysis in mice. In fact, life in the complete absence of adipose tissue is possible in a laboratory setting, making even the most extreme adipose tissue phenotypes genetically amenable to be analyzed by disruption of specific genes or overexpression of others.Here, we briefly discuss some basic aspects of adipocyte physiology and the systemic impact of adipocyte-derived factors on energy homeostasis.
Neonatal Screening for Congenital Hypothyroidism in The Netherlands: Cognitive and Motor Outcome at 10 Years of Age
Authors: Kempers Marlies J. E. , van der Sluijs Veer Liesbeth , Nijhuis-van der Sanden Ria W. G. , Lanting Caren I. , Kooistra Libbe , Wiedijk Brenda M. , Last Bob F. , de Vijlder Jan J. M. , Grootenhuis Martha A. , Vulsma Thomas 
Published: December 2006

Abstract
Context: Patients with thyroidal congenital hypothyroidism (CH-T) born in The Netherlands in 1981–1982 showed persistent intellectual and motor deficits during childhood and adulthood, despite initiation of T4 supplementation at a median age of 28 d after birth.
Objective: The present study examined whether advancement of treatment initiation to 20 d had resulted in improved cognitive and motor outcome.
Design/Setting/Patients: In 82 Dutch CH-T patients, born in 1992 to 1993 and treated at a median age of 20 d (mean, 22 d; range, 2–73 d), cognitive and motor outcome was assessed (mean age, 10.5 yr; range, 9.6–11.4 yr). Severity of CH-T was classified according to pretreatment free T4 concentration.
Main Outcome Measure: Cognitive and motor outcome of the 1992–1993 cohort in comparison to the 1981 to 1982 cohort was the main outcome measure.
Results: Patients with severe CH-T had lower full-scale (93.7), verbal (94.9), and performance (93.9) IQ scores than the normative population (P &lt; 0.05), whereas IQ scores of patients with moderate and mild CH-T were comparable to those of the normative population. In all three severity subgroups, significant motor problems were observed, most pronounced in the severe CH-T group. No correlations were found between starting day of treatment and IQ or motor outcome.
Conclusions: Essentially, findings from the 1992–1993 cohort were similar to those of the 1981–1982 cohort. Apparently, advancing initiation of T4 supplementation from 28 to 20 d after birth did not result in improved cognitive or motor outcome in CH-T patients.
Simulation of vehicle kinematics in rollover tests with quaternions
Authors: Hu Y , Neal-Sturgess C E , Hassan A M 
Published: December 2006

The paper provides a method to simulate the vehicle kinematics in rollover tests. There are several rollover tests in use: SAE J2114 dolly rollover, ditch rollover, corkscrew, curb trip, and soil trip. Sensors located on board the vehicle record the various accelerations and make it possible to reconstruct the whole event with high accuracy, which is difficult in real-world accidents. Euler parameters, as a useful method to describe the orientation of a rigid body, have been widely used in three-dimensional multi-body and rollover crash simulations. A method based on the Euler parameters derived from the test data is used to simulate the vehicle rollover kinematics in a SAE J2114 dolly rollover test. The detailed procedure from the raw data to the Euler parameters is described and the influence of gravity included in the test data is removed by projecting to a local vehicle reference system. The method is validated by simulating the dolly rollover test in MADYMO, using a simple rigid body model to represent the vehicle. Good agreement is obtained from the comparison between the simulated vehicle orientation and the test video, and the comparison between simulated displacements and calculated displacements using the recorded test accelerations at the same points. This demonstrated that the method proposed is a useful and effective method for simulating vehicle kinematics in rollover tests.
A Biomimetic Approach for Hierarchically Structured Inorganic Crystals through Self-Organization
Authors: Imai Hiroaki , Oaki Yuya , Kotachi Akiko 
Published: December 2006

Abstract
Here, we describe a biomimetic pathway for the synthesis of hierarchically structured inorganic crystals. In artificial systems mimicking biomineralization, versatile morphogenesis was achieved with the construction of bridged nanocrystals through self-organization by controlling growth with polymeric molecules such as a gel matrix and soluble anionic polymers. The self-organized formation of bridged crystals in hierarchical architectures is a possible new paradigm for advanced materials processing which could afford new inorganic–organic nanocomposites for use as novel functional materials.
syn-Selective Direct Catalytic Asymmetric Mannich-Type Reactions of Aromatic and Heteroaromatic Hydroxy Ketones Promoted by Y[N(SiMe3)2]3/Linked-BINOL Complexes
Authors: Matsunaga Shigeki , Sugita Mari , Yamagiwa Noriyuki , Handa Shinya , Yamaguchi Akitake , Shibasaki Masakatsu 
Published: December 2006

Abstract
Full details of syn-selective catalytic asymmetric direct Mannich-type reactions of aromatic and heteroaromatic hydroxy ketones promoted by Y[N(SiMe3)2]3/linked-BINOL complexes are described. From a screening of various rare-earth metals and linked-BINOL derivatives, a Y[N(SiMe3)2]3/TMS-linked-BINOL (1.7/1) complex was determined to be the most effective. Mannich-type reactions of aromatic and heteroaromatic hydroxy ketones with aryl and alkenyl N-diphenylphosphinoylimines, catalyzed by 0.1 molar amount of Y[N(SiMe3)2]3 and 0.059 molar amount of TMS-linked-BINOL, afforded syn-β-amino-α-hydroxy ketones in good yields (78–98%), high diastereoselectivity (syn/anti = 81/19–96/4), and high enantioselectivity (86–98% ee).
Sitaxsentan for Treatment of Pulmonary Hypertension
Authors: Wittbrodt Eric T , Abubakar Amina 
Published: December 2006

Objective: To review the literature pertinent to the efficacy and safety of sitaxsentan, a selective endothelin (ET)-A receptor antagonist under evaluation for the treatment of pulmonary arterial hypertension (PAH). Data Sources: Articles were identified through searches of the MEDLINE (1966–November 2006) and International Pharmaceutical Abstracts (1970–November 2006) databases, using the key words endothelin antagonist, pulmonary arterial hypertension, pulmonary hypertension, sitaxsentan, and TBC11251. Searches were limited to articles published in English. Study Selection And Data Extraction: Due to the limited number of articles on sitaxsentan, all studies captured in the search results were evaluated. Data Synthesis: Four studies of sitaxsentan in humans with PAH have been published to date. An uncontrolled open-label study and a randomized placebo-controlled study (STRIDE-1; Sitaxsentan to Relieve Impaired Exercise-1) showed sitaxsentan to improve exercise tolerance in patients with PAH, as evidenced by significant increases in the distance walked in 6 minutes. Significant hepatotoxicity developed in patients receiving sitaxsentan 300 mg. The benefits of sitaxsentan with respect to exercise tolerance and hemodynamics were sustained in a one year extension of the placebo-controlled study. The results of a multicenter, randomized, placebo-controlled trial of 2 doses of sitaxsentan with an open-label bosentan arm (STRIDE-2) suggested that only the 100 mg dose provided superior benefit in exercise tolerance and improvement in functional class. Treatment-related adverse effects were similar for all groups. Conclusions: Sitaxsentan appears to be superior to placebo in improving exercise tolerance in patients with PAH but may produce therapeutic outcomes similar to those of bosentan, a comparator agent. The optimal dose of sitaxsentan appears to be 100 mg once daily. Information about the use of sitaxsentan in a greater number of patients with PAH for longer periods is necessary to further define its place in the treatment of PAH.