bluuebunny/crossref_metadata_2025 huggingface dataset:
Articular Cartilage Changes in Patients With Osteoarthritis After Osteotomy
Authors: Parker David A. , Beatty Karen T. , Giuffre Bruno , Scholes Corey J. , Coolican Myles R. J.
Published: February 2011

Background: High tibial osteotomy (HTO) is a method used to treat medial compartmental osteoarthritis in the knee. The realignment of the knee changes the loading patterns within the joint and may allow for regeneration of articular cartilage. Magnetic resonance imaging methods can be used to assess the quality of the regenerated cartilage.

Hypothesis: Altering mechanical alignment through HTO will have predictable effects on articular cartilage, allowing cartilage preservation and possible regeneration. Quality of regenerated cartilage will be inferior to normal articular cartilage.

Study Design: Case series; Level of evidence, 4.

Methods: Ten patients undergoing medial opening wedge HTO were evaluated using dGEMRIC methods (ie, delayed gadolinium-enhanced magnetic resonance imaging of cartilage) preoperatively and at 6 months, 1 year, and 2 years after HTO. Magnetic resonance images were evaluated by hand segmentation, and T1Gd relaxation times reflective of glycosaminoglycan content were determined for these regions of interest using magnetic resonance imaging analysis software.

Results: The lateral compartment displayed higher T1Gd values than the medial compartment at baseline. Initially, a decrease in T1Gd values on the medial side were observed for all patients at 6 months and remained reduced for all but 2 participants at 1 year and 2 years after HTO. However, on the medial side after 6 months, the rate of change for T1Gd values shifted from being negative (−9.6 milliseconds per month) to being positive (1.7 milliseconds per month). A positive change in the T1Gd of the medial tibial plateau was responsible for the positive overall change in the medial compartment. There was no significant difference in the rate of change on the lateral side ( P = .141), with the average over the 2-year period being a decrease of 2.28 milliseconds per month.

Conclusion: Medial opening wedge HTO provides subjective improvements in pain and quality of life, but the potential benefit of allowing articular cartilage preservation and possible regeneration is not well established. Results showed that after a nonweightbearing period, the rate of change in the medial compartment changes from negative to positive, indicating the potential for articular cartilage recovery secondary to an improved mechanical environment.
Sagittal Alignment of the Knee and Its Relationship to Noncontact Anterior Cruciate Ligament Injuries
Authors: Terauchi Masanori , Hatayama Kazuhisa , Yanagisawa Sinya , Saito Kenichi , Takagishi Kenji
Published: February 2011

Background: Knee hyperextension and tibial posterior slope are related to sagittal alignment of the knee. The relationship of sagittal alignment to noncontact anterior cruciate ligament (ACL) injuries has been reported with conflicting results.

Purpose: To determine whether there is a difference in sagittal alignment of the knee between an ACL-deficient group and a negative control group and to find risk factors contributing to noncontact ACL injuries.

Study Design: Cross-sectional study; Level of evidence, 3.

Methods: Magnetic resonance images of the knee in full extension were acquired in the patient group, which consisted of 33 male and 40 female patients with noncontact ACL injuries, and in the negative control group, which consisted of 28 male and 30 female participants. Three angles were measured: the angle between the femoral axis and the tibial axis, designated as the extension angle; the femoral plateau angle, between the femoral axis and a line tangent to the concave profile of the medial tibial plateau (P line); and the tibial posterior slope angle, 90° minus the angle made by the intersection of the tibial axis and the P line.

Results: In the female group, the femoral plateau angle and the tibial posterior slope angle were significantly larger in the ACL-deficient patients than in the negative control group, although these differences were not seen in the male group. In the female subjects, a negative correlation between the extension angle and the tibial posterior slope angle was seen in the ACL-deficient group, suggesting that knees with hyperextension had a small tibial posterior slope, whereas knees without hyperextension had a large tibial posterior slope.

Conclusion: There were 2 types of large femoral plateau angles: one had its origin in an increasing tibial posterior slope; the other resulted from hyperextension of the knee. Large posterior tibial slope and hyperextension are both correlated with noncontact ACL injury in women.
Illness Intrusiveness Mediates the Relationship Between Heart Failure Severity and Depression in Older Adults
Authors: LeMaire Ashley W. , Shahane Amit , Dao Tam K. , Kibler Jeffrey L. , Cully Jeffrey A.
Published: February 2011

Depression frequently co-occurs in heart failure (HF) patients, causing significant interference and negative health outcomes. This case-controlled study explored the construct of illness intrusiveness and examined its relationship to HF severity and depression. Older veterans ( n = 104) with an HF diagnosis completed a one-time assessment that included demographics, depressive symptoms (Geriatric Depression Scale), the Illness Intrusiveness Rating Scale (IIRS), and HF quality of life and functional abilities (Kansas City Cardiomyopathy Questionnaire [KCCQ]). Analyses included exploratory correlations between IIRS and KCCQ items, a confirmatory factor analysis (IIRS), and formal mediational analyses. Results indicated that the IIRS had adequate internal consistency and concurrent validity, with support for its established three-factor model. Regression analyses indicated that illness intrusiveness mediated HF illness severity and depression. In conclusion, illness intrusiveness may be a better indicator of depression than illness severity (HF symptoms); thus research methods and interventions targeted at reducing illness intrusiveness merit further investigation.
The Housing Enabler Screening Tool
Authors: Iwarsson Susanne , Slaug Björn , Fänge Agneta Malmgren
Published: February 2011

The ambition underlying this study is to provide a valid and efficient screening tool targeting accessibility problems in the ordinary housing stock. The study aims to test the feasibility and interrater agreement of a screening-tool version of the Housing Enabler in a real estate company practice context. Two rater pairs administer the screening in 35 apartments in a Swedish municipality. The overall agreement for the rater pairs was 83% and 78%. For 29 of the 61 items of the tool, the agreement was >80% for both rater pairs; for 8 items, it was <80%. The findings show that the tool is feasible for use in a real estate practice context but that there is a need for more rater training and an instrument manual. This study contributes to the development of research-based strategies for the identification of accessibility problems in ordinary housing, with the long-term aim to increase accessibility in the housing stock, ultimately supporting activity and participation among senior citizens.
Older Adults’ Ways of Dealing With Daily Life While Living With Long-Term Musculoskeletal Pain at Home
Authors: Gillsjö Catharina , Schwartz-Barcott Donna , Bergh Ingrid , Dahlgren Lars Owe
Published: February 2011

Long-term musculoskeletal pain is a global health problem among older adults. Yet little is known about how these older adults actually deal with daily life. This study’s aim is to describe the ways these older adults dealt with daily life at home. Phenomenography is used to collect and analyze data from semistructured interviews with 19 older adults and to identify the range in which they dealt with daily life. Findings consist of an outcome space that encompassed four categories: ignore, struggle, adjust, and resign. The different ways older adults dealt with daily life when living with long-term pain at home strengthen the importance of individualized plans of care in the home and a holistic perspective. Findings contribute to enhanced understanding of a common health problem among older adults that can be used to promote quality of care and improve the quality of life of older adults.
Aging Populations’ Everyday Life Perspectives on Healthy Aging
Authors: Naaldenberg Jenneken , Vaandrager Lenneke , Koelen Maria , Leeuwis Cees
Published: February 2011

Population aging makes policy makers face the challenge of supporting people as they age. Strategies designed to promote healthy aging should take the viewpoints of this target group into account. To strengthen interventions on healthy aging, this study aims to investigate how aging individuals experience healthy aging in their locality. A salutogenic background is used to ensure a broad perspective on health. Data collected from 79 in-depth interviews (using an appreciative inquiry approach) in the Netherlands were analyzed for interviewees’ experiences on healthy aging. Results indicate that healthy aging is perceived within the context of everyday life, and interviewees who are content with their health often have an assets-based and positive view on health. Often, however, interventions and facilities address isolated health themes, and such an approach does not match well with these perceptions. Framing interventions positively in terms of assets, resources, and everyday life may increase their effectiveness.
Optic Nerve Enlargement in Krabbe Disease: A Pathophysiologic and Clinical Perspective
Authors: Hussain Syed A. , Zimmerman Holly H. , Abdul-Rahman Omar A. , Hussaini Syed M. , Parker Colette C. , Khan Majid
Published: February 2011

Krabbe disease is an infantile-onset progressive leukodystrophy. The classic presentation includes excessive irritability, muscle hypertonicity, developmental delay, failure to thrive, peripheral neuropathy, seizures, and optic nerve atrophy. The authors report a rare case of optic nerve enlargement early in infantile Krabbe disease. Their case demonstrates proximal prechiasmatic enlargement of the nerves. They discuss the pathophysiological and clinical correlation of optic nerve enlargement in Krabbe disease and in other disorders. Although Krabbe disease does not feature in initial differential of optic nerve enlargement in children, its inclusion and early identification facilitate a timely diagnosis of this rapidly progressive fatal disease.
Comparison of Structural Magnetic Resonance Imaging and Development in Toddlers Born Very Low Birth Weight and Full-term
Authors: Lowe Jean , Duvall Susanne W. , MacLean Peggy C. , Caprihan Arvind , Ohls Robin , Qualls Clifford , Phillips John
Published: February 2011

Research suggests that regional structural differences can be associated with the neurodevelopmental impairments faced by children born very low birth weight. However, most studies have used magnetic resonance imaging (MRI) during the neonatal period or during adolescence. The current study used structural MRI to examine relationships between regional volume differences in toddlers (18—22 months adjusted age) born very low birth weight (n = 16) and full-term (n = 10) and neurodevelopmental outcomes, including cognition, language, and early executive functioning. Compared with the full-term group, the very low birth weight group had larger third ventricles and smaller cerebral white matter, thalamus, hippocampus, cerebellum white matter, and anterior cingulate volume. Additionally, a significant interaction was found between language and early executive function scores and cerebral white matter volumes between groups, suggesting that young children born very low birth weight can have different trajectories in the growth and development of overall brain structure.
Experiences of Racism by Female Minority and Immigrant Nursing Assistants
Authors: Ryosho Natsuko
Published: February 2011

In the long-term care system, gender, race, ethnicity, and class intersect. While both care providers and consumers are predominantly women, their caregiving and working relationships reflect a hierarchical pattern that is based on race and socioeconomic status. This qualitative study explored perceived racism and cultural conflicts of eight female minority and immigrant certified nursing assistants (CNAs) who work at the bottom of the nursing home industry hierarchy. On the basis of the findings, the author discusses implications for feminist practice in addressing interracial and cultural issues in nursing homes.
Rebecca Salti: The Bani Hamida Weaving Project and Women’s Empowerment
Authors: Saleh Mahasin F.
Published: February 2011

Rebecca Salti is a pioneer of women’s empowerment in Jordan. In 1985, she established the Bani Hamida Weaving Project as country director of Save the Children in Jordan. The project became a model income-generation project throughout the developing world and is internationally known. It continues today with the participation of three generations of rural Bedouin women of the Bani Hamida Tribe. Rebecca’s skills, energy, and vision led her to establish other income-generation programs in Jordan. This article includes excerpts of an interview with Rebecca, a U.S. native, which presents her insights about the project and women’s empowerment.
Moving Beyond Family-Friendly Policies for Faculty Mothers
Authors: Gerten Annette M.
Published: February 2011

This article reports the findings of a study of family-friendly workplace policies at 17 institutions in one midwestern state to analyze the potential impact of policies on the career pathways of social work faculty on the tenure track who are mothers. The findings suggest that although institutions have responded by establishing a supportive environment for faculty mothers, they lack formal policies that support career success. The study highlights the importance of separating career-friendly policies from family-friendly policies to tackle persistent gender inequity for this subgroup of women academics.
Role Occupancy, Quality, and Psychological Distress Among Caucasian and African American Women
Authors: Davis Cindy , Sloan Melissa , Tang Catherine
Published: February 2011

This article presents a study that examined the relationship between involvement in multiple roles and psychological distress among 380 Caucasian and African American women aged 18—60, focusing on women’s roles as paid workers, wives, and mothers. The quality of the mother role was significantly associated with psychological distress, while role occupancy and role quantity were not. Furthermore, the African American and white women appeared to be affected similarly by the quality of their experience in the mother role.
Electronic Government Interoperability
Authors: Santos Ernani Marques dos , Reinhard Nicolau
Published: February 2011

Interoperability is a crucial issue for electronic government due to the need of agencies’ information systems to be totally integrated and able to exchange data in a seamless way. A way to achieve it is by establishing a government interoperability framework (GIF). However, this is a difficult task to be carried out due not only to technological issues but also to other aspects. This research is expected to contribute to the identification of the barriers to the adoption of interoperability standards for electronic government. The article presents the preliminary findings from a case study of the Brazilian Government framework (e-PING), based on the analyses of documents and face-to-face interviews. It points out some aspects that may influence the establishment of these standards, becoming barriers to their adoption.
Sport and social development: Promise and caution from an incipient Cambodian football league
Authors: Okada Chiaki , Young Kevin
Published: February 2011

One of the enduring controversies found in the literature on the role that sport plays in social development is whether this assumed relationship is weak or robust. Despite evidence both for and against the ‘sport-enhances-social-development’ model, a rapidly expanding cluster of case studies and a growing literature in a number of disciplines, there remain entire countries which have not been systematically explored and where almost no sociological research is available in English. Cambodia is one such case. Based upon qualitative methods (specifically interviews and observation) and as part of an ongoing study, this article reports on an incipient sport initiative (the Siem Reap Hotel Football League) in northern Cambodia. Emphasizing that sport is ‘contested terrain’ and may simultaneously improve and exacerbate existing social relations in any setting, our data show that any promise sport offers communities in either a micro or macro sense should be viewed through the lens of caution and circumspection.
Identity Structures: Holons, Boundaries, Hierarchies, and the Formation of the Collaborative Identity
Authors: Fish Jessica N. , Priest Jacob B.
Published: February 2011

An individual’s identity and identity processes are important factors in understanding the individual within a system. Drawing on Marcia’s identity theory and Minuchin’s ideas of structural family therapy, in this article, we aim to further the understanding of identity. It puts forth a theory of identity that suggests that identity is not a single entity, but rather it is a structure formed by identity holons. The status of each identity holon (diffused, foreclosed, achieved, or moratorium) creates a boundary around the holon that influences the hierarchy of the identity. The hierarchy of the identity creates the collaborative identity. Further, we discuss the application of this theory in a therapeutic setting.
Six Sigma DMAIC Quality Study: Expanded Nurse Practitioner’s Role in Health Care During and Posthospitalization Within the United States
Authors: Kumar Sameer , McKewan Gregory W.
Published: February 2011

Aim: The purpose of this study is to leverage application of Six Sigma DMAIC Cycle in examining the expanded role of nurses in the United States for delivering improved health care during and posthospitalization of patients. Method: This study makes use of the operations management service tools, such as service blueprints and poka-yokes (mistake-proofing), as well as the DMAIC (Define, Measure, Analyze, Improve, and Control) method of the Six Sigma (these concepts are explained in the article) to define the failures of the process, reduce variability, improve the care process, and propose solutions. Fifty-three nurses from hospitals and small medical clinics responded to survey for this study. Results: This study reveals that nurses feel that increasing the number of nurses in hospitals would improve the care of patients. Nurses feel they could take on certain tasks currently only performed by doctors after receiving proper training. This would reduce the workload of doctors. Conclusions: Analysis of the current open-ended health care process allowed determining failure points and how to prevent such failures. Recommended poka-yokes include greater involvement of nurses in education and counseling patients during hospitalization and posthospitalization. Structured home visits and nurses role in improving communication with patients to foster better understanding and self-care compliance would decrease the number of unplanned readmissions. Expanding the current education process in nursing schools and nursing roles is crucial to implement a closed-loop health care delivery system, which incorporates suggested poka-yokes.
OASIS Update
Authors: Niewenhous Susan S.
Published: February 2011

The OASIS-C data set has been in use for more than a year now. The “large” questions have been answered; however, astute clinicians continue to seek to fine-tune their understanding of this important document. The October 2010 release of the CMS OASIS Certificate and Competency Board Q&As covers a wide range of topics, including wounds, dyspnea, pain, and patient education. CMS’ answers to the most recent questions are reviewed in this article.
THERAPY IS A JOURNEY as a discourse metaphor
Authors: Tay Dennis
Published: February 2011

Although much has been written about the use of metaphors during psychotherapy sessions, the complementary question of how the therapeutic process might itself be metaphorically conceptualized is seldom asked. This article adopts the notion of ‘discourse metaphors’ (Zinken et al., 2008) and provides a case study of the metaphor THERAPY IS A JOURNEY across various levels of psychotherapeutic discourse, including the formulation of theoretical constructs, pedagogical frameworks and transcripts of actual therapeutic talk. I show how the inherent meaning stability as well as flexibility afforded by conceptual metaphors renders them particularly suitable for conveying a necessary sense of theoretical continuity across the levels, while accommodating variations according to situated discourse objectives within each level. Answering calls for metaphor research to be more practically relevant, I also suggest how the present approach can contribute to the increasing therapeutic concern with establishing ‘feedback’ across the different participatory levels of psychotherapy.
Epistemic authority in employment interviews: Glancing, pointing, touching
Authors: Glenn Phillip , LeBaron Curtis
Published: February 2011

Interviewers routinely orient to applicant files as they produce first pair parts (e.g. questions) that forward the business of the interview. As they do so, they make clear what they know, whether they already know it or are discovering it in the moment, whether it comes from the file in hand, and whether the applicant holds primary rights to confirm or amend that information. In these moments, participants work out issues of epistemic authority through an orchestration of multimodal behaviors, including talk, gesture, gaze, and touch. Our analysis focuses specifically on two discourse slots: when interviewers confirm specific information in side sequences; and when they gloss and assess general information while calling for an account. In the former, interviewers display minimal knowledge and secondary (deferred) epistemic authority; in the latter, they show strong knowledge and assert primary epistemic authority. This article demonstrates how epistemic authority, negotiated through embodied talk-in-interaction, contributes to how interviews unfold.
Recontextualizing participatory journalists’ mobile media in British television news: A case study of the live coverage and commemorations of the 2005 London bombings
Authors: Lorenzo-Dus Nuria , Bryan Annie
Published: February 2011

This article examines contributions from members of the public featured in British television news coverage of the 2005 London bombings (‘7/7’). Specifically, it explores how images (photographs and videos) captured by ordinary people on their mobile devices were used in the live news reportage of 7/7 and, given the current salience of commemorative journalism, how these were (re-)used in the tragedy’s first year anniversary coverage. The analysis reveals broadcasters’ selection of uniform, repetitive and ‘sanitized’ mobile media footage, as well as a tendency towards non-attribution. This article contributes to the scant body of discourse analytic research into ‘participatory journalism’ practices, particularly their interaction with ‘traditional’ forms of journalism.
What’s in a name? Stance markers in oral argument about marriage laws
Authors: Tracy Karen
Published: February 2011

This study examines the relationship between person-referencing terms and attorney and judges’ stances during oral argument in three US state supreme courts as each considered whether its existing state law could restrict marriage to one man and one woman. After reviewing past work on stancetaking and person referencing, I provide background on appellate oral argument and the three cases. Combining discourse analysis with simple quantitative coding, the study shows that attorneys’ and judges’ choices of terms for gay parties and the frequency of their use marked the stance of appellate parties toward same-sex marriage. Then, I describe how person-referencing terms for gays, both in the larger society and in appellate courts, changed in the 20 years preceding the cases. The article concludes by arguing for the value of studying state appellate court discourse; I also reflect about the complexities in linking changes in usage of person-referencing terms with attitudinal stance changes.
An employee-centered model of organizational justice and social responsibility
Authors: E. Rupp Deborah
Published: February 2011

This paper reviews recent research within the area of organizational justice. It argues that a key element of the employee experience is the formation of perceptions about how both the self and others are treated by organizational stakeholders, as well as the level of dignity and respect bestowed by the organization to external groups. Employees, therefore, look in, around, and out, in order to comprehend their working experiences, and depend on these judgments to navigate the organizational milieu. A full understanding of justice phenomena requires consideration of individual differences; contextual influences; affective, cognitive, and social processes; as well as a person-centric orientation that allows for both time and memory to influence the social construction of worker phenomena.
A functional model of hierarchy
Authors: Halevy Nir , Y. Chou Eileen , D. Galinsky Adam
Published: February 2011

We propose that hierarchy is such a prevalent form of social organization because it is functionally adaptive and enhances a group’s chances of survival and success. We identify five ways in which hierarchy facilitates organizational success. Hierarchy (a) creates a psychologically rewarding environment; (b) motivates performance through hierarchy-related incentives; (c) capitalizes on the complementary psychological effects of having versus lacking power; (d) supports division of labor, and, as a result, coordination; and (e) reduces conflict and enhances voluntary cooperation. Overall, we specify a causal model linking organizational structure (hierarchy), processes (motivation, leadership, coordination, and cooperation) and outcomes (performance). We also discuss three variables that moderate the need for and acceptance of hierarchy—(a) the level of task interdependence; (b) the legitimacy of hierarchical differentiation; and (c) the alignment of different bases of hierarchy—and link them to the mediating processes through which hierarchy facilitates organizational success.
Activation of the unfolded protein response is associated with impaired granulopoiesis in transgenic mice expressing mutant Elane
Authors: Nanua Suparna , Murakami Mark , Xia Jun , Grenda David S. , Woloszynek Jill , Strand Marie , Link Daniel C.
Published: February 2011

Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis that in many cases is caused by mutations of the ELANE gene, which encodes neutrophil elastase (NE). Recent data suggest a model in which ELANE mutations result in NE protein misfolding, induction of endoplasmic reticulum (ER) stress, activation of the unfolded protein response (UPR), and ultimately a block in granulocytic differentiation. To test this model, we generated transgenic mice carrying a targeted mutation of Elane (G193X) reproducing a mutation found in SCN. The G193X Elane allele produces a truncated NE protein that is rapidly degraded. Granulocytic precursors from G193X Elane mice, though without significant basal UPR activation, are sensitive to chemical induction of ER stress. Basal and stress granulopoiesis after myeloablative therapy are normal in these mice. Moreover, inaction of protein kinase RNA-like ER kinase (Perk), one of the major sensors of ER stress, either alone or in combination with G193X Elane, had no effect on basal granulopoiesis. However, inhibition of the ER-associated degradation (ERAD) pathway using a proteosome inhibitor resulted in marked neutropenia in G193X Elane. The selective sensitivity of G913X Elane granulocytic cells to ER stress provides new and strong support for the UPR model of disease patho-genesis in SCN.
Regulation of Insulin-Stimulated Glucose Uptake in Rat White Adipose Tissue upon Chronic Central Leptin Infusion: Effects on Adiposity
Authors: Bonzón-Kulichenko Elena , Fernández-Agulló Teresa , Moltó Eduardo , Serrano Rosario , Fernández Alejandro , Ros Manuel , Carrascosa José M. , Arribas Carmen , Martínez Carmen , Andrés Antonio , Gallardo Nilda
Published: February 2011

Leptin enhances the glucose utilization in most insulin target tissues and paradoxically decreases it in white adipose tissue (WAT), but knowledge of the mechanisms underlying the inhibitory effect of central leptin on the insulin-dependent glucose uptake in WAT is limited. After 7 d intracerebroventricular leptin treatment (0.2 μg/d) of rats, the overall insulin sensitivity and the responsiveness of WAT after acute in vivo insulin administration were analyzed. We also performed unilateral WAT denervation to clarify the role of the autonomic nervous system in leptin effects on the insulin-stimulated [3H]-2-deoxyglucose transport in WAT. Central leptin improved the overall insulin sensitivity but decreased the in vivo insulin action in WAT, including insulin receptor autophosphorylation, insulin receptor substrate-1 tyrosine-phosphorylation, and Akt activation. In this tissue, insulin receptor substrate-1 and glucose transporter 4 mRNA and protein levels were down-regulated after central leptin treatment. Additionally, a remarkable up-regulation of resistin, together with an augmented expression of suppressor of cytokine signaling 3 in WAT, was also observed in leptin-treated rats. As a result, the insulin-stimulated glucose transporter 4 insertion at the plasma membrane and the glucose uptake in WAT were impaired in leptin-treated rats. Finally, denervation of WAT abolished the inhibitory effect of central leptin on glucose transport and decreased suppressor of cytokine signaling 3 and resistin levels in this tissue, suggesting that resistin, in an autocrine/paracrine manner, might be a mediator of central leptin antagonism of insulin action in WAT. We conclude that central leptin, inhibiting the insulin-stimulated glucose uptake in WAT, may regulate glucose availability for triacylglyceride formation and accumulation in this tissue, thereby contributing to the control of adiposity.
Distinct Roles of Deiodinases on the Phenotype of Mct8 Defect: A Comparison of Eight Different Mouse Genotypes
Authors: Liao Xiao-Hui , Di Cosmo Caterina , Dumitrescu Alexandra M. , Hernandez Arturo , Van Sande Jacqueline , St. Germain Donald L. , Weiss Roy E. , Galton Valerie Anne , Refetoff Samuel
Published: February 2011

Mice deficient in the thyroid hormone (TH) transporter Mct8 (Mct8KO) have increased 5′-deiodination and impaired TH secretion and excretion. These and other unknown mechanisms result in the low-serum T4, high T3, and low rT3 levels characteristic of Mct8 defects. We investigated to what extent each of the 5′-deiodinases (D1, D2) contributes to the serum TH abnormalities of the Mct8KO by generating mice with all combinations of Mct8 and D1 and/or D2 deficiencies and comparing the resulting eight genotypes. Adding D1 deficiency to that of Mct8 corrected the serum TH abnormalities of Mct8KO mice, normalized brain T3 content, and reduced the impaired expression of TH-responsive genes. In contrast, Mct8D2KO mice maintained the serum TH abnormalities of Mct8KO mice. However, the serum TSH level increased 27-fold, suggesting a severely impaired hypothalamo-pituitary-thyroid axis. The brain of Mct8D2KO manifested a pattern of more severe impairment of TH action than Mct8KO alone. In triple Mct8D1D2KO mice, the markedly increased serum TH levels produced milder brain defect than that of Mct8D2KO at the expense of more severe liver thyrotoxicosis. Additionally, we observed that mice deficient in D2 had an unexplained marked reduction in the thyroid growth response to TSH. Our studies on these eight genotypes provide a unique insight into the complex interplay of the deiodinases in the Mct8 defect and suggest that D1 contributes to the increased serum T3 in Mct8 deficiency, whereas D2 mainly functions locally, converting T4 to T3 to compensate for distinct cellular TH depletion in Mct8KO mice.
Impairment of Peripheral Circadian Clocks Precedes Metabolic Abnormalities in ob/ob Mice
Authors: Ando Hitoshi , Kumazaki Masafumi , Motosugi Yuya , Ushijima Kentarou , Maekawa Tomohiro , Ishikawa Eiko , Fujimura Akio
Published: February 2011

Recent studies have demonstrated relationships between the dysfunction of circadian clocks and the development of metabolic abnormalities, but the chicken-and-egg question remains unresolved. To address this issue, we investigated the cause-effect relationship in obese, diabetic ob/ob mice. Compared with control C57BL/6J mice, the daily mRNA expression profiles of the clock and clock-controlled genes Clock, Bmal1, Cry1, Per1, Per2, and Dbp were substantially dampened in the liver and adipose tissue, but not the hypothalamic suprachiasmatic nucleus, of 10-wk-old ob/ob mice. Four-week feeding of a low-calorie diet and administration of leptin over a 7-d period attenuated, to a significant and comparable extent, the observed metabolic abnormalities (obesity, hyperglycemia, hyperinsulinemia, and hypercholesterolemia) in the ob/ob mice. However, only leptin treatment improved the impaired peripheral clocks. In addition, clock function, assessed by measuring levels of Per1, Per2, and Dbp mRNA at around peak times, was also reduced in the peripheral tissues of 3-wk-old ob/ob mice without any overt metabolic abnormalities. Collectively these results indicate that the impairment of peripheral clocks in ob/ob mice does not result from metabolic abnormalities but may instead be at least partially caused by leptin deficiency itself. Further studies are needed to clarify how leptin deficiency affects peripheral clocks.
The gsp Oncogene Disrupts Ras/ERK-Dependent Prolactin Gene Regulation in gsp Inducible Somatotroph Cell Line
Authors: Pertuit M. , Romano D. , Zeiller C. , Barlier A. , Enjalbert A. , Gerard C.
Published: February 2011

The MAPK ERK1/2 cascade regulates all the critical cellular functions, and in many pathological situations, these regulatory processes are perturbed. It has been clearly established that this cascade is an integrative point in the control of the pituitary functions exerted by various extracellular signals. In particular, ERK1/2 cross talk with the cAMP pathway is determinant in the control of somatolactotroph hormonal secretion exerted via neuropeptide receptors. GH-secreting adenomas are characterized by frequent cAMP pathway alterations, such as constitutive activation of the α-subunit of the heterotrimeric Gs protein (the gsp oncogene), overexpression of Gsα, and changes in the protein kinase A regulatory subunits. However, it has not yet been established exactly how these alterations result in GH-secreting adenomas or how the ERK1/2 cascade contributes to the process of GH-secreting adenoma tumorigenesis. In this study on the conditional gsp-oncogene-expressing GH4C1 cell line, expression of the gsp oncogene, which was observed in up to 40% of GH-secreting adenomas, was found to induce sustained ERK1/2 activation, which required activation of the protein kinase A and the GTPases Ras and Rap1. All these signaling components contribute to the chronic activation of the human prolactin promoter. The data obtained here show that Ras plays a crucial role in these processes: in a physiopathological context, i.e. in the presence of the gsp oncogene, it switched from being a repressor of the cAMP/ protein kinase A ERK-sensitive prolactin gene control exerted by neuropeptides to an activator of the prolactin promoter.
Bar Code Medication Administration Technology: Characterization of High-Alert Medication Triggers and Clinician Workarounds
Authors: Miller Daniel F , Fortier Christopher R , Garrison Kelli L
Published: February 2011

BACKGROUND:

Bar code medication administration (BCMA) technology is gaining acceptance for its ability to prevent medication administration errors. However, studies suggest that improper use of BCMA technology can yield unsatisfactory error prevention and introduction of new potential medication errors.

OBJECTIVE:

To evaluate the incidence of high-alert medication BCMA triggers and alert types and discuss the type of nursing and pharmacy workarounds occurring with the use of BCMA technology and the electronic medication administration record (eMAR).

METHODS:

Medication scanning and override reports from January 1, 2008, through November 30, 2008, for all adult medical/surgical units were retrospectively evaluated for high-alert medication system triggers, alert types, and override reason documentation. An observational study of nursing workarounds on an adult medicine step-down unit was performed and an analysis of potential pharmacy workarounds affecting BCMA and the eMAR was also conducted.

RESULTS:

Seventeen percent of scanned medications triggered an error alert of which 55% were for high-alert medications. Insulin aspart, NPH insulin, hydromorphone, potassium chloride, and morphine were the top 5 high-alert medications that generated alert messages. Clinician override reasons for alerts were documented in only 23% of administrations. Observational studies assessing for nursing workarounds revealed a median of 3 clinician workarounds per administration. Specific nursing workarounds included a failure to scan medications/patient armband and scanning the bar code once the dosage has been removed from the unit-dose packaging. Analysis of pharmacy order entry process workarounds revealed the potential for missed doses, duplicate doses, and doses being scheduled at the wrong time.

CONCLUSIONS:

BCMA has the potential to prevent high-alert medication errors by alerting clinicians through alert messages. Nursing and pharmacy workarounds can limit the recognition of optimal safety outcomes and therefore workflow processes must be continually analyzed and restructured to yield the intended full benefits of BCMA technology.
Safety of the HPV Bivalent and Quadrivalent Vaccines during Pregnancy
Authors: Forinash Alicia B , Yancey Abigail M , Pitlick Jamie M , Myles Thomas D
Published: February 2011

OBJECTIVE:

To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy.

DATA SOURCE:

PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information.

STUDY SELECTION AND DATA EXTRACTION:

All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated.

DATA SYNTHESIS:

Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials.

CONCLUSIONS:

Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk.
Histochemistry
Authors: Lavis Luke D.
Published: February 2011

Histochemistry—chemistry in the context of biological tissue—is an invaluable set of techniques used to visualize biological structures. This field lies at the interface of organic chemistry, biochemistry, and biology. Integration of these disciplines over the past century has permitted the imaging of cells and tissues using microscopy. Today, by exploiting the unique chemical environments within cells, heterologous expression techniques, and enzymatic activity, histochemical methods can be used to visualize structures in living matter. This review focuses on the labeling techniques and organic fluorophores used in live cells.
Selective inhibition of dipeptidyl peptidase 4 by targeting a substrate-specific secondary binding site
Authors: Kühn-Wache Kerstin , Bär Joachim W. , Hoffmann Torsten , Wolf Raik , Rahfeld Jens-Ulrich , Demuth Hans-Ulrich
Published: February 2011

Dipeptidyl peptidase 4/CD26 (DP4) is a multifunctional serine protease liberating dipeptide from the N-terminus of (oligo)peptides which can modulate the activity of these peptides. The enzyme is involved in physiological processes such as blood glucose homeostasis and immune response. DP4 substrate specificity is characterized in detail using synthetic dipeptide derivatives. The specificity constant k
cat/K
m strongly depends on the amino acid in P1-position for proline, alanine, glycine and serine with 5.0×105 m
-1s-1, 1.8×104 m
-1s-1, 3.6×102 m
-1s-1, 1.1×102 m
-1s-1, respectively. By contrast, kinetic investigation of larger peptide substrates yields a different pattern. The specific activity of DP4 for neuropeptide Y (NPY) cleavage comprising a proline in P1-position is the same range as the k
cat/K
m values of NPY derivatives containing alanine or serine in P1-position with 4×105 m
-1s-1, 9.5×105 m
-1s-1 and 2.1×105 m
-1s-1, respectively. The proposed existence of an additional binding region outside the catalytic center is supported by measurements of peptide substrates with extended chain length. This ‘secondary’ binding site interaction depends on the amino acid sequence in P4′–P8′-position. Interactions with this binding site could be specifically blocked for substrates of the GRF/glucagon peptide family. By contrast, substrates not belonging to this peptide family and dipeptide derivative substrates that only bind to the catalytic center of DP4 were not inhibited. This more selective inhibition approach allows, for the first time, to distinguish between substrate families by substrate-discriminating inhibitors.
New localities and perspectives on the sympatry between two endangered primates (Callicebus coimbraiandCebus xanthosternos) in northeastern Brazil
Authors: Beltrão-Mendes Raone , Cunha André A. , Ferrari Stephen F.
Published: February 2011

No abstract available
Enlarging the knowledge onGraomys griseoflavus(Rodentia: Sigmodontinae) in Patagonia: distribution and environments
Authors: Sauthier Daniel Edgardo Udrizar , Formoso Anahí Elizabeth , Teta Pablo , Pardiñas Ulyses Francisco José
Published: February 2011

No abstract available
Sensory Neuropathy Attributable to Loss of Bcl-w
Authors: Courchesne Stephanie L. , Karch Christoph , Pazyra-Murphy Maria F. , Segal Rosalind A.
Published: February 2011

Small fiber sensory neuropathy is a common disorder in which progressive degeneration of small-diameter nociceptors causes decreased sensitivity to thermal stimuli and painful sensations in the extremities. In the majority of patients, the cause of small fiber sensory neuropathy is unknown, and treatment options are limited. Here, we show that Bcl-w (Bcl-2l2) is required for the viability of small fiber nociceptive sensory neurons.Bcl-w−/−mice demonstrate an adult-onset progressive decline in thermosensation and a decrease in nociceptor innervation of the epidermis. This denervation occurs without cell body loss, indicating that lack of Bcl-w results in a primary axonopathy. Consistent with this phenotype, we show that Bcl-w, in contrast to the closely related Bcl-2 and Bcl-xL, is enriched in axons of sensory neurons and that Bcl-w prevents the dying back of axons.Bcl-w−/−sensory neurons exhibit mitochondrial abnormalities, including alterations in axonal mitochondrial size, axonal mitochondrial membrane potential, and cellular ATP levels. Collectively, these data establishbcl-w−/−mice as an animal model of small fiber sensory neuropathy and provide new insight regarding the role of Bcl-w and of mitochondria in preventing axonal degeneration.
Gateways of Ventral and Dorsal Streams in Mouse Visual Cortex
Authors: Wang Quanxin , Gao Enquan , Burkhalter Andreas
Published: February 2011

It is widely held that the spatial processing functions underlying rodent navigation are similar to those encoding human episodic memory (Doeller et al., 2010). Spatial and nonspatial information are provided by all senses including vision. It has been suggested that visual inputs are fed to the navigational network in cortex and hippocampus through dorsal and ventral intracortical streams (Whitlock et al., 2008), but this has not been shown directly in rodents. We have used cytoarchitectonic and chemoarchitectonic markers, topographic mapping of receptive fields, and pathway tracing to determine in mouse visual cortex whether the lateromedial field (LM) and the anterolateral field (AL), which are the principal targets of primary visual cortex (V1) (Wang and Burkhalter, 2007) specialized for processing nonspatial and spatial visual information (Gao et al., 2006), are distinct areas with diverse connections. We have found that the LM/AL border coincides with a change in type 2 muscarinic acetylcholine receptor expression in layer 4 and with the representation of the lower visual field periphery. Our quantitative analyses also show that LM strongly projects to temporal cortex as well as the lateral entorhinal cortex, which has weak spatial selectivity (Hargreaves et al., 2005). In contrast, AL has stronger connections with posterior parietal cortex, motor cortex, and the spatially selective medial entorhinal cortex (Haftig et al., 2005). These results support the notion that LM and AL are architecturally, topographically, and connectionally distinct areas of extrastriate visual cortex and that they are gateways for ventral and dorsal streams.
Anti-Ganglioside Antibody-Mediated Activation of RhoA Induces Inhibition of Neurite Outgrowth
Authors: Zhang Gang , Lehmann Helmar C. , Manoharan Sowmia , Hashmi Mohammedali , Shim Sangwoo , Ming Guo-Li , Schnaar Ronald L. , Lopez Pablo H. , Bogdanova Nataliia , Sheikh Kazim A.
Published: February 2011

Anti-ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barré syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al., 2007). An implication of these findings is that anti-GD1a Abs can mediate inhibition of axon regeneration and limit recovery in some patients with GBS. The downstream inhibitory intracellular signaling that mediates anti-ganglioside Ab-induced axon inhibition remains unclear. In the current study, we show that disease-relevant and GBS patient's anti-ganglioside Abs can inhibit neurite outgrowth in dissociated primary neuronal cultures. Activation of small GTPase RhoA and its key downstream effector Rho kinase (ROCK) are critical mediators of growth cone and neurite outgrowth inhibition. Therefore, we examined the role of these intracellular signaling molecules in our primary neuronal cultures by molecular and pharmacologic approaches. Our results show that the Ab-mediated inhibition of neurite outgrowth involves the activation of RhoA and ROCK pathway and this activation is through the engagement of specific cell-surface gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway involved in anti-ganglioside Ab-mediated inhibition of neurite outgrowth.