bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human cystathionine β-synthase (CBS) contains two classes of binding sites for S-adenosylmethionine (SAM): complex regulation of CBS activity and stability by SAM
Authors: Pey Angel L. , Majtan Tomas , Sanchez-Ruiz Jose M. , Kraus Jan P. 
Published: September 2012

CBS (cystathionine β-synthase) is a multidomain tetrameric enzyme essential in the regulation of homocysteine metabolism, whose activity is enhanced by the allosteric regulator SAM (S-adenosylmethionine). Missense mutations in CBS are the major cause of inherited HCU (homocystinuria). In the present study we apply a novel approach based on a combination of calorimetric methods, functional assays and kinetic modelling to provide structural and energetic insight into the effects of SAM on the stability and activity of WT (wild-type) CBS and seven HCU-causing mutants. We found two sets of SAM-binding sites in the C-terminal regulatory domain with different structural and energetic features: a high affinity set of two sites, probably involved in kinetic stabilization of the regulatory domain, and a low affinity set of four sites, which are involved in the enzyme activation. We show that the regulatory domain displays a low kinetic stability in WT CBS, which is further decreased in many HCU-causing mutants. We propose that the SAM-induced stabilization may play a key role in modulating steady-state levels of WT and mutant CBS in vivo. Our strategy may be valuable for understanding ligand effects on proteins with a complex architecture and their role in human genetic diseases and for the development of novel pharmacological strategies.
Small dense LDL is more susceptible to glycation than more buoyant LDL in Type 2 diabetes
Authors: Younis Nahla N. , Soran Handrean , Pemberton Philip , Charlton-Menys Valentine , Elseweidy Mohamed M. , Durrington Paul N. 
Published: September 2012

Glycation of apoB (apolipoprotein B) of LDL (low-density lipoprotein) increases its atherogenicity. Concentrations of both serum glyc-apoB (glycated apoB) and SD-LDL (small dense LDL) (syn LDL3; D=1.044–1.063 g/ml) are increased in diabetes and are closely correlated. We studied whether SD-LDL is more susceptible to glycation in vitro than more buoyant LDL in statin- and non-statin-treated Type 2 diabetes mellitus. Serum SD-LDL apoB and glyc-apoB on statins was 20±2 (means±S.D.) and 3.6±0.41 compared with 47±3 and 5.89±0.68 mg/dl in those not receiving statins (P&lt;0.001 and &lt;0.01, respectively). There was a dose-dependent increase in glycation on incubation of LDL subfractions with glucose, which was accompanied by an increase in LPO (lipid peroxide) and electrophoretic mobility and a decrease in free amino groups. SD-LDL was more susceptible to these changes than more buoyant LDL. Both SD-LDL and more buoyant LDL from statin-treated patients were less susceptible to glycation. There were fewer free amino groups on LDL subfractions from statin-treated patients, which may contribute to this resistance. In conclusion, greater susceptibility of SD-LDL to glycation is likely to contribute to the raised levels of circulating glyc-apoB in diabetes. Statins are associated with lower levels of both SD-LDL and glyc-apoB.
Perspectives From General Education Teachers, Students and Their Parents: Including Students With Robust Communication Devices in General Education Classrooms
Authors: Kramlich Christine 
Published: September 2012

Abstract
Teachers face a number of challenges with regard to including students, but especially when including those who have complex communication needs and use speech-generating devices (SGDs). Parents are interested in collaborating with teachers, but may find themselves with differing opinions than school and staff. Students using SGDs want to be part of the class, not just physically in the classroom. Finding ways to communicate and work together is critical to overcoming these challenges and facilitating inclusion. In this process, it is important to consider the perspectives of the general education teacher, the parent of the student using the SGD, classmates, and, most important, the student using the SGD.
Making It A Reality: Using Standards-Based General Education Science and Math Curriculum To Teach Vocabulary and Language Structures to Students Who Use AAC
Authors: Boruta Michele Caputo , Bidstrup Kara 
Published: September 2012

Abstract
Students who use AAC to access vocabulary and language typically receive much of their language intervention in a classroom environment. Given this, it is important to teach emerging vocabulary and language concepts as well as academic content when delivering curriculum to students who use AAC. In this article, we will focus on identifying the language level of the student, providing him or her with a linguistically based AAC system, and delivering language intervention within the context of standards-based science and math curriculum. In addition, we will show how a standards-based science and math curriculum can serve as an excellent platform for language instruction. We will also discuss and demonstrate backwards planning as a method to create authentic and meaningful lessons for students who use AAC. The sample lessons will include a national standard, that standard reframed into an appropriate language target, assessment tools, strategies for teaching and learning, and an instructional activity and materials.
Stream Conductivity: Relationships to Land Use, Chloride, and Fishes in Maryland Streams
Authors: Morgan Raymond P. , Kline Kathleen M. , Kline Matthew J. , Cushman Susan F. , Sell Matthew T. , Weitzell Roy E. , Churchill John B. 
Published: September 2012

Abstract
Stream conductivity reflects both landscape and anthropogenic interactions, although increasing chloride inputs from road salt in eastern North America is also important. Employing a spatially extensive database derived from the Maryland Biological Stream Survey (MBSS), we examined relationships of stream conductivity to landscape attributes and determined relationships between stream MBSS fish metrics, abundance, and biomass as well as fish assemblages by means of conductivity (as a chloride surrogate) to estimate potential effects. Background stream conductivity for the MBSS strata and Maryland L3 ecoregions ranged from 51 to 150 μS/cm, with the Piedmont having the highest background conductivity (145–160 μS/cm). For MBSS sites there were strong relationships of stream conductivity and chloride with both impervious surface and road density, and 0.26% of the MBSS sites exceeded the U.S. Environmental Protection Agency's acute chloride criterion and 1.5% the chronic chloride criterion. For the Maryland Piedmont species assemblage, observed conductivity values between 230 and 540 μS/cm caused important alterations in the biotic community as measured by the series of fish metrics, and thus affected fish species assemblages associated with chloride concentrations between 33 and 108 mg/L. Maryland coastal, coldwater, and highland species assemblages displayed variable responses of conductivity to fish metrics, abundance, and biomass. If regional conductivity and chloride levels continue to increase or remain high from road deicing owing to an increase in urbanization in a watershed or climatic changes, differences in stream fish assemblages and therefore fish diversity may become more apparent. Because of the linkage between salt usage and impervious road surfaces resulting from urbanization, it is important to manage effectively the use of road salt to protect biotic resources.
Received January 24, 2012; accepted June 5, 2012
Quality of life and survival in patients with heart failure
Authors: Hoekstra Tialda , Jaarsma Tiny , van Veldhuisen Dirk J. , Hillege Hans L. , Sanderman Robbert , Lesman‐Leegte Ivonne 
Published: September 2012

AimsTo examine whether self‐rated disease‐specific and generic quality of life predicts long‐term mortality, independent of brain natriuretic peptide (BNP) levels, and to explore factors related to low quality of life in a well‐defined heart failure (HF) population.Methods and resultsA cohort of 661 patients (62% male; age 71 years; left ventricular ejection fraction 34%) was followed prospectively for 3 years. Quality of life questionnaires (Ladder of Life, RAND36, and Minnesota Living with Heart Failure Questionnaire) and BNP levels were assessed at discharge after a hospital admission for HF. Three‐year mortality was 42%. After adjustment for demographic variables, clinical variables, and BNP levels, poor quality of life scores predicted higher mortality; per 10 units on the physical functioning [hazard ratio (HR) 1.08, 95% confidence interval (CI) 1.02–1.14] and general health (HR 1.08, 95% CI 1.01–1.16) dimensions of the RAND36. Patients with low scores on these dimensions were more likely to be in New York Heart Association class III–IV, diagnosed with co‐morbidities, have suffered longer from HF, have lower estimated glomerular filtration rates, and have fewer beta‐blocker prescriptions.ConclusionQuality of life was independently related to survival in a cohort of hospitalized patients with HF.Trial registration:NCT 98675639.
Prevention of Intraoperative Awareness with Explicit Recall in an Unselected Surgical Population
Authors: Mashour George A. , Shanks Amy , Tremper Kevin K. , Kheterpal Sachin , Turner Christopher R. , Ramachandran Satya Krishna , Picton Paul , Schueller Christa , Morris Michelle , Vandervest John C. , Lin Nan , Avidan Michael S. 
Published: September 2012

Background
Intraoperative awareness with explicit recall occurs in approximately 0.15% of all surgical cases. Efficacy trials based on the Bispectral Index® (BIS) monitor (Covidien, Boulder, CO) and anesthetic concentrations have focused on high-risk patients, but there are no effectiveness data applicable to an unselected surgical population.

Methods
We conducted a randomized controlled trial of unselected surgical patients at three hospitals of a tertiary academic medical center. Surgical cases were randomized to alerting algorithms based on either BIS values or anesthetic concentrations. The primary outcome was the incidence of definite intraoperative awareness; prespecified secondary outcomes included postanesthetic recovery variables.

Results
The study was terminated because of futility. At interim analysis the incidence of definite awareness was 0.12% (11/9,376) (95% CI: 0.07-0.21%) in the anesthetic concentration group and 0.08% (8/9,460) (95% CI: 0.04-0.16%) in the BIS group (P = 0.48). There was no significant difference between the two groups in terms of meeting criteria for recovery room discharge or incidence of nausea and vomiting. By post hoc secondary analysis, the BIS protocol was associated with a 4.7-fold reduction in definite or possible awareness events compared with a cohort receiving no intervention (P = 0.001; 95% CI: 1.7-13.1).

Conclusion
This negative trial could not detect a difference in the incidence of definite awareness or recovery variables between monitoring protocols based on either BIS values or anesthetic concentration. By post hoc analysis, a protocol based on BIS monitoring reduced the incidence of definite or possible intraoperative awareness compared with routine care.
The γ-Carbonic Anhydrase Subcomplex of Mitochondrial Complex I Is Essential for Development and Important for Photomorphogenesis of Arabidopsis
Authors: Wang Qin , Fristedt Rikard , Yu Xuhong , Chen Zugen , Liu Hongtao , Lee Yurhee , Guo Hongwei , Merchant Sabeeha S. , Lin Chentao 
Published: September 2012

AbstractComplex I (NADH:ubiquinone oxidoreductase) is the entry point for electrons into the respiratory electron transport chain; therefore, it plays a central role in cellular energy metabolism. Complex I from different organisms has a similar basic structure. However, an extra structural module, referred to as the γ-carbonic anhydrase (γCA) subcomplex, is found in the mitochondrial complex I of photoautotrophic eukaryotes, such as green alga and plants, but not in that of the heterotrophic eukaryotes, such as fungi and mammals. It has been proposed that the γCA subcomplex is required for the light-dependent life style of photoautotrophic eukaryotes, but this hypothesis has not been successfully tested. We report here a genetic study of the genes γCAL1 and γCAL2 that encode two subunits of the γCA subcomplex of mitochondrial complex I. We found that mutations of γCAL1 and γCAL2 in Arabidopsis (Arabidopsis thaliana) result in defective embryogenesis and nongerminating seeds, demonstrating the functional significance of the γCA subcomplex of mitochondrial complex I in plant development. Surprisingly, we also found that reduced expression of γCAL1 and γCAL2 genes altered photomorphogenic development. The γcal1 mutant plant expressing the RNA interference construct of the γCAL2 gene showed a partial constitutive photomorphogenic phenotype in young seedlings and a reduced photoperiodic sensitivity in adult plants. The involvement of the γCA subcomplex of mitochondrial complex I in plant photomorphogenesis and the possible evolutionary significance of this plant-specific mitochondrial protein complex are discussed.
A longitudinal study of patients' symptoms before and during the first year after lung transplantation
Authors: Lanuza Dorothy M. , Lefaiver Cheryl A. , Brown Roger , Muehrer Rebecca , Murray Margaret , Yelle Maria , Bhorade Sangeeta 
Published: September 2012

AbstractBackgroundLung transplantation provides a viable option for survival of end‐stage respiratory disease. In addition to prolonging survival, there is considerable interest in improving patient‐related outcomes such as transplant recipients' symptom experiences.MethodsA prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000 and 2005. The transplant symptom inventory was administered before and at one, three, six, nine, and 12 months post‐transplant. Ridit analysis provided a unique method for describing symptom experiences and changes.ResultsAfter lung transplantation, significant (p < 0.05) improvements were reported for the most frequently occurring and most distressing pre‐transplant symptoms (e.g., shortness of breath with activity). Marked increases in the frequency and distress of new symptoms such as tremors were also reported. Patterns of symptom frequency and distress varied with time since transplant.ConclusionThe findings provide data‐based information that can be used to inform pre‐ and post‐transplant patient education and also help caregivers anticipate a general time frame for symptom changes to prevent or minimize symptoms and their associated distress. In addition, symptoms are described, using an innovative method of illustration which shows “at‐a‐glance” change or lack of change in patients' symptoms from pre‐ to post‐lung transplant.
Economic evaluations of prophylaxis with clotting factor for people with severe haemophilia: why do the results vary so much?
Authors: Miners A. H. 
Published: September 2012

SummaryA number of studies examining the cost effectiveness of haemophilia prophylaxis have been published, but they report a wide range of results. The aim of this study was to explain why the results from existing economic evaluations of prophylaxis with clotting factor vary so much and to suggest areas of further research that will help to generate stronger economic evidence. Results from a previous systematic review were updated using a textword search of a number of electronic databases. Eleven economic evaluations were identified. They reported incremental cost‐effectiveness ratios for prophylaxis ranging from ‘cost saving and clinically beneficial’ (i.e. ‘dominant’) to over €1 million per additional quality‐adjusted life year (QALY) if prophylaxis replaces treatment following a bleed. A number of reasons are likely to explain this breadth of results, most notably differences in choice of time horizon, estimates of treatment effect, clotting factor unit cost, discount rates and definitions of prophylaxis. Although the existing cost‐effectiveness literature for haemophilia prophylaxis appears to report a wide range of results, closer inspection suggests that differences are largely explained by a number of design features. Some are likely to reflect local economic conditions and should be expected. However, others, such as differences in the choice of appropriate time horizon, are more concerning as they reflect differences in opinion over appropriate methodology. A number of studies to help address these evidence gaps are suggested: however, it is also recommended that analysts continue to adhere to established conventions when conducting and reporting economic evaluations.
Perceptions of job satisfaction relating to affective organisation commitment
Authors: Papinczak Tracey 
Published: September 2012

Medical Education 2012: 46: 953–962Objectives  Affective organisation commitment, which refers to a psychological attachment to, and involvement with, an employing institution, is regarded as important because of its effects on employee identification with the employer and its causal effects on work effort and staff retention. This paper explores the experiences of casual tutors facilitating problem‐based learning (PBL) tutorials and aims to identify aspects of their role that strengthen and detract from employee job satisfaction and affective commitment.Methods  Qualitative data were gathered from first‐ and second‐year tutors (N = 13) through 2 focus groups. Both clinicians and non‐clinicians were recruited, including highly experienced staff and those with < 12 months of tutoring experience.Results  Four main themes arose from inductive analysis of data: job‐related factors; job‐involvement characteristics; professional challenges and responsibilities, and mentoring for learning and support. The first 2 themes are congruent with previous literature on organisation commitment; novel findings include the supportive and compensatory nature of the collegial relationships formed between casual tutors. Role attenuation, a job‐related factor, was a predominant perception as it related to dysfunctional groups and increasing student disengagement with PBL.Conclusions  Within the unique learning environment of PBL, positive factors relating to job satisfaction may have an important role to play in improving tutors’ commitment to their employing organisation. Aspects of the role which are viewed most negatively and relate most significantly to affective commitment need to be addressed promptly. Attention should be directed to supporting tutors to maximise the perceived benefits and providing professional development and improved communication to better address issues associated with difficult or disengaged students as well as isolation from decision‐makers.
Conducting systematic reviews in medical education: a stepwise approach
Authors: Cook David A , West Colin P 
Published: September 2012

Medical Education 2012: 46: 943–952Objectives  As medical education research continues to proliferate, evidence syntheses will become increasingly important. The purpose of this article is to provide a concise and practical guide to the conduct and reporting of systematic reviews.Results  (i) Define a focused question addressing the population, intervention, comparison (if any) and outcomes. (ii) Evaluate whether a systematic review is appropriate to answer the question. Systematic and non‐systematic approaches are complementary; the former summarise research on focused topics and highlight strengths and weaknesses in existing bodies of evidence, whereas the latter integrate research from diverse fields and identify new insights. (iii) Assemble a team and write a study protocol. (iv) Search for eligible studies using multiple databases (MEDLINE alone is insufficient) and other resources (article reference lists, author files, content experts). Expert assistance is helpful. (v) Decide on the inclusion or exclusion of each identified study, ideally in duplicate, using explicitly defined criteria. (vi) Abstract key information (including on study design, participants, intervention and comparison features, and outcomes) for each included article, ideally in duplicate. (vii) Analyse and synthesise the results by narrative or quantitative pooling, investigating heterogeneity, and exploring the validity and assumptions of the review itself. In addition to the seven key steps, the authors provide, information on electronic tools to facilitate the review process, practical tips to facilitate the reporting process and an annotated bibliography.
Phenomenological analysis of patient experiences of medical student teaching encounters
Authors: McLachlan Emma , King Nigel , Wenger Etienne , Dornan Tim 
Published: September 2012

Medical Education 2012: 46: 963–973Context  It is important to know how patients are affected by becoming opportunistically involved in medical student education. In previous studies, researchers rather than patients set the research agenda and expert patients or people well known to teachers were more often involved than ordinary people.Objectives  This study aimed to explore how ordinary patients experience undergraduate medical teaching when they become involved in it opportunistically and to derive practical insights from the lived experiences of these patients.Methods  The research was conducted in line with a conceptual orientation towards communities of practice theory and used phenomenology as a way of exploring patients’ lived experiences in depth. Minimally structured interviews were carried out with 10 patients following ordinary out‐patient or general practice appointments in which students were being taught. Template analysis was used to generate provisional themes and a process of phenomenological reduction was used to distil individual respondents’ lived experiences to their essence.Results  The presence of students in ambulatory consultations was normal. Nine respondents described transactional relationships in which they remained outside the community of practice of which the doctor and student were members. Only an intimate problem would engage them deeply enough for a student’s presence to ‘bother’ them. One patient’s personal and professional background led her to regard doctors’ handling of consultation dynamics as factors contributing to whether teaching consultations were negative or positive experiences. When doctors’ sensitive and inclusive behaviour drew her into a triadic relationship with the student and doctor, she experienced mutual benefits with students. When it did not, she felt objectified and alienated.Conclusions  Provided they receive the clinical care for which they are attending a consultation and are treated respectfully, patients may sometimes willingly become ‘objects’ from which students learn. They may, however, become more deeply engaged in teaching consultations in which they participate actively in a triadic relationship of mutual benefit with a doctor and student. Teaching consultations call for doctors to be sensitive and adaptable.