bluuebunny/crossref_metadata_2025 huggingface dataset:
Carboplatin-Induced Oxidative Injury in Rat Inferior Colliculus
Authors: Husain Kazim , Whitworth Craig , Hazelrigg Stephen , Rybak Leonard
Published: June 2009

Carboplatin is currently being used as an anticancer drug against human cancers. However, high dose of carboplatin chemotherapy resulted in ototoxicity in cancer patients. Carboplatin-induced ototoxicity was related to oxidative stress to the cochlea and inner hair cell loss in animals. It is likely that initial oxidative injury spreads throughout the neuroaxis of the auditory system later. The study aim was to evaluate carboplatin-induced hearing loss and oxidative injury to the central auditory system (inferior colliculus) of the rat. Male Wistar rats were divided into two groups of seven animals each and treated as follows: (1) control (normal saline, intraperitoneal [IP]) and (2) carboplatin (256 mg/kg, IP). Auditory brain-evoked responses (ABRs) were recorded before and 4 days after treatments. The animals were sacrificed on the 4th day and inferior colliculus from brain stem and cerebellum were isolated and analyzed. Carboplatin significantly elevated the hearing threshold shifts at clicks, 2-, 4-, 8-, 16-, and 32-k Hz tone burst stimuli. Carboplatin significantly increased nitric oxide and lipid peroxidation, xanthine oxidase, and manganese superoxide dismutase activities in the inferior colliculus, but not in the cerebellum, indicating an enhanced flux of free radicals in the central auditory system. Carboplatin significantly depressed the reduced to oxidized glutathione ratio, antioxidant enzyme activities, such as copper-zinc superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione S-transferase, and enzyme protein expressions in the inferior colliculus, but not in the cerebellum, 4 days after treatment. The data suggest that carboplatin induced oxidative injury specifically in the inferior colliculus of the rat leading to hearing loss.
The Use of Unallowed Excipients
Authors: Steinberg Marshall , Silverstein Irwin
Published: June 2009

The laws governing the U.S. Food and Drug Administration (FDA) do not provide for the approval of stand-alone excipients. Current regulations do not permit the use of excipients, but allow their use. The acceptance process for excipients is slow and only recently did the FDA propose draft guidance for nonclinical studies for pharmaceutical excipients. The FDA has made four suggestions to the U.S. Pharmacopoeia concerning including excipient monographs in the National Formulary for excipients not yet allowed. This article reviews these four proposals to identify the proposal that is most appropriate.
The Dietary Supplement and Health Education Act and Supplements: Dietary and Nutritional Supplements Need No More Regulations
Authors: Wollschlaeger Bernd
Published: June 2009

The Dietary Supplement and Health Education Act (DSHEA) of 1994 was intended to ensure consumer access to safe dietary supplements, e.g., herbs, minerals, and vitamins. It granted the Food and Drug Administration (FDA) considerable enforcement authority to regulate dietary supplement industry. This article discusses relevant components of the DSHEA, explains the division of regulatory responsibilities between the FDA and the Federal Trade Commission (FTC), and refutes the often cited allegation that the herb and dietary supplement industry are unregulated.
Why Consumers Need More Protection Against Claims for Dietary Supplements and Herbs
Authors: Barrett Stephen
Published: June 2009

Federal agencies have never had enough resources to cope with the enormous amount of deception in the supplement and health-food marketplace. Passage of the 1994 Dietary Supplement Health and Education Act (DSHEA) has worsened the situation by encouraging dubious claims and weakening the Food and Drug Administration (FDA)'s ability to ban dangerous products.
Food Safety: Risk Assessment Methodology and Decision-Making Criteria
Authors: Brock William J. , Rodricks Joseph V. , Rulis Alan , Dellarco Vicki L. , Gray George M. , Lane Richard W.
Published: June 2009

As our scientific technology grows, risk assessment methods become more complex and, therefore, open to greater scientific debate. Risk assessment has always been a part of the regulatory notification and approval process for foods. However, the methodologies applied to risk assessment and decision-making have become diverse, dependent on a number of features, including the areas of the world in which one operates, the need to use cumulative risk assessment for pesticides and otheringredients or alternative risk assessment considerations for evaluating nontraditional or bioengineered foods. Diverse institutional structures within a single federal regulatory authority may tend to lead to diversity in risk outcomes that creates policy decisions that complicate and confuse the risk management process. On top of this challenge, decisions become more complicated by the need to examine beneficial factors of foods rather than the adverse effects of foods and food additives. Foods are a complex mixture ofingredients. Regulatory groups recognize the need to use new approaches for evaluating the safety and risks associated with foods and food additives, and to do so in a timely manner. The United States Food and Drug Administration (US FDA) in its need to ensure standards of “reasonable certainty of no harm” continues to explore alternative means to be responsive to petitioners as well as continue to examine scientifically validated means, e.g., quantitative structure-activity relationship (QSAR), and computer-assisted programs, within the approval process to assist in the evaluation of risks. Another means to improve the risk management process would include the cumulative risk assessment of pesticides that will, no doubt, be the beginning of more intensive efforts to understand cumulative exposures and the inherent risks from multiple pathways of exposure. The passage of the Food Quality Protection Act (FQPA) resulted in developing additional risk assessment methodologies and approaches to assess the potential for multiple exposures and risks. Addressing the international criteria used in decision-making related to foods safety assessment has resulted in acceptable intake values for foodingredients for carcinogens and noncarcinogens that, in general, tend to be more stringent in the United States compared to Europe. Clearly, the need for harmonization of risk assessment criteria and the impact of the decision process on regulatory approvals and safety assessment is a future need for the continued assurances of food safety. The topics presented in this paper are based on a symposium held in November 2002 at the annual meeting of the American College of Toxicology.
HPC and Grid Computing for Integrative Biomedical Research
Authors: Kurc Tahsin , Hastings Shannon , Kumar Vijay , Langella Stephen , Sharma Ashish , Pan Tony , Oster Scott , Ervin David , Permar Justin , Narayanan Sivaramakrishnan , Gil Yolanda , Deelman Ewa , Hall Mary , Saltz Joel
Published: June 2009

Integrative biomedical research projects query, analyze, and integrate many different data types and make use of datasets obtained from measurements or simulations of structure and function at multiple biological scales. With the increasing availability of high-throughput and high-resolution instruments, the integrative biomedical research imposes many challenging requirements on software middleware systems. In this paper, we look at some of these requirements using example research pattern templates. We then discuss how middleware systems, which incorporate Grid and high-performance computing, could be employed to address the requirements.
Parallel Programming in MATLAB
Authors: Luszczek Piotr
Published: June 2009

A visit to the neighborhood PC retail store provides ample proof that we are in the multi-core era. The key differentiator among manufacturers today is the number of cores that they pack onto a single chip. The clock frequency of commodity processors has reached its limit, however, and is likely to stay below 4 GHz for years to come. As a result, adding cores is not synonymous with increasing computational power. To take full advantage of the performance enhancements offered by the new multi-core hardware, a corresponding shift must take place in the software infrastructure — a shift to parallel computing.
The role of vision for online control of manual aiming movements in persons with autism spectrum disorders
Authors: Glazebrook Cherylm. , Gonzalez David , Hansen Steve , Elliott Digby
Published: June 2009

Recent studies suggest motor skills are not entirely spared in individuals with an autism spectrum disorder (ASD). Previous reports demonstrated that young adults with ASD were able to land accurately on a target despite increased temporal and spatial variability during their movement. This study explored how a group of adolescents and young adults with an ASD used vision and proprioception to land successfully on one of two targets. Participants performed eye movements and/or manual reaching movements, either with or without vision. Although eye movements were executed in a similar timeframe, participants with ASD took longer to plan and execute manual reaching movements. They also exhibited significantly greater variability during eye and hand movements, but were able to land on the target regardless of the vision condition. In general, individuals with autism used vision and proprioception. However, they took considerably more time to perform movements that required greater visual-proprioceptive integration.
Perceiving the impossible
Authors: Sheppard Elizabeth , Ropar Danielle , Mitchell Peter
Published: June 2009

Mottron and colleagues found that individuals with autism were less affected by geometric impossibility than comparison participants on a copying task. The current experiment sought to determine whether a local perceptual style could account for this. Participants with and without autism copied possible and impossible geometric figures. Geometric impossibility had a larger effect on drawing time for comparison participants than for those with autism. However, participants with autism did not use more localized drawing strategies. Strength of impossibility effect was associated with a global strategy amongst comparison participants but this relationship was not found amongst participants with autism. The findings suggest that differences in high-level conceptual processing may account for group differences in effects of impossibility.
Developmental regression in children with an autism spectrum disorder identified by a population-based surveillance system
Authors: Wiggins Lisa D. , Rice Catherine E. , Baio Jon
Published: June 2009

This study evaluated the phenomenon of autistic regression using population-based data. The sample comprised 285 children who met the autism spectrum disorder (ASD) case definition within an ongoing surveillance program. Results indicated that children with a previously documented ASD diagnosis had higher rates of autistic regression than children who met the ASD surveillance definition but did not have a clearly documented ASD diagnosis in their records (17—26 percent of surveillance cases). Most children regressed around 24 months of age and boys were more likely to have documented regression than girls. Half of the children with regression had developmental concerns noted prior to the loss of skills. Moreover, children with autistic regression were more likely to show certain associated features, including cognitive impairment.These data indicate that some children with ASD experience a loss of skills in the first few years of life and may have a unique symptom profile.
Complex Problem Solving after Unstructured Discussion: Effects of Information Distribution and Experience
Authors: Meyer Bertolt , Scholl Wolfgang
Published: June 2009

This study analyzes the effect of information overlap in groups discussing a complex problem on individual post-discussion complex problem solving (CPS). We hypothesize that information distribution among group members has an inverse u-shaped effect on individual post-discussion performance, favoring groups with a medium informational heterogeneity. As CPS is presumably correlated with experience, we also assume that exposure to the problem before the actual task leads to higher performance than less or no exposure. Experimental results support the first hypothesis: A medium overlap of instructional text paragraphs in dyads led to higher performance in a computer-simulated complex problem than complete or no overlap. The second hypothesis is not supported. Limitations of the study and practical implications are discussed.
The Relative Impact of Anger and Efficacy on Collective Action is Affected by Feelings of Fear
Authors: Miller Daniel A. , Cronin Tracey , Garcia Amber L. , Branscombe Nyla R.
Published: June 2009

Two well-established predictors of collective action are perceptions of group efficacy and feelings of anger. The current research investigates the extent to which the relative impact of these variables differs when fear is or is not also included as a predictor of collective action. The results of two experiments indicate that when fear is not assessed, the importance of anger as a predictor of action is underestimated while the importance of group efficacy is overestimated. The results further indicate that fear, in addition to affecting the impact of known causes of collective action (anger and group efficacy), is a powerful inhibitor of collective action. The implications for current theoretical models of collective action instigators are discussed.
Behavioral (In)tolerance of Equality Violation in Social Dilemmas: When Trust Affects Contribution Decisions after Violations of Equality
Authors: Stouten Jeroen , De Cremer David , van Dijk Eric
Published: June 2009

In public good dilemmas, people often coordinate their decisions by applying the equality rule. Prior research has shown that if one member violates equality, negative emotions emerge among the other group members. In two experimental studies we investigated whether the presence of a violator also affects contribution decisions. A first experiment demonstrated that a violation of equality does not always influence people's contributions. Even after an equality violation, group members continued to base their decisions on the equality rule if they faced a social dilemma with the same group members. But when group members faced a social dilemma with only the violator of equality, contributions were lowered. Experiment 2 showed that this is especially true for low trusters.
Executing Charles Starkweather
Authors: Lachance Daniel
Published: June 2009

In the 1950s, the use and popularity of the death penalty declined as penal welfarism pervaded political and academic approaches to crime control. Analysis of responses to the 1958 crimes and 1959 execution of teenage serial killer Charles Starkweather reveals, however, that the integrity of penal welfarism was badly shaken by a conflict between the political and intellectual commitments required for its maintenance. As a result, Starkweather's crime and the responses it elicited called into question the core assumptions upon which 1950s penology was based: a belief that the world was a knowable, controllable place and that a competent state could use social science to maximize social harmony. Starkweather's case ultimately reveals one impetus for the return of retributive responses to crime in political and academic circles and the re-emergence of the death penalty in the last three decades of the 20th century.
Policing after the crisis
Authors: Waiton Stuart
Published: June 2009

The growth of laws, surveillance and policing across British society can be linked back to changes under the Conservative governments of the 1970s and 1980s. However, despite some `authoritarian' developments at this time, it was not until Margaret Thatcher's demise, that there was a quantitative and qualitative shift in governing towards a form of `governing through crime'. Many of these developments have been associated with the rise of a right wing, or neo-liberal dynamic in society. However, this article argues that the obsession with crime, antisocial behaviour and the regulation of everyday life did not emerge as part of an aggressive form of neo-liberalism. Rather than their being an energetic politics behind these developments, it is more accurate to see the growth in law and the more direct regulation of society as a consequence of the collapse of politics on both the left and the right. Rather than competing for the conflicting political subject in society, the role of politicians now became to act as advocates for a diminished subject — the crime victim and the vulnerable public. Crime expanded as a field of governance due both to the political elite's sense of diminished capacity and control over society, and with the construction of a more fragile subject that needed ever more protections.
Strength of Messaging in Changing Attitudes in a Workplace Wellness Program
Authors: Langille Jessie-Lee D. , Berry Tanya R. , Reade Ian L. , Witcher Chad , Loitz Christina C. , Rodgers Wendy M.
Published: June 2009

The potential benefits of workplace wellness programs are limited by low participation rates of employees, which could be due in part to ineffective persuasion by program providers. This study uses the Elaboration Likelihood Model, as a guiding theory in mixed methods research, to investigate feedback messages about physical activity delivered in a workplace wellness program. This study uses questionnaire and interview data from 32 employees to determine if personally relevant health messages are associated with either positive or negative responses to the messages and subsequent attitude change. General feedback is more appreciated by those who are less fit but are not effective in changing attitudes toward physical activity. Individually targeted messages result in a significant positive attitude change for participants responding positively to the messages. This suggests that individualized health promotion messages provide a stronger argument for individuals, thus increasing the likelihood of attitude change.
Something New Under the Sun: Lutein’s Role in Skin Health
Authors: Evans Julie A. , Johnson Elizabeth J.
Published: June 2009

Lutein has a well-established role in eye health. There is accumulating evidence that lutein may also play a role in skin health. Its presence in human skin along with its antioxidant and anti-inflammatory activity provide a rationale for a role in preventing ultraviolet-induced damage to skin. Epidemiological studies support a role for diets high in lutein and decreased risk of wrinkling and cancer. Recent intervention studies have shown lutein to prevent ultraviolet-induced carcinogenesis in animals and to improve skin physiology parameters in humans, including antioxidant protection from ultraviolet light irradiation. In this review, the authors explore the rationale and plausibility of a role for lutein in skin health.
Dual ACE-inhibition and AT1 receptor antagonism improves ventricular lusitropy without affecting cardiac fibrosis in the congenic mRen2.Lewis rat
Authors: Jessup Jewell A. , Westwood Brian M. , Chappell Mark C. , Groban Leanne
Published: June 2009

Background: Hypertension and left ventricular (LV) hypertrophy often precede diastolic dysfunction and are risk factors for diastolic heart failure. Although pharmacologic inhibition of the renin-angiotensin system (RAS) improves diastolic function and functional capacity in hypertensive patients with LV hypertrophy, the effects of combination therapy with an angiotensin converting enzyme inhibitor (ACEi) and an angiotensin receptor blocker (ARB) are unclear.

Method: We assessed the effects of the combined 10-week administration of lisinopril (10 mg/kg/ day, p.o.) and losartan (10 mg/kg/day, p.o.) (LIS/LOS) on diastolic function and LV structure in seven young (5 weeks), prehypertensive congenic mRen2.Lewis male rat, a model of tissue renin overexpression and angiotensin II (Ang II)-dependent hypertension compared to vehicle (VEH) treated (n = 7), age-matched rats.

Results: Systolic blood pressures were 64% lower with the combination therapy (p < 0.001), but there were no differences in heart rate or systolic function between groups. RAS inhibition increased myocardial relaxation, defined by tissue Doppler mitral annular descent (e') by 2.2 fold (p < 0.001). The preserved lusitropy in the LIS/LOS-treated rats was accompanied by a reduction in phospholamban-to-SERCA2 ratio (p < 0.001). Despite lower relative wall thicknesses (VEH: 1.56±0.17 versus LIS/LOS: 0.78±0.05) and filling pressures, defined by the transmitral Doppler-to-mitral annular descent ratio (E/e', VEH: 28.7±1.9 versus LIS/LOS: 17.96±1.5), no differences in cardiac collagen were observed.

Conclusion: We conclude that the lusitropic benefit of early dual RAS blockade may be due to improved vascular hemodynamics and/or cardiac calcium handling rather than effects on extracellular matrix reduction.
Electronic Systems for Student Clinical Records
Authors: Baker Anthony L. , Dubose Terry J.
Published: June 2009

Proper documentation of a student’s clinical education is a critical component of a diagnostic medical sonography program’s administrative functions. Traditional paper documents have been used for decades to record and verify a student’s clinical training. However, these paper records can rapidly become a paperwork nightmare, especially for large sonographic programs spread over a broad geographical area. This article examines the reasons for keeping accurate clinical records, discusses paper clinical records systems, and reviews some of the new electronic systems for student clinical records that are now emerging in the allied health professions.
The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways
Authors: Lim Megan S. , Carlson Mary L. , Crockett David K. , Fillmore G. Chris , Abbott David R. , Elenitoba-Johnson Olaotan F. , Tripp Sheryl R. , Rassidakis George Z. , Medeiros L. Jeffrey , Szankasi Philippe , Elenitoba-Johnson Kojo S. J.
Published: June 2009

Constitutive expression of the chimeric NPM/ALK fusion protein encoded by the t(2;5)(p32;q35) is a key oncogenic event in the pathogenesis of most anaplastic large cell lymphomas (ALCLs). The proteomic network alterations produced by this aberration remain largely uncharacterized. Using a mass spectrometry (MS)–driven approach to identify changes in protein expression caused by the NPM/ALK fusion, we identified diverse NPM/ALK-induced changes affecting cell proliferation, ribosome synthesis, survival, apoptosis evasion, angiogenesis, and cytoarchitectural organization. MS-based findings were confirmed using Western blotting and/or immunostaining of NPM/ALK-transfected cells and ALK-deregulated lymphomas. A subset of the proteins distinguished NPM/ALK-positive ALCLs from NPM/ALK-negative ALCLs and Hodgkin lymphoma. The multiple NPM/ALK-deregulated pathways identified by MS analysis also predicted novel biologic effects of NPM/ALK expression. In this regard, we showed loss of cell adhesion as a consequence of NPM/ALK expression in a kinase-dependent manner, and sensitivity of NPM/ALK-positive ALCLs to inhibition of the RAS, p42/44ERK, and FRAP/mTOR signaling pathways. These findings reveal that the NPM/ALK alteration affects diverse cellular pathways, and provide novel insights into NPM/ALK-positive ALCL pathobiology. Our studies carry important implications for the use of MS-driven approaches for the elucidation of neoplastic pathobiology, the identification of novel diagnostic biomarkers, and pathogenetically relevant therapeutic targets.
Remodelling sympathetic innervation in rat pancreatic islets ontogeny
Authors: Cabrera-Vásquez Siraam , Navarro-Tableros Víctor , Sánchez-Soto Carmen , Gutiérrez-Ospina Gabriel , Hiriart Marcia
Published: June 2009

Background

Pancreatic islets are not fully developed at birth and it is not clear how they are vascularised and innervated. Nerve Growth Factor (NGF) is required to guide sympathetic neurons that innervate peripheral organs and also in cardiovascular system and ovary angiogenesis. Pancreatic beta cells of a transgenic mouse that over-expressed NGF in attracts sympathetic hyper-innervation towards them. Moreover, we have previously demonstrated that adult beta cells synthesize and secrete NGF; however, we do not know how is NGF secreted during development, nor if it might be trophic for sympathetic innervation and survival in the pancreas.

We analyzed sympathetic innervation and vasculature development in rat pancreatic islets at different developmental stages; foetal (F19), early postnatal (P1), weaning period (P20) and adults. We temporarily correlated these events to NGF secretion by islet cells.

Results

Sympathetic fibres reached pancreatic islets in the early postnatal period, apparently following blood vessels. The maximal number of sympathetic fibres (TH immunopositive) in the periphery of the islets was observed at P20, and then fibres entered the islets and reached the core where beta cells are mainly located. The number of fibres decreased from that stage to adulthood. At all stages studied, islet cells secreted NGF and also expressed the high affinity receptor TrkA. Foetal and neonatal isolated islet cells secreted more NGF than adults. TrkA receptors were expressed at all stages in pancreatic sympathetic fibres and blood vessels. These last structures were NGF–immunoreactive only at early stages (foetal and P0).

Conclusion

The results suggest that NGF signalling play an important role in the guidance of blood vessels and sympathetic fibres toward the islets during foetal and neonatal stages and could also preserve innervation at later stages of life.
Functional and comparative genomics analyses of pmp22 in medaka fish
Authors: Itou Junji , Suyama Mikita , Imamura Yukio , Deguchi Tomonori , Fujimori Kazuhiro , Yuba Shunsuke , Kawarabayasi Yutaka , Kawasaki Takashi
Published: June 2009

Background

Pmp22, a member of the junction protein family Claudin/EMP/PMP22, plays an important role in myelin formation. Increase of pmp22 transcription causes peripheral neuropathy, Charcot-Marie-Tooth disease type1A (CMT1A). The pathophysiological phenotype of CMT1A is aberrant axonal myelination which induces a reduction in nerve conduction velocity (NCV). Several CMT1A model rodents have been established by overexpressing pmp22. Thus, it is thought that pmp22 expression must be tightly regulated for correct myelin formation in mammals. Interestingly, the myelin sheath is also present in other jawed vertebrates. The purpose of this study is to analyze the evolutionary conservation of the association between pmp22 transcription level and vertebrate myelin formation, and to find the conserved non-coding sequences for pmp22 regulation by comparative genomics analyses between jawed fishes and mammals.

Results

A transgenic pmp22 over-expression medaka fish line was established. The transgenic fish had approximately one fifth the peripheral NCV values of controls, and aberrant myelination of transgenic fish in the peripheral nerve system (PNS) was observed. We successfully confirmed that medaka fish pmp22 has the same exon-intron structure as mammals, and identified some known conserved regulatory motifs. Furthermore, we found novel conserved sequences in the first intron and 3'UTR.

Conclusion

Medaka fish undergo abnormalities in the PNS when pmp22 transcription increases. This result indicates that an adequate pmp22 transcription level is necessary for correct myelination of jawed vertebrates. Comparison of pmp22 orthologs between distantly related species identifies evolutionary conserved sequences that contribute to precise regulation of pmp22 expression.
Assess suitability of hydroaeroponic culture to establish tripartite symbiosis between different AMF species, beans, and rhizobia
Authors: Tajini Fatma , Suriyakup Porntip , Vailhe Hélène , Jansa Jan , Drevon Jean-Jacques
Published: June 2009

Background

Like other species of thePhaseoleaetribe, common bean (Phaseolus vulgarisL.) has the potential to establish symbiosis with rhizobia and to fix the atmospheric dinitrogen (N2) for its N nutrition. Common bean has also the potential to establish symbiosis with arbuscular mycorrhizal fungi (AMF) that improves the uptake of low mobile nutrients such as phosphorus, from the soil. Both rhizobial and mycorrhizal symbioses can act synergistically in benefits on plant.

Results

The tripartite symbiosis of common bean with rhizobia and arbuscular mycorrhizal fungi (AMF) was assessed in hydroaeroponic culture with common bean (Phaseolus vulgarisL.), by comparing the effects of three fungi spp. on growth, nodulation and mycorrhization of the roots under sufficientversusdeficient P supplies, after transfer from initial sand culture. AlthoughGlomus intraradicesSchenck & Smith colonized intensely the roots of common bean in both sand and hydroaeroponic cultures,Gigaspora roseaNicolson & Schenck only established well under sand culture conditions, and no root-colonization was found withAcaulospora melleaSpain & Schenck under either culture conditions. Interestingly, mycorrhization byGlomuswas also obtained by contact with mycorrhizedStylosanthes guianensis(Aubl.) sw in sand culture under deficient P before transfer into hydroaeroponic culture. The effect of bean genotype on both rhizobial and mycorrhizal symbioses withGlomuswas subsequently assessed with the common bean recombinant inbreed line 7, 28, 83, 115 and 147, and the cultivar Flamingo. Significant differences among colonization and nodulation of the roots and growth among genotypes were found.

Conclusion

The hydroaeroponic culture is a valuable tool for further scrutinizing the physiological interactions and nutrient partitioning within the tripartite symbiosis.
KIDMAP, a web based system for gathering patients' feedback on their doctors
Authors: Chien Tsair-Wei , Wang Weng-Chung , Lin Sho-Be , Lin Ching-Yih , Guo How-Ran , Su Shih-Bin
Published: June 2009

Background

The gathering of feedback on doctors from patients after consultations is an important part of patient involvement and participation. This study first assesses the 23-item Patient Feedback Questionnaire (PFQ) designed by the Picker Institute, Europe, to determine whether these items form a single latent trait. Then, an Internet module with visual representation is developed to gather patient views about their doctors; this program then distributes the individualized results by email.

Methods

A total of 450 patients were randomly recruited from a 1300-bed-size medical center in Taiwan. The Rasch rating scale model was used to examine the data-fit. Differential item functioning (DIF) analysis was conducted to verify construct equivalence across the groups. An Internet module with visual representation was developed to provide doctors with the patient's online feedback.

Results

Twenty-one of the 23 items met the model's expectation, namely that they constitute a single construct. The test reliability was 0.94. DIF was found between ages and different kinds of disease, but not between genders and education levels. The visual approach of the KIDMAP module on the WWW seemed to be an effective approach to the assessment of patient feedback in a clinical setting.

Conclusion

The revised 21-item PFQ measures a single construct. Our work supports the hypothesis that the revised PFQ online version is both valid and reliable, and that the KIDMAP module is good at its designated task. Further research is needed to confirm data congruence for patients with chronic diseases.
Maximum recovery after knee replacement – the MARKER study rationale and protocol
Authors: Lin Chung-Wei Christine , March Lyn , Crosbie Jack , Crawford Ross , Graves Stephen , Naylor Justine , Harmer Alison , Jan Stephen , Bennell Kim , Harris Ian , Parker David , Moffet Helene , Fransen Marlene
Published: June 2009

Background

There is little scientific evidence to support the usual practice of providing outpatient rehabilitation to patients undergoing total knee replacement surgery (TKR) immediately after discharge from the orthopaedic ward. It is hypothesised that the lack of clinical benefit is due to the low exercise intensity tolerated at this time, with patients still recovering from the effects of major orthopaedic surgery. The aim of the proposed clinical trial is to investigate the clinical and cost effectiveness of a novel rehabilitation strategy, consisting of an initial home exercise programme followed, approximately six weeks later, by higher intensity outpatient exercise classes.

Methods/Design

In this multicentre randomised controlled trial, 600 patients undergoing primary TKR will be recruited at the orthopaedic pre-admission clinic of 10 large public and private hospitals in Australia. There will be no change to the medical or rehabilitative care usually provided while the participant is admitted to the orthopaedic ward. After TKR, but prior to discharge from the orthopaedic ward, participants will be randomised to either the novel rehabilitation strategy or usual rehabilitative care as provided by the hospital or recommended by the orthopaedic surgeon. Outcomes assessments will be conducted at baseline (pre-admission clinic) and at 6 weeks, 6 months and 12 months following randomisation. The primary outcomes will be self-reported knee pain and physical function. Secondary outcomes include quality of life and objective measures of physical performance. Health economic data (health sector and community service utilisation, loss of productivity) will be recorded prospectively by participants in a patient diary. This patient cohort will also be followed-up annually for five years for knee pain, physical function and the need or actual incidence of further joint replacement surgery.

Discussion

The results of this pragmatic clinical trial can be directly implemented into clinical practice. If beneficial, the novel rehabilitation strategy of utilising outpatient exercise classes during a later rehabilitation phase would provide a feasible and potentially cost-effective intervention to optimise the physical well-being of the large number of people undergoing TKR.

Trial Registration

ACTRN12609000054213
Intra-articular adhesions of the temporomandibular joint: Relation between arthroscopic findings and clinical symptoms
Authors: Zhang ShanYong , Li u XiuMing , Yang Chi , Cai XieYi , Chen MinJie , Haddad Majd S , Yun Bai , Chen ZhuoZhi
Published: June 2009

Background

Intra-articular adhesion (IA) is one of the important pathologic signs of intracapsular temporomandibular joint (TMJ) diseases, but this factor has been rarely described with respect to its arthroscopic characteristics and histology. The purpose of this study was to describe the incidence and distribution of IA in patients with internal derangement (ID) and to investigate the correlation between adhesions and the clinical symptoms of patients with ID of TMJ with closed-lock.

Methods

A retrospective analysis was conducted of 1822 TMJs with ID that were refractory to nonsurgical treatments and underwent arthroscopic surgery between May 2001 and June 2008 in our department. Clinical findings were assessed on the basis of mandibular range of motion, patients' age and locking duration at the initial visit. ID stages were judged according to the Wilkes and Bronstein classification based on clinical symptoms and pre-operative magnetic resonance imaging. 1506 patients (1822 joints) with ID were divided into an adhesion group (486 patients) and a non-adhesion group (1020 patients). The associations between the two groups with respect to interincisal opening, clicking duration, locking duration and patients' age were statistically analyzed using a t-test.

Results

Arthroscopy confirmed occurrences of adhesion in 28.76% of the joints (524 joints out of a total of 1822). Grade 1 adhesion was found in 68.89% of those cases; grade 2 in 20.61%; grade 3 in 4.58%; and grade 4 in 5.92%. The percentages of instances of adhesion in different stages were as follows: 13.89% of the joints in Stage II had adhesion, 25.47% in Stage III, 37.99% in Stage IV, and 40.37% in Stage V. There were statistically significant differences for patients' age (t = 10.41, P < 0.001), interincisal opening (t = 9.54, P < 0.001), paining duration (t = 3.66, P < 0.001) and locking duration (t = 3.89, P < 0.001) between the two groups, while no statistically significant difference was found for clicking duration (t = 1.08, P > 0.05).

Conclusion

The arthroscopic findings confirmed that the incidence ratio of adhesion was high and occurred predominantly with older patients with longer locking duration and less interincisal opening. As the stage of ID increased, the adhesion grade rose.
Genetic relatedness and molecular characterization of multidrug resistant Acinetobacter baumannii isolated in central Ohio, USA
Authors: Srinivasan Vijaya B , Rajamohan Govindan , Pancholi Preeti , Stevenson Kurt , Tadesse Daniel , Patchanee Prapas , Marcon Mario , Gebreyes Wondwossen A
Published: June 2009

Background

Over the last decade, nosocomial infections due to Acinetobacter baumannii have been described with an increasing trend towards multidrug resistance, mostly in intensive care units. The aim of the present study was to determine the clonal relatedness of clinical isolates and to elucidate the genetic basis of imipenem resistance.

Methods

A. baumannii isolates (n = 83) originated from two hospital settings in central Ohio were used in this study. Pulsed-field gel electrophoresis genotyping and antimicrobial susceptibility testing for clinically relevant antimicrobials were performed. Resistance determinants were characterized by using different phenotypic (accumulation assay for efflux) and genotypic (PCR, DNA sequencing, plasmid analysis and electroporation) approaches.

Results

The isolates were predominantly multidrug resistant (>79.5%) and comprised of thirteen unique pulsotypes, with genotype VII circulating in both hospitals. The presence of bla
OXA-23 in 13% (11/83) and IS
Aba1
linked bla
OXA-66 in 79.5% (66/83) of clinical isolates was associated with high level imipenem resistance. In this set of OXA producing isolates, multidrug resistance was bestowed by bla
ADC-25, class 1 integron-borne aminoglycoside modifying enzymes, presence of sense mutations in gyrA/parC and involvement of active efflux (with evidence for the presence of adeB efflux gene).

Conclusion

This study underscores the major role of carbapenem-hydrolyzing class D β-lactamases, and in particular the acquired OXA-23, in the dissemination of imipenem-resistant A. baumannii. The co-occurrence of additional resistance determinant could also be a significant threat.
A novel mechanism of hippocampal LTD involving muscarinic receptor-triggered interactions between AMPARs, GRIP and liprin-α
Authors: Dickinson Bryony A , Jo Jihoon , Seok Heon , Son Gi Hoon , Whitcomb Daniel J , Davies Ceri H , Sheng Morgan , Collingridge Graham L , Cho Kwangwook
Published: June 2009

Background

Long-term depression (LTD) in the hippocampus can be induced by activation of different types of G-protein coupled receptors, in particular metabotropic glutamate receptors (mGluRs) and muscarinic acethycholine receptors (mAChRs). Since mGluRs and mAChRs activate the same G-proteins and isoforms of phospholipase C (PLC), it would be expected that these two forms of LTD utilise the same molecular mechanisms. However, we find a distinct mechanism of LTD involving GRIP and liprin-α.

Results

Whilst both forms of LTD require activation of tyrosine phosphatases and involve internalisation of AMPARs, they use different molecular interactions. Specifically, mAChR-LTD, but not mGluR-LTD, is blocked by peptides that inhibit the binding of GRIP to the AMPA receptor subunit GluA2 and the binding of GRIP to liprin-α. Thus, different receptors that utilise the same G-proteins can regulate AMPAR trafficking and synaptic efficacy via distinct molecular mechanisms.

Conclusion

Our results suggest that mAChR-LTD selectively involves interactions between GRIP and liprin-α. These data indicate a novel mechanism of synaptic plasticity in which activation of M1 receptors results in AMPAR endocytosis, via a mechanism involving interactions between GluA2, GRIP and liprin-α.
Can health care databases be used to identify incident cases of osteonecrosis?
Authors: Vlad Steven C , Felson David T , Miller Donald R
Published: June 2009

Introduction

Osteonecrosis (ON) is a rare disease associated with alcohol and glucocorticoid use. Identifying additional risk factors is difficult as the number of cases at any single center is small. We investigated whether data available in large health care databases can be used to identify incident ON cases.

Methods

Using data from the Boston Veterans Affairs Healthcare system, we identified potential cases of ON. These records, including available radiographs and reports, were reviewed. Using published criteria, we evaluated whether the subjects had confirmed ON (radiographs/reports met criteria), incident ON (onset of symptoms within 6 months of first code), or prevalent ON (onset more than 6 months prior to first code or onset could not be determined). We tested different definitions for incident ON using information derived from administrative data. These were compared to the 'gold standard' (record review) and positive predictive values (PPVs) were derived. Since PPVs for incident cases were low, we found the number of incident cases expected for every 1,000 potential cases identified, using the definitions as an initial screening tool to reduce the number of medical records that required examination.

Results

We identified 87 potential cases. No case of jaw ON was identified. Only 15 (17%) incident cases of ON were identified. PPVs never exceed 50% for incident ON. However, if we used the definition '(at least 1 inpatient ON code) and (no prior codes for osteoarthritis)' as an initial screen, then for every 1,000 records, we would need to review only 150 to find 69 incident cases.

Conclusions

Though the precise PPVs we found may not be generalizable to other databases, we believe that administrative data alone should not be used to identify incident cases of ON without confirming the diagnosis through a review of medical records. By applying the above definition, the number of records requiring review can be markedly reduced. This method can be used to find cases for valid case-control studies of risk factors for ON.
The novel conserved mitochondrial inner-membrane protein MTGM regulates mitochondrial morphology and cell proliferation
Authors: Zhao Jian , Liu Tong , Jin Shao-Bo , Tomilin Nikolay , Castro Juan , Shupliakov Oleg , Lendahl Urban , Nistér Monica
Published: June 2009

Although several proteins involved in mediating mitochondrial division have been reported in mammals, the mechanism of the fission machinery remains to be elucidated. Here, we identified a human nuclear gene (named MTGM) that encodes a novel, small, integral mitochondrial inner-membrane protein and shows high expression in both human brain tumor cell lines and tumor tissues. The gene is evolutionarily highly conserved, and its orthologs are 100% identical at the amino acid level in all analyzed mammalian species. The gene product is characterized by an unusual tetrad of the GxxxG motif in the transmembrane segment. Overexpression of MTGM (mitochondrial targeting GxxxG motif) protein results in mitochondrial fragmentation and release of mitochondrial Smac/Diablo to the cytosol with no effect on apoptosis. MTGM-induced mitochondrial fission can be blocked by a dominant negative Drp1 mutant (Drp1-K38A). Overexpression of MTGM also results in inhibition of cell proliferation, stalling of cells in S phase and nuclear accumulation of γ-H2AX. Knockdown of MTGM by RNA interference induces mitochondrial elongation, an increase of cell proliferation and inhibition of cell death induced by apoptotic stimuli. In conclusion, we suggest that MTGM is an integral mitochondrial inner-membrane protein that coordinately regulates mitochondrial morphology and cell proliferation.
The Hippo tumor-suppressor pathway regulates apical-domain size in parallel to tissue growth
Authors: Hamaratoglu Fisun , Gajewski Kathleen , Sansores-Garcia Leticia , Morrison Clayton , Tao Chunyao , Halder Georg
Published: June 2009

The Hippo tumor-suppressor pathway controls tissue growth in Drosophila and mammals by regulating cell proliferation and apoptosis. The Hippo pathway includes the Fat cadherin, a transmembrane protein, which acts upstream of several other components that form a kinase cascade that culminates in the regulation of gene expression through the transcriptional coactivator Yorkie (Yki). Our previous work in Drosophila indicated that Merlin (Mer) and Expanded (Ex) are members of the Hippo pathway and act upstream of the Hippo kinase. In contrast to this model, it was suggested that Mer and Ex primarily regulate membrane dynamics and receptor trafficking, thereby affecting Hippo pathway activity only indirectly. Here, we examined the effects of Mer, Ex and the Hippo pathway on the size of the apical membrane and on apical-basal polarity complexes. We found that mer;ex double mutant imaginal disc cells have significantly increased levels of apical membrane determinants, such as Crb, aPKC and Patj. These phenotypes were shared with mutations in other Hippo pathway components and required Yki, indicating that Mer and Ex signal through the Hippo pathway. Interestingly, however, whereas Crb was required for the accumulation of other apical proteins and for the expansion of the apical domain observed in Hippo pathway mutants, its elimination did not significantly reverse the overgrowth phenotype of warts mutant cells. Therefore, Hippo signaling regulates cell polarity complexes in addition to and independently of its growth control function in imaginal disc cells.
BRCA1-mediated chromatin silencing is limited to oocytes with a small number of asynapsed chromosomes
Authors: Kouznetsova Anna , Wang Hong , Bellani Marina , Camerini-Otero R. Daniel , Jessberger Rolf , Höög Christer
Published: June 2009

Transcriptional silencing of the sex chromosomes during male meiosis is regarded as a manifestation of a general mechanism active in both male and female germ cells, called meiotic silencing of unsynapsed chromatin (MSUC). MSUC is initiated by the recruitment of the tumor suppressor protein BRCA1 to the axes of unsynapsed chromosomes. We now show that Sycp3, a structural component of the chromosome axis, is required for localization of BRCA1 to unsynapsed pachytene chromosomes. Importantly, we find that oocytes carrying an excess of two to three pairs of asynapsed homologous chromosomes fail to recruit enough BRCA1 to the asynapsed axes to activate MSUC. Furthermore, loss of MSUC function only transiently rescues oocytes from elimination during early postnatal development. The fact that the BRCA1-dependent synapsis surveillance system cannot respond to higher degrees of asynapsis and is dispensable for removal of aberrant oocytes argues that MSUC has a limited input as a quality control mechanism in female germ cells.
How do ESCRT proteins control autophagy?
Authors: Rusten T. E. , Stenmark Harald
Published: June 2009

Autophagy, a conserved mechanism for lysosomal degradation of cytoplasmic components, has received much attention recently owing to its importance in tissue remodelling and innate immunity, and because it has been proposed that autophagy protects against cancer and neurodegenerative diseases. Although much of the molecular machinery that mediates autophagy has been identified, there are still aspects of this pathway that remain enigmatic. One open issue is the involvement of endosomal sorting complex required for transport (ESCRT) proteins, which were originally identified for their role in sorting ubiquitylated membrane proteins into multivesicular bodies. In this Opinion article, we discuss four possible models that could explain the observation that autophagosomes accumulate in ESCRT-depleted cells. We propose that the involvement of ESCRT proteins in the fusion of autophagosomes with the endolysosomal system is the most plausible model.